Kaoru Matsuzaki

Antimicrobial Activities of Piperacillin-Tazobactam against Haemophilus influenzae Isolates, Including β-Lactamase-Negative Ampicillin-Resistant and β-Lactamase-Positive Amoxicillin- Clavulanate-Resistant Isolates, and Mutations in Their Quinolone Resistance-Determining Regions

ABSTRACT β-Lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (≤1 μg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. influenzae should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant H. influenzae isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to β-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent H. influenzae clinical isolates, including 100 β-lactamase-negative ampicillin-susceptible, β-lactamase-positive ampicillin-resistant, BLNAR, and β-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the ftsI gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among β-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of H. influenzae, with all MICs at ≤0.5 μg/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of ≥21 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the ftsI gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 μg/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 μg/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent β-lactam tested against all classes of H. influenzae isolates. It is possible that fluoroquinolone-resistant H. influenzae will emerge since several clinical isolates carried mutations in their QRDRs.

Rapidly spreading CTX-M-type β-lactamase-producing Proteus mirabilis in Japan

In recent years, increased isolation of extended-spectrum beta-lactamase (ESBL)-producing Proteus mirabilis has been reported in Japan. We undertook an investigation to determine the prevalence of ESBL-producing P. mirabilis isolated in Japan and to characterise the genotype. Seventy-four P. mirabilis isolates recovered from specimens at 54 hospitals in Japan between March and October 2006 were included in the study. Of the 74 P. mirabilis isolates examined, 28 (37.8%) were ESBL-producers. The bla(CTX-M-2) gene was found in 27 isolates, whilst 1 isolate possessed bla(CTX-M-3). Amongst the 28 ESBL-producers, 25 (89.3%) were non-susceptible to ciprofloxacin, whilst 11 (23.9%) of 46 ESBL-non-producing isolates were non-susceptible to ciprofloxacin. Pulsed-field gel electrophoresis (PFGE) analysis of the 28 ESBL-producing isolates from 19 hospitals revealed 17 clusters. The same PFGE type was observed in two or more hospitals especially in the greater Tokyo area, suggesting possible clonal spread and the need for monitoring to determine whether emergence of a dominant clone occurs. Our results show that in Japan there is a high prevalence of CTX-M-type beta-lactamase-producing P. mirabilis. Moreover, these isolates are characterised by reduced susceptibility to fluoroquinolones.

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006).

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 μg/ml to 0.5 μg/ml and a MIC90 value of 0.5 μg/ml. The MIC90s of vancomycin and linezolid were 1.0μg/ml and 2 μg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.