CHAPTER 3: Gynecologic Infection

The vaginal flora of a normal, asymptomatic reproductive-aged woman includes multiple aerobic, facultative anaerobic, and obligate anaerobic species (Table 3-1). Of these, anaerobes predominate and outnumber aerobic species approximately 10 to 1 (Bartlett, 1977). These bacteria exist in a symbiotic relationship with the host and are alterable, depending on the microenvironment. They localize where their survival needs are met and have exemption from the infection-preventing destructive capacity of the human host. The function of this vaginal bacterial colonization, however, remains unknown.

Within this vaginal ecosystem, some microorganisms produce substances such as lactic acid and hydrogen peroxide that inhibit nonindigenous organisms (Marrazzo, 2006). Several other antibacterial compounds, termed bacteriocins, play a similar role. For protection from many of these toxic substances, a secretory leukocyte protease inhibitor is found in the vagina. This protein protects local tissues against toxic inflammatory products and infection.

Certain bacterial species normally found in vaginal flora have access to the upper reproductive tract. The female upper reproductive tract is not sterile, and the presence of these bacteria does not indicate active infection (Hemsell, 1989; Spence, 1982). Together, these findings do illustrate the potential for infection following gynecologic surgery and the need for antimicrobial prophylaxis. They also explain the potential acceleration of a local acute infection if a pathogen, such as Neisseria gonorrhoeae, gains access to the upper tract.

Vaginal pH

Typically, the vaginal pH ranges between 4 and 4.5. Although not completely understood, Lactobacillus species contribute by production of lactic acid, fatty acids, and other organic acids. Other bacteria can also add organic acids from protein catabolism, and anaerobic bacteria donate by amino acid fermentation.

Glycogen, which is present in healthy vaginal mucosa, provides nutrients for many vaginal ecosystem species and is metabolized to lactic acid (Boskey, 2001). Accordingly, as glycogen content within vaginal epithelial cells diminishes after menopause, this decreased substrate for acid production leads to a rise in vaginal pH. Specifically, if no pH-altering pathogens are present, a vaginal pH of 6.0 to 7.5 is strongly suggestive of menopause (Caillouette, 1997).

Altered Flora

Changing any element of this ecology may alter the prevalence of various species. For example, postmenopausal women not receiving estrogen replacement and young girls have a lower prevalence of Lactobacillus species compared with that of reproductive-aged women. However, for menopausal women, hormone replacement therapy restores vaginal lactobacilli populations, which protect against vaginal pathogens (Dahn, 2008).

Other events predictably alter lower reproductive tract flora and may lead to infection. With the menstrual cycle, transient changes in flora are observed. These are predominantly during the first days of the cycle and are presumed to be associated with hormonal changes (Keane, 1997). Menstrual fluid can also serve as a nutrient source for several bacterial species, resulting in their overgrowth. What role this plays in the development of upper reproductive tract infection following menstruation is unclear, but an association may be present. For example, women symptomatic with acute gonococcal upper reproductive tract infection characteristically are menstruating or have just completed their menses. Last, treatment with a broad-spectrum antibiotic may result in symptoms attributed to inflammation from Candida albicans or other Candida spp by eradicating other balancing species in the flora.

Bacterial Vaginosis

This common, complex, and poorly understood clinical syndrome reflects abnormal vaginal flora. It has been variously named, and former terms are Haemophilus vaginitis, Corynebacterium vaginitis, Gardnerella or anaerobic vaginitis, and nonspecific vaginitis. With bacterial vaginosis (BV), the vaginal flora’s symbiotic relationship shifts for unknown reasons to one in which anaerobic species overgrow and include Gardnerella vaginalis, Ureaplasma urealyticum, Mobiluncus species, Mycoplasma hominis, and Prevotella species. Bacterial vaginosis (BV) is also associated with a significant reduction or absence of normal hydrogen peroxide-producing Lactobacillus species. Whether an altered ecosystem leads to lactobacilli disappearance or whether its disappearance results in the changes observed with BV is unclear.

In evaluating risks for BV, this condition is not considered by the Centers for Disease Control and Prevention (CDC) (2015) to be a sexually transmitted disease (STD). However, an increased risk of BV is associated with sexual contact with multiple and new male and female partners, and condom use lowers the risk (Table 3-2) (Fethers, 2008). Further, rates of STD acquisition are increased in affected women, and a possible role of sexual transmission in the pathogenesis of recurrent BV has been proposed (Atashili, 2008; Bradshaw, 2006; Wiesenfeld, 2003). Successful prevention of BV is limited, but elimination or diminished use of vaginal douches may be beneficial (Brotman, 2008; Klebanoff, 2010).

Bacterial vaginosis is the most common cause of vaginal discharge among reproductive-aged women. Of symptoms, a nonirritating, malodorous vaginal discharge is characteristic, but may not always be present. The vagina is usually not erythematous, and cervical examination reveals no abnormalities.

Clinical diagnostic criteria were first proposed by Amsel and associates (1983) and include: (1) microscopic evaluation of a vaginal-secretion saline preparation, (2) release of volatile amines produced by anaerobic metabolism, and (3) determination of the vaginal pH. A saline preparation, also known as a “wet prep,” contains a swab-collected sample of discharge mixed with drops of saline on a microscope slide. Clue cells are the most reliable indicators of BV and were originally described by Gardner and Dukes (1955) (Fig. 3-1). These vaginal epithelial cells contain many attached bacteria, which create a poorly defined stippled cellular border. At least 20 percent of the epithelial cells should be clue cells. The positive predictive value of this test for BV is 95 percent.

Adding 10-percent potassium hydroxide (KOH) to a fresh sample of vaginal secretions releases volatile amines that have a fishy odor. This is often colloquially referred to as a “whiff test.” The odor is frequently evident even without KOH. Similarly, alkalinity of seminal fluid and blood are responsible for foul-odor complaints after intercourse and with menses. The finding of both clue cells and a positive whiff test result is pathognomonic, even in asymptomatic patients.

Characteristically with BV, the vaginal pH is >4.5, and this stems from diminished acid production by bacteria. Similarly, Trichomonas vaginalis infection is also associated with anaerobic overgrowth and resultant elaborated amines. Thus, women diagnosed with BV should have no microscopic evidence of trichomoniasis.

Last, and used primarily in research studies rather than clinical practice, the Nugent Score is a system employed for diagnosing BV. During microscopic examination of a gram-stained vaginal discharge smear, scores are calculated by assessing bacteria staining and morphology.

Several gynecologic adverse health outcomes have been observed in women with BV. These include vaginitis, endometritis, postabortal endometritis, pelvic inflammatory disease (PID) unassociated with N gonorrhoeae or Chlamydia trachomatis, and acute pelvic infections following pelvic surgery, especially hysterectomy (Larsson, 1989, 1991, 1992; Soper, 1990). Pregnant patients with BV have an elevated risk of preterm delivery (Flynn, 1999; Leitich, 2007).

Several regimens have been proposed by the 2014 Centers for Disease Control and Prevention BV working group and are for nonpregnant women (Table 3-3). Cure rates with these regimens range from 80 to 90 percent at 1 week, but within 3 months, 30 percent of women have experienced a recurrence of altered flora. At least half have another episode of symptoms associated with this flora change, many of which are correlated with heterosexual contacts (Amsel, 1983; Gardner, 1955; Wilson, 2004). However, treatment of male sexual partners does not benefit women with this recurring condition and is not recommended. Moreover, other forms of therapy such as introduction of lactobacilli, acidifying vaginal gels, and use of probiotics have shown inconsistent effectiveness (Senok, 2009).

These drugs are commonly used in gynecology to restore altered flora or treat various infections. As a group, antibiotics have been implicated in decreasing the efficacy of oral contraceptives. Fortunately, this has been proven in very few, and these are listed in Table 5-9.

Penicillins

The heart of all penicillins is a thiazolidine ring with an attached β-lactam ring and a side chain. The β-lactam ring provides antibacterial activity, which is primarily directed against gram-positive aerobic bacteria. Because of the numerous substitutions at the side chain, various antibiotics with altered antibacterial spectra and pharmacologic properties have been synthesized.

Some bacteria produce an enzyme (β-lactamase) that opens the β-lactam ring and inactivates the drug as a primary bacterial defense mechanism. Inhibitors of β-lactamase are clavulanic acid, sulbactam, and tazobactam, and these have been combined with several penicillins to enhance the activity spectrum against a broader variety of aerobic and anaerobic bacteria. Additionally, oral probenecid can be administered separately with penicillins. This drug lowers the renal-tubular secretion rate of these antibiotics and is used to increase penicillin or cephalosporin plasma levels.

Adverse reactions to penicillins may include allergic (e.g., anaphylaxis, urticaria, drug fever), neurologic (e.g., dizziness, seizure), hematologic (e.g., neutropenia, hemolytic anemia, thrombocytopenia), renal (interstitial cystitis), hepatic (elevated transaminases), or gastrointestinal (e.g., nausea, vomiting, diarrhea, pseudomembranous colitis) reactions (Mayo Clinic, 1991). Up to 10 percent of the general population may manifest an allergic reaction to penicillins. The lowest risk is associated with oral preparations, whereas the highest follows those combined with procaine and given intramuscularly. True anaphylactic reactions are rare, and mortality rates approximate 1 in every 50,000 treatment regimens. If penicillin allergy is noted, yet treatment is still required, desensitization can be performed relatively safely as described by Wendel and coworkers (1985) and outlined at the CDC website: http://www.cdc.gov/std/treatment/2010/penicillin-allergy.htm.

Excellent tissue penetration is achieved with these agents. Penicillin remains the primary antibiotic for treatment of syphilis, and this antibiotic family is also useful in treating skin infections, breast cellulitis, and breast abscess. The combination of amoxicillin and clavulanic acid (Augmentin) provides the best oral broad-spectrum antibiotic coverage. Moreover, the ureidopenicillins and those combined with a β-lactamase enzyme inhibitor are effective against acute community-acquired or postoperative pelvic infections. In addition, Actinomyces israelii infections, which are an infrequent complication of intrauterine device (IUD) use, are treated with penicillins (Westhoff, 2007).

Cephalosporins

Cephalosporins also are β-lactam antimicrobials. Substitutions at their side chains significantly alter the spectrum of activity, potency, toxicity, and half-life of these antibiotics. Organization of these qualities has resulted in their division into five generations. This classification does allow grouping based on general spectra of activity.

Rash and other hypersensitivity reactions are the most common and may develop in up to 3 percent of patients. Cephalosporins are β-lactam antibiotics and, if used in those allergic to penicillin, may create the same or accentuated response. Theoretically, this may happen in up to 16 percent of patients (Saxon, 1987). Thus, if an individual developed anaphylaxis with penicillin therapy, cephalosporin administration is contraindicated.

First-generation cephalosporins are used primarily for surgical prophylaxis and in the treatment of superficial skin cellulitis. Their activity spectrum is greatest against gram-positive aerobic cocci, with some activity against community-acquired gram-negative rods. However, there is little activity against β-lactamase producing organisms or anaerobic bacteria. Despite this inactivity against many pathogens of pelvic infection that may be acquired during surgery, there is prophylactic efficacy.

Second-generation cephalosporins have enhanced activity against gram-negative aerobic and anaerobic bacteria, with some diminution in effectiveness against aerobic gram-positive cocci. Their primary use is in surgical prophylaxis or for single-agent therapy of major community-acquired or postoperative pelvic infections, including abscess.

Third-generation cephalosporins provide gram-positive activity, even greater gram-negative coverage, and some anaerobic effects. Fourth-generation agents have a similar profile but are less susceptible to β-lactamases. Last, fifth-generation drugs, such as ceftaroline, share a similar profile but also cover methicillin-resistant Staphylococcus aureus (MRSA). All three groups are effective in treatment of major postoperative pelvic infections, including abscess. These agents have documented efficacy as prophylactic agents, but should be reserved for therapy.

Aminoglycosides

This family of compounds includes gentamicin, tobramycin, netilmicin, and amikacin. Gentamicin is primarily selected because of its low cost and clinical efficacy for pathogens recovered from pelvic infections. For gynecologists, it may be combined with clindamycin with or without ampicillin as a regimen for treatment of serious pelvic infections. Alternatively, gentamicin may be joined with ampicillin and metronidazole. Last, it can be used as adjuvant-agent for outpatient pyelonephritis. Aminoglycoside antibacterial activity is related to its serum/tissue concentration, and the higher the concentration, the greater the potency.

Aminoglycosides have the potential for significant patient toxicity, which can include ototoxicity, nephrotoxicity, and neuromuscular blockade. The inner ear is particularly susceptible to aminoglycosides because of selective accumulation within the hair cells and prolonged half-life within inner ear fluids. Those with vestibular toxicity complain of headaches, nausea, tinnitus, and loss of equilibrium. Cochlear toxicity leads to high-frequency hearing loss. If either of these develops, aminoglycoside administration is stopped promptly. Ototoxicity may be permanent, and risk correlates positively with therapy dose and duration.

Nephrotoxicity is reversible and may develop in up to 25 percent of patients (Bertino, 1993). Risk factors include older age, renal insufficiency, hypotension, volume depletion, frequent dosing intervals, treatment for 3 or more days, multiple antibiotic administration, or multisystem disease. Toxicity leads to a nonoliguric decrease in creatinine clearance and resultant rise in serum creatinine levels.

Neuromuscular blockade is a rare but potentially life-threatening complication and is dose-related. This family of antibiotics inhibits presynaptic acetylcholine release, blocks acetylcholine receptors, and prevents presynaptic calcium absorption. For this reason, aminoglycoside contraindications include myasthenia gravis or concurrent succinylcholine use. Blockade frequently follows rapid intravenous infusion. For this reason, aminoglycosides are ideally given intravenously over at least 30 minutes. Toxicity is usually detected before respiratory arrest, and at its first signs, intravenous calcium gluconate is administered to reverse this form of aminoglycoside toxicity.

Because of these potential adverse reactions, consideration must be given to dosing regimen. In those with normal renal function, aminoglycosides are commonly given parenterally every 8 hours. In those with reduced renal function, doses are reduced, intervals are lengthened, or both. To monitor serum concentration, provide adequate therapeutic levels, and prevent toxicity in patients given multiple daily doses, serum aminoglycoside concentrations are measured at peak (30 minutes after a 30-minute infusion or 1 hour after intramuscular [IM] injection) and at trough (immediately before a next dose). For gentamicin, tobramycin, and netilmicin, peak range ideally is 4 to 6 μg/mL, and troughs are 1 to 2 μg/mL. For amikacin, peaks and troughs are 20 to 30 μg/mL and 5 to 10 μg/mL, respectively.

