Q&a attempts to provide balanced answers to those curly-yet-common questions in obstetrics and gynaecology for the broader O&G Magazine readership including Diplomates, Trainees, medical students and other health professionals.
A 25-year-old primigravida has asymptomatic bacteriuria found on her booking MSU at ten weeks of pregnancy. What implications does this have for the pregnancy and how is it best managed?
a Asymptomatic bacteriuria (ASB) is usually defined as isolation of >105 colony-forming units of a single bacterial species per millilitre of urine, in the absence of urinary symptoms.1 Pregnant women will certainly benefit from treatment, unlike the general population in whom there is usually no indication to treat. The benefits of treatment during pregnancy have been recognised to such an extent that screening for ASB is found in many countries’ guidelines and is considered a standard of antenatal care.2,3 Estimates of the prevalence of ASB during pregnancy range from two to ten per cent, depending on the population sampled and the inclusion criteria used.4
Being sexually active is a recognised risk factor for bacteriuria in young women.5,6 Other risk factors include low socioeconomic status, anatomical abnormalities of the urinary tract, diabetes, or a personal or family history of recurrent urinary tract infection.4
Asymptomatic bacteriuria is associated with pregnancy complications. Of women with ASB in early pregnancy, 30 per cent go on to develop pyelonephritis, compared with 1.8 per cent of controls without bacteriuria.7 Treatment of ASB detected in early pregnancy has been consistently shown to reduce the incidence of pyelonephritis. A recent Cochrane systematic review showed treating women for ASB led to approximately a 75 per cent reduction in the incidence of pyelonephritis during pregnancy. Seven women need to be treated in order to prevent one episode of pyelonephritis.4
There is evidence that ASB is associated with low birthweight and preterm birth, if left untreated.8 The evidence surrounding the effect of treatment is less consistent. If ASB is merely a marker for low socio-economic status, which is also associated with low birthweight, then one would expect there would be no effect of treatment of ASB on low birthweight. A Cochrane systematic review found a statistically significant reduction in the incidence of low birthweight; however, the poor methodological quality of the studies means conclusions for this outcome should be drawn cautiously. The same review included three studies comparing the effect of treatment of asymptomatic bacteriuria on preterm birth with no treatment and found no significant reduction in incidence of preterm birth.4
In Australia, screening is usually conducted by sending a urine sample at the booking visit. Internationally, there is controversy about the ideal timing of the screening urine culture. Most studies include screening before 20 weeks gestation, but one study suggested a single culture before 20 weeks may miss more than half of women with ASB.9 There is also controversy about whether one specimen is adequate to make the diagnosis. Some guidelines suggest sending specimens at two consecutive visits, reserving treatment for women in whom a pathogen is consistently identified.10 If two consecutively voided cultures yield the same organism, there is a probability of 95 per cent that the woman has true bacteriuria whereas one positive culture gives a specificity of 80 per cent.11 Sending one specimen for culture provides a practical and effective alternative.
Screening for ASB appears to be cost-effective in most populations. An American analysis concluded that, unless the prevalence of ASB is less than two per cent, screening is cost-effective during pregnancy.12, 13 After a woman has had one positive urine culture, repeat screening at every visit has been suggested by some clinical guidelines.2 This is based on management in large multinational clinical trials.14 The cost-effectiveness of this approach has not been assessed.
A clean catch midstream specimen has traditionally been viewed as the ideal. Some evidence suggests this technique may not reduce the number of contaminated specimens compared with giving no specific instructions to the patient.15 A culture is the gold standard as it is much more effective in detecting bacteriuria when compared with reagent strip dipstick testing. Reagent strip testing has the advantage of being quick and inexpensive when compared with urine culture. The sensitivity of reagent strip testing ranges from 8.18 to 50.0 per cent, and the specificity has ranged from 47 to 92 per cent. This means the maximum performance using reagent strip testing will be detection of half of the women with asymptomatic bacteriuria.2 If reagent strip testing is performed, women who test positive should have urine sent for culture and sensitivity testing.
Antibiotics are the mainstay of management of asymptomatic bacteriuria. E. coli accounts for the majority of positive cultures.4 Empirical treatment is only recommended in the setting of symptomatic urinary tract infection. Culture and sensitivity testing should be used to guide antibiotic selection for eradication of ASB. Antibiotic resistance appears to be increasing, so the use of broad spectrum agents is discouraged. Nitrofurantoin and cephalexin regimens are recommended in the current therapeutic guidelines. The use of amoxicillin alone is recommended if the organism is known to be sensitive. Clavulanic acid should be avoided as it has been associated with an increased incidence of necrotising enterocolitis in neonates whose mothers given antibiotic prophylaxis in the setting of preterm premature rupture of membranes, however, there was no difference at long-term follow up.16-18
Due to the heterogeneity in the body of evidence, analysis in relation to the optimal duration of antibiotic therapy has been difficult. A systematic review that compared single-dose antibiotic treatment with a four- to seven-day course of antibiotic treatment for asymptomatic bacteriuria showed no difference in the prevention of preterm birth or pyelonephritis. Longer duration of treatment, however, was associated with increased reports of adverse effects.19
If group B streptococcus (GBS) is found in a woman’s booking urine, it is indicated to treat this with antibiotics, both at that time and later intrapartum.3 This recommendation comes from a retrospective cohort study in which 82 per cent of women with group B streptococcal bacteriuria were treated with intrapartum antibiotics, and no association was found between GBS bacteriuria and an increased risk of early-onset disease. The authors concluded that this represented successful prevention.20 A much older randomised controlled trial compared the treatment of GBS bacteriuria with penicillin to treatment with placebo. Results indicated a significant reduction in rates of premature rupture of membranes and preterm delivery in the women who received antibiotics.21
For this patient, I would recommend and prescribe appropriate antibiotic treatment, based on culture and sensitivity testing. The patient should be counselled about the role of treatment to prevent adverse pregnancy outcomes such as low birthweight and pyelonephritis. It should be emphasised that despite being asymptomatic at the present time, compliance with antibiotic treatment is important. She should also be re-screened once the antibiotic course is complete to ensure adequate treatment has occurred. If the pathogen was GBS, intrapartum antibiotic prophylaxis would be indicated.
