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Resistance in GBS
GBS isolates with confirmed resistance to penicillin or ampicillin have not been observed to date (78--83). Penicillin remains the agent of choice for intrapartum antibiotic prophylaxis. Ampicillin is an acceptable alternative, but penicillin is preferred because it has a narrower spectrum of antimicrobial activity and may be less likely to select for resistant organisms. The efficacy of both penicillin (27) and ampicillin (5) as intrapartum agents for the prevention of early-onset neonatal GBS disease has been demonstrated in clinical trials. Although the intramuscular route of administration for penicillin has been evaluated (25), intravenous administration is the only route of administration recommended for intra-partum chemoprophylaxis to prevent perinatal GBS disease, regardless of the antimicrobial agent used, because of the higher intraamniotic concentrations achieved with this method.
In contrast, the proportions of GBS isolates with in vitro resistance to clindamycin and erythromycin have increased since 1996. The prevalence of resistance among invasive GBS isolates in the United States and Canada ranged from 7% to 25% for erythromycin and from 3% to 15% for clindamycin in reports published between 1998 and 2001(79--81,84). Resistance to erythromycin is frequently but not always associated with clindamycin resistance. Resistance of GBS isolates to cefoxitin, a second-generation cephalosporin sometimes used as a component of broad-spectrum coverage for chorioamnionitis, has also been reported (85); cefoxitin resistance has similarly been observed among invasive GBS isolates collected from 1996 to 2000 as part of CDC's active surveillance. Whether in vitro resistance of GBS has direct clinical implications remains unclear (86). Despite emerging resistance to some drug classes, minimum inhibitory concentrations of cefazolin, a first-generation cephalosporin available in an intravenous formulation, were low (<0.5 µg/ml) among a sample of invasive U.S. isolates from 1996 to 2000 (87), suggesting that GBS isolates are currently susceptible to this agent. Although NCCLS guidelines do not specify susceptibility breakpoints for cefazolin, they recommend that all isolates susceptible to penicillin be considered susceptible to cefazolin (88).
In light of the increasing prevalence of resistance to clindamycin, erythromycin, or both, recommended strategies for providing intrapartum antibiotic prophylaxis to penicillin-allergic women are updated (Box 2). Because the efficacy of recommended alternatives to penicillin or ampicillin has not been measured in controlled trials, and because some of the recommended alternatives have a broad spectrum of activity and may be more complicated and costly to administer, verification of a reported history of penicillin allergy is important. Patients with reported penicillin allergy should then be assessed to determine their risk for anaphylaxis. Persons at high risk for anaphylaxis are those who have had immediate hypersensitivity reactions to penicillin (e.g., anaphylaxis, angioedema, or urticaria) or who have a history of asthma or other conditions that would make anaphylaxis more dangerous (89,90). An estimated 10% of persons with penicillin allergy also have immediate hypersensitivity reactions to cephalosporins (90). Among penicillin-allergic women not at high risk for anaphylaxis, cefazolin, because of its narrow spectrum of activity and ability to achieve high intraamniotic concentrations, is the agent of choice for intrapartum chemoprophylaxis.
For penicillin-allergic women at high risk for anaphylaxis, testing of GBS isolates from prenatal screening for susceptibility to clindamycin and erythromycin is recommended if feasible (Box 1). One of these agents should be employed for intrapartum GBS prophylaxis if the screening isolate is susceptible to both agents.
Vancomycin should be reserved for penicillin-allergic women at high risk for beta-lactam anaphylaxis when clindamycin or erythromycin are not options because of in vitro resistance or unknown susceptibility of a prenatal isolate. Vancomycin use is generally restricted because of emerging vancomycin resistance among some gram-positive organisms (e.g., vancomycin-resistant enterococcus and vancomycin-resistant Staphylococcus aureus). An estimated 13.8 million hospitalized patients received vancomycin therapy in 1998 (91). If penicillin allergy occurs in approximately 10% of adults, and 25% of parturients are colonized with GBS prenatally, approximately 100,000 of the 4 million annual deliveries would require prophylaxis with vancomycin in the absence of clindamycin and erythromycin susceptibility testing of GBS prenatal isolates. This represents a 7% increase in the number of patients exposed to vancomycin. The total grams of vancomycin used annually would increase by less than 1% if all penicillin-allergic colonized women received vancomycin prophylaxis.