Antibiotics for Culture‐Positive Asymptomatic Bacteriuria in Pregnant Women

Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2019;2019(11):CD000490

Study Population: Pregnant women in all three trimesters of pregnancy in 12 studies (N=2,017)

Rates of pyelonephritis, preterm birth, low birth weight

Maternal side effects

Asymptomatic bacteriuria, occurring in 2-15% of pregnancies, is generally defined as at least one urine culture showing >100,000 colony-forming units (CFUs)/mL in the absence of fever or symptoms of urinary tract infection.1 Escherichia coli is the most commonly associated pathogen, comprising up to 80% of isolates.2 While asymptomatic bacteriuria in non-pregnant women is generally benign, in pregnant women there is an increased likelihood for progression to pyelonephritis likely due to mechanical compression of the ureters by an enlarged uterus, as well as smooth muscle relaxation induced by progesterone.3 Some studies suggest if asymptomatic bacteriuria is left untreated, up to 30% of pregnant women will develop acute pyelonephritis,4 which may be associated with potentially serious maternal complications such as sepsis,5 and pregnancy outcomes such as low birth weight and preterm birth.6

The systematic review summarized here included 2,017 pregnant women from twelve randomized controlled trials that compared antibiotic treatment of asymptomatic bacteriuria to placebo or no treatment.7 Most of the women were enrolled through prenatal screening in hospital-based clinics, and the studies included women in all stages of pregnancy. The definition of pyelonephritis varied across studies but mainly encompassed women with flank tenderness, fever, with or without urinary symptoms (such as frequency, dysuria, and hematuria), and >100,000 CFUs/mL of urine. Incidence of pyelonephritis ranged from 2.2% to 36%. Included studies were performed in the 1960s through the 1980s, and study antibiotics included sulfa drugs, tetracycline, methenamine, nalidixic acid, nitrofurantoin, and ampicillin. Duration of treatment varied including single dose, short course (three to seven days), intermediate course (three to six weeks), and continuous antibiotic until delivery.

As compared to placebo or no treatment, [in 11 studies of 1932 subjects] antibiotic treatment reduced the incidence of pyelonephritis (Relative risk [RR]: 0.2, 95% confidence interval [CI] 0.1 to 0.4; Absolute Risk Difference [ARD]: 15%; Number-Needed-To-Treat [NNT]: 7). Data from three studies (n=327) also found antibiotic treatment reduced the incidence of preterm birth (gestational age <37 weeks) [RR 0.3, 95% CI 0.1 to 0.9; ARD: 11%; NNT: 9]. Finally, data from six studies (N=1437) found antibiotics also decreased the incidence of birth weight <2500g [RR 0.6, 95% CI 0.5 to 0.9; ARD: 5%; NNT: 20].

The findings of this review suggest a potentially important, clinically meaningful benefit with the use of antibiotics for asymptomatic bacteriuria in pregnancy. The underlying data, however, are heterogeneous, rife with potential systematic bias, and mostly generated 40-60 years ago.

The wide variation in pyelonephritis incidence among studies (2-36%), for instance, may partially originate from the variability in definitions of pyelonephritis, or patient level characteristics such as infecting organisms, socioeconomic status, and prenatal care. Regardless of source, this variation in baseline risk introduces major clinical heterogeneity and reduces the applicability of results. Moreover, the lack of consistent blinding (four studies were doubleblinded) and the significant heterogeneity across studies led the review authors to judge the quality of evidence as low. It is, in addition, difficult to confidently attribute the development of pyelonephritis to asymptomatic bacteriuria. Similarly, data on the incidence of preterm birth and low birth weight were also deemed low quality, again due to lack of blinding, heterogeneity, and small sample size.

Another important weakness is the lack of reporting on maternal side effects, making it impossible to characterize the potential for adverse events in the treatment group.

In summary, although antibiotics may reduce the risk of pyelonephritis in pregnancy, as well as preterm birth and low birth weight, the evidence for treatment of asymptomatic bacteruria is low quality. More robust research is needed, particularly in a contemporary milieu, using standardized treatment protocols, and stratification for baseline risk. Despite limitations, however, the data suggest significant benefit in preventing pyelonephritis, preterm birth, and low birth weight. Based on these findings it seems likely benefits outweigh harms. It should be emphasized that this signal of benefit is based upon a definition of asymptomatic bacteriuria that requires a positive urine culture, not simply a suggestive urinalysis. We would expose many more pregnant women to unclear harms for reduced benefit if we do not adhere to the clinical definition of asymptomatic bacteriuria. Therefore, we have rated antibiotic treatment for culturepositive asymptomatic bacteriuria during pregnancy Green (Benefit>Harms).

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

April 5, 2021