Urinary tract infections and asymptomatic bacteriuria in pregnancyAuthorsThomas M Hooton, MDKalpana Gupta, MD, MPHSection EditorsStephen B Calderwood, MDCharles J Lockwood, MD, MHCMDeputy EditorAllyson Bloom, MDAll topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through:Jan 2015.|This topic last updated:Jan 23, 2015.

INTRODUCTIONUrinary tract infections (UTIs) are common in pregnant women. By convention, UTI is defined either as a lower tract (acute cystitis) or upper tract (acute pyelonephritis) infection. UTIs (acute cystitis and pyelonephritis) and asymptomatic bacteriuria in pregnant women will be reviewed here.Issues related to urinary tract infections or asymptomatic bacteriuria in other populations are discussed in detail elsewhere. (See "Acute uncomplicated cystitis and pyelonephritis in women" and "Acute uncomplicated cystitis, pyelonephritis, and asymptomatic bacteriuria in men" and "Acute complicated cystitis and pyelonephritis" and "Approach to the adult with asymptomatic bacteriuria" and "Asymptomatic bacteriuria in patients with diabetes mellitus" and "Catheter-associated urinary tract infection in adults".)EPIDEMIOLOGYIncidence and risk factorsThe incidence of bacteriuria in pregnant women is approximately the same as that in nonpregnant women, however, recurrent bacteriuria is more common during pregnancy. Additionally, the incidence of pyelonephritis is higher than in the general population, likely as a result of physiologic changes in the urinary tract during pregnancy. (See 'Pathogenesis' below.)Asymptomatic bacteriuria occurs in 2 to 7 percent of pregnant women [1,2]. It typically occurs during early pregnancy, with only approximately a quarter of cases identified in the second and third trimesters [3]. Factors that have been associated with a higher risk of bacteriuria include a history of prior urinary tract infection, pre-existing diabetes mellitus, increased parity, and low socioeconomic status [4-6].Without treatment, as many as 30 to 40 percent of pregnant women with asymptomatic bacteriuria will develop a symptomatic urinary tract infection (UTI), including pyelonephritis, during pregnancy [7]. This risk is reduced by 70 to 80 percent if bacteriuria is eradicated. (See 'Rationale for treatment' below.)Acute cystitis occurs in approximately 1 to 2 percent of pregnant women, and the estimated incidence of acute pyelonephritis during pregnancy is 0.5 to 2 percent [8-11]. Most cases of pyelonephritis occur during the second and third trimesters. As an example, the incidence of acute pyelonephritis in pregnancy in the setting of routine prenatal screening for asymptomatic bacteriuria was examined in a prospective study of a general obstetric population [10]. During the two year study period, 440 cases of acute pyelonephritis were identified in 32,282 pregnant women (14 per 1000 deliveries). The majority of cases occurred in the second trimester (53 percent). In addition to prior untreated bacteriuria, other clinical characteristics that have been associated with acute pyelonephritis during pregnancy include age 38C or 100.4F), flank pain, nausea, vomiting,and/orcostovertebral angle tenderness. Symptoms of cystitis (eg, dysuria) are not always present. Pyuria is a typical finding. (See "Acute uncomplicated cystitis and pyelonephritis in women".)Most cases of pyelonephritis occur during the second and third trimesters. (See 'Incidence and risk factors' above.)Pregnant women may become quite ill and are at risk for both medical and obstetrical complications from pyelonephritis. It has been estimated that as many as 20 percent of women with severe pyelonephritis develop complications that include septic shock syndrome or its variants, such as acute respiratory distress syndrome (ARDS) [52-54]. As an example, in a prospective study of 440 cases of acute pyelonephritis identified among 32,282 pregnant women in a general obstetric population, complications included anemia (23 percent), bacteremia (17 percent in the minority of patients who were tested), respiratory insufficiency (7 percent), and renal dysfunction (2 percent) [10]. The mechanism of anemia is not well understood, but hemolysis, perhaps mediated by endotoxin, may be important [55]. Acute renal failure associated with microabscesses and suppurative pyelonephritis has been described in isolated cases, independent of sepsis [56]. (See "Acute kidney injury (acute renal failure) in pregnancy".)Diagnosis and evaluationAcute pyelonephritis is suggested by the presence of flank pain,nausea/vomiting,fever (>38C or 100.4F),and/orcostovertebral angle tenderness, with or without the typical symptoms of cystitis, and is confirmed by the finding of bacteriuria in the setting of these symptoms. (See "Acute uncomplicated cystitis and pyelonephritis in women".)For pregnant women who present with such symptoms, we check a urinalysis and urine culture. Pyuria is present in the majority of women with pyelonephritis, and its absence suggests an alternative diagnosis or complete obstruction. Although many pregnant women have back or flank pain without pyelonephritis, we have a low threshold for evaluation for