Miyuki Hasegawa

Sitafloxacin Activity against Helicobacter pylori Isolates, Including Those with gyrA Mutations

ABSTRACT Sitafloxacin showed MICs of less than or equal to 0.5 μg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.

Antifungal activity of micafungin against Candida and Aspergillus spp. isolated from pediatric patients in Japan

The in vitro antifungal activities of micafungin in comparison to caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B were evaluated against 93 Candida and 23 Aspergillus isolates recovered from pediatric patients with fungal infections. MICs were determined by the CLSI M27-A2 and M38-A for Candida and Aspergillus species, respectively. Micafungin showed potent activity against Candida albicans, Candida tropicalis, and Candida glabrata with a MIC range of <= 0.002 to 0.015mug/ml. In contrast, micafungin demonstrated higher MIC levels against Candida parapsilosis with a MIC range of 0.12 to 2 mug/ml. Micafungin showed potent antifungal activity against Aspergillus species tested with a MIC range of 0.004 to 0.015 mug/ml. Overall, micafungin had excellent in vitro antifungal activities against Candida and Aspergillus species recovered from pediatric patients with fungal infections.

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.

Drug-Resistance Patterns of Clinical Isolates of Pseudomonas aeruginosa with Reference to Their Lipopolysaccharide Compositions

Fifty-nine strains of Pseudomonas aeruginosa, isolated from blood, urine, pus, sputum and feces, were divided into three groups on the basis of differences in their LPS composition, in long- and short-LPS strains and in LPS-deficient strains. The long-LPS strains were far more frequently isolated among blood, urine and fecal specimens than in the remainder, and the frequency of LPS-deficient strains was higher in sputum specimens than in the remainder. The drug resistance patterns of the three LPS-type strains to six different kinds of anti-pseudomonal drugs, including gentamicin, differed significantly.

Ionic binding of 3H-gentamicin and short-time bactericidal activity of gentamicin against Pseudomonas aeruginosa isolates with different lipopolysaccharide structures.

The clinical isolates of Pseudomonas aeruginosa can be roughly classified into long- and short-LPS strains and LPS-deficient strains. Ionic binding of 3H-gentamicin was the highest in the long-LPS strains followed in descending order by short-LPS and LPS-deficient strains. However, PAC605 strain, completely lacking in the repeated units of O-polysaccharide and also lacking in some of the neutral sugar residues of the core oligosaccharide region, highly bound to 3H-gentamicin and it is suggested that the negatively charged sites on the deep-core oligosaccharide region and/or on lipid A participated in the binding to 3H-gentamicin. This manner of binding may be also applied to P. aeruginosa No. 45 (LPS-deficient), a clinical isolate.

Co-existence of colonies with different serotypes and other biological characteristics in clinical isolates of Pseudomonas