Once-daily dosing has been evaluated and found to be as or less toxic than multiple daily dosing without sacrificing clinical efficacy (Bertino, 1993). Tulkens and colleagues (1988) reported that once-daily dosing of netilmicin was less toxic than administration three times daily, without jeopardizing efficacy in the treatment of women with PID. In 1992, Nicolau and associates presented pharmacokinetic data and a nomogram for administering aminoglycosides once daily, which starts with an initial dose based on creatinine clearance and subsequent dosing based on a random serum concentration drawn 8 to 12 hours later.

Carbapenems

This is a third class of β-lactam antibiotics that differ from penicillins by changes to the thiazolidine ring attached to penicillin. The three antibiotics in this family are imipenem (Primaxin), meropenem (Merrem), and ertapenem (Invanz). Adverse reactions are comparable to those of the other β-lactam antibiotics. As is true with other β-lactams, if patients have experienced a type 1 hypersensitivity reaction to either a penicillin or cephalosporin, then a carbapenem should not be administered.

These antibiotics are designed for polymicrobial bacterial infections, primarily those with resistant aerobic gram-negative bacteria not susceptible to other β-lactam agents. They should be reserved to preserve efficacy by preventing the development of resistance.

Monobactam

The marketed monobactam, aztreonam, is a synthetic β-lactam. It has a spectrum of activity similar to that of aminoglycosides, that is, gram-negative aerobic species. Like other β-lactam antibiotics, these compounds inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins or causing cell lysis. Aztreonam has affinity only for the binding proteins of the gram-negative bacteria and lacks affinity for either gram-positive bacteria or anaerobic organisms. For the gynecologist, aztreonam provides coverage for gram-negative aerobic bacteria, which is usually provided by aminoglycosides, for patients with significantly impaired renal function or aminoglycoside allergy.

Clindamycin

This antibiotic is a workhorse in the treatment of serious gynecologic infections. Clindamycin is primarily active against aerobic gram-positive bacteria and most anaerobic bacteria, with little activity against aerobic gram-negative bacteria. It is also active against C trachomatis. N gonorrhoeae is moderately sensitive, and G vaginalis, which is typically present in BV, is very susceptible to clindamycin. It may be delivered by one of three routes: orally, intravenously, or vaginally (ovules or 2-percent cream).

The principal application of clindamycin for the gynecologist has been its combination with gentamicin and administration to women with serious community-acquired or postoperative soft-tissue infections or pelvic abscess. Its activity against MRSA has increased its use in these cases. Clindamycin is also used as monotherapy vaginally in the treatment of women with BV. Moreover, in women with early stages of hidradenitis suppurativa, some patients improve with long-term topical or oral clindamycin. Because there are parenteral and oral forms of this antibiotic, patients can transition from the more expensive parenteral therapy to oral therapy early.

Vancomycin

This is a glycopeptide antibiotic that is active only against aerobic gram-positive bacteria. It is primarily used by the gynecologist to treat patients in whom β-lactam therapy is impossible due to a type 1 allergic reaction. Additionally, an oral dose of 120 mg every 6 hours can be given to patients who have developed antibiotic-associated Clostridium difficile colitis and who do not respond to oral metronidazole. Last, vancomycin is often selected for MRSA infections.

Of adverse events, the most remarkable is the “red man” syndrome, which is a dermal reaction developing usually within minutes after initiation of a rapid drug infusion. The reaction, which is a response to histamine release, is an erythematous pruritic rash involving the neck, face, and upper torso. Hypotension also may develop. Intravenous administration over 1 hour or administration of an antihistamine may be protective, if given prior to infusion. Also associated with rapid administration may be painful back and chest muscle spasms.

The most significant of vancomycin’s side effects is nephrotoxicity, which is enhanced with aminoglycoside therapy, as is ototoxicity. Both are associated with high serum vancomycin concentrations. For this reason, serum peak and trough concentrations are recommended and ideally range between 20 and 40 μg/mL and 5 and 10 μg/mL, respectively. The initial dose is 15 mg/kg of ideal body weight. Other side effects include reversible neutropenia that may develop after prolonged use and peripheral intravenous-catheter-related thrombophlebitis.

Metronidazole

This antibiotic is the principal therapy of trichomoniasis and commonly used for BV. Moreover, it is one of the mainstays of combination antimicrobial therapy given to women with serious postoperative or community-acquired pelvic infections, including pelvic abscess. Since it is active only against obligate anaerobes, metronidazole must be combined with agents effective against gram-positive and gram-negative aerobic bacterial species, such as ampicillin and gentamicin. It is as effective as vancomycin in the treatment of C difficile–associated pseudomembranous colitis.

Up to 12 percent of patients taking oral metronidazole may have nausea, and an unpleasant metallic taste has also been described. Patients should abstain from alcohol use to avoid a disulfiram-like effect and emesis. Peripheral neuropathy and convulsive seizures have been reported, are probably dose-related, and are rare.

Fluoroquinolones

Also known simply as quinolones, these antibiotics have become first-line agents for treating various infections because of their excellent bioavailability with oral administration, tissue penetration, broad-spectrum antibacterial activity, long half-lives, and good safety profile. As with cephalosporins, fluoroquinolones are separated into generations by their development, antibacterial activity, and pharmacokinetic properties.

Quinolones are contraindicated in children, adolescents, and pregnant and breastfeeding women because they may affect cartilage development. As a family, they are safe, and severe adverse reactions are rare. The side-effect rate ranges from 4 to 8 percent and primarily affects the gastrointestinal (GI) tract following oral administration. Central nervous system (CNS) symptoms such as headache, confusion, tremors, and seizures have been described, and these develop more frequently in patients with underlying brain disorders.

These agents are widely used by gynecologists to treat acute lower urinary tract infections and some sexually transmitted diseases. However, overuse has limited their usefulness in certain infections due to bacterial resistance (Centers for Disease Control and Prevention, 2007). If a less expensive, safer, and equally effective alternative agent is available to treat a given infection, it should be used to preserve fluoroquinolone efficacy.

Tetracyclines

These bacteriostatic antimicrobials are commonly used orally and inhibit bacterial protein synthesis. Doxycycline, tetracycline, and minocycline are active against many gram-positive and gram-negative bacteria, although their activity is greater against gram-positive species. Susceptible organisms also include several anaerobes, Chlamydia and Mycoplasma species, and some spirochetes. Accordingly, cervicitis, PID, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale respond to these agents. Moreover, tetracyclines are among treatment options for community-acquired skin and soft-tissue MRSA infections. Specifically, for these infections, minocycline and doxycycline are superior to tetracycline. Tetracycline is active against Actinomyces species and is an alternative for treating actinomycosis. Last, these antibiotics also bind specific nonmicrobial targets, such as matrix metalloproteinases (MMPs), and are potent MMP inhibitors. As such, they provide antiinflammatory as well as antimicrobial activity for inflammatory conditions such as acne vulgaris and hidradenitis suppurativa.

With oral administration, tetracyclines can produce direct local GI irritation that manifests as abdominal discomfort, nausea, vomiting, or diarrhea. In teeth and growing bones, tetracyclines readily bind calcium, causing deformity, growth inhibition, or discoloration. Accordingly, tetracyclines are not prescribed for pregnant or nursing women or for children younger than 8 years. Sensitivity to sunlight or ultraviolet light may develop with use. Dizziness, vertigo, nausea, and vomiting may be seen with higher doses. In addition, thrombophlebitis frequently follows intravenous administration. Tetracyclines modify the normal GI flora, which can result in intestinal functional disturbances. Specifically, overgrowth of C difficile may lead to pseudomembranous colitis. Vaginal flora also may be altered with resultant Candida species overgrowth and symptomatic vulvovaginitis.

Ulceration defines complete loss of the epidermal covering with invasion into the underlying dermis. In contrast, erosion describes partial loss of the epidermis without dermal penetration. These are distinguished by clinical examination. Biopsies are generally not helpful. But if taken, samples obtained from the edge of a new lesion are the most likely to be informative. Importantly, biopsy is mandatory if carcinoma is suspected, and Figure 4-2 illustrates technique.

Most young sexually active women in the United States who have genital ulcers will have herpes simplex infection or syphilis, but some will have chancroid, lymphogranuloma venereum, or granuloma inguinale. Essentially all are sexually transmitted and are associated with increased risk for human immunodeficiency virus (HIV) transmission. For this reason, HIV and other STD testing is offered to such patients. Sexual contacts require examination and treatment, and both require reevaluation following treatment.

Herpes Simplex Virus Infection

Genital herpes is the most prevalent genital ulcer disease and is a chronic viral infection. The virus enters sensory nerve endings and undergoes retrograde axonal transport to the dorsal root ganglion, where the virus develops lifelong latency. Spontaneous reactivation by various events results in anterograde transport of viral particles/protein to the surface. Here virus is shed, with or without lesion formation. It is postulated that immune mechanisms control latency and reactivation (Cunningham, 2006).

There are two types of herpes simplex virus, HSV-1 and HSV-2. Type 1 HSV is the most frequent cause of oral lesions. Type 2 HSV is found more typically with genital lesions, although both types can cause genital herpes. It is estimated that of American females aged 14 to 49 years, 21 percent have suffered a genital HSV-2 infection, and 60 percent of women are seropositive to HSV-1 (Centers for Disease Control and Prevention, 2010; Xu, 2006).

Most women who have been infected with HSV-2 lack this diagnosis because of mild or unrecognized infections. Infected patients can shed infectious virus while asymptomatic, and most infections are transmitted sexually by patients who are unaware of their infection. Most (65 percent) with active infection are women.

Symptoms

Patient symptoms at initial presentation will depend primarily on whether or not a patient during the current episode has antibody from previous exposure. If a patient has no antibody, the attack rate in an exposed person approaches 70 percent. The mean incubation period is approximately 1 week. Up to 90 percent of those who are symptomatic with their initial infection will have another episode within a year.

The virus infects viable epidermal cells, the response to which is erythema and papule formation. With cell death and cell wall lysis, blisters form (Fig. 3-2). The covering then disrupts, leaving a usually painful ulcer. These lesions develop crusting and heal, but may become secondarily infected. The three stages of lesions are: (1) vesicle with or without pustule formation, which lasts approximately a week; (2) ulceration; and (3) crusting. Virus is predictably shed during the first two phases of an infectious outbreak.

Burning and severe pain accompany initial vesicular lesions. With ulcers, urinary frequency and/or dysuria from direct contact of urine with ulcers may be complaints. Local swelling can result from vulvar lesions and cause urethral obstruction. Alternatively or additionally, herpetic lesions can involve the vagina, cervix, bladder, anus, and rectum. Commonly, a woman has other signs of viremia such as a low-grade fever, headache, malaise, and myalgias.

Viral load undoubtedly contributes to the number, size, and distribution of lesions. Normal host defense mechanisms inhibit viral growth, and healing starts within 1 to 2 days. Early treatment with an antiviral medication decreases the viral load. Immune-deficient patients are at increased susceptibility but display diminished response and delayed healing.

For a previously uninfected patient, the vesicular stage is longer. The period of new lesion formation and time to healing are both longer. Pain persists for the first 7 to 10 days, and lesion healing requires 2 to 3 weeks. If a patient has had prior exposure to HSV-2, the initial episode is significantly less severe, with shorter pain and tenderness duration, and time to healing approximates 2 weeks. Virus is shed usually only during the first week.

Recurrence following HSV-2 infection is common, and almost two thirds of patients have a prodrome prior to lesion onset. Heralding paresthesias are frequently described as pruritus or tingling in the area prior to lesion formation. However, prodromal symptoms may develop without actual lesion formation. Clinical manifestations for women with recurrences are more limited, with only 1 week or less of symptoms.

Diagnosis

The gold standard for the diagnosis of genital herpes is tissue culture. Specificity is high, but sensitivity is low and declines as lesions heal. In recurrent disease, less than 50 percent of cultures are positive. Polymerase chain reaction (PCR) testing of exudate swabbed from the ulcer is many times more sensitive than culture and will probably replace it. Importantly, a negative culture result does not mean that there is no herpetic infection.

Serologic testing may also add clarity. The herpes simplex virus is surrounded by envelope glycoproteins, and of these, glycoprotein G is the antigen of interest for antibody screening. Serologic assays can detect antibodies specific to the HSV type-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Assay specificity is ≥96 percent, and the sensitivity of HSV-2 antibody testing ranges from 80 to 98 percent. Importantly, with serologic screening, only IgG antibody assays are ordered. IgM testing can lead to ambiguous results as the IgM assays are not type-specific and also may be positive during a recurrent outbreak. Although these tests may be used to confirm herpes simplex infection, seroconversion following initial HSV-2 infection takes approximately 3 weeks (Ashley-Morrow, 2003). Thus, in clinically obvious cases, immediate treatment and additional STD screening can be initiated following physical examination alone. In general, STD screening for a woman found to have any STD typically includes testing directed to identify syphilis, gonorrhea, trichomoniasis, and HIV, chlamydial, and hepatitis B infections.

Serologic screening for HSV in the general population is not recommended. However, HSV serologic testing can be considered for HIV-infected individuals or for women presenting for an STD evaluation, especially for those with multiple partners and for those in demographics with high prevalence (Centers for Disease Control and Prevention, 2015). It can also add management information for couples thought but not confirmed to be discordant for infection (American College of Obstetricians and Gynecologists, 2014b).

Treatment

Clinical management is with currently available antiviral therapy. Analgesia with nonsteroidal antiinflammatory drugs or a mild narcotic such as acetaminophen with codeine may be prescribed. In addition, topical anesthetics such as lidocaine ointment may provide relief. Local care to prevent secondary bacterial infection is important.

Patient education is mandatory, and specific topics include the natural history of the disease, its sexual transmission, methods to reduce transmission, and obstetric consequences. Notably, HSV can be passed to the neonate during vaginal delivery through an infected field. A comprehensive discussion of obstetric management is found in Williams Obstetrics, 24th edition (Cunningham, 2014). For all women, acquisition of this infection may have significant psychological impact, and several websites provide patient information and support. The CDC website can be accessed at http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm.

Women with genital herpes should refrain from sexual activity with uninfected partners when prodrome symptoms or lesions are present. Latex condom use potentially reduces the risk for herpetic transmission (Martin, 2009; Wald, 2005).