bacteriuria and a diagnosis of pyelonephritis in pregnant women with these symptoms, given the risk of complications and adverse pregnancy outcomes with untreated pyelonephritis. (See 'Pregnancy outcomes' above.)Some investigators have questioned the value of obtaining routine blood cultures in pregnant women with pyelonephritis [57]. Although there is no evidence that bacteremia portends a worse prognosis or requires longer therapy in an otherwise healthy pregnant woman with pyelonephritis, it is reasonable to obtain blood cultures in those with signs of sepsis or serious underlying medical conditions such as diabetes.Imaging is not routinely used to diagnose pyelonephritis. However, in patients with pyelonephritis who are severely ill or who also have symptoms of renal colic or history of renal stones, diabetes, history of prior urologic surgery, immunosuppression, repeated episodes of pyelonephritis, or urosepsis, imaging of the kidneys can be helpful to evaluate for complications. In pregnant women, renal ultrasound is the preferred imaging modality in order to avoid contrast or radiation exposure.Differential diagnosisNephrolithiasis can present with significant flank or back pain and abnormal findings on the urinalysis, but fever is uncommon with uncomplicated stone disease. This can also be distinguished from pyelonephritis by visualization of the stones on renal ultrasound. (See "Diagnosis and acute management of suspected nephrolithiasis in adults".)For pregnant women presenting with feverand/orflank or back pain, certain obstetric complications are important to consider in the differential:Intraamniotic infection, with or without preterm labor, is an important diagnostic consideration in pregnant women who have fever and abdominal pain. The following features suggest intraamniotic infection over pyelonephritis: presentation with premature rupture of membranes, uterine tendernessand/orfoul odor of the amniotic fluid, and the absence of bacteriuria. Other potential causes of fever and back or flank pain in the absence of bacteriuria include other infections (eg, influenza, pneumonia, appendicitis). (See "Intraamniotic infection (chorioamnionitis)", section on 'Diagnosis of clinical chorioamnionitis'.)Placental abruption is a key differential diagnosis of acute back or abdominal pain during pregnancy. Back pain is prominent with abruption when the placenta is on the posterior wall of the uterus. Fever is absent and vaginal bleeding is classically present with abruption, in contrast to pyelonephritis. The uterus is often firm, and may be rigid and tender in patients with abruption, but is usually soft in patients with pyelonephritis. Both conditions can be associated with uterine contractions. If present, a retroplacental hematoma on ultrasound supports the diagnosis of abruption. (See "Placental abruption: Clinical features and diagnosis".)ManagementManagement of acute pyelonephritis in pregnant women includes hospital admission for parenteral antibiotics. Antibiotic therapy can be converted to an oral regimen tailored to the susceptibility profile of the isolated organism following clinical improvement. Following the treatment course, suppressive antibiotics are typically used for the remainder of the pregnancy to prevent recurrence.Site of careBased upon the higher risk of complications in pregnant women, pyelonephritis has traditionally been treated with hospitalization and intravenous antibiotics until the woman is afebrile for 24 to 48 hours and symptomatically improved [58]. Initial outpatient therapy of pregnant women with pyelonephritis has been attempted in carefully selected populations (eg, no underlying serious medical conditions, renal or urologic abnormalities, pregnancy complications, signs of sepsis, or recent antibiotic use). However, we suggest not initiating therapy of pyelonephritis in pregnant women in the outpatient setting given the limited data evaluating its safety and the need for close monitoring of the patient.Evidence on the safety of outpatient initiation of pyelonephritis treatment during pregnancy is limited to two trials by the same group [59,60]. Although the studies suggested that outpatient treatment resulted in similar outcomes as inpatient management, several limitations of the studies create uncertainty about the safety and practicality of outpatient management:In the first trial, 120 pregnant women with pyelonephritis prior to 24 weeks gestation were randomly assigned to receive an outpatient regimen consisting of intramuscular ceftriaxone for 2 days followed by oral cephalexin for 10 days or an inpatient regimen consisting of IV cefazolin followed at discharge by oral cephalexin for 10 days [59]. Clinical responses to therapy and birth outcomes were similar for both outpatients and inpatients. However, six patients initially treated with ceftriaxone were ultimately admitted to the hospital for intravenous therapy, and one woman developed septic shock during the emergency department observation period. Of note, the outpatient regimen included initial parenteral antibiotics, and home health nurses monitored patients assigned to the outpatient