Screening for asymptomatic bacteriuria is performed at 12 to 16 weeks gestation (or the first prenatal visit, if that occurs later) with a urine culture [32]. Rescreening among those who did not have bacteriuria on the initial test is generally not performed in low-risk women. It is reasonable to rescreen women at high risk for infection (eg, history of UTI or presence of urinary tract anomalies, diabetes mellitus, hemoglobin S, or preterm labor), however the optimal target populations for this is uncertain. There is minimal evidence informing the benefits and harms of repeat screening following an initial negative culture.(See "Prenatal care: Initial assessment".)

Specimen collection — The diagnosis of asymptomatic bacteriuria should be based on culture of a urine specimen collected in a manner that minimizes contamination. Although the optimal method for collecting voided urine is uncertain, instructing women to spread their labia and collect a midstream urine (without requiring a clean-catch) seems most reasonable. Routine catheterization to screen for bacteriuria is not warranted due to the risk of introducing infection. (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults".)

In order to minimize contamination of the voided specimen, it is often recommended that the patient collect a clean-catch (after local cleansing of the urethral meatus and surrounding mucosa) midstream (collection of the second portion of the voided urine after discarding the initial stream) specimen. However, it is not clear that these measures reduce contamination. In a study of 113 asymptomatic pregnant women, each was instructed to collect a sample from the first concentrated morning urine, a midstream sample, and a clean-catch midstream sample, in that order, over the course of a day [33]. Rates of mixed growth and growth of skin flora on culture in midstream urine were comparable with those observed in the morning and clean-catch samples. Overall rates of contamination were high in all three samples, and the women were tested at a mean of 32 weeks of gestation as opposed to the recommended period of 16 weeks. Findings from this and other studies suggest that collection of a clean-catch voided urine specimen is of little value [34,35].

Proper handling and processing of the specimen is crucial to avoid false-positive results. (See "Microbiology specimen collection and transport".)

Diagnostic criteria — For asymptomatic women, bacteriuria is formally defined as two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts of ≥105 colony-forming units (cfu)/mL or a single catheterized urine specimen with one bacterial species isolated in a quantitative count of ≥102 cfu/mL [2]. In clinical practice, however, only one voided urine specimen is typically obtained, and diagnosis (and treatment initiation) is made in women with ≥105 cfu/mL without obtaining a confirmatory repeat culture. The diagnosis (and treatment) of asymptomatic bacteriuria due to group B streptococcus during pregnancy is discussed in detail elsewhere. (See "Group B streptococcal infection in pregnant women", section on 'Asymptomatic bacteriuria'.)

If bacteria that are not typical uropathogens (such as lactobacillus) are isolated, treatment should be reserved for patients in whom the organism grows as a single isolate on consecutive cultures.

Rapid screening tests, such as dipstick, enzymatic screen, reagent strip, or interleukin-8 testing, do not come close to urine culture in terms of sensitivity and specificity for detecting asymptomatic bacteriuria in pregnant women and should not be used [36-38]. In addition, cultures are useful in guiding therapy. This can be particularly important in pregnancy, during which the number of safe treatment alternatives is reduced.

Management — Management of asymptomatic bacteriuria in pregnant women includes antibiotic therapy tailored to culture results and follow-up cultures to confirm sterilization of the urine.

Rationale for treatment — Asymptomatic bacteriuria during pregnancy increases the risk of pyelonephritis and has been associated with adverse pregnancy outcomes, such as preterm birth and low birth weight infants (see 'Epidemiology' above). Antimicrobial treatment reduces the risk of subsequent development of pyelonephritis and is associated with improved pregnancy outcomes [7,39-44]. This was illustrated in a meta-analysis of 15 randomized trials of antibiotic treatment versus placebo or no treatment for pregnant women with asymptomatic bacteriuria [7]. Antibiotic therapy was more likely to clear asymptomatic bacteriuria (odds ratio [OR] 0.30, 95% CI 0.18-0.53) and to lower the incidence of pyelonephritis (OR 0.24, 95% CI 0.13-0.41). There was also a reduction in the incidence of low birth weight infants with antibiotic treatment. However, the included studies that evaluated these outcomes were deemed to be of poor quality.