Currently available antiviral therapy includes acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex). The CDC-recommended oral medications regimens are listed in Table 3-4. Although these agents may hasten healing and decrease symptoms, therapy does not eradicate latent virus or affect future rate of recurrent infections.

For women with established HSV-2 infection, therapy may not be necessary if their symptoms are minimal and tolerated by the patient. Episodic therapy for recurrent disease is ideally initiated at least within 1 day of lesion outbreak or during the prodrome, if it exists. Patients may be given a prescription ahead of time so that medication is available to begin therapy with prodromal symptoms.

If episodes recur at frequent intervals, a woman may elect daily suppressive therapy, which reduces recurrences by 70 to 80 percent. Suppressive therapy may eliminate recurrences and decreases sexual transmission of virus by approximately 50 percent (Corey, 2004). Once-daily dosing may result in enhanced compliance and decreased cost.

Syphilis

Pathophysiology

Syphilis is an STD caused by the spirochete Treponema pallidum, which is a slender spiral-shaped organism with tapered ends. Women at highest risk are those from lower socioeconomic groups, adolescents, those with early onset of sexual activity, and those with a large number of lifetime sexual partners. The attack rate for this infection approximates 30 percent. In 2011, more than 49,000 cases (all stages) of syphilis were reported by state health departments in the United States (Centers for Disease Control and Prevention, 2012).

The natural history of syphilis in untreated patients can be divided into four stages. With primary syphilis, the hallmark lesion is the chancre, in which spirochetes are abundant. Classically, it is an isolated nontender ulcer with raised rounded borders and an uninfected base (Fig. 3-3). However, it may become secondarily infected and painful. Chancres are often found on the cervix, vagina, or vulva but may also form in the mouth or around the anus. This lesion can develop 10 days to 12 weeks after exposure, with a mean incubation period of 3 weeks. The incubation period is directly related to inoculum size. Without treatment, these lesions spontaneously heal in up to 6 weeks.

With secondary syphilis, bacteremia develops 6 weeks to 6 months after a chancre appears. Its hallmark is a maculopapular rash that may involve the entire body and includes the palms, soles, and mucous membranes (Fig. 3-4). As is true for the chancre, this rash actively sheds spirochetes. In warm, moist body areas, this rash may produce broad, pink or gray-white, highly infectious plaques called condylomata lata. Because syphilis is a systemic infection, other manifestations may include fever and malaise. Moreover, organ systems such as the kidney, liver, joints, and CNS (meningitis) can be involved.

During the first year following secondary syphilis without treatment, termed early latent syphilis, secondary signs and symptoms may recur. However, lesions associated with these outbreaks are not usually contagious. Late latent syphilis is defined as a period greater than 1 year after the initial infection.

Tertiary syphilis is the phase of untreated syphilis that may appear up to 20 years after latency. During this phase, cardiovascular, CNS, and musculoskeletal involvement become apparent. However, cardiovascular and neurosyphilis are half as common in females as in males.

Diagnosis

Spirochetes are too thin to retain Gram stain. Early syphilis is diagnosed primarily by dark-field examination or direct fluorescent antibody testing of lesion exudate. In lieu of this, presumptive diagnosis may be reached with serologic tests that are nontreponemal: (1) Venereal Disease Research Laboratory (VDRL) or (2) rapid plasma reagin (RPR) tests. Alternatively, treponemal-specific tests may be selected: (1) fluorescent treponemal antibody-absorption (FTA-ABS) or (2) Treponema pallidum particle agglutination (TP-PA) tests. For population screening, RPR or VDRL testing is appropriate. A positive test result in a woman who has not been treated previously for syphilis or a fourfold titer (two dilutions) increase in a woman previously treated for syphilis should prompt confirmation with treponemal-specific tests. Thus, for diagnosis confirmation in a woman with a positive nontreponemal antibody test result or with a suspected clinical diagnosis, FTA-ABS or TP-PA testing is selected. Last, for quantitative measurement of antibody titers to assess response to treatment, RPR or VDRL tests are typically used.

Following treatment, sequential nontreponemal tests are performed. During this surveillance, the same type of test should be used for consistency—either RPR or VDRL. A fourfold titer decrease is required by 6 months after therapy for primary or secondary syphilis or within 12 to 24 months for those with latent syphilis or women with initially high titers (>1:32)(Larsen, 1998). These tests usually become nonreactive after treatment and with time. However, some women may have a persistent low titer, and these patients are described as serofast. Moreover, women with a reactive treponemal-specific test will more than likely have a positive test for the remainder of their lives, but up to 25 percent may revert to a negative result after several years.

Treatment

Penicillin is the first-line therapeutic agent for this infection, and benzathine penicillin is primarily chosen. Specific recommendations for therapy by the CDC (2015) are listed in Table 3-5. For patients with penicillin allergy who cannot be surveilled posttherapy or whose compliance is questioned, skin testing, desensitization, and treatment with IM benzathine penicillin is recommended (Wendel, 1985). For all patients, an acute, self-limited febrile response, termed a Jarisch-Herxheimer reaction, may develop within the first 24 hours after treatment of early disease and is associated with headache and myalgia.

As with other STDs, all patients treated for syphilis and their sexual contacts are screened for other STDs. Patients with evidence of neurologic or cardiac involvement are treated by an infectious disease specialist. After initial treatment, women are seen at 6-month intervals for clinical evaluation and serologic retesting. A fourfold dilution decrease is anticipated. If this does not occur, a patient either has failed treatment or was reinfected and should be reevaluated and retreated. Retreatment recommendations are benzathine penicillin G, 2.4 million units IM weekly for 3 weeks.

Chancroid

This is considered one of the classic STDs but is an uncommon infection in the United States. It appears as local outbreaks predominantly in black and Hispanic males. It is caused by a nonmotile, non-spore-forming, facultative, gram-negative bacillus, Haemophilus ducreyi. Incubation usually spans 3 to 10 days, and host access probably requires a break in the skin or mucous membrane.

Chancroid lacks a systemic reaction and prodrome. Infection presents initially with an erythematous papule that becomes pustular and ulcerates within 48 hours. Edges of these painful ulcers are usually irregular with erythematous nonindurated margins. The ulcer bases are usually red and granular and, in contrast to a syphilitic chancre, are typically soft. Lesions are frequently covered with purulent material and may become secondarily infected. The most common locations in women include the fourchette, vestibule, clitoris, and labia. Ulcers on the cervix or vagina may be nontender. Concurrently, approximately half of patients will develop unilateral or bilateral tender inguinal lymphadenopathy. If large and fluctuant, they are termed buboes. These may occasionally suppurate and form fistulas, the drainage from which will result in other ulcer formation.

Chancroid most commonly imitates syphilis and genital herpes. These may coexist, but uncommonly. Definitive diagnosis requires growth of H ducreyi on special media, but sensitivity for culture is less than 80 percent. A presumptive diagnosis can be made with identification of gram-negative, nonmotile rods on a Gram stain of lesion contents. Before obtaining either specimen, superficial pus or crusting ideally is removed with sterile, saline-soaked gauze.

For treatment, the CDC’s (2015) recommended regimens for nonpregnant women include single doses of oral azithromycin (1 g) or IM ceftriaxone (250 mg). Multiple-dose options are ciprofloxacin 500 mg orally twice daily for 3 days or erythromycin base 500 mg orally three times daily for 7 days. Successful treatment leads to symptomatic improvement within 3 days, and objective evidence of improvement within 1 week. Lymphadenopathy resolves more slowly, and if fluctuant, incision and drainage may be warranted. Those with coexisting HIV infection may require longer therapy courses, and treatment failures are more common. Accordingly, some recommend longer regimens for initial management of known HIV-infected patients.

Granuloma Inguinale

Also known as donovanosis, granuloma inguinale genital ulcerative disease is caused by the intracellular gram-negative bacterium Calymmatobacterium (Klebsiella) granulomatis. This bacterium is encapsulated and appears as a “closed safety pin” in stained tissue biopsy or cytology specimens. Apparently this disease is only mildly contagious, requires repeated exposures, and has a long incubation period of weeks to months.

Granuloma inguinale presents as painless inflammatory nodules that progress to highly vascular, beefy red ulcers that bleed easily on contact. If secondarily infected, they may become painful. These ulcers heal by fibrosis, which can result in scarring resembling keloids. Lymph nodes are usually uninvolved but can become enlarged, and new lesions can appear along these lymphatic drainage channels. Distant lesions have also been reported.

Diagnosis is confirmed by identification of Donovan bodies during microscopic evaluation of a specimen following Wright-Giemsa staining. Currently, there are no Food and Drug Administration (FDA)-approved PCR tests for C granulomatis DNA.

Treatment does stop lesion progression and may be lengthy without formation of granulation tissue in ulcer bases and reepithelialization (Table 3-6). Relapses have been reported up to 18 months after “effective” treatment. A few prospective treatment trials have been published, but these are limited. If successful, improvement will be evident within the first few treatment days.

Lymphogranuloma Venereum

This ulcerative genital disease is caused by trachomatis serotypes L1, L2, and L3 and is uncommon in the United States. As is true with other STDs, this infection is found in lower socioeconomic groups among persons with multiple sexual partners. Incubation ranges from 3 days to 2 weeks, and its clinical course is divided into three stages: (1) small vesicle or papule, (2) inguinal or femoral lymphadenopathy, and (3) anogenitorectal syndrome. Initial papules appear primarily on the fourchette and posterior vaginal wall up to and including the cervix. Repeated inoculation may result in lesions at multiple sites. These primary lesions heal quickly and without scarring.

During the second stage, sometimes referred to as the inguinal syndrome, inguinal and femoral lymph nodes progressively enlarge. Painful nodes can mat together on either side of the inguinal ligament and create a characteristic “groove sign,” which appears in up to one fifth of infected women (Fig. 3-5). Moreover, enlarging nodes may rupture through the skin and lead to chronically draining sinuses. Women with lymphogranuloma venereum (LGV) commonly develop systemic infection, manifest by malaise and fever. Additionally, pneumonitis, arthritis, and hepatitis have been reported.

In the third stage of LGV, a patient develops rectal pruritus and a mucoid discharge from rectal ulcers. If these become infected, the discharge turns purulent. This presentation stems from lymphatic obstruction that follows lymphangitis and that may result in elephantiasis of external genitalia initially and fibrosis of the rectum. Stenosis of the urethra and the vagina has also been reported. Rectal bleeding is common, and a woman may complain of crampy, abdominal pain with abdominal distention, rectal pain, and fever. Peritonitis may follow bowel perforation.

LGV may be diagnosed following clinical evaluation with exclusion of other etiologies and positive chlamydial testing. Specifically, culture or immunofluorescence or nucleic acid amplification tests (NAAT) testing of samples from genital lesions, affected lymph nodes, or rectum are suitable. Moreover, a chlamydial serologic titer that is >1:64 can support the diagnosis.

For treatment, the CDC-recommended regimen (2015) is doxycycline, 100 mg orally twice daily for 21 days. Alternatively, one may use erythromycin base 500 mg orally four times daily for the same duration. Sexual contacts exposed to a patient within the prior 60 days are tested for urethral or cervical infection and treated with either standard anti-chlamydial regimen.

Symptomatic vaginal discharge most often reflects BV, candidiasis, or trichomoniasis. Bacterial vaginosis typically evokes complaints of foul discharge odor. In contrast, if abnormal discharge is associated with vulvar burning, irritation, or itching, then vaginitis is diagnosed. Between 7 and 70 percent of women who have vaginal discharge complaints will have no definitive diagnosis (Anderson, 2004). For those in whom identifiable infection is absent, an inflammatory diagnosis and treatment for infection should not be given. In such instances, a woman may seek reassurance, having concern about a recent sexual exposure, and STD screening may alleviate this.

Importantly, during evaluation, a clinician obtains a complete history regarding prior vaginal infections and their treatment, symptom duration, specifics of self-treatment with over-the-counter (OTC) preparations, and a complete menstrual and sexual history. The salient features of a menstrual history are outlined in Chapter 8. A sexual history typically includes questions regarding age at coitarche, date of most recent sexual activity, number of recent partners, gender of those partners, use of condom barrier protection, method of birth control, prior STD history, and type of sexual activity—anal, oral, or vaginal.

A thorough physical examination of the vulva, vagina, and cervix is also performed. Several etiologies may be identified in the office by microscopic examination of the discharge (Table 3-7). First, a saline preparation, described earlier, can be inspected. In contrast, a “KOH-prep” contains a swab-collected sample of discharge mixed with several drops of 10-percent potassium hydroxide (KOH). KOH leads to osmotic swelling and then lysis of squamous cell membranes. This visually clears the microscopic view and aids identification of fungal buds or hyphae. Finally, vaginal pH analysis may add supportive information. Vaginal pH can be estimated using chemical testing paper strips. Appropriate readings are obtained by pressing a test strip directly to the upper vaginal wall and resting it there for a few seconds to absorb vaginal fluid. Once the strip is removed, its color is determined and matched to a color indicator chart on the test strip dispenser. Importantly, blood and semen are alkaline and often will artificially elevate pH. Unfortunately, inexpensive laboratory tests such as these are not as accurate as a clinician would hope (Bornstein, 2001; Landers, 2004).

Fungal Infection

This infection is most commonly caused by Candida albicans, which can be found in the vagina of asymptomatic patients and is a commensal of the mouth, rectum, and vagina. Occasionally, other Candida species may be involved and include C tropicalis and C glabrata, among others. Candidiasis is seen more often in warmer climates and in obese patients. Additionally, immunosuppression, diabetes mellitus, pregnancy, and recent broad-spectrum antibiotic use predispose women to clinical infection. It can be sexually transmitted, and several studies have reported an association between candidiasis and orogenital sex (Bradshaw, 2005; Geiger, 1996).

With candidiasis, pruritus, pain, vulvar erythema, and edema with excoriations are frequent findings (Fig. 3-6). The typical vaginal discharge is described as curdy or cottage cheese-like. Microscopic examination of vaginal discharge with saline and with 10-percent KOH preparations allows yeast identification. Candida albicans is dimorphic, with both yeast buds and hyphal forms. It may be present in the vagina as a filamentous fungus (pseudohyphae) or as germinated yeast with mycelia. Vaginal candidal culture is not routinely recommended. However, it may be warranted for those who fail empiric treatment and for women with evidence of infection yet absence of microscopic yeast.

The CDC classifies vulvovaginal candidiasis (2015) into “uncomplicated” and “complicated.” Uncomplicated candidiasis cases are sporadic or infrequent, mild to moderate in symptom severity, likely caused by Candida albicans, and involve nonimmunocompromised women. For both uncomplicated and complicated infection, effective treatment formulations are listed in Table 3-8. For uncomplicated infection, azoles are extremely effective, and women warrant specific follow-up only if therapy is unsuccessful.