strategy.In the second trial, 92 women who presented after 24 weeks gestation were hospitalized for intramuscular ceftriaxone for 24 hours and then randomly assigned to early discharge on oral cephalexin or continued hospitalization until afebrile for 48 hours [60]. Clinical response and birth outcomes were similar for those who completed the assigned strategy. However, 51 percent of patients either did not qualify for outpatient management based upon study criteria or developed complications, which precluded early discharge from the hospital.Empiric antibioticsParenteral, broad spectrum beta-lactams are the preferred antibiotics for initial empiric therapy of pyelonephritis (table 2). The choice between them should be guided by local microbiology and susceptibility data as well as expected patient tolerance. Fluoroquinolones and aminoglycosides, which are often used for pyelonephritis in nonpregnant individuals, should be avoided in pregnancy if possible. (See 'Antibiotic safety in pregnancy' below.)The efficacy of beta-lactams was demonstrated in a randomized trial of 179 pregnant women with acute pyelonephritis before the 24th week of gestation: intravenous cefazolin or intramuscular ceftriaxone had equivalent efficacy to intravenous ampicillin plus gentamicin [61]. Although rates of resistance to first generation cephalosporins have generally been less than 10 percent in surveillance studies [62-65], beta-lactams (including first generation cephalosporins) have been less effective than trimethoprim-sulfamethoxazole or the fluoroquinolones for treatment of cystitis in studies of nonpregnant individuals [66]. Given these data and the paucity of data evaluating narrow spectrum cephalosporins in the treatment of pyelonephritis [66], we favor third generation cephalosporins over first or second generation cephalosporins, such as cefazolin, for the empiric treatment of acute pyelonephritis.For women with a history of infections with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (or other risk factors), a carbapenem is an appropriate choice for empiric therapy. Of note, some animal studies have shown adverse fetal effects with imipenem-cilastatin, so meropenem, ertapenem, or doripenem are the preferred carbapenems for use during pregnancy. (See 'Antibiotic safety in pregnancy' below.)Directed antibiotic therapy and follow-upAs with nonpregnant patients with complicated pyelonephritis, pregnant women generally have definite improvement within 24 to 48 hours of appropriate antibiotic therapy. Once afebrile for 48 hours, pregnant patients can be switched to oral therapy guided by culture susceptibility results and discharged to complete 10 to 14 days of treatment [58]. Oral options are mainly limited to beta-lactams or, if in the second trimester, trimethoprim-sulfamethoxazole. Nitrofurantoin and fosfomycin are not appropriate for treatment of pyelonephritis due to inadequate tissue levels. General principles regarding the safety of antibiotics in pregnancy are discussed elsewhere. (See 'Antibiotic safety in pregnancy' below.)If symptoms and fever persist beyond the first 24 to 48 hours of treatment, a repeat urine culture and renal ultrasound should be performed to rule out persistent infection and urinary tract pathology.For women who do not use antimicrobial prophylaxis for the duration of pregnancy following an episode of pyelonephritis (see 'Preventing recurrence' below), we generally check monthly urine cultures to evaluate for recurrent bacteriuria and treat as indicated because of the risk of recurrent pyelonephritis. (See 'Asymptomatic bacteriuria' above.)Obstetric managementPyelonephritis is not itself an indication for delivery. If induction of labor or cesarean delivery for standard obstetrical indications is planned in a patient on treatment for pyelonephritis, we favor waiting until the patient is afebrile, as long as delaying the delivery is relatively safe for the mother and fetus.Since pyelonephritis is associated with preterm birth, an important obstetric consideration is whether tocolysis should be used when pyelonephritis triggers preterm labor at various gestational ages. Detailed discussion of the benefits and risks of tocolysis for acute preterm labor are found elsewhere. (See "Inhibition of acute preterm labor", section on 'Patient selection and treatment goals'.)Preventing recurrenceRecurrent pyelonephritis during pregnancy occurs in 6 to 8 percent of women [61,67,68]. As a result, low dose antimicrobial suppressive therapy with an agent to which the original organism is susceptible is warranted for the remainder of the pregnancy; reasonable options include nitrofurantoin (50 to 100 mg orally at bedtime) or cephalexin (250 to 500 mg orally at bedtime) [58,69].Monthly cultures are not necessary if preventive therapy is administered; however, breakthrough bacteriuria can occur during preventive therapy, so we usually perform at least one later culture, such as at the start of the third trimester, to ensure preventive therapy is working. If a follow-up culture is positive (105colony formingunits/mL),then a course of antimicrobial therapy based on