This meta-analysis included a trial of pregnant women in the Netherlands (where screening for asymptomatic bacteriuria is not performed routinely), which suggested generally similar effects of treatment [9]. Women with asymptomatic bacteriuria between 16 and 22 weeks gestation who were not treated or received placebo treatment had a higher rate of pyelonephritis (2.4 percent of 208 women) compared with both those who received nitrofurantoin treatment for asymptomatic bacteriuria (0 percent of 40 women) and those who did not have asymptomatic bacteriuria (0.6 percent of 4035 women). Likewise, low birth weight occurred in 17 of 208 untreated or placebo-treated women with asymptomatic bacteriuria (8 percent) compared with 1 of 40 of nitrofurantoin-treated women (2.5 percent). While this difference was not statistically significant, the study was under-powered for this outcome. Preterm birth did not differ between these two groups. Notably, the study included only women who were at low risk for UTI, pre-term birth, or other complications, and the pyelonephritis rate was lower than in previous studies of pregnant women with asymptomatic bacteriuria [21].

Antimicrobial treatment — Asymptomatic bacteriuria is treated with an antibiotic tailored to the susceptibility pattern of the isolated organism, which is generally available at the time of diagnosis. Potential options include beta-lactams, nitrofurantoin, and fosfomycin (table 1). The choice of antimicrobial agent should also take into account safety during pregnancy (including the particular stage of pregnancy). (See 'Antibiotic safety in pregnancy' below.)

The optimal duration of antibiotics for asymptomatic bacteruria is uncertain. Short courses of antibiotics are preferred to minimize the antimicrobial exposure to the fetus. Short course antibiotic therapy is usually effective in eradicating asymptomatic bacteriuria of pregnancy, although single-dose regimens may not be as effective as slightly longer regimens [45-47]. As an example, in a meta-analysis of 13 studies comparing single-dose treatment with four to seven day treatments, there was a trend towards lower rates of bacteriuria clearance with the single-dose regimen [47].

An exception is single-dose fosfomycin, which successfully treats bacteriuria. In three trials comparing this drug with other therapies administered for a longer time, eradication of the organism was comparable (77 to 94 percent versus 68 to 94 percent with other agents) [48].

Follow-up — Up to 30 percent of women fail to clear asymptomatic bacteriuria following a short course of therapy [1]. Thus, a repeat culture is generally recommended as a test of cure, which can be performed a week after completion of therapy for asymptomatic bacteriuria [49]. However, there are insufficient data informing the utility of repeat testing following an initial episode of asymptomatic bacteriuria, and it is not known whether retreatment of recurrent or persistent bacteriuria improves outcomes [2]. Thus, our approach is based primarily on expert opinion:

●If repeat culture has no growth, there is no indication for further testing for bacteriuria in the absence of symptoms suggestive of urinary tract infection.

●If repeat culture is positive for bacterial growth (≥105 cfu/mL), optimal management is uncertain. We generally repeat antibiotic treatment tailored to antimicrobial susceptibility testing (table 1); if the repeat culture yielded the same species as the first culture, we give either the same antimicrobial as administered the first time for a longer course (eg, seven days, if a three-day regimen was used previously) or a different antimicrobial for a typical duration. However, we do not continue testing for asymptomatic bacteriuria following this second treatment course.

There are insufficient data to support the use of suppressive or prophylactic antibiotics for persistent or recurrent asymptomatic bacteriuria, and we do not do this.

ACUTE CYSTITIS

Clinical manifestations — Cystitis is a symptomatic infection of the bladder. The typical symptoms of acute cystitis in the pregnant woman are the same as in nonpregnant women and include the sudden onset of dysuria and urinary urgency and frequency. Hematuria and pyuria are also frequently seen on urinalysis.

Systemic symptoms, such as fevers and chills, are absent in simple cystitis.

Diagnosis — Acute cystitis should be suspected in pregnant women who complain about dysuria. Although urinary frequency and urgency are typical findings of acute cystitis, they are also frequently a normal physiologic change of pregnancy and reported by pregnant women without cystitis or bacteriuria [50,51]. The presence of fever and chills, flank pain, and costovertebral angle tenderness should raise suspicion for pyelonephritis (see 'Acute pyelonephritis' below). A urinalysis and urine culture should be performed in pregnant women who have new onset dysuria. Specimen collection is the same as for asymptomatic bacteriuria. (See 'Specimen collection' above.)

The diagnosis of acute cystitis is confirmed by finding of bacterial growth on urine culture. Prior to confirming the diagnosis, empiric treatment is typically initiated in a patient with consistent symptoms and pyuria on urinalysis (see 'Management' below). As in nonpregnant women, pyuria is usually present in almost all pregnant women with symptomatic urinary tract infection, and its absence strongly suggests an alternative diagnosis. (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Interpretation of pyuria'.)