However, 10 to 20 percent of women have complicated candidiasis, which implies greater symptom severity, perhaps involvement of non-albicans species, affected patients with relative immunosuppression, or recurrent disease. By definition, recurrent disease reflects four or more candidal infections during a year. For women in these complicated candidiasis categories, cultures are obtained to direct care, and longer therapy may be needed to achieve clinical cure. Examples include local intravaginal therapy for 7 to 14 days.

For recurrent C albicans disease, local intravaginal therapy for 7 to 14 days or oral fluconazole (Diflucan) in 100-mg, 150-mg, or 200-mg doses once every third day for a total of three doses (day 1, 4, and 7) are options. Suppressive maintenance regimen for recurrence prevention is oral fluconazole, 100 to 200 mg weekly for 6 months. Non-albicans candidal species are not as responsive to topical azole therapy. For non-albicans recurrent infection, a 600-mg boric acid gelatin capsule intravaginally daily for 2 weeks has been successful. These capsules require a compounding pharmacy, and care is taken if children are in the household as accidental oral ingestion of boric acid capsules can be fatal.

Oral azole therapy has been associated with serum liver enzyme elevation. Thus, prolonged oral therapy may not be feasible for that reason or because of interactions with other patient medications such as calcium-channel blockers, warfarin, protease inhibitors, trimetrexate, terfenadine, cyclosporine A, phenytoin, and rifampin. In these cases, local intravaginal therapy once or twice weekly may give a similar clinical response.

Trichomoniasis

This protozoan infection is the most prevalent nonviral STD in the United States (Van der Pol, 2005, 2007). Unlike other STDs, its incidence appears to increase with patient age in some studies. Trichomoniasis is more often diagnosed in women because most men are asymptomatic. However, up to 70 percent of male partners of women with vaginal trichomoniasis will have trichomonads in their urinary tract.

This parasite is usually a marker of high-risk sexual behavior, and co-infection with other sexually transmitted pathogens is common, especially N gonorrhoeae. Trichomonas vaginalis has predilection for squamous epithelium, and lesions may increase accessibility to other sexually transmitted species. Vertical transmission during birth is possible andmay persist for a year.

Diagnosis

Incubation with T vaginalis requires 3 days to 4 weeks, and the vagina, urethra, endocervix, and bladder can be infected. No symptoms are noted in up to one half of women with trichomoniasis, and such colonization can persist for months or years. However, in those with complaints, vaginal discharge is typically described as foul, thin, and yellow or green. Additionally, dysuria, dyspareunia, vulvar pruritus, vaginal spotting, and pain may be noted. At times, clinical findings are identical to those of acute PID.

With trichomoniasis, the vulva may be erythematous, edematous, and excoriated. The vagina contains the discharge just described, and subepithelial hemorrhages or “strawberry spots” dot the vagina and cervix. Trichomonads are oval anaerobic protozoa that are slightly larger than a white blood cell (WBC) and have anterior flagella (Fig. 3-7). Microscopic identification of these motile parasites in a saline preparation of the discharge is diagnostic. However, trichomonads are less motile with cooling, and slides ideally are examined within 20 minutes. Inspection of a saline preparation is highly specific, yet sensitivity is only 60 to 70 percent. In addition to microscopy, vaginal pH is often elevated.

The most sensitive diagnostic technique is culture, which is impractical because special media (Diamond media) is required and few laboratories are equipped. NAATs for trichomonal DNA are sensitive and specific but not widely available. Alternatively, the OSOM Trichomonas Rapid Test is an immunochromatographic assay, which has 88-percent sensitivity and 99-percent specificity. It is available for office use, and results are available in 10 minutes (Huppert, 2005, 2007). Trichomonads may also be noted on Pap smear screening and sensitivity approximates 60 percent (Wiese, 2000). If trichomonads are reported from a Pap smear slide, confirmation by microscopic evaluation of a saline preparation is encouraged prior to treatment (American College of Obstetricians and Gynecologists, 2013b). Women with trichomoniasis are tested for other STDs. Additionally, sexual contact(s) are evaluated or referred for evaluation.

Treatment

Oral regimens recommended by the CDC (2015) are either metronidazole 2 g once or tinidazole (Tindamax) 2 g once. Although each is effective, some report that an oral 7-day treatment regimen with metronidazole 500 mg twice daily may be more effective in compliant patients. However, compliance may be poor because of longer treatment length and metronidazole side effects. Because of drug disulfiram-like effects, patients should abstain from alcohol during use and for 24 hours following metronidazole therapy and for 72 hours after tinidazole.

Affected women are retested within 3 months of treatment.Recurrence occurs in approximately 30 percent of patients. Sex partners are encouraged to seek treatment, and patients are reminded to abstain from sex until they and their partners are cured. Condom use may be protective.

Infrequently, patients may have strains that are highly resistant to metronidazole, but these organisms are usually sensitive to tinidazole. Culture and sensitivity are performed on specimens from patients with frequently recurring infections or from those who do not respond to the initial therapy and who are regimen compliant. Oral tinidazole at doses of 500 mg orally three times daily for 7 days or four times daily for 14 days have been effective in curing patients with resistant organisms (Sobel, 2001). Cases of allergy to these two nitroimidazoles require desensitization by a specialist (Helms, 2008).

Neisseria gonorrhoeae

Many women with cervical N gonorrhoeae are asymptomatic. For this reason, women at risk are screened periodically (Table 1-1). Risk factors for gonococcal carriage and potential upper reproductive tract infection that merit screening are: age ≤24 years, prior or current STDs, new or multiple sexual partners, a partner with other concurrent partners, a partner with an STD, lack of barrier protection in those without a monogamous relationship, and commercial sex work (U.S. Preventive Services Task Force, 2014). Screening for women at low risk is not recommended.

Diagnosis

Symptomatic lower female reproductive tract gonorrhea may present as vaginitis or cervicitis. Those with cervicitis commonly describe a profuse odorless, nonirritating, and white-to-yellow vaginal discharge. Patients may report intermenstrual or postcoital vaginal bleeding, or gentle passage of a cotton swab into the cervical os often produces endocervical bleeding. Gonococcus can also infect the Bartholin and Skene glands, the urethra, and ascend into the endometrium and fallopian tube to cause upper reproductive tract infection.

N gonorrhoeae is a gram-negative coccobacillus that invades columnar and transitional epithelial cells, becoming intracellular. For this reason, the vaginal epithelium, which is squamous cell, is not involved.

For gonococcal identification, NAATs are available and have replaced culture in most laboratories. Previously, acceptable specimens were recovered only from the endocervix or urethra. However, newer NAAT collection kits are available for specific collection from the vagina, endocervix, or urine. For women without a cervix following hysterectomy, first-void urine samples are collected. For those with a cervix, vaginal-swab specimens are as sensitive and specific as cervical-swab specimens. Urine samples, although acceptable, are least preferred for those with a cervix (Association of Public Health Laboratories, 2009). However, if selected, the initial urine stream, not midstream, is collected. Of note, these noncultural tests are not FDA-cleared for diagnostic identification of rectal or pharyngeal disease. Thus, cultures are obtained in those screened at these anatomic sites.

All patients with gonorrhea are tested for other STDs, and sexual contacts from the preceding 60 days are evaluated and treated or referred for this. Abstinence is practiced until therapy is completed and until they and their treated sexual partners have symptom resolution.

Expedited Partner Therapy

To prevent and control STDs, guidelines for expedited partner therapy (EPT) have been created by the CDC. EPT is the delivery of a prescription by persons infected with an STD to their sexual partners without clinical assessment of the partners or professional counseling. EPT ideally does not replace traditional strategies, such as standard patient referral, when these are available. Although acceptable for treatment of heterosexual contacts with gonorrhea or chlamydial infection, data do not support EPT for trichomoniasis or syphilis. Although sanctioned by the CDC, EPT is not legal in several states within the United States. Moreover, the risk of litigation in the event of adverse outcomes may be elevated when a practice has uncertain legal status or is outside formally accepted community practice standards (Centers for Disease Control and Prevention, 2006). The legal status of EPT in each of the 50 states can be found at: http://www.cdc.gov/std/ept/legal/default.htm.

Treatment

CDC recommendations for single-dose therapy of uncomplicated cervical, urethral, or rectal infection are outlined in Table 3-9. Importantly, widespread quinolone-resistant gonococci in the United States prompted removal of this antibiotic class from the CDC STD guidelines, and declining effectiveness of cefixime has shifted its role to an alternative agent (Centers for Disease Control and Prevention, 2015). Uncomplicated gonococcal pharyngeal infection treatment mirrors the recommended regimen in Table 3-9. Test-of-cure cultures are not usually necessary unless an alternative to ceftriaxone is used. In cases of cephalosporin allergy, one potential option is single oral doses of gemifloxacin 320 mg plus azithromycin 2 g. Another is single doses of gentamicin 240 mg IM plus oral azithromycin 2 g. For azithromycin allergy, ceftriaxone alone suffices. However, if the alternative regimen with cefixime is used, then doxycycline, 100 mg orally twice daily for 7 days, replaces the azithromycin (Centers for Disease Control and Prevention, 2015).

Chlamydia trachomatis

This organism is among the most prevalent of the STD species recovered in the United States, and its highest prevalence is found in individuals younger than 25 years. Chlamydia prevalence was 4.7 percent overall among sexually active females aged 14 to 24 years based on national survey estimates from 2007 to 2012 (Torrone, 2014). This increased to 13.5 percent among non-Hispanic black females. Since many with this organism are asymptomatic, women with the same risks that prompt gonococcal screening, listed on page 64, are screening candidates.

This obligate intracellular parasite is dependent on host cells for survival. It infects columnar epithelial cells, and endocervical glandular infection leads to mucopurulent discharge or endocervical secretions. If infected, the endocervical tissue is commonly edematous and hyperemic. Urethritis can also develop, and dysuria is prominent.

Microscopic inspection of secretions in a saline preparation typically reveals 20 or more leukocytes per high-power field. More specifically, culture, NAAT, and enzyme-linked immunosorbent assay (ELISA) are available for endocervical specimens. Alternatively, combined gonococcal and chlamydial tests are widely used. As with gonorrhea testing, newer NAAT collection kits permit specific collection from the vagina, the endocervix, or urine. Vaginal-swab specimens are as sensitive and specific as cervical-swab specimens. Urine samples, although acceptable, are least preferred for women with a cervix. However, for women following hysterectomy, first-void urine samples are preferred. Again, these noncultural tests are not FDA-cleared for diagnostic identification of rectal or pharyngeal disease. If C trachomatis is diagnosed or suspected, then screening for other STDs is indicated.

Recommended therapy for C trachomatis infection is described in Table 3-10. Azithromycin has the obvious therapeutic compliance advantage of allowing clinicians to observe ingestion at the time of diagnosis. Following treatment, retesting is not recommended if symptoms resolve. To prevent further infection, abstinence is recommended until a woman and her partner(s) are treated and are asymptomatic. Sexual partner(s) are referred for evaluation, or they are examined, counseled, tested, and treated. As with gonorrhea in heterosexual partners, expedited partner therapy is sanctioned by the CDC for selected patients.

Mycoplasma genitalium

Discovered in 1980, this bacterium’s role in female lower reproductive tract pathology is poorly defined. Most women carriers are asymptomatic, but it has been linked in some but not all studies to urethritis, cervicitis, PID, and later to tubal-factor infertility (Taylor-Robinson, 2011; Weinstein, 2012). Thus, in women with persistent or recurrent urethritis, cervicitis, or PID, M genitalium may be considered. It has a much more established role in male urethritis (Daley, 2014). As such, gynecologists may more frequently encounter the exposed female partner of an infected male. Currently, the CDC (2015) comments that NAAT testing for exposed women and treatment of subsequently identified infections can be considered. NAATs for this organism are not widely available, but samples from voided urine, the vagina, or the endocervix are appropriate (Lillis, 2011).

For urethritis, cervicitis, or exposure coverage, azithromycin 1 g orally once is recommended. Antibiotic-resistant strains are not uncommon, and for treatment failure, moxifloxacin 400 mg once orally for 7 to 14 days may be used. This same moxifloxacin regimen for 14 days may be considered for women with PID who fail to respond after 7 to 10 days of standard regimens and in whom M genitalium is detected (Centers for Disease Control and Prevention, 2015; Manhart, 2011).

This is an infection of the upper female reproductive tract organs. Another diagnosis given to this disease is acute salpingitis. Although all reproductive tract organs may be involved, the organ of importance, with or without abscess formation, is the fallopian tube. Because of difficulty in accurately diagnosing this infection, its true magnitude is unknown. Many women report that they have been treated for PID when they did not have it, and vice versa. The clinical importance of diagnosing PID is emphasized by its known sequelae, which include tubal-factor infertility, ectopic pregnancy, and chronic pelvic pain. Thus, clinicians ideally carry a low threshold for diagnosing and treating PID.

Microbiology and Pathogenesis

The exact microbiologic pathogens in the fallopian tube cannot be known for any given patient. Studies have shown that transvaginal culture of the endocervix, endometrium, and cul-de-sac contents reveals different organisms from each site in the same patient. For that reason, treatment protocols are designed so that most potential pathogens are covered by antibiotic regimens.

Classic salpingitis is associated with and secondary to N gonorrhoeae infection, and C trachomatis is also commonly recovered (Table 3-11). Another species frequently found is T vaginalis. The lower reproductive tract flora in women with PID and in those with bacterial vaginosis is predominately anaerobic species. The microenvironment changes produced by BV may aid ascension of the causative organisms of PID (Soper, 2010). However, Ness and colleagues (2004) and others have shown that bacterial vaginosis is not a risk factor for PID development.

Upper tract infection is believed to be caused by bacteria that ascend from the lower reproductive tract. It is assumed that this ascension is enhanced during menstruation due to loss of endocervical barriers. The gonococcus can cause a direct inflammatory response in the human endocervix, endometrium, and fallopian tube and is one of the true pathogens of human fallopian tube epithelial cells. If normal human fallopian tube cells in cell culture are exposed to potential pathogens such as Escherichia coli, Bacteroides fragilis, or Enterococcus faecalis, no inflammatory response follows. If the above bacteria are introduced into a fallopian tube cell culture in which gonococci are present and have caused inflammatory damage, then an exaggerated inflammatory response results.

