Group B streptococcal infection primary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]
Overview
Primary Prevention of Early-Onset Group B Streptococcal Disease
Intravenous Intrapartum Antibiotic Prophylaxis
The use of intravenous intrapartum antibiotic prophylaxis to prevent early-onset GBS disease in the infant was first studied in the 1980s. Clinical trials and well-designed observational studies found that intrapartum antibiotic prophylaxis reduced vertical transmission of GBS, as measured by infant colonization or by protection against early-onset disease. Early trials suggested an efficacy of 100% for intrapartum antibiotic prophylaxis to prevent early-onset disease among infants born to women with GBS colonization. Subsequent observational studies have found the effectiveness to be 86%--89% among infants born to women who received intrapartum GBS prophylaxis.
Other strategies to reduce maternal colonization and vertical transmission have been studied, including intramuscular intrapartum antibiotic prophylaxis, antenatal (oral or intramuscular) antibiotics, and chlorhexidine vaginal wipes or douches; however, none has proven to be effective at preventing early-onset disease. Although some non-randomized studies on chlorhexidine have yielded promising results, randomized clinical trials have found no protection against early-onset GBS disease or neonatal sepsis.
Intrapartum Antibiotic Prophylaxis Agents
The efficacy of both penicillin and ampicillin as intravenously administered intrapartum agents for the prevention of early-onset neonatal GBS disease was demonstrated in clinical trials. Penicillin has a narrower spectrum of antimicrobial activity and therefore might be less likely to select for resistant organisms, although one clinical trial found that penicillin and ampicillin administered intravenously intrapartum were associated equally with the presence of ampicillin-resistant gram-negative organisms on postpartum vaginal-perineal culture. The dosages of penicillin and ampicillin used for intrapartum GBS prophylaxis are aimed at achieving adequate levels in the fetal circulation and amniotic fluid rapidly while avoiding potentially neurotoxic serum levels in the mother or fetus. Although the exact duration of antibiotics needed to prevent vertical transmission of GBS has been debated, beta-lactam antibiotics for GBS prophylaxis administered for ≥4 hours before delivery have been found to be highly effective at preventing vertical transmission of GBS and early-onset GBS disease. Shorter durations of appropriate antibiotics might provide some protection; in particular, colonization data suggest durations of ≥2 hours before delivery might confer some protection.
The efficacy of alternatives to penicillin or ampicillin that have been used to prevent early-onset GBS disease among infants born to penicillin-allergic mothers (including cefazolin, clindamycin, erythromycin, and vancomycin) has not been measured in controlled trials. Cefazolin has a relatively narrow spectrum of activity, similar pharmacokinetics and dynamics to penicillin and ampicillin, and achieves high intra-amniotic concentrations. However, an estimated 10% of persons with penicillin allergy also have immediate hypersensitivity reactions to cephalosporins. In contrast, data on the ability of clindamycin, erythromycin, and vancomycin to reach bactericidal levels in the fetal circulation and amniotic fluid are very limited; available data suggest that erythromycin and clindamycin provided to pregnant women do not reach fetal tissues reliably.
The following are key components of intrapartum antibiotic prophylaxis agents and dosing:
- Penicillin remains the agent of choice for intrapartum antibiotic prophylaxis, with ampicillin as an acceptable alternative (AI).
- Penicillin-allergic women who do not have a history of anaphylaxis, angioedema, respiratory distress, or urticaria following administration of a penicillin or a cephalosporin should receive cefazolin (BII).
- Antimicrobial susceptibility testing should be ordered for antenatal GBS cultures performed on penicillin-allergic women at high risk for anaphylaxis because of a history of anaphylaxis, angioedema, respiratory distress, or urticaria following administration of a penicillin or a cephalosporin (AII). To ensure proper testing, clinicians must inform laboratories of the need for antimicrobial susceptibility testing in such cases (AIII).
- Penicillin-allergic women at high risk for anaphylaxis should receive clindamycin if their GBS isolate is susceptible to clindamycin and erythromycin, as determined by antimicrobial susceptibility testing; if the isolate is sensitive to clindamycin but resistant to erythromycin, clindamycin may be used if testing for inducible clindamycin resistance is negative (CIII). Penicillin-allergic women at high risk for anaphylaxis should receive vancomycin if their isolate is intrinsically resistant to clindamycin as determined by antimicrobial susceptibility testing, if the isolate demonstrates inducible resistance to clindamycin, or if susceptibility to both agents is unknown (CIII).
- The recommended dosing regimen of penicillin G is 5 million units intravenously, followed by 2.5--3.0 million units intravenously every 4 hours (AII). The range of 2.5--3.0 million units is recommended to achieve adequate drug levels in the fetal circulation and amniotic fluid while avoiding neurotoxicity. The choice of dose within that range should be guided by which formulations of penicillin G are readily available in order to reduce the need for pharmacies to specially prepare doses.
- Erythromycin is no longer an acceptable alternative for intrapartum GBS prophylaxis for penicillin-allergic women at high risk for anaphylaxis.
Shown below is an algorithm depicting the choice of antibiotics for the primary prevention of early-onset GBS neonatal infection.
Is the patient allergic to penicillin? | |||||||||||||||||||||
| No | Yes | ||||||||||||||||||||
Penicillin G, 5 million units IV initial dose, then 2.5-3.0 million units every 4 hours until delivery OR Ampicillin, 2 g IV initial dose, then 1 g IV every 8 hours until delivery | Does the patient a history of any of the following after receiving penicillin or cephalosporin? Anaphylaxis Angioedema Respiratory distress Urticaria | ||||||||||||||||||||
| No | Yes | ||||||||||||||||||||
Cefazolin, 2 g IV initial dose, then 1 g IV every 8 hours until delivery | Is the isolate susceptible to clindamycin and erythromycin? | ||||||||||||||||||||
| No | Yes | ||||||||||||||||||||
Vancomycin, 1 g IV every 12 hours until delivery | Clindamycin, 900 mg IV every 8 hours until delivery | ||||||||||||||||||||
Safety
Maternal anaphylaxis associated with GBS intrapartum chemoprophylaxis occurs but is sufficiently rare that any morbidity associated with anaphylaxis is offset greatly by reductions in the incidence of maternal and neonatal invasive GBS disease. Allergic reactions occur in an estimated 0.7%--4.0% of all treatment courses with penicillin, the most common of which is a maculopapular rash.
Because a fetus or newborn is unlikely to have had a previous exposure to the antibiotic, and because specific maternal IgE antibodies are not transmitted across the placenta, there is no risk for anaphylaxis in the fetus or newborn resulting from intrapartum antibiotic prophylaxis.