Studies defining the threshold of bacterial growth on voided urine that represents significant bacteriuria in pregnant women have not been performed, but based on studies in nonpregnant women, relatively low colony counts can reflect true bacteriuria in the presence of symptoms. In nonpregnant women with acute simple cystitis, coliform colony counts in voided urine as low as 102 colony-forming units (cfu)/mL have been noted to reflect bladder infection [52-54]. As most clinical laboratories do not routinely quantify urine isolates to 102 cfu/mL, it is reasonable to use a quantitative count ≥103 cfu/mL in a symptomatic pregnant woman as an indicator of symptomatic UTI. If bacteria that are not typical uropathogens (such as lactobacillus) are isolated, the diagnosis of cystitis is typically made only if they are isolated in high bacterial counts (≥105 cfu/mL). (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Definition of a positive culture'.)

Differential diagnosis — As in nonpregnant women, dysuria in pregnant women can be a result of other infectious and noninfectious processes, such as vaginitis or urethritis. Similarly, urinary frequency and urgency may be symptoms of normal pregnancy in the absence of urinary tract infection. However, true bacteriuria is typically not present in these settings and thus distinguishes acute cystitis. If not already performed, testing for sexually transmitted infections (such as chlamydia and gonorrhea) is warranted for pregnant women with dysuria without bacteriuria or women who have persistent dysuria despite successful treatment of bacteriuria. (See "Acute simple cystitis in women", section on 'Differential diagnosis'.)

Management — Management of acute cystitis in pregnant women includes empiric antibiotic therapy that is subsequently tailored to culture results and follow-up cultures to confirm sterilization of the urine. For those women with persistent or recurrent bacteriuria, prophylactic or suppressive antibiotics may be warranted in addition to retreatment.

Antimicrobial treatment — Antibiotic treatment of acute cystitis in pregnant women is often empiric, initiated at the time of complaints of dysuria, and then tailored to the susceptibility pattern of the isolated organism once urine cultures return. Potential options for empiric and directed therapy include beta-lactams, nitrofurantoin, and fosfomycin (table 1). The choice of an antimicrobial agent should also take into account any prior microbiological data and drug safety during pregnancy (including the particular stage of pregnancy). (See 'Antibiotic safety in pregnancy' below.)

For empiric therapy, we typically choose between cefpodoximeamoxicillin-clavulanate, and fosfomycin, given their safety in pregnancy and the somewhat broader spectrum of activity compared with other agents (such as amoxicillin or cephalexin). Nitrofurantoin is another option during the second or third trimester or if the others cannot be used for some reason (eg, drug allergy). The choice between them should be individualized on the basis of several factors, including patient allergy history, local practice patterns, local community resistance prevalence, availability, and cost [55].

Although there are limited data in pregnant women, a meta-analysis suggested that there are no large differences in outcomes between different antibiotic regimens in terms of cure rates, recurrent infection, incidence of preterm delivery, and the need for a change of antibiotics [56]. All of the antibiotics studied were very effective and complications were rare. There was not enough evidence to recommend a particular treatment scheme.

For women who are thought to be at risk for or have documented infection with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, nitrofurantoin and fosfomycin are active in vitro against many such strains and are potential oral options [28,57].

The optimal duration of treatment of acute cystitis during pregnancy is uncertain. As with asymptomatic bacteriuria, short courses of antibiotics are preferred, to minimize the antimicrobial exposure to the fetus. We treat acute cystitis with a three to seven day course of antibiotics as long as there are no symptoms suggestive of pyelonephritis (eg, flank pain, nausea/vomiting, fever [>38°C], and/or costovertebral angle tenderness). Based on data among nonpregnant individuals, there appear to be no differences between short antibiotic courses (three to seven days) and longer ones [1,55,58]. Single-dose therapy is generally limited to fosfomycin.

Follow-up — As with asymptomatic bacteriuria, a follow-up culture should be obtained as a test of cure. We typically perform this a week after completion of therapy. As above, if the patient is asymptomatic but has bacteriuria on test of cure, the optimal management is uncertain. (See 'Follow-up' above.)

Management of recurrent cystitis — In women who have three or more episodes of recurrent cystitis during pregnancy, antimicrobial prophylaxis for the duration of pregnancy is a reasonable strategy to prevent additional episodes. Prophylaxis can be postcoital if the cystitis is thought to be sexually related (which it commonly is) or continuous. However, there are no data to guide whether treatment of isolated recurrent episodes or prophylaxis is a better approach in terms of risks versus benefits.

In the setting of other conditions that potentially increase the risk of urinary complications during episodes of cystitis (eg, diabetes or sickle cell trait), prophylaxis following the first episode of cystitis during pregnancy is also reasonable.

The choice of antimicrobial used for prophylaxis should be based on the susceptibility profile of the pathogens causing the cystitis. Ideally, daily or postcoital prophylaxis with low-dose nitrofurantoin (50 to 100 mg orally postcoitally or at bedtime) or cephalexin (250 to 500 mg orally postcoitally or at bedtime) can be used.

 

 

 

 

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