susceptibility data should be administered. In addition, the preventive regimen should be reassessed and adjusted if needed.PREVENTION IN WOMEN WITH HISTORY OF RECURRENT UTIA separate issue is the management of pregnant women with a history of recurrent urinary tract infections (UTIs) prior to pregnancy, which is often related to sexual intercourse. We use postcoital prophylaxis in pregnant women who have recurrent UTIs that appear to be temporally related to sexual intercourse. The preferred regimen is a single postcoital dose of either cephalexin (250 mg) or nitrofurantoin (50 mg). (See "Recurrent urinary tract infection in women", section on 'Prevention strategies'.)The potential efficacy of postcoital prophylaxis to prevent UTIs during pregnancy was evaluated in a report of 33 women with a history of recurrent UTIs who had 39 pregnancies [70]. The women were treated with a single postcoital dose of either cephalexin (250 mg) or nitrofurantoin (50 mg). Only one UTI occurred during pregnancy; this was in sharp contrast to 130 UTIs during a mean observation period of seven months before prophylaxis.ANTIBIOTIC SAFETY IN PREGNANCYMuch of the information regarding the safe use of antibiotics during pregnancy was obtained decades ago, before pregnant women were excluded from drug studies because of concerns about risk to the fetus. Thus, there is little direct information about the safety of many newer antibiotics in pregnancy, and concern about the use of certain antibiotics generally derives from indirect evidence (eg, animal studies) or observational studies that may have numerous confounders. Overall, the safest course is to use the antibiotics that have well-established safety profiles in pregnancy and limit the use of antibiotics of potential concern to cases in which no safer alternative exists. (See "Initial prenatal assessment and first trimester prenatal care", section on 'Antibiotic therapy'.)It is generally accepted that penicillins (with or without beta-lactamase inhibitors), cephalosporins, and aztreonam are safe in pregnancy. However, drugs with very high protein binding, such as ceftriaxone, may be inappropriate the day before parturition because of the possibility of bilirubin displacement and subsequent kernicterus. Of the carbapenems, some animal studies have shown adverse fetal effects with imipenem-cilastatin, so meropenem, ertapenem, or doripenem are the preferred carbapenems for use during pregnancy.Fosfomycin is also generally considered safe in pregnancy [71]. In several studies of single-dose fosfomycin during pregnancy, it was well-tolerated, and adverse fetal effects were not observed.Nitrofurantoin is frequently used during pregnancy, although some potential concerns exist. Nitrofurantoin was associated with birth defects in a case control study [72], but this finding should be interpreted with caution as multiple comparisons involving small numbers of affected exposed infants may have led by chance to the observed association. The safest course is to avoid using nitrofurantoin in the first trimester if another antibiotic that is safe and effective is available. Nitrofurantoin has also been reported to cause hemolytic anemia in the mother and fetus with G-6PD deficiency [73]. The risk of hemolytic anemia is estimated to be only 0.0004 percent of cases, but its use should be avoided near term for this reason [69,74].Use of trimethoprim-sulfamethoxazole is typically limited to mid-pregnancy, avoiding the first trimester and near term. Trimethoprim is generally avoided in the first trimester because it is a folic acid antagonist, has caused abnormal embryo development in experimental animals, and some case control studies have reported a possible association with a variety of birth defects [72]. However, it is not a proven teratogen in humans. Women are routinely prescribed folic acid supplementation during pregnancy; this may be particularly important in those who are taking trimethoprim. Sulfonamides should be avoided in the last days before delivery because they can displace bilirubin from plasma binding sites in the newborn, with the theoretical increased risk for kernicterus, although kernicterus related solely to in utero sulfonamide exposure has never been reported. Sulfonamides have also been associated with birth defects in a case control study [72], but the limitations of the study discussed above lead to uncertainty about the association.Aminoglycosides have been associated with ototoxicity following prolonged fetal exposure [74], and therefore should be avoided unless intolerance or resistance prohibits the use of less toxic agents.Fluoroquinolones and tetracyclines are contraindicated during pregnancy.INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5thto 6thgrade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10thto 12thgrade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)Beyond the Basics topics (see "Patient information: Urinary tract infections in adolescents and adults (Beyond the Basics)")SUMMARY AND RECOMMENDATIONSBacteriuria occurs commonly in pregnancy, typically during early pregnancy. Without treatment, as many as 30 to 