In contrast, intracellular C trachomatis does not cause an acute inflammatory response, and little direct permanent damage results from chlamydial tubal involvement (Patton, 1983). However, cell-mediated immune mechanisms may be responsible for subsequent tissue injury. Specifically, persistent chlamydial antigens can trigger a delayed hypersensitivity reaction with continued tubal scarring and destruction (Toth, 2000).

Last, women with pulmonary tuberculosis can develop salpingitis and endometritis. This pathogen is thought to be blood-borne, but ascension may still be a possible route. The fallopian tubes also can be infected by direct extension from inflammatory GI disease, especially ruptured abscess, for example, appendiceal or diverticular.

Diagnosis

Silent Pelvic Inflammatory Disease

Pelvic inflammatory disease can be segregated into “silent” PID and PID. The latter can be further subdivided into acute and chronic.

Silent PID is thought to follow multiple or continuous low-grade infection in asymptomatic women. Silent PID is not a clinical diagnosis. Rather, it is an ultimate diagnosis given to women with tubal-factor infertility who lack a history compatible with upper tract infection. Many of these patients have antibodies to C trachomatis and/or N gonorrhoeae. At laparoscopy or laparotomy, affected women may have evidence of prior tubal infection such as adhesions, but for the most part, the fallopian tubes are grossly normal. Internally, however, tubes show flattened mucosal folds, extensive deciliation of the epithelium, and secretory epithelial cell degeneration (Patton, 1989). Alternatively, hydrosalpinx may be found. Grossly, these fallopian tubes are distended along their entire length. Their distal ends are dilated and clubbed, and fimbria are replaced by or encased by smooth adhesions (Fig. 9-22). Sonographically, a hydrosalpinx tends to be anechoic, tubular, serpentine, and often with incomplete septa (Figs. 9-23). Last, fine adhesions between the liver capsule and anterior abdominal wall may also reflect prior silent disease.

Acute Pelvic Inflammatory Disease

Symptoms and Physical Findings

The most recent diagnostic criteria presented by the CDC (2015) are for sexually active women at risk for STDs who have pelvic or lower abdominal pain and in whom other etiologies are excluded or unlikely. PID is diagnosed if uterine tenderness, adnexal tenderness, or cervical motion tenderness is present. One or more of the following enhances diagnostic specificity: (1) oral temperature >38.3°C (101.6°F), (2) mucopurulent cervical discharge or cervical friability, (3) abundant WBCs on saline microscopy of cervical secretions, (4) elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), and (5) presence of cervical N gonorrhoeae or C trachomatis. Thus, a diagnosis of PID is one typically based on clinical findings.

With acute PID, symptoms characteristically develop during or soon following menstruation. These can include lower abdominal and/or pelvic pain, yellow vaginal discharge, heavy menstrual bleeding, fever, chills, anorexia, nausea, vomiting, diarrhea, dysmenorrhea, and dyspareunia. Patients also may have complaints suggesting urinary tract infection. Unfortunately, no single symptom is associated with a physical finding that is specific for this diagnosis. Accordingly, other possible sources of acute pelvic pain are considered and listed in Table 11-1.

In women with acute PID, leukorrhea or mucopurulent endocervicitis is common and is diagnosed visually and microscopically. During bimanual pelvic examination, affected women will usually have pelvic organ tenderness. Cervical motion tenderness (CMT) is typically elicited by quickly moving the cervix with examining vaginal fingers. This reflects pelvic peritonitis and can be considered a vaginal “rebound” test. If a woman has pelvic peritonitis secondary to bacteria and purulent debris that has exuded from the fimbriated end of the fallopian tube, this rapid peritoneal movement usually causes a marked pain response. Tapping the cul-de-sac with examining finger(s) will give the examiner similar information. This latter maneuver usually causes a patient significantly less pain because less inflamed peritoneum is stretched.

Abdominal peritonitis may be identified by deep probing and quick release of a hand placed on the abdomen—a test for rebound. Alternatively, an examining hand may be positioned with a palm against a woman’s midabdomen and gently and quickly moved back and forth (shake). This can identify abdominal peritonitis, often with less patient discomfort.

In women with PID and peritonitis, usually only the lower abdomen is involved. However, inflammation of the liver capsule, which can accompany PID, may lead to right upper quadrant pain, a condition known as Fitz-Hugh-Curtis syndrome. Classically, symptoms of this perihepatitis include sharp, pleuritic right upper quadrant pain that accompanies pelvic pain. The upper abdominal pain may refer to the shoulder or upper arm. With auscultation, a friction rub may be heard along the right anterior costal margin. Importantly, during examination, if all abdominal quadrants are involved, suspicion for a ruptured tuboovarian abscess (TOA) is heightened.

Testing

In women with lower abdominal pain, tests directed at diagnosing PID or excluding other pain sources are selected. Pregnancy complications can be identified by serum or urine beta-human chorionic gonadotropin testing. A complete blood count (CBC) is selected as a baseline test to exclude hemoperitoneum as the cause of symptoms and identify WBC elevation. In those with significant nausea and vomiting or Fitz-Hugh-Curtis syndrome, liver enzyme values may be normal or mildly elevated. If properly collected, urinalysis findings for infection will be absent. Saline preparation of cervical or vaginal discharge will typically show sheets of leukocytes. In women with suspected acute PID, endocervical testing for both N gonorrhoeae and C trachomatis is performed as described earlier. Screening for other STDs is also completed.

In the opinion of many, an endometrial biopsy (EMB) in women with mucopurulent secretions and suspected PID does not provide useful information to alter the diagnosis or therapy (Achilles, 2005). However, some do recommend EMB to diagnose endometritis. Polymorphonuclear leukocytes on the endometrial surface correlate with acute endometritis, whereas plasma cells in the endometrium are found with chronic endometritis. However, women with uterine leiomyomas or endometrial polyps but without PID may also often have plasma cells present in the endometrium, as do essentially all women in their lower uterine segment.

Sonography

In women with marked abdominal pain and tenderness, appreciation of upper reproductive tract organs during bimanual examination may be limited, and sonography is a primary imaging tool (Fig. 2-21). Normal fallopian tubes are rarely imaged. However, with acute tubal inflammation, the tube swells, its lumen occludes distally, it distends, and its walls and endosalpingeal folds thicken. Characteristic findings include: (1) distended, ovoid-shaped tube filled with anechoic or echogenic fluid, (2) fallopian tube wall thickening, (3) incomplete internal septa, and (4) a “cogwheel” appearance when inflamed tubes are imaged in cross section (Timor-Tritsch, 1998). If color or power Doppler is applied, marked vascularity with low-impedance blood flow, which reflects hyperemia, is seen within thickened fallopian tube walls and if present, within septa (Molander, 2001; Romosan, 2013). Sonography may also be used to identify TOA or exclude other pathology as the pain source. If sonography does not lead to a clear diagnosis, computed-tomography (CT) scanning is often selected (Sam, 2002). Magnetic resonance (MR) imaging is a suitable alternative. In women with right upper quadrant pain suggestive of perihepatitis, chest radiography or upper abdominal sonography may be needed to exclude other pathology.

Laparoscopy

In Scandinavian countries, women suspected of having acute PID undergo laparoscopy for diagnosis. Tubal serosal hyperemia, tubal wall edema, and purulent exudate issuing from the fimbriated ends of the fallopian tubes, termed pyosalpinx, and pooling in the cul-de-sac confirm this diagnosis. Because of this routine practice, Hadgu and coworkers (1986) assembled criteria that preoperatively clinically predicted acute PID and assessed their validity by the absence or presence of disease at laparoscopy. Criteria included: (1) single status, (2) adnexal mass, (3) age <25 years, (4) temperature >38°C, (5) cervical N gonorrhoeae, (6) purulent vaginal discharge, and (7) ESR ≥15 mm/hr. The preoperative clinical diagnosis of PID was 97-percent accurate if a woman met all seven criteria, allowing avoidance of surgery. Thus, due to the risks of laparoscopy, use of clinical findings alone to diagnose PID is reasonable. In those with a less clear presentation, laparoscopy may be needed to exclude other pathology such as appendicitis or adnexal torsion.

Tuboovarian Abscess

With infection, the inflamed and suppurative fallopian tube can adhere to the ovary. Sonographically, if both tube and ovary are recognizable, the term tuboovarian complex is used. If inflammation proceeds, tissue planes and distinction between the two is lost, and the term tuboovarian abscess is applied. Tuboovarian abscesses are typically unilateral and may also involve adjacent structures that include bowel, bladder, and contralateral adnexa. With abscess progression, further structural weakening may lead to abscess rupture and potentially life-threatening peritonitis. Although PID is an important cause of TOA, these may also follow appendicitis, diverticulitis, inflammatory bowel disease, or surgery.

Classically, affected women display signs of PID and a concurrent adnexal or cul-de-sac mass. Sonographically, with TOA, a complex cystic adnexal or cul-de-sac mass with thick irregular walls, areas of mixed echogenicity, septations, and internal echoes from debris is seen (Fig. 2-22). If the clinical picture is unclear, CT scanning may add information. A thick-walled, cystic adnexal mass with internal septations and surrounding inflammatory changes is characteristic (Fig. 3-8). Although not routinely used for TOA imaging, MR imaging usually shows a complex pelvic mass with low signal intensity on T1-weighted sequences and heterogeneously high signal intensity on T2-weighted sequences.

Microorganisms frequently cultured include E coli, Bacteroides spp, Peptostreptococcus spp, and aerobic Streptococcus spp. (Landers, 1983). Thus, broad-spectrum antibiotic coverage, including that for anaerobes, is selected for initial management of women with unruptured TOA. Most women with TOA will respond to intravenous (IV) antibiotic therapy alone and avoid the need for drainage. Combination antimicrobial regimens will predictably be more successful, and CDC (2015) recommendations for TOA complicating PID include IV regimens in Table 3-12. Parenteral antimicrobial therapy is continued until the patient has been afebrile for at least 24 hours, preferably 48 to 72 hours. In transitioning to oral therapy, doxycycline 100 mg twice daily is combined with either metronidazole 500 mg twice daily or clindamycin 450 mg four times daily to complete a 14-day course.

For those not improved within 2 to 3 days of treatment, prior to attempts at abscess drainage, antimicrobial regimen modification is indicated. Drainage plus antibiotic therapy can be considered as initial treatment for larger abscesses (≥8 cm). For this, drainage can be accomplished with or without surgery. Radiologic drainage is minimally invasive and potentially avoids the higher risks associated with general anesthesia and surgery. In general, pelvic collections can be emptied using transabdominal, transvaginal, transgluteal, or transrectal routes with either CT or sonographic guidance and adequate analgesia. Depending on abscess size and characteristics, contents can be removed with needle aspiration or with pigtail catheter placement and short-term drainage. In cases that are refractory or not amenable to these more conservative measures, exploratory laparoscopy or laparotomy is typically warranted. In those with TOA rupture, emergency surgery is required. Goals of surgery include abscess drainage, excision of necrotic tissues, and peritoneal cavity irrigation.

As is true in all abscesses, drainage is the key to clinical improvement. Although perhaps tempting at laparotomy, removal of the abscess is not necessary unless ovarian parenchyma is involved. This is rare. Electively opening the protective peritoneal and other tissue planes to remove tissues—especially the uterus—in the presence of acute infection does not improve patient outcome compared with percutaneous drainage. As a clinical comparison, infected Bartholin glands are not excised. Rather, they are drained and definitively treated later, when not infected, if necessary.

Infection confined within one organ, such as a pyosalpinx, responds more favorably to antimicrobial therapy because of adequate blood and lymphatic supply. This is true even if attached to an adjacent ovary. A cul-de-sac or interloop abscess is more likely to require drainage, however, because of poor blood and lymphatic supply and a less prompt response to antimicrobial therapy.

Following successful conservative treatment, bilateral adnexal abscesses cannot be equated with guaranteed infertility. In a clinical trial evaluating such patients, 25 percent of women subsequently became pregnant (Hemsell, 1993).

Chronic Pelvic Inflammatory Disease

This diagnosis is given to women who describe a history of acute PID and who have subsequent pelvic pain. Accuracy of this diagnosis clinically is orders of magnitude less than for acute PID. A hydrosalpinx might qualify as a criterion for this diagnosis. Realistically, however, it is a histologic diagnosis (chronic inflammation) made by a pathologist. Thus, the clinical utility of this diagnosis is limited.

Treatment of Pelvic Inflammatory Disease

The most successful patient outcomes follow early diagnosis and prompt, appropriate therapy. The primary therapy goal is to eradicate bacteria, relieve symptoms, and prevent sequelae. Tubal damage or occlusion resulting from infection may lead to infertility. Rates following one episode approximate 15 percent; two episodes, 35 percent; and three or more episodes, 75 percent (Westrom, 1975). Also, ectopic pregnancy risk is increased six- to 10-fold and may reach a 10-percent risk for those who conceive. Other sequelae include chronic pelvic pain (15 to 20 percent), recurrent infection (20 to 25 percent), and abscess formation (5 to 15 percent). Unfortunately, women with mild symptoms may remain at home for days or weeks prior to presentation for diagnosis and therapy.

Exactly where a patient is treated remains controversial. There are proposed criteria that predict better outcome for certain patients with in-hospital parenteral antimicrobial therapy (Table 3-13). However, the high cost of in-hospital treatment prevents routine hospitalization for all women given this diagnosis.

Another potential clinical decision involves management of a coexistent IUD. During the first 3 weeks after device insertion, patients have an increased IUD-associated PID risk. After this time, other PID risks are considered causative. With PID, theoretical concerns are that a coexistent IUD might worsen the infection or delay resolution. Although a provider may choose to remove the device, evidence supports leaving an IUD during treatment in those hospitalized with mild or moderate PID (Centers for Disease Control and Prevention, 2015; Tepper, 2013). Severe disease warrants IUD removal. With or without an IUD, women are treated with similar antibiotic regimens. But, if a patient fails to improve within 48 to 72 hours, the device is removed.

Oral Treatment

In women with a mild to moderate clinical presentation, outpatient treatment and inpatient therapy yield similar results. Clinical treatment with oral therapy is also appropriate for women with HIV infection and PID. These women have the same species recovered compared with non-HIV-infected patients, and their response to therapy is similar.

If women have more than moderate disease, they require hospitalization. Dunbar-Jacob and associates (2004) showed that women treated as outpatients took 70 percent of prescribed doses, and for less than 50 percent of their outpatient treatment days. If patients are treated as outpatients, an initial parenteral dose may be beneficial. Women treated as outpatients are reevaluated in approximately 72 hours by phone or in person. If women do not respond to oral therapy within 72 hours, parenteral therapy is initiated either as an inpatient or as an outpatient if home nursing care is available. This assumes that the diagnosis is confirmed at reevaluation.