- Rubin RH, Shapiro ED, Andriole VT et al. Evaluation of new antiinfectivedrugs for the treatment of urinary tract infection. InfectiousDiseases Society of America and the Food and Drug Administration.Clinical infectious diseases: an official publication of the InfectiousDiseases Society of America. 1992;15 Suppl 1:S216-27. Epub1992/11/01.
- NICE. Antenatal care: routine care for the healthy pregnantwoman (NICE guideline). National Institute for Health and ClinicalExcellence. 2008.
- RANZCOG. Screening and treatment for group B streptococcus inpregnancy. RANZCOG (College Statement C-Obs 19). 2011.
- Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuriain pregnancy. Cochrane database of systematic reviews.2007(2):CD000490. Epub 2007/04/20.
- Kunin CM, McCormack RC. An epidemiologic study of bacteriuriaand blood pressure among nuns and working women. New EnglandJournal of Medicine. 1968;278(12):635-42. Epub 1968/03/21.
- Hooton TM, Scholes D, Stapleton AE, et al. A prospective studyof asymptomatic bacteriuria in sexually active young women.New England Journal of Medicine. 2000;343(14):992-7. Epub2000/10/06.
- Whalley P. Bacteriuria of pregnancy. AJOG. 1967;97(5):723-38.Epub 1967/03/01.
- Romero R, Oyarzun E, Mazor M, et al. Meta-analysis of therelationship between asymptomatic bacteriuria and preterm delivery/low birth weight. Obstetrics and Gynecology. 1989;73(4):576-82.Epub 1989/04/01.
- McIsaac W, Carroll JC, Biringer A, et al. Screening for asymptomaticbacteriuria in pregnancy. JOGC. 2005;27(1):20-4. Epub2005/06/07.
- Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society ofAmerica guidelines for the diagnosis and treatment of asymptomaticbacteriuria in adults. Clinical Infectious Diseases. 2005;40(5):643-54. Epub 2005/02/17.11
- Kass EH. Bacteriuria and pyelonephritis of pregnancy. Archives ofInternal Medicine. 1960;105:194-8. Epub 1960/02/01.
- Rouse DJ, Andrews WW, Goldenberg RL, Owen J. Screeningand treatment of asymptomatic bacteriuria of pregnancy toprevent pyelonephritis: a cost-effectiveness and cost-benefitanalysis. Obstetrics and Gynecology. 1995;86(1):119-23. Epub1995/07/01.
- Wadland WC, Plante DA. Screening for asymptomatic bacteriuriain pregnancy. A decision and cost analysis. The Journal of FamilyPractice. 1989;29(4):372-6. Epub 1989/10/01.
- Lumbiganon P, Villar J, Laopaiboon M, Widmer M, Thinkhamrop J,Carroli G, et al. One-day compared with 7-day nitrofurantoin forasymptomatic bacteriuria in pregnancy: a randomized controlledtrial. Obstetrics and Gynecology. 2009;113(2 Pt 1):339-45. Epub2009/01/22.
- Lifshitz E, Kramer L. Outpatient urine culture: doescollection technique matter? Archives of Internal Medicine.2000;160(16):2537-40. Epub 2000/09/09.
- Kenyon SL, Taylor DJ, Tarnow-Mordi W, Group OC. Broadspectrumantibiotics for spontaneous preterm labour: the ORACLEII randomised trial. ORACLE Collaborative Group. Lancet.2001;357(9261):989-94. Epub 2001/04/11.17
- Kenyon SL, Taylor DJ, Tarnow-Mordi W, Group OC. Broad-spectrumantibiotics for preterm, prelabour rupture of fetal membranes: theORACLE I randomised trial. ORACLE Collaborative Group. Lancet.2001;357(9261):979-88. Epub 2001/04/11.
- Pike K, Brocklehurst P, Jones D, et al. Outcomes at 7 years for babieswho developed neonatal necrotising enterocolitis: the ORACLEChildren Study. Archives of Disease in Childhood Fetal and NeonatalEdition. 2012. Epub 2012/01/24.
- Widmer M, Gulmezoglu AM, Mignini L, Roganti A. Duration oftreatment for asymptomatic bacteriuria during pregnancy. Cochranedatabase of systematic reviews. 2011(12):CD000491. Epub2011/12/14.20
- Schrag SJ, Zell ER, Lynfield R, et al. A population-based comparisonof strategies to prevent early-onset group B streptococcal disease inneonates. New England Journal of Medicine. 2002;347(4):233-9.Epub 2002/07/26.
- Thomsen AC,Morup L, Hansen KB. Antibiotic elimination of group-Bstreptococci in urine in prevention of preterm labour. Lancet.1987;1(8533):591-3. Epub 1987/03/14.