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Resistance in GBS

Antibiotic Resistance of GBS

The widespread use of intrapartum antibiotic prophylaxis to prevent early-onset GBS disease has raised concern about the development of antibiotic resistance among GBS isolates. GBS continues to be susceptible to penicillin, ampicillin, and first-generation cephalosporins (19,105–109). However, isolates with increasing minimum inhibitory concentrations (MICs) to penicillin or ampicillin have been reported, including 14 noninvasive isolates during 1995–2005 among adults in Japan (110), and 11 (0.2%) of 5,631 invasive isolates recovered dur­ing 1999–2005 from patients of varying ages in the United States (111). Alterations in a penicillin-binding protein (PBP 2X) were found in all of the isolates from Japan and four of those from the United States. The measured MICs from the 11 invasive isolates from the United States are just at the threshold of susceptibility (≤0.12 μg/ml for penicillin and ≤0.25 μg/ml for ampicillin) (112), but the clinical significance of these MIC values is as yet unclear.

Relatively elevated MICs to cefazolin (1 μg/ml) also were reported among three (0.05%) of 5,631 invasive GBS iso­lates collected through CDC’s active surveillance during 1999–2005; two of the three isolates also had elevated MICs to penicillin (0.12 μg/ml) (111). Although Clinical and Laboratory Standards Institute guidelines do not specify sus­ceptibility breakpoints for cefazolin, they recommend that all isolates susceptible to penicillin be considered susceptible to cefazolin (112). As with the elevated MICs to penicillin and ampicillin, the clinical significance of higher MICs to cefazolin among GBS isolates remains unclear.

The proportions of GBS isolates with in vitro resistance to clindamycin or erythromycin have increased over the past 20 years. The prevalence of resistance among invasive GBS isolates in the United States ranged from 25% to 32% for erythromycin and from 13% to 20% for clindamycin in reports published during 2006–2009 (19,106,108). Resistance to erythromycin is associated frequently but not always with resistance to clin­damycin. One longitudinal study of GBS early-onset sepsis found that although the overall rate of GBS early-onset disease declined over time, erythromycin-resistant GBS caused an increasing proportion of disease during this interval; however, the incidence of antibiotic-resistant GBS early-onset sepsis remained stable (105).

Antimicrobial Susceptibility Testing

Antimicrobial susceptibility testing of GBS isolates is crucial for appropriate antibiotic prophylaxis selection for penicillin-allergic women who are at high risk for anaphylaxis because resistance to clindamycin, the most common agent used in this population, is increasing among GBS isolates. In addi­tion, appropriate methodologies for susceptibility testing are important because inducible clindamycin resistance can occur in some strains that appear susceptible in broth suscep­tibility tests (193,194). D-zone testing using the double-disk diffusion method has been used to identify isolates that are erythromycin-resistant and clindamycin-susceptible, yet have inducible resistance to clindamycin (195). Isolates that are D-zone positive are considered to have inducible clindamycin resistance and are presumed to be resistant although the clinical significance of this resistance is not clear (196).


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