Specific treatment recommendations from the CDC are found in Table 3-14. Anaerobes are believed by some to play an important role in upper tract infection and are treated. Hence, metronidazole may be added to improve anaerobic coverage. If patients have BV or trichomoniasis, then metronidazole addition is required, although perhaps not for 14 days.

Parenteral Treatment

Any woman who has criteria as outlined in Table 3-13 is hospitalized for parenteral treatment for at least 24 hours. Following this, if home parenteral treatment is available, this is a reasonable option. Alternatively, if a woman responds clinically and will be appropriately treated by one of the oral regimens in Table 3-14, then she can be discharged on those medications.

Recommendations for parenteral antibiotic treatment of PID are found in Table 3-12. Of these antibiotics, oral and parenteral routes of doxycycline have almost identical bioavailability, but parenteral doxycycline is caustic to veins. Many prospective clinical trials have shown that either of the listed cephalosporins alone, without doxycycline, will result in a clinical cure. For that reason, doxycycline administration could be reserved until the patient can take oral medication. The recommendation is to continue parenteral therapy until 24 hours after the patient clinically improves, and the oral doxycycline 100 mg twice daily is continued to complete 14 days of therapy. Alternatively, if the IV gentamycin/clindamycin regimen is used, then transition to a 14-day oral agent may involve clindamycin orally four time daily or doxycycline 100 mg twice daily.

External Genital Warts

These lesions are created from infection with the human papillomavirus (HPV), and 86 percent of cases stem from HPV 6 or 11 (Garland, 2009). A fuller discussion of HPV pathophysiology is found in Chapter 29. Genital warts display differing morphologies, and appearances range from flat papules to the classic verrucous, exophytic lesions, termed condyloma acuminata (Fig. 3-9) (Beutner, 1998). Involved tissues vary, and external genital warts may develop at sites in the lower reproductive tract, urethra, anus, or mouth. They are usually asymptomatic but can be pruritic or painful depending on their size and location. Warts are typically diagnosed by clinical inspection, and biopsy is not required unless coexisting neoplasia is suspected (Wiley, 2002). Similarly, HPV serotyping is not required for routine diagnosis.

Condyloma acuminata may remain unchanged or spontaneously resolve, and the effect of treatment on future viral transmission is unclear. However, many women prefer removal, and lesions can be destroyed with sharp or electrosurgical excision, cryotherapy, or laser ablation. In addition, very large, bulky lesions may be managed with cavitational ultrasonic surgical aspiration (CUSA) (Section 43-28).

Alternatively, topical agents can be applied to resolve lesions through various mechanisms (Table 3-15). One of these, 5-percent imiquimod cream (Aldara), is a patient-applied, immunomodulatory topical treatment for genital warts. This agent induces macrophages to secrete several cytokines, and of these, interferon-γ is probably the most important. For genital wart clearance, this cytokine stimulates a cell-mediated immune response against HPV (Scheinfeld, 2006). Another topical immune-modulating agent is a 15-percent sinecatechin ointment (Veregen) derived from green tea leaf extracts (Meltzer, 2009). Podophyllin is an antimitotic agent available in a 10- to 25-percent tincture of benzoin solution and disrupts viral activity by inducing local tissue necrosis. Podophyllin resin is no longer a first-line CDC-recommended option due to risks of systemic toxicity if used incorrectly. However, a biologically active extract of podophyllin, podofilox, also termed podophyllotoxin, is available in a 0.5-percent solution or gel (Condylox) and can be self-applied by the patient. Alternatively, trichloroacetic acid and bichloroacetic acid are proteolytic agents and are applied serially to warts by clinicians. Intralesion injection of interferon is an effective treatment for warts (Eron, 1986). However, its high cost and painful administration render it an alternative option.

Of therapy choices, no data suggest the superiority of one treatment. Thus, in general, treatment is selected based on clinical circumstances and patient and provider preferences. Importantly, no treatment option, even surgical excision, boasts 100-percent clearance rates. Indeed, clearance rates range from 30 to 80 percent. Accordingly, recurrences are common following treatment.

Molluscum Contagiosum

The molluscum contagiosum virus is a DNA poxvirus that is transmitted by direct human-to-human contact or by infected fomites. An incubation period of 2 to 7 weeks is typical, but can be longer. The host response to viral invasion is papular with central umbilication, giving a characteristic appearance (Fig. 3-10). It may be single or multiple and is commonly seen on the vulva, vagina, thighs, and/or buttocks. Molluscum contagiosum is contagious until lesions resolve.

These papules are typically diagnosed by visual inspection alone. However, material from a lesion can be collected on a swab, applied to a slide, and submitted to a laboratory for diagnostic staining with Giemsa, Gram, or Wright stains. Molluscum bodies, which are large intracytoplasmic structures, are diagnostic.

Most lesions spontaneously regress within 6 to 12 months. If removal is preferred, lesions may be treated by cryotherapy, electrosurgical needle coagulation, or sharp needle-tip curettage of a lesion’s umbilicated center. Alternatively, topical application of agents used in the treatment of genital warts may also be effective treatment for molluscum contagiosum (see Table 3-15).

Scabies

Sarcoptes scabiei infect skin and result in an intensely pruritic rash. This mite is crab-shaped, and the female digs into the skin and remains there for approximately 30 days, elongating her burrow. Several eggs are laid daily and begin hatching after 3 to 4 days (Fig. 3-11). The baby mites furrow their own burrows, becoming reproductive adults in approximately 10 days. The number of adult mites present on an affected patient averages a dozen. Sexual transmission is the most likely cause of initial infection, although it can be seen in household contacts.

Burrows are thin elevated skin tracks measuring 5 to 10 mm in length. A delayed-type 4 hypersensitivity reaction to the mites, eggs, and feces develops and results in erythematous papules, vesicles, or nodules in association with skin burrows. Secondary infection, however, may develop and hide these tracks. Most common infection sites include the hands, wrist, elbows, groin, and ankles. Itching in these areas is the predominant symptom.

Definitive testing requires scraping across the burrow with a scalpel blade and mixing these fragments in immersion oil on a microscope slide. Identification of mites, eggs, egg fragments, or fecal pellets is diagnostic.

Once diagnosed, 5-percent permethrin cream (Elimite) is a recommended agent. A thin layer is applied from the neck downward with special attention to pruritic areas and the hands, feet, and genital regions. Ideally, all family members are treated with the exception of infants younger than 2 years. Eight to 14 hours after application, a shower or bath is taken to remove the medication. Only one application is necessary. Another option is the oral antihelminth ivermectin (Stromectol) 200 μg/kg once and then repeated 2 weeks later. Bed linens and recently worn clothing are washed to prevent reinfection. A less-preferred option is 1-percent lindane, because it is not recommended in pregnancy or in children younger than 2 years and because seizures have occurred if spread on areas with extensive dermatitis or immediately after showering. If used, a 30-g dose of cream is applied and rinsed off similar to permethrin.

An antihistamine will help reduce pruritus, which can also be treated with a hydrocortisone-containing cream in adults or with emollients or lubricating agents in infants. If these lesions become infected, antibiotic therapy may be necessary.

Pediculosis

Lice are small ectoparasites that measure approximately 1 mm (Fig. 3-12). Three species infest humans and include the body louse (Pediculus humanus), the crab louse (Phthirus pubis), and the head louse (Pediculus humanus capitis). Lice attach to the base of human hair with claws that vary in diameter between species. It is this claw’s diameter that determines the infestation site. For this reason, the crab louse is found on pubic hair and other hair of similar diameter, such as axillary and facial hair, including eyelashes and eyebrows. As is true for mites, the number of lice populating a patient averages a dozen. Lice depend on frequent human blood meals, and pubic lice must travel for new attachment sites. Accordingly, pubic lice usually are sexually transmitted, whereas head and body lice may be transmitted by sharing of personal objects such as combs, brushes, and clothing.

The main symptom from louse attachment and biting is pruritus. Scratching results in erythema and inflammation, which increases blood supply to the area. Patients may develop pyoderma and fever if bites become secondarily infected. Each female adult pubic louse lays approximately four eggs a day, which are glued to the base of hairs. Incubation approximates 1 month. Their attached eggs, termed nits, can be seen attached to the hair shaft away from the skin line as hair growth progresses. These nits usually require a magnifying glass for identification. Moreover, suspicious flecks on pubic hair or in clothing can be examined microscopically to see the characteristic louse. Following diagnosis, patient screening for other STDs is encouraged. Other family members and sexual contacts require evaluation for infestation.

Pediculicides kill not only adult lice, but also the eggs. A single application is usually effective, but a second dose is recommended within 7 to 10 days to kill new hatches. Nonprescription cream rinses or shampoos contain 1-percent permethrin (Nix) or pyrethrins with piperonyl butoxide (Rid, Pronto, R&C). These remain on affected areas for 10 minutes. CDC alternative regimens include 0.5-percent malathion lotion (Ovide) applied for 8 to 12 hours. Also, ivermectin 250 μg/kg orally once can be taken and then repeated in 2 weeks.

In selected cases, 1-percent lindane shampoo can be used, but again, it is less favored due to potential toxicity. Last, eyelash and eyebrow treatment is problematic. These areas are best treated by applying petrolatum (Vaseline) with a cotton swab at night and washing it off in the morning. Bedding and infested clothing are washed and dried with a heat cycle.

In spite of treatment, pruritus may continue and can be relieved by oral antihistamines, antiinflammatory cream or ointment, or both. The patient is reevaluated after 1 week to document louse eradication.

Symptomatic acute bacterial urinary tract infections (UTIs) are among the most common bacterial infections treated by clinicians. Cystitis accounts for most of these, whereas acute pyelonephritis treatment accounts for a greater number of hospitalizations. Because of their pelvic anatomy, women have many more UTIs than men. Bacteria ascending from the short, colonized urethra easily enter the bladder and perhaps the kidneys. Contributing to contamination, the warm moist vulva and rectum are both in close proximity. Similarly, sexual intercourse increases bladder inoculation.

Infections result from the interaction between bacteria and host. Bacterial virulence factors are important, as they enhance colonization and invasion of the lower and upper urinary tract. The principal virulence factors are increased adherence to either vaginal or uroepithelial cells and hemolysin production. The bacterial species most frequently recovered from infected urine culture is E coli (75–95 percent). Other identified species are Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus saprophyticus (Czaja, 2007; Echols, 1999).

Once within the bladder, bacteria may ascend within the ureters into the renal pelvis and cause upper tract infection. The renal parenchyma also can be infected by blood-borne organisms, especially during staphylococcal bacteremia. Mycobacterium tuberculosis gains access to the kidney through this route and also perhaps by ascension.

Acute Bacterial Cystitis

The most frequent presenting complaints in otherwise healthy, immunocompetent nonpregnant women are dysuria, frequency, urgency, hematuria, and incontinence. If the patient prefers, most women can be treated with a short course of antibiotics without examination, urinalysis, or urine culture for an isolated episode of acute uncomplicated bacterial cystitis. However, patients are instructed on clinical changes that merit further attention such as fever >100.4°C and persistence or recurrence of hematuria, dysuria, and frequency despite treatment. Women with these exclusions and others require evaluation to exclude other potential causes of their symptoms (Table 3-16). For example, hematuria in a postmenopausal woman may reflect cervical, uterine, or colonic bleeding evident at the time of urination. Similarly, burning with urination may indicate vulvitis.

As many as 50 percent of women who suffer an uncomplicated acute bacterial episode of cystitis will have another infection within a year. Up to 5 percent have recurring symptoms soon after treatment. When symptoms develop in such women, the likelihood that a true infection is present is greater than 80 percent.

Diagnosis

Thus, for selected women with complicated or recurrent infections or with persistent or new symptoms during treatment, urinalysis and urine culture are mandatory. For a culture specimen to be informative, it must be accurately collected. A “clean catch” midstream voided urine specimen is usually sufficient. A patient is counseled on reasons for and the steps associated with urine specimen collection, which are designed to prevent contamination by other bacteria from the vulva, vagina, and rectum. More than one bacterial species identified in a urine culture usually indicates specimen collection contamination.

Initially, a patient spreads her labia and wipes the periurethral area from front to back with an antiseptic tissue. With labia spread, she begins urinating but does not collect the initial stream. A sample is then collected into a sterile specimen cup. The specimen cup is handled by the patient in such a way to avoid contamination. After collection, a urine specimen is delivered promptly to the laboratory and is plated for culture within 2 hours of collection unless it is refrigerated.

Culture

Urine culture allows accurate identification of an inciting pathogen and susceptibility testing of that pathogen to various antibiotics. Classically, significant bacteriuria is defined as ≥10⁵ bacteria (colony-forming units [cfu]) per milliliter of urine. If urine is collected by either suprapubic aspirate or catheterization, colony counts ≥10² cfu/mL are diagnostic. As an exception, Hooton and colleagues (2013) demonstrated that E coli in midstream urine is highly predictive of bladder bacteriuria even at very low counts of 10² cfu/mL.

Although anaerobic bacteria are part of the vaginal, colonic, and skin flora, they rarely cause UTIs. Hence, urine culture reports do not note anaerobes except in rare instances in which the laboratory has been alerted to and specifically requested to look for an anaerobic species. Fungi can be identified on routine bacteria media and are reported but are rare causes of acute cystitis.

Culture is the gold standard, and bacterial species may be identified preliminarily, but a final urine culture report usually is not available for 48 hours. However, rapid test surrogates for culture can support a UTI diagnosis and include microscopy, nitrite testing, and leukocyte esterase testing. Empiric treatment is initially begun but modified, as needed, after culture results are available.

Culture Surrogates

Gram staining is a simple, rapid, and sensitive method for detecting a concentration ≥10⁵ cfu/mL of a bacterial species. Rapid identification allows appropriate selection of empiric antimicrobial therapy. However, realistically, such testing is typically limited to patients with complicated UTIs or acute pyelonephritis. Instead, simple microscopic examination of a urine specimen allows identification of both pyuria and bacteriuria. A specimen is examined expeditiously because leukocytes deteriorate quickly in urine that has not been appropriately preserved. Standards to define pyuria are inadequate, other than gross counts. Accordingly, the rapid test for leukocyte esterase has become a surrogate for the microscopic WBC count.

