• Screen for asymptomatic bacteriuria on the first antenatal visit by sending urine for culture. If asymptomatic bacteriuria is found, send a second urine sample for culture.
• If the second urine culture confirms asymptomatic bacteriuria, treat for 7 days with an antibiotic to which the organism is sensitive.
• Preferred options when sensitivities are known are (in order of preference):
• Amoxicillin: 250 mg three times daily, for 7 days.
• Nitrofurantoin: 50 mg four times daily, or 100 mg (modified-release) twice daily, for 7 days.
• Trimethoprim: 200 mg twice daily, for 7 days (unless the woman is folate deficient or taking a folate antagonist).
• Cefalexin (500 mg twice daily, or 250 mg 6-hourly, for 7 days) may be used but is less preferred.
• After treatment, send urine for culture to screen for asymptomatic bacteriuria at every antenatal visit until delivery.
• If a group B streptococcus is isolated, inform the antenatal care service, as prophylactic antibiotics may be indicated during labour and delivery.

Screening for asymptomatic bacteriuria

• Guidelines from the National Institute for Health and Clinical Excellence (NICE) on antenatal care recommend that 'Women should be offered routine screening for asymptomatic bacteriuria by midstream urine culture early in pregnancy' [NICE, 2008a]. Guidelines from the Scottish Intercollegiate Guidelines Network (SIGN) are clearer: 'Women who do not have bacteriuria in the first trimester should not have repeat urine cultures' [SIGN, 2006].
• Culture of urine is recommended rather than dipstick (reagent strip) tests because there is good evidence that dipstick tests are insufficiently sensitive (in whatever combination) to be used for screening. Urine culture is regarded as the gold standard and is assumed to have (close to) 100% sensitivity for detecting bacteriuria.
• The recommendation that a positive culture be confirmed with a second culture before treating asymptomatic bacteriuria in pregnancy is based on expert opinion [Nicolle et al, 2005; SIGN, 2006].
• The recommendation to continue to screen for asymptomatic bacteriuria at each subsequent visit after completing antibiotic treatment is consistent with practice in multinational clinical trials, such as that conducted by the World Health Organization's Asymptomatic Bacteriuria Trial Group [Lumbiganon et al, 2009].

Treating asymptomatic bacteriuria

• Asymptomatic bacteriuria in pregnancy should be treated with an antibiotic because there is consistent evidence from a Cochrane systematic review that the risk of pyelonephritis is reduced: about seven women need to be treated to prevent one episode of pyelonephritis.
• There is inconsistent evidence that treatment may also reduce the incidence of low birthweight and prematurity.

Choosing antibiotic treatment

• Where sensitivities are known, amoxicillin is preferred.
• The manufacturer of amoxicillin states that its use in pregnancy has been well documented in clinical studies. Unlike nitrofurantoin and trimethoprim, amoxicillin is licensed for the treatment of bacteriuria in pregnancy [ABPI Medicines Compendium, 2008].
• Penicillin and cephalosporins are generally the antibiotics of choice for use in pregnancy [Schaefer et al, 2007].
• Nitrofurantoin is an alternative if amoxicillin is not suitable.
• Nitrofurantoin has been used extensively since the 1950s, and its safety profile in human pregnancy has been well documented [Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2007].
• There is evidence from a Cochrane systematic review which supports the use of nitrofurantoin for treating asymptomatic bacteriuria in pregnancy [Smaill and Vazquez, 2007]. Nitrofurantoin was studied in five of the 14 studies identified (none on trimethoprim). Although significant heterogeneity was present, pooled results from five trials (two used nitrofurantoin) found antibiotics to be more effective than placebo in treating asymptomatic bacteriuria in pregnancy.
• The efficacy and safety profiles of nitrofurantoin are further supported in a recent large multicentre study undertaken by the World Health Organization (WHO) in which 778 pregnant women with asymptomatic bacteriuria were treated with nitrofurantoin [Lumbiganon et al, 2009]. A cure rate of 86% was achieved with a 7-day course.
• Trimethoprim, used carefully, has a good safety profile during pregnancy.
• Concerns have been expressed about the use of trimethoprim during pregnancy because it is a folic acid antagonist, and low levels of folic acid have been associated with serious birth defects.
• The evidence on the risks of trimethoprim during pregnancy has been critically assessed by the UK Teratology Information Service (UKTIS), formerly the National Teratology Information Service (NTIS) [NTIS, 2008]. A similar systematic review was conducted by the Centers for Disease Control (CDC) in the USA, to assess the safety of trimethoprim-sulfamethoxazole used for prophylaxis in HIV-infected pregnant women [Forna et al, 2006]. The NTIS and CDC concluded that the benefits outweighed the risks, which were small. Additionally the NTIS concluded that:
• Trimethoprim should not be used in pregnant women who are folate deficient, or who are taking a folate antagonist (unless they are taking a folate supplement).
• In women with normal folate status, who are well nourished, use of trimethoprim for a short period is unlikely to induce folate deficiency.
• For further information, see Pregnancy and breastfeeding with trimethoprim.
• Cefalexin is less preferred because:
• Although cefalexin can be used in pregnancy [Schaefer et al, 2007], the Health Protection Agency recommends avoiding the use of broad spectrum antibiotics (such as co-amoxiclav, cephalosporins, and quinolones) when narrow spectrum antibiotics remain effective [HPA, 2009]. There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs.
• Duration of antibiotic treatment
• The use of a 7-day course is supported by evidence from a recent WHO study which found that a 1-day course of nitrofurantoin is less effective than a 7-day course for treating asymptomatic bacteriuria in pregnant women (n = 778) [Lumbiganon et al, 2009].
• Antibiotic dosages
• These are in line with dosages recommended by the manufacturers of these antibiotics.

Managing incidentally-found group B streptococcus infection

• The antenatal care service should be informed when a group B streptococcus (GBS), Streptococcus agalactiae, is isolated in urine. GBS bacteriuria, even if treated, may be associated with increased risk of neonatal GBS disease, and so antibiotic prophylaxis should be offered to the woman during delivery. This recommendation is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2003].