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These infections are the most frequent bacterial infections complicating pregnancy. Although asymptomatic bacteriuria is the most common, symptomatic infection includes cystitis, or it may involve the renal calyces, pelvis, and parenchyma to cause pyelonephritis. Organisms that cause urinary infections are those from the normal perineal flora. Approximately 90 percent of Escherichia coli strains that cause nonobstructive pyelonephritis have adhesins such as P- and S-fimbriae. These are cell-surface protein structures that enhance bacterial adherence and, thereby, virulence (Foxman, 2010; Hooton, 2012). Data suggest that pregnant women have more severe sequelae from urosepsis. One possible underlying factor is the T-helper cell—Th1/Th2 ratio—reversal of normal pregnancy, which is discussed in Chapter 4 (Leukocytes and Lymphocytes). Other perturbations of cytokine or of adhesin expression may be contributory (Chaemsaithong, 2013; Sledzińska, 2011). But even if pregnancy itself does not enhance these virulence factors, urinary stasis, vesicoureteral reflux, and diabetes predispose to symptomatic upper urinary infections (Czaja, 2009).
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In the puerperium, several risk factors predispose to urinary infections. Bladder sensitivity to intravesical fluid tension is often diminished due to labor trauma or epidural analgesia. Bladder sensations can also be obscured by discomfort from vaginal or perineal injury. Normal postpartum diuresis may worsen bladder overdistention, and catheterization to relieve retention often leads to urinary infection. Postpartum pyelonephritis is treated in the same manner as antepartum renal infections (McDonnold, 2012).
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Asymptomatic Bacteriuria
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This refers to persistent, actively multiplying bacteria within the urinary tract in asymptomatic women. The incidence during pregnancy is similar to that in nonpregnant women. It varies from 2 to 7 percent, and it is characteristically population dependent. The highest incidence is in African-American multiparas with sickle-cell trait, and the lowest is in affluent white women of low parity. Asymptomatic infection is also more common in diabetics (Schneeberger, 2014).
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Bacteriuria is typically present at the first antepartum visit. An initial positive urine culture result done as a part of prenatal care should prompt treatment. After this, fewer than 1 percent of women develop a urinary tract infection (Whalley, 1967). A clean-voided specimen containing more than 100,000 organisms/mL is diagnostic. It may be prudent to treat when lower concentrations are identified, because pyelonephritis develops in some women despite colony counts of only 20,000 to 50,000 organisms/mL (Lucas, 1993).
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Most studies indicate that if asymptomatic bacteriuria is not treated, approximately 25 percent of infected women will develop symptomatic infection during pregnancy (Smaill, 2015). In a more recent study, only 2.4 percent of treated women developed pyelonephritis (Kazemier, 2015). Eradication of bacteriuria with antimicrobial agents prevents most of these serious infections. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2017), as well as the U.S. Preventive Services Task Force (2008), recommend screening for bacteriuria at the first prenatal visit. Standard urine cultures may not be cost effective when the prevalence is low. Less expensive screening tests such as the leukocyte esterase/nitrite dipstick are cost effective when the prevalence is ≤2 percent (Rogozinska, 2016; Rouse, 1995). Also, a dipstick culture technique has excellent positive- and negative-predictive values (Mignini, 2009). With this, a special agar-coated dipstick is first placed into urine and then also serves as the culture plate. Because of a high prevalence—5 to 8 percent—at Parkland Hospital, most women are screened by traditional urine culture. Susceptibility determination is not necessary because initial treatment is empirical (Hooton, 2012).
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In some but not all studies, covert bacteriuria has been associated with preterm or low-birthweight infants. It is even more controversial whether eradication of bacteriuria decreases these complications. Evaluating a cohort of 25,746 mother-infant pairs, Schieve and coworkers (1994) reported urinary tract infection to be associated with greater risks for low-birthweight infants, preterm delivery, pregnancy-associated hypertension, and anemia. These findings vary from those of others (Gilstrap, 1981b; Whalley, 1967). Notably, in most studies, cohorts with asymptomatic infection are not evaluated separately from those with acute renal infection (Banhidy, 2007). One Cochrane database review noted insufficient data to answer this question (Smaill, 2015).
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Bacteriuria responds to empirical treatment with any of several antimicrobial regimens listed in Table 53-1. Although selection can be based on in vitro susceptibilities, in our extensive experience, empirical oral treatment for 10 days with nitrofurantoin macrocrystals, 100 mg at bedtime, is usually effective. Satisfactory results are also achieved with a 7-day oral course of nitrofurantoin, 100 mg given twice daily (Lumbiganon, 2009). Single-dose antimicrobial therapy is less successful (Widmer, 2015). The important caveat is that, regardless of regimen given, the recurrence rate is approximately 30 percent. This may indicate covert upper tract infection and the need for longer therapy. Thus, after initial therapy, periodic surveillance is necessary to prevent recurrent urinary infections (Schneeberger, 2015).