Leukocyte esterase testing measures esterase enzyme found in urinary leukocytes. If used alone diagnostically, this test is most beneficial for its high negative-predictive value, especially with bacterial colony counts ≥10⁵ cfu/mL. If one combines nitrite and leukocyte esterase testing of a clean-catch uncontaminated voided specimen, the specificity of positive test results approaches 100 percent when uropathogen colony counts are ≥10⁵ cfu/mL. The negative predictive value is comparable. However, if these specimens have been contaminated with vaginal or colonic bacteria or with trichomonads, the test result can be falsely positive for uropathogens. In addition, very concentrated urine or urine with significant proteinuria or glucosuria will decrease test accuracy.

Nitrites are produced from nitrates metabolized by bacteria. This is most frequently observed in the gram-negative uropathogen family typically responsible for acute UTIs in women. Unfortunately, this test does not identify Pseudomonas species or gram-positive pathogens such as staphylococci, streptococci, and enterococci. Moreover, first morning urine specimens are ideally tested, because more than 4 hours are required for bacteria to convert nitrates to nitrites at levels that are detectable. As a single test, the specificity of a positive nitrite test is very high when uropathogen counts are ≥10⁵ cfu/mL. Its negative predictive value is higher than its positive predictive value. Of note, substances that turn the urine red, such as the bladder analgesic phenazopyridine (Pyridium) or ingestion of beets, can lead to false-positive nitrite test results.

Treatment

During the past two decades, the frequency of infections caused by group B Streptococcus and Klebsiella species has increased, whereas E coli infection rates have diminished. Also, in many locations, sensitivity patterns in E coli may warrant a shift in initial empiric treatment (Table 3-17).

For significant dysuria, up to 2 days of a bladder analgesic such as phenazopyridine (Pyridium), 200 mg orally up to three times daily, may give significant relief. However, GI upset, yellow-orange stained urine and clothing, and hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are potential side effects.

Following treatment, recurrences may develop. In those recurrently linked with intercourse, low-dose postcoital dosing with agents found in Table 3-17 is usually effective at preventing infection recurrence. A woman with two or more episodes of cystitis within 6 months or three infections within a year is considered for urologic evaluation of her urinary tract. These patients are commonly treated with daily prophylaxis for 6 months, in addition to modification of any risk factors such as diaphragm-spermicide use.

Asymptomatic Bacteriuria

This is defined as isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection (Rubin, 1992). In healthy nonpregnant women, the prevalence of this condition increases with age. It is associated with sexual activity and is more common in diabetics. Moreover, one fourth to one half of elderly women in long-term care facilities have bacteriuria, which is seen primarily in those with chronic neurologic illness and functional impairment.

The Infectious Disease Society of America recommends that nonpregnant premenopausal women not be screened or treated for asymptomatic bacteriuria (Nicolle, 2005). The same is true for diabetic women and for older persons living in the community.

Acute Pyelonephritis

This infection may be divided into mild (no nausea or vomiting, normal to slightly elevated blood leukocyte count, and normal to low-grade fever) and severe (vomiting, dehydration, evidence of sepsis, high leukocyte count, and fever). Other symptoms include those of a lower urinary tract infection and varying degrees of back pain and tenderness to percussion over the region of the kidney(s).

Traditional therapy for this infection has included hospitalization, hydration, and intravenous antibiotic treatment for up to 2 weeks. However, studies in young healthy women with normal urinary tracts indicate that 7 to 14 days of oral therapy are sufficient for compliant women with mild infection (Gupta, 2011). In one study of more than 50 college women with acute uncomplicated pyelonephritis, resistance to trimethoprim-sulfamethoxazole was 30 percent (Hooton, 1997). Accordingly, for outpatient therapy, an oral fluoroquinolone is recommended treatment unless a pathogen is susceptible to trimethoprim-sulfamethoxazole. At initial diagnosis, clinicians may also administer a parenteral dose prior to starting oral therapy (see Table 3-17). Alternatively, if a causative organism is gram-positive, then amoxicillin-clavulanate, cefdinir, cefaclor, or cefpodomine-proxetil are recommended options (Gupta, 2011).

Hospitalization is warranted for women who display clinical indications at initial evaluation or who fail to improve with outpatient therapy. Appropriate initial IV regimens include a fluoroquinolone; an aminoglycoside with or without ampicillin; an extended-spectrum cephalosporin or extended-spectrum penicillin with or without an aminoglycoside; or a carbapenem. The choice among these agents is based on local resistance data and is tailored based on culture-derived susceptibility results.

Development of a postoperative infection can create significant patient morbidity, most seriously sepsis. Risks for postoperative infection are varied and include patient and surgical factors (Table 3-18). Of these, the degree of wound contamination at the time of surgery plays an important role. Because most gynecologic surgeries are elective, a gynecologist has time to decrease microbial inoculum. Thus, BV, trichomoniasis, cervicitis, and active urinary tract or respiratory infections ideally are treated and eradicated prior to surgery.

Wound Classification

Since 1964, surgical wounds have been classified according to the degree of bacterial contamination of the operative site at the time of surgery. In general, as the number of operative site bacteria (inoculum) increases, so too does the postoperative infection rate.

Clean wounds are most commonly found in procedures performed for nontraumatic indications, that are without operative site inflammation, and that avoid the respiratory, alimentary, and genitourinary tracts. No breaks occur in surgical technique. Thus, most laparoscopic and adnexal surgeries are considered to be in this category. Without prophylaxis, infection rates range from 1 to 5 percent. Prophylactic antimicrobial administration does not decrease infection rates following these procedures and is not required.

Clean contaminated wounds are those in which the respiratory, gastrointestinal, genital, or urinary tract is entered under controlled conditions, without unusual bacterial contamination. Criteria further define that there is no break in surgical technique. Infection rates range from 5 to 15 percent. This group encompasses many gynecologic procedures including total hysterectomy, cervical conization, and dilatation and curettage (D & C). Of these, hysterectomy is the gynecologic procedure most frequently followed by surgical site infection. These procedures are usually elective, and only hysterectomy and obstetric D & C require antimicrobial prophylaxis to reduce postoperative infection rates (American College of Obstetricians and Gynecologists, 2014a).

Contaminated wounds reflect operations with major breaks in sterile technique or gross GI spillage or incisions in which acute, nonpurulent inflammation is encountered (Mangram, 1999). Infection rates approximate 10 to 25 percent. For this reason, a minimum of 24 hours of perioperative antimicrobial administration is required, and delayed wound closure may be selected. Laparoscopy or laparotomy for acute salpingitis is included in this category.

Dirty wounds are typically old traumatic wounds or those that involve existing clinical infection or perforated viscera. If an abscess is present, these are considered dirty wounds. These operative sites are clinically infected at the time of surgery, and infection rates range from 30 to 100 percent. Accordingly, therapeutic antimicrobial therapy is required, and these wounds typically are allowed to close by secondary intention.

Surgical Site Infection Classification

The CDC provides definitions of hospital-acquired surgical site infections (SSIs). The Joint Commission currently is emphasizing this morbidity during their hospital accreditation process. Thus, hospitals are more attentive to infection rates and to the rates of individual surgeons.

In classifying SSIs, there are two categories, incisional and organ space (Fig. 3-13). Criteria for each category are detailed in Table 3-19. The incisional group is further subdivided into superficial and deep classes. Organ/space infections develop in spaces or organs other than that opened by the original incision or manipulated during the surgical procedure. Specific sites include the vaginal cuff, urinary tract, and intraabdominal sites. Of note, vaginal cuff infections are generally considered in the organ/space class, presuming they meet at least one of these criteria: purulent drainage from the cuff, abscess at the cuff, or pathogens cultured from fluid or tissue obtained from the cuff. Pelvic infections such as adnexal infection, pelvic abscess, or infected pelvic hematoma also fall into the category of organ/space infection.

Diagnosis

Physical Findings

For febrile morbidity, the most frequently used definition is an oral temperature of ≥38°C (≥100.4°F) on two or more occasions, 4 or more hours apart, and 24 or more hours following surgery. This condition is seen most often after hysterectomy, particularly abdominal hysterectomy; usually is not associated with other symptoms or signs of infection; and does not require antimicrobial therapy! It has been reported in up to 40 percent of women following abdominal and almost 30 percent of women after vaginal hysterectomy with antimicrobial prophylaxis. It resolves without antibiotic treatment in the absence of other symptoms or signs of infection.

A remote nonsurgical site may also serve as an origin of fever. These may include pulmonary complications, IV site phlebitis, and UTI. Thus, women who develop recurrent temperature elevation require a thorough history and a careful physical examination by the surgeon, seeking not only surgical but also nonsurgical causes (Fig. 42-2).

Operative site pain (incisional, lower abdominal, pelvic, and/or lower back) following surgery is normal. However, those with an operative site infection report increasing pain at the surgery site, and increasing tenderness is present during physical examination. With superficial SSI, pain is superficial and localized to the incision. With pelvic infection, there is deep lower abdominal and/or pelvic pain, and the most common infection sites are the parametria and the vaginal surgical margin. Pelvic abscess or infected pelvic hematoma is least common, and pain is central.

Abdominal palpation is an integral part of SSI diagnosis. Avoiding an abdominal incision if present, a surgeon slowly, gently, and deeply palpates the lower abdomen over the surgical site following hysterectomy and normally elicits patient discomfort. Tenderness does not mean an acute surgical abdomen or infection. In the immediate postoperative period, this tenderness is expected and decreases quickly. Women who develop pelvic cellulitis or cuff cellulitis will have increasing tenderness at gentle depression of the lower abdominal wall over the infected area. Tenderness may be bilateral, but more commonly is more marked on one side. Peritoneal signs are not present. Cellulitis, whether it involves the parametria, adnexa, or vaginal cuff, is not associated with a mass.

In the absence of increasing lower abdominal pain and tenderness, a bimanual examination is not necessary for asymptomatic temperature elevation. However, with a combination of fever, increasing tenderness, and new-onset pain, gentle bimanual examination is required to accurately identify the infection site and to exclude or diagnose a mass. Speculum examination usually is not required, and findings are similar with or without an existing infection. As is true for routine pelvic examination, most information at bimanual examination is obtained from the vaginal fingers. If a patient is too tender to allow adequate examination, vaginal sonography is indicated. Bowel function is usually not altered by soft-tissue cellulitis but can be by pelvic abscess or infected pelvic hematoma.

Testing

Pelvic infections following hysterectomy are polymicrobial, and for that reason, it is difficult to identify true pathogens. Research has demonstrated that bacteria recovered transvaginally from the pelves of infected and clinically uninfected women are similar. Accordingly, routine transvaginal culturing of women with cuff or pelvic cellulitis does not add useful information. Moreover, a surgeon should not wait for culture results before starting empiric broad-spectrum antibiotic therapy. However, if initial therapy is partially effective or unsuccessful, then a culture will more predictably identify pathogen(s) since therapy will have eradicated other species. The antibiotic regimen should be changed, and culture results may direct this change. In contrast, abscess or infected hematoma fluid are cultured since those species are less likely to be vaginal contaminants. The same is true for any fluid or purulent material present in an abdominal incision.

For many postoperative SSIs, imaging is not mandatory. However, if additional anatomic information is needed, then transvaginal sonography or CT scanning are the most often used, and selection depends on clinical circumstances and suspected etiology.

Specific Infections

Vaginal Cuff Cellulitis

Essentially all women develop this infection at the vaginal surgical margin after hysterectomy (Fig. 3-14). Normal response to healing is characterized by small-vessel engorgement, which results in erythema and heat. There is vascular stasis with endothelial leakage resulting in interstitial edema, which causes induration. This area is tender, microscopic evaluation of a wet prep reveals numerous WBCs, and purulent discharge is seen in the vagina. This process usually subsides, does not require treatment, and accordingly, does not require reporting as a SSI.

The few women who do require treatment are usually those who present after hospital discharge with mild, but increasing, new-onset lower abdominal pain and have a yellow vaginal discharge. Findings are as above, but the vaginal cuff is more tender than anticipated at this interval from the initial surgical procedure. Oral antimicrobial therapy with a single broad-spectrum agent is appropriate (Table 3-20). A patient is then reevaluated in several days to assess therapeutic efficacy. This may be completed by phone or with an examination if necessary.

Pelvic Cellulitis

This is a common infection following either vaginal or abdominal hysterectomy. It develops when host humoral and cellular defense mechanisms, combined with preoperative antibiotic prophylaxis, cannot overcome the bacterial inoculum and inflammatory process at the vaginal surgical margin. The inflammatory process spreads into the parametrial region(s) resulting in lower abdominal pain, regional tenderness, and fever, usually during the late second or third postoperative day. There are no peritoneal signs and bowel and urinary function are normal, but the patient may note anorexia.

Patients are discharged on perhaps their first or second postoperative day following vaginal hysterectomy, and affected women may be at home before symptom onset. Hospitalization and treatment with an IV broad-spectrum antibiotic regimen found in Table 3-20 is indicated until a patient has been afebrile for 24 to 48 hours. She then may be redischarged home. Most patients requiring hospitalization for IV antibiotic therapy are discharged with a 5- to 7-day oral antimicrobial prescription. Single-agent therapeutic regimens have been shown in prospective randomized trials to be as effective as combination-agent regimens. These infections are polymicrobial, and the regimen selected must have coverage for gram-positive and gram-negative aerobic and anaerobic bacteria.

Adnexal Infection

This infection is uncommon and presents almost exactly like pelvic cellulitis. The difference is in the location of tenderness during bimanual pelvic examination. The cuff and parametrial areas are not usually tender, but the adnexa are. This infection also may develop after tubal ligation, surgical therapy for ectopic pregnancy, or other adnexal surgery. Empiric antibiotic regimens are identical to those for pelvic cellulitis (see Table 3-20).

Ovarian Abscess

A rare but life-threatening complication following primarily vaginal hysterectomy is ovarian abscess. Presumably with this infection, surgery is performed in the late proliferative phase of an ovulatory menstrual cycle, and ovaries are in close proximity to the vaginal surgical margin. As expected, physiologic cuff cellulitis develops normally, but when ovulation occurs, local bacteria gain access to the ovulation site and the corpus luteum. The corpus luteum often is hemorrhagic, and the blood in this functional cyst provides a perfect medium for bacterial growth.

