First Molecular Characterization of Group B Streptococci with Reduced Penicillin Susceptibility

Abstract

Group B streptococci (GBS; Streptococcus agalactiae) are the leading cause of neonatal invasive diseases and are also important pathogens for adults. Penicillins are the drugs of first choice for the treatment of GBS infections, since GBS have been regarded to be uniformly susceptible to penicillins so far. Here we characterize the first strains of GBS with reduced penicillin susceptibility (PRGBS) identified in Japan. Fourteen PRGBS strains were clinically isolated from the sputa of elderly patients from 1995 to 2005; and the MICs of penicillin, oxacillin, and ceftizoxime ranged from 0.25 to 1 g/ml, 2 to 8 g/ml, and 4 to 128 g/ml, respectively. Moreover, some strains were also insusceptible to ampicillin, cefazolin, cefepime, and cefotaxime. All the PRGBS isolates tested possessed a few amino acid substitutions adjacent to the conserved SSN and KSG motifs (amino acids 402 to 404 and 552 to 554, respectively) of PBP 2X, and the amino acid substitutions could be classified into two types, Q557E and V405A. Western blotting analysis of the 14 clinical isolates with anti-PBP 2X-specific serum suggested that the amount of PBP 2X among the 14 PRGBS isolates was reduced, although the 2 ATCC strains produced a significant amount of PBP 2X. The introduction of PRGBS-derived PBP 2X genes into penicillin-susceptible strains through allelic exchange elevated their penicillin insusceptibility, suggesting that these altered PBP 2X genes are responsible for the penicillin insusceptibility in PRGBS strains. In this study, we characterized for the first time PRGBS strains on a molecular basis, although several reports have so far mentioned the existence of ␤-lactam-insusceptible GBS from a phenotypic standpoint.

Serotypes and antibiotic resistance in Group B streptococcus isolated from patients at the Maternity Hospital, Kuwait

“…of strains (and % of total) for which the MIC value (mg ml "1 ) was: Although the isolates were susceptible to the b-lactam antibiotics tested, the MICs of penicillin, ampicillin and cefotaxime for the majority of them were in the range 0.047-0.094 mg ml -1 , similar to the results of a previous study on GBS isolated in the same hospital in 2003 (AlSweih et al, 2005b). However, in view of recent reports of reduced susceptibility to penicillin in some GBS isolates (Chu et al, 2007;Dahesh et al, 2008;Kimura et al, 2008;Nagano et al, 2008), these data suggest that further regular surveillance studies should be carried out on b-lactam susceptibility in GBS isolates.…”

“…However, in view of recent reports of reduced susceptibility to penicillin in some GBS isolates (Chu et al, 2007;Dahesh et al, 2008;Kimura et al, 2008;Nagano et al, 2008), these data suggest that further regular surveillance studies should be carried out on b-lactam susceptibility in GBS isolates.…”

“…of strains (and % of total) for which the MIC value (mg ml "1 ) was: Although the isolates were susceptible to the b-lactam antibiotics tested, the MICs of penicillin, ampicillin and cefotaxime for the majority of them were in the range 0.047-0.094 mg ml -1 , similar to the results of a previous study on GBS isolated in the same hospital in 2003 (AlSweih et al, 2005b). However, in view of recent reports of reduced susceptibility to penicillin in some GBS isolates (Chu et al, 2007;Dahesh et al, 2008;Kimura et al, 2008;Nagano et al, 2008), these data suggest that further regular surveillance studies should be carried out on b-lactam susceptibility in GBS isolates.In contrast to the resulsts for b-lactams, the 12.6 % erythromycin-resistance rate in the present study represents a significant increase (P,0.001) in the proportion of erythromycin-resistant isolates from the 0.7 % prevalence reported in GBS isolates obtained from patients in the same hospital in 2003 (Al-Sweih et al, 2005b). This increase may be related to the increased use of macrolides in the hospital.…”

“…As GBS isolates remain uniformly susceptible to penicillin, its prophylactic use has been instrumental in significantly reducing the incidence of early-onset diseases in neonates (Pylipow et al, 1994). However, GBS isolates with reduced susceptibility to penicillin have recently been reported (Chu et al, 2007;Dahesh et al, 2008;Kimura et al, 2008;Nagano et al, 2008).…”

“…As GBS isolates remain uniformly susceptible to penicillin, its prophylactic use has been instrumental in significantly reducing the incidence of early-onset diseases in neonates (Pylipow et al, 1994). However, GBS isolates with reduced susceptibility to penicillin have recently been reported (Chu et al, 2007;Dahesh et al, 2008;Kimura et al, 2008;Nagano et al, 2008).Erythromycin and clindamycin are used as alternative treatments for patients who are allergic to penicillin. However, erythromycin and clindamycin resistance have emerged in several countries (Aracil et al, 2002;Betriu et al, 2003;de Azavedo et al, 2001;De Mouy et al, 2001).…”