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For recurrent bacteriuria, we have had success with nitrofurantoin, 100 mg orally at bedtime for 21 days (Lucas, 1994). For women with persistent or frequent bacteriuria recurrences, suppressive therapy for the remainder of pregnancy can be given. We routinely use nitrofurantoin, 100 mg orally at bedtime. This drug may rarely cause an acute pulmonary reaction that dissipates on its withdrawal (Boggess, 1996).
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Cystitis and Urethritis
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Lower urinary infection during pregnancy may develop without antecedent covert bacteriuria (Harris, 1981). Cystitis produces dysuria, urgency, and frequency, but with few associated systemic findings. Pyuria and bacteriuria are usually found. Microscopic hematuria is common, and occasionally there is gross hematuria from hemorrhagic cystitis. Although cystitis is usually uncomplicated, the upper urinary tract may become involved by ascending infection. Almost 40 percent of pregnant women with acute pyelonephritis have preceding symptoms of lower tract infection (Gilstrap, 1981a).
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Women with cystitis respond readily to any of several regimens. Most of the 3-day regimens listed in Table 53-1 are usually 90-percent effective (Fihn, 2003). Single-dose therapy is less effective, and if it is used, concomitant pyelonephritis must be confidently excluded.
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Lower urinary tract symptoms with pyuria accompanied by a sterile urine culture may stem from urethritis caused by Chlamydia trachomatis. Mucopurulent cervicitis usually coexists, and azithromycin therapy is effective (Chap. 65, Chlamydial Infections).
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Renal infection is one of the most frequent serious medical complications of pregnancy. Data from the 2006 Nationwide Inpatient Sample showed that nearly 29,000 pregnancy-associated hospitalizations were for acute pyelonephritis (Jolley, 2012). In one hospital-system database of nearly 550,000 births, its incidence was 0.5 percent (Wing, 2014). Importantly, pyelonephritis is a leading cause of septic shock during pregnancy (Snyder, 2013). In one Parkland Hospital Obstetrical Intensive Care Unit review, 12 percent of antepartum admissions were for sepsis syndrome caused by renal infections (Zeeman, 2003). Urosepsis may be related to an increased incidence of cerebral palsy in preterm infants (Jacobsson, 2002). Fortunately, affected mothers suffer no serious long-term sequelae (Raz, 2003).
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Renal infection develops more frequently in the second trimester, and nulliparity and young age are risks (Hill, 2005). Pyelonephritis is unilateral and right-sided in more than half of cases, and it is bilateral in a fourth. Fever and shaking chills usually develop rather abruptly, and patients have aching pain in one or both lumbar regions. Anorexia, nausea, and vomiting may worsen dehydration. Tenderness usually can be elicited by percussion in one or both costovertebral angles. The differential diagnosis includes, among others, labor, chorioamnionitis, adnexal torsion, appendicitis, placental abruption, or infarcted leiomyoma. Evidence of the sepsis syndrome is common (Chap. 47, Sepsis Syndrome).
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If this infection is suspected, a urine sample obtained by catheterization may be preferred to avoid obscuring contamination from the lower genital tract. The urinary sediment contains many leukocytes, frequently in clumps, and numerous bacteria. Bacteremia is demonstrated in 15 to 20 percent of these women. E coli is isolated from urine or blood in 70 to 80 percent of infections, Klebsiella pneumoniae in 3 to 5 percent, Enterobacter or Proteus species in 3 to 5 percent, and gram-positive organisms, including group B Streptococcus and Staphylococcus aureus, in up to 10 percent of cases (Hill, 2005; Wing, 2000).
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Plasma creatinine is monitored because early studies reported that 20 percent of pregnant women developed acute kidney injury. More recent findings, however, show this to be only 5 percent if aggressive fluid resuscitation is provided (Hill, 2005). Follow-up studies have demonstrated that this endotoxin-induced damage is reversible long term. As shown in Figure 53-2, varying degrees of respiratory distress syndrome from endotoxin-induced alveolar injury are manifest in up to 2 percent of women (Cunningham, 1987; Snyder, 2013; Wing, 2014).
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Uterine activity from endotoxin is common and is related to fever severity (Graham, 1993). In one study, women with pyelonephritis averaged five contractions per hour at admission, and this decreased to two per hour within 6 hours of intravenous fluid and antimicrobial administration (Millar, 2003). Notably, β-agonist therapy for tocolysis increases the likelihood of respiratory insufficiency from permeability edema (Lamont, 2000). The incidence of pulmonary edema in women with pyelonephritis who were given β-agonists was reported to be 8 percent—a fourfold increase over that expected (Towers, 1991). Endotoxin-induced hemolysis is common, and approximately a third of these women with pyelonephritis develop anemia (Cox, 1991). With recovery, hemoglobin regeneration is normal, and acute infection does not affect erythropoietin production (Cavenee, 1994).