40 percent of pregnant women with asymptomatic bacteriuria will develop a symptomatic urinary tract infection (UTI). The smooth muscle relaxation and subsequent ureteral dilatation that occurs in pregnancy are thought to facilitate the ascent of bacteria from the bladder to the kidney, accounting for the greater risk of pyelonephritis. Additionally, untreated bacteriuria is associated with an increased risk of preterm birth, low birth weight, and perinatal mortality. (See 'Epidemiology' above and 'Pathogenesis' above.)As in nonpregnant women,Escherichia coliis the predominant uropathogen found in both asymptomatic bacteriuria and UTI in pregnant women. (See 'Microbiology' above.)We screen all pregnant women at least once for asymptomatic bacteriuria. Screening for asymptomatic bacteriuria is performed at 12 to 16 weeks gestation with a midstream urine for culture. The diagnosis is made by finding high-level bacterial growth (105colony forming units[cfu]/mL)on urine culture in the absence of symptoms consistent with UTI. (See 'Diagnosis' above.)Management of asymptomatic bacteriuria in pregnant women includes antibiotic therapy tailored to culture results, which reduces the risk of subsequent pyelonephritis and is associated with improved pregnancy outcomes. Potential options include beta-lactams, nitrofurantoin, and fosfomycin (table 1). Following treatment, follow-up cultures are performed to confirm sterilization of the urine. For those women with persistent bacteriuria, prophylactic or suppressive antibiotics may be warranted in addition to retreatment. (See 'Management' above.)Acute cystitis should be suspected in pregnant women who complain about new onset dysuria, frequency, or urgency. The diagnosis is made by finding of bacterial growth on urine culture in this setting. Management of acute cystitis in pregnant women includes empiric antibiotic therapy that is subsequently tailored to culture results. Potential options for empiric and directed therapy include beta-lactams, nitrofurantoin, and fosfomycin (table 1). As with asymptomatic bacteriuria, follow-up cultures are performed to confirm sterilization of the urine. For those women with persistent bacteriuria or recurrent cystitis, prophylactic or suppressive antibiotics may be warranted in addition to retreatment. (See 'Acute cystitis' above.)Acute pyelonephritis during pregnancy is suggested by the presence of flank pain,nausea/vomiting,fever (>38C),and/orcostovertebral angle tenderness, with or without the typical symptoms of cystitis, and is confirmed by the finding of bacteriuria in the setting of these symptoms. Pregnant women may become quite ill and are at risk for both medical (eg, sepsis, respiratory failure) and obstetrical complications from pyelonephritis. (See 'Clinical manifestations' above and 'Diagnosis and evaluation' above.)Management of acute pyelonephritis in pregnant women includes hospital admission for parenteral antibiotics, preferably broad spectrum beta-lactams (table 2). Antibiotic therapy can be converted to an oral regimen tailored to the susceptibility profile of the isolated organism following clinical improvement. Oral options are generally limited to beta-lactams or, if in the second trimester, trimethoprim-sulfamethoxazole. Following the treatment course, suppressive antibiotics are typically used for the remainder of the pregnancy to prevent recurrence. (See 'Management' above.)It is generally accepted that penicillins (with or without beta-lactamase inhibitors), cephalosporins, aztreonam, and fosfomycin are safe in pregnancy. Because of possible but uncertain associations with adverse birth outcomes, we generally avoid nitrofurantoin during the first trimester and trimethoprim-sulfamethoxazole during the first trimester and near term unless no other options are available. (See 'Antibiotic safety in pregnancy' above.)Use of UpToDate is subject to theSubscription and License Agreement.REFERENCES1Patterson TF, Andriole VT. Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era. Infect Dis Clin North Am 1997; 11:593.

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Topic 8065 Version 27.0All rights reserved.2015UpToDate, Inc.Disclosures

Disclosures:Thomas M Hooton, MDConsultant/Advisory Boards: Cubist [Complicated UTI (Ceftolozane/tazobactam)]; Vifor Pharma [Uncomplicated UTI (Immunostimulant uro-vaxom)]. Equity Ownership/Stock Options: Fimbrion Therapeutics [Prevention of UTI (Developing mannosides that may eventually be useful in prevention of UTI)].Kalpana Gupta, MD, MPHConsultant/Advisory Boards: Boehringer Ingelheim GmbH [UTI (Empagliflozin)]; Paratek [UTI (Omadacycline)]; Melinta Pharmaceuticals [UTI].Stephen B Calderwood, MDConsultant/Advisory Boards: Pulmatrix [Inhaled antimicrobial products (Not currently released)]. Patent Holder: Vaccine Technologies [Cholera (Cholera vaccines)]. Equity Ownership/Stock Options: PharmAthene [Biodefense (Anthrax)].Charles J Lockwood, MD, MHCMNothing to disclose.Allyson Bloom, MDEmployee of UpToDate, Inc.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policyUpToDate Customer Service

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