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Abstract
ABSTRACT β-Lactam antibiotics are first-line agents for the treatment and prevention of group B Streptococcus (GBS) infections. We previously reported clinical GBS isolates with reduced β-lactam susceptibility (GBS-RBS) and characterized them as harbouring amino acid substitutions in penicillin-binding proteins (PBPs). However, to our knowledge, GBS-RBS clinical isolates have never previously been isolated from pregnant women worldwide. We obtained 477 clinical GBS isolates from vaginal/rectal swabs of 4530 pregnant women in Japan. We determined the MICs of seven β-lactams for all 477 clinical isolates. Five clinical isolates showed reduced ceftibuten susceptibility. For these isolates, we performed sequencing analysis of pbp genes. None of the 477 isolates were non-susceptible to penicillin G, ampicillin, and meropenem. For five isolates, the MICs of ceftibuten were relatively high (64–128 μg/ml). Each of these isolates possessed a single amino acid substitution in PBP2X, and some of the substitutions had been previously found in GBS with reduced penicillin susceptibility. This is the first report of the isolation of clinical GBS-RBS isolates harbouring amino acid substitutions in PBP2X that confer reduced ceftibuten susceptibility from pregnant women.
Highlights
Group B Streptococcus (GBS; Streptococcus agalactiae) is a gram-positive bacterium that causes neonatal invasive infections such as sepsis and meningitis
The minimum inhibitory concentration (MIC) of ceftibuten were relatively high (64–128 μg/ml), and for two of these isolates, the MIC of ceftizoxime was high (4 μg/ml) (Table 2). These findings suggested that these five clinical isolates might be GBS-RBS clinical isolates harbouring amino acid substitutions in penicillin-binding proteins (PBPs)
MICs for BAA-611, the MICs of ceftibuten and ceftizoxime for the allelic-exchange strains were elevated and were comparable to those for the parental clinical isolates, P-071, P-122, P-139, P-319, and P-334 (Table 3). These results indicated that amino acid substitutions in PBP2X of the five GBS isolates with reduced ceftibuten susceptibility are responsible for penicillin G (PEN) AMP OXA CFZ CTB ZOX meropenem their reduced β-lactam susceptibility (MEM)
Summary
Group B Streptococcus (GBS; Streptococcus agalactiae) is a gram-positive bacterium that causes neonatal invasive infections such as sepsis and meningitis. The Centers for Disease Control and Prevention (CDC) issued guidelines for the prevention of perinatal GBS disease in 1996 [2]. In these guidelines, universal screening for GBS of all pregnant women at 35–37 weeks of gestation and intrapartum antimicrobial prophylaxis for GBS-positive pregnant women are recommended to prevent vertical GBS transmission. The Japanese Society of Obstetrics and Gynecology (JSOG) published “Guidelines for Obstetrical Practice in Japan” in 2007 (revised in 2011 and 2014), in which they recommend universal screening for GBS of all pregnant women at 33–37 weeks of gestation for the prevention of vertical GBS transmission nationwide [3]
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