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One scheme for management of acute pyelonephritis is shown in Table 53-2. Urine cultures are taken, but prospective trials show that blood cultures are of limited clinical utility (Gomi, 2015; Wing, 2000). We obtain blood cultures if the temperature is >39°C. Intravenous hydration to ensure adequate urinary output is the cornerstone of treatment. Antimicrobials are also begun promptly with the caveat that they may initially worsen endotoxemia from bacterial lysis. Surveillance for worsening sepsis syndrome includes serial monitoring of urinary output, blood pressure, pulse, temperature, and oxygen saturation. High fevers are lowered with a cooling blanket and acetaminophen. This is especially important in early pregnancy because of possible teratogenic effects from hyperthermia.
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Antimicrobial therapy usually is empirical, and ampicillin plus gentamicin; cefazolin or ceftriaxone; or an extended-spectrum antibiotic are all 95-percent effective in randomized trials (Sanchez-Ramos, 1995; Wing, 1998, 2000). Fewer than half of E coli strains are sensitive to ampicillin in vitro, but cephalosporins and gentamicin generally have excellent activity. Serum creatinine levels are monitored if nephrotoxic drugs are given. Initial treatment at Parkland Hospital is ampicillin plus gentamicin. Some recommend suitable substitutes if bacterial studies show in vitro resistance. With any of the regimens discussed, response is usually prompt, and 95 percent of women are afebrile by 72 hours (Hill, 2005; Sheffield, 2005). After discharge, most recommend oral therapy for a total of 7 to 14 days (Hooton, 2012).
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Generally, intravenous hydration and antimicrobial therapy are followed by stepwise defervescence of approximately 1°F per day. With persistent spiking fever or lack of clinical improvement by 48 to 72 hours, urinary tract obstruction, another complication, or both are considered. In these women, renal sonography is recommended to search for obstruction, which is manifest by abnormal ureteral or pyelocaliceal dilatation (Seidman, 1998). Although most women with continuing infection have no evidence of obstruction, some are found to have calculi. Although renal sonography will detect hydronephrosis, stones are not always seen in pregnancy (Butler, 2000; Maikranz, 1987). If stones are strongly suspected despite a nondiagnostic sonographic examination, a plain abdominal radiograph will identify nearly 90 percent. Another option is the modified one-shot intravenous pyelogram—a single radiograph obtained 30 minutes after contrast injection—which usually provides adequate imaging (Butler, 2000).
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In some women, MR imaging may disclose the cause of persistent infection (Spencer, 2004). Even without urinary obstruction, persistent infection can be due to an intrarenal or perinephric abscess or phlegmon (Cox, 1988; Rafi, 2012). Obstruction relief is important, and one method is cystoscopic placement of a double-J ureteral stent (Rodriguez, 1988). Because these stents are usually left in place until after delivery, they frequently become encrusted and require replacement. We have found that percutaneous nephrostomy is preferable because the stents are more easily replaced. Finally, surgical removal of stones may be required in some women (Nephrolithiasis).
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Outpatient Management
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This is sometimes done for nonpregnant women with uncomplicated pyelonephritis (Hooton, 2012). Outpatient management was described in 92 pregnant women who were first given in-hospital intramuscular ceftriaxone, two 1-g doses 24 hours apart (Wing, 1999). After this, only a third of the group was considered suitable for outpatient therapy, and these women were randomly assigned either to discharge home and oral antimicrobials or to continued hospitalization with intravenous therapy. A third of the outpatient management group was unable to adhere to the treatment regimen and required readmission. This suggests that outpatient management is applicable to very few gravidas.
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Recurrent urinary tract infection—either covert or symptomatic—develops in 30 to 40 percent of women following completion of pyelonephritis treatment (Cunningham, 1973). Unless other measures are taken to ensure urine sterility, nitrofurantoin, 100 mg orally at bedtime given for the remainder of the pregnancy, reduces bacteriuria recurrence (Van Dorsten, 1987).
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Vesicoureteral reflux in early childhood can cause recurrent urinary tract infections, and subsequent chronic interstitial nephritis is attributed to chronic pyelonephritis. Moreover, high-pressure sterile reflux impairs normal renal growth. Combined, this leads to patchy interstitial scarring, tubular atrophy, and loss of nephron mass and is termed reflux nephropathy. In some cases—especially those with staghorn calculi—xanthogranulomatous pyelonephritis causes suppurative destruction of renal tissue. In adults, long-term complications of chronic pyelonephritis include hypertension, which may be severe (Beck, 2015; Diamond, 2012).
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Perhaps half of women with reflux nephropathy were treated during childhood for renal infections. Many also had surgical correction of reflux as children, and these women commonly have bacteriuria when pregnant (Mor, 2003). In the other half of women with reflux nephropathy, a clear history of recurrent cystitis, acute pyelonephritis, or obstructive disease is lacking. Reports describing 939 pregnancies in 379 women with reflux nephropathy indicate that impaired renal function and bilateral renal scarring were associated with increased maternal complications (El-Khatib, 1994; Jungers, 1996; Köhler, 2003). Chronic renal disease and pregnancy outcome are discussed in Chronic Kidney Disease.