Affected women have an essentially normal postoperative course until approximately 10 days following surgery. At this time, they experience acute unilateral lower abdominal pain, which then involves multiple quadrants. These symptoms reflect rupture of their abscess and development of generalized abdominal peritonitis. Sepsis commonly follows, and this is a true gynecologic emergency. Immediate exploratory laparotomy is necessary, with IV administration of perioperative broad-spectrum antimicrobials, abscess evacuation, and adnexectomy if easily accessible. At a minimum, necrotic tissues are debrided. After hospital discharge, oral antibiotics are typically continued for an additional 5 to 7 days, and this is variable depending on the clinical course.

Similarly, women rarely may develop a tuboovarian abscess (usually a pyosalpinx) identical to that seen as an end result of acute PID. This process can be managed medically with IV antimicrobials, and surgery is usually not required unless rupture follows. Combination antimicrobial therapy is continued until a woman has been afebrile for 48 to 72 hours. At this point, IV antibiotics may be replaced by oral agents, which are continued outpatient to complete a 2-week course of therapy. Patients diagnosed with TOA are reevaluated approximately 3 days following hospital discharge and then again 1 and 2 weeks later to document abscess resolution.

Pelvic Abscess/Infected Pelvic Hematoma

Pelvic abscess not involving an adnexal structure may also uncommonly complicate hysterectomy (Fig. 3-15). This develops from blood, serum, and/or lymph collections following hysterectomy that provide an excellent milieu for the overgrowth of bacteria inoculated into the adjacent tissues during the surgical procedure. An alternative infection can originate within a surgical pelvic hematoma. With hematoma, a postoperative-day-1 hemoglobin classically is significantly lower than that predicted by measured intraoperative blood loss. Reoperation is not required in most instances, and fluid or blood product resuscitation suffices. Unlike women who develop tissue cellulitis following surgery and whose early symptom of infection is pain and not fever, women with an infected hematoma will have low-grade temperature elevation (>37.8°C) as their early finding. Pain is a late symptom for these women. Accordingly, women with an unexplained postoperative hemoglobin decrease are discharged with instructions to monitor their temperature twice daily for approximately 1 week. Temperatures ≥37.8°C typically warrant evaluation.

Signs and symptoms of pelvic abscess or infected hematoma are midline, and a mass is discernible centrally. Transvaginal sonography can accurately characterize the dimensions (Fig. 3-16). For both, hospital readmission for therapy is usually necessary. Combination-agent IV antimicrobial therapy is indicated, and selected regimens provide gram-positive and gram-negative aerobic and anaerobic coverage. Additionally, opening the vaginal surgical margin, if possible, to allow drainage will aid treatment and accelerate patient response. This can usually be done in a treatment room early, avoiding return to the operating room. If necessary, these can be drained with sonographic transvaginal guidance or in the operating room. These abscesses or infected hematomas usually remain confined to the extraperitoneal space, and a patient does not usually develop peritonitis. Some patients may develop diarrhea due to the proximity of the rectum, which is usually adjacent to the infected space.

Combination IV antibiotics are administered until a woman has been afebrile 48 to 72 hours. IV antibiotics may then be replaced by oral agents, which are continued outpatient to complete a 2-week course of therapy, if the abscess or hematoma is not drained. If drained, then oral agents continued for 5 to 7 days following IV agents typically is sufficient. Commonly, patients are reevaluated 3 days following hospital discharge and then again 1 and 2 weeks later to document infection resolution.

Abdominal Incision Infection

The superficial and easily accessible location of this infection aids its diagnosis. Although abdominal incision infection may develop alone or with pelvic infection following abdominal hysterectomy, it develops uncommonly after other gynecologic procedures. Unlike pelvic infection, the incidence of this infection is not altered by antimicrobial prophylaxis. Risk factors include obesity, immunosuppression, diabetes, excessive electrosurgical coagulation use, passive drains, and coexistent skin inflammation at the time of surgical incision.

Abdominal incisions are usually the most uncomfortable following gynecologic surgery, but pain decreases daily. Erythema and heat are the first physical signs of this infection, which is usually diagnosed on the fourth or fifth postoperative day—again, after discharge from the hospital. A hematoma or seroma may develop in the abdominal wall incision without infection. If these collections are large, opening of the incision and evacuation to prevent infection in those fluids is warranted. Similarly, pus requires incision opening to ensure an intact fascia, as should be done with large seromas or hematomas.

Drainage and local care are usually the basis of successful therapy for abdominal incision infection or for large hematoma or seroma. Wet-to-dry dressings stimulate fibroblastic proliferation and development of healthy granulation tissue. Moistening the dry dressing prior to its removal will ease removal and decrease patient discomfort. At this stage, secondary closure can be considered. Importantly, wounds are irrigated with normal saline. Povidone-iodine, iodophor gauze, hydrogen peroxide, and Daiken solution are avoided as they are caustic to healing tissues. Some recommend their use early but follow with normal saline irrigation. Negative-pressure wound therapy provided by vacuum-assisted wound closure devices is available for more serious or larger wound areas that are slow to respond once the wound has a clean, granulating base (Chap. 42).

If there is soft-tissue cellulitis adjacent to the incision, antimicrobial therapy is required. If the initial surgery was a clean procedure, then Staphylococcus species predominate. Following clean-contaminated or dirty procedures, isolated organisms commonly include gram-negative bacteria such as E coli, Pseudomonas aeruginosa, and Enterobacter species and gram-positive bacteria, namely, Staphylococcus and Enterococcus species (Kirby, 2009). Anaerobes are typically not prominent pathogens in these infections but may be present, especially following hysterectomy. Thus, these infections are usually polymicrobial. Antibiotics found in Table 3-20 are suitable regimens.

Toxic Shock Syndrome

This condition, caused by an exotoxin (TSS toxin-1) produced by Staphylococcus aureus, appears approximately 2 days following surgery or menstruation onset. Menstrual-associated toxic shock syndrome (TSS) rates have diminished following changes in tampon composition and use. For TSS, the vagina or wound must be colonized by a toxigenic staphylococcal strain, and the patient must lack the specific antibody that can block the superantigen.

The classic TSS symptoms include fever, malaise, and diarrhea. If postoperative, there are minimal signs of wound infection. A patient has conjunctival and pharyngeal hyperemia without purulence. The tongue is usually reddened, and the skin on the trunk is erythematous but not painful or pruritic. Temperatures are usually above 38.8°C, and orthostatic hypotension or shock may be present. This syndrome results from host cytokines released in response to superantigenic properties of the toxin. The criteria for this diagnosis are presented in Table 3-21.

The wound, if present, is treated like any other wound. It is cultured to confirm presence of S aureus. However, results from other cultures (e.g., blood, throat, and cerebrospinal fluid) will be negative. To meet the strict criteria, a woman must have all major and at least three minor criteria. If this is suspected early and therapy is initiated, the complete syndrome may not develop. Serologies for Rocky Mountain spotted fever, measles, and leptospirosis must be negative. Viral infection and group A streptococci can cause a similar presentation.

While awaiting culture results for selection of specific anti­staphylococcal antibiotics, empiric therapy covers both methicillin-susceptible and methicillin-resistant S aureus. Vancomycin (15 to 20 mg/kg/dose) can be given every 8 to 12 hours, not exceeding 2 g per dose. Some experts argue for the addition of clindamycin, but further evidence is needed. Regardless, the hallmark of therapy is entire system support with large volumes of IV fluids and electrolytes to replace massive body fluid losses from diarrhea, capillary leakage, and insensible loss. These patients may develop significant edema and are best managed in an intensive care unit. Even with appropriate management, the death rate has been reported to be as high as 5 percent because of subsequent acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), or hypotension unresponsive to therapy with resultant myocardial failure. This syndrome may also follow gynecologic surgical procedures such as D & C, hysterectomy, urethral suspension, and tubal ligation.

Necrotizing Fasciitis

Although described in the 1870s, it was not named until 1952, by a Parkland Hospital surgeon (Wilson, 1952). Risk factors for this postoperative incision infection are age older than 50 years, arteriosclerotic heart disease, diabetes mellitus, obesity, debilitating disease, smoking, and previous radiation therapy, all of which are associated with decreased tissue perfusion. In our clinical service, vulvar infection in obese diabetic women is a prominent risk. Only approximately 20 percent of cases follow surgery, the majority developing after minor injuries or insect bites. Bacteria recovered from women with this infection are similar to those recovered from any postoperative gynecologic infection site, namely predominantly E coli, E faecalis, Bacteroides spp, Peptostreptococcus spp, S aureus, and groups A and B hemolytic streptococci.

Although this postoperative superficial incisional infection begins like any other postoperative infection with pain and erythema, its hallmark is subcutaneous and superficial fascial necrosis, manifested by excessive tissue edema in adjacent areas. There also may be associated myonecrosis. Blisters or bullae form in tissue that has become avascular and is discolored (Fig. 3-17). Crepitus or induration and edema beyond the region of visible erythema may be present. Tissue destruction is far more extensive than is evident by surface examination. The skin will slip over underlying tissue, and if incised, due to the lack of vascularity, there will be no bleeding but instead usually a thin gray transudate. Severe systemic toxicity and fever may develop. In obvious cases, no imaging is needed, and patients are prepared for surgical debridement. In less-clear cases, radiographs or CT scans, if these can be quickly obtained, may add information by revealing gas in affected tissues produced by clostridial species such as Clostridium perfringens.

Although broad-spectrum antibiotic administration is required, the cornerstone of treatment is prompt recognition and immediate surgical removal of necrotic tissue to a level at which viable bleeding tissue is reached. To achieve this, excision of large tissue volumes are often needed. Although this is potentially disfiguring, postponing surgery while waiting for antimicrobial activity only increases the volume of tissue death. Gynecologists may enlist assistance from a general surgeon or gynecologic oncologist if extensive debridement into the posterior perineal triangle, buttock, or inner thigh is anticipated. Early fatality rates for patients with this infection approximated 20 percent in the systematic review of 1463 patients by Goh and associates (2014).

Wounds are left open and treated as wound infections as described earlier with local hydrotherapy or a wound vacuum device. Assistance from a general surgeon for potential grafting is often necessary.

Methicillin-resistant Staphylococcus aureus

Any of the polymicrobial infections discussed in this section may be complicated by MRSA. To cover MRSA, suitable outpatient oral antibiotics for uncomplicated infection include trimethoprim-sulfamethoxazole DS (160 mg/800 mg) twice daily, clindamycin 300 or 450 mg three times daily, doxycycline or minocycline 100 mg twice daily, or linezolid (Zyvox) 600 mg twice daily. For complicated infections, the Infectious Disease Society of America recommends MRSA coverage with IV vancomycin, IV or oral clindamycin, IV or oral linezolid 600 mg twice daily, IV daptomycin (Cubicin) 4 mg/kg once daily, or IV telavancin (Vibativ) 10 mg/kg once daily (Liu, 2011). Newer FDA-approved agents against complicated MRSA infections include ceftaroline (Teflaro), dalbavancin (Dalvance), oritavancin (Orbactive), and tedizolid (Sivextro) (Holmes, 2014). These newer drugs are expensive and may have restricted formulary use to only infectious disease specialists.

Vulvar Abscess

These infections develop similarly to other superficial abscesses but have the potential for significant expansion due to the loose areolar subcutaneous tissue in this area. Risk factors include diabetes, obesity, perineal shaving, and immunosuppression. Common isolates include Staphylococcus, group B Streptococcus, Enterococcus species, E coli, and P mirabilis. Importantly, Thurman (2008) and Kilpatrick (2010) and their coworkers found MRSA in 40 to 60 percent of cultured vulvar abscesses.

In early stages, surrounding cellulitis may be the most prominent finding and only a small or no abscess is identified. In these cases, sitz baths and oral antibiotics are reasonable treatment. When present, smaller abscesses may be treated with incision and drainage, abscess packing if indicated, and oral antibiotics to treat surrounding cellulitis. For uncomplicated infection, suitable oral agents will be broad-spectrum and will cover MRSA. Trimethoprim-sulfamethoxazole may be used alone. Two-drug therapy with clindamycin or doxycycline combined with a second-generation cephalosporin or with a fluoroquinolone is also a suitable choice, among others. However, for those with immunosuppression or diabetes, hospitalization and IV antibiotic therapy is often warranted due to increased risks for necrotizing fasciitis in these individuals. Again, coverage for MRSA is included in IV regimens (Table 3-20).

Large abscesses typically require admission for drainage under anesthesia. This provides adequate pain control for abscess drainage and for abscess cavity exploration to disrupt loculated areas of pus, as described in Section 43-21.

Bartholin Gland Duct Abscess

This infection is managed primarily by drainage (Fig. 3-18). Drainage can typically be completed in an outpatient setting and is described in Section 43-18. Antibiotics are commonly added to treat surrounding tissue cellulitis. The most common bacteria isolated from these abscesses include anaerobic Bacteroides and Peptostreptococcus spp and aerobic E coli, S aureus, and E faecalis (Bhide, 2010; Kessous, 2013). Also, N gonorrhoeae and C trachomatis may be identified (Bleker, 1990). Accordingly, polymicrobial coverage is selected, and suitable single-agent oral outpatient therapy includes, among others, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, second-generation cephalosporins, or fluoroquinolones, such as ciprofloxacin. In most cases, abscess aerobic cultures are obtained. Depending on patient risks, NAATs for N gonorrhoeae and C trachomatis and screening for other STDs may be included.

Actinomyces Infection

Actinomyces israelii is a gram-positive, slow-growing, anaerobic bacterium found to be part of the indigenous genital flora of healthy women (Persson, 1984). Some have found it more frequently in the vaginal flora of IUD users, and rates of colonization increase with duration of IUD use (Curtis, 1981). Actinomyces is also identified in Pap smears, and Fiorino (1996) cited a 7-percent incidence in IUD users compared with less than 1 percent in nonusers. Pelvic infection and abscess are rare, even in those identified to harbor the bacteria. Accordingly, in the absence of symptoms, the incidental finding of Actinomyces on cytology may be managed by: (1) expectant management, (2) extended oral antibiotic treatment with the IUD in place, (3) IUD removal, or (4) IUD removal followed by antibiotic treatment (American College of Obstetricians and Gynecologists, 2013a). In support of conservative observation, reviews by Lippes (1999) and Westhoff (2007) suggest that asymptomatic women may retain their IUDs and do not require antibiotic treatment. With the higher rate of current IUD use, this will no doubt be an increasingly important topic. Importantly, if signs or symptoms of infection develop in women who harbor Actinomyces, the device is removed and antimicrobial therapy instituted. Early findings include fever, weight loss, abdominal pain, and abnormal vaginal bleeding or discharge. Actinomyces is sensitive to antimicrobials with gram-positive coverage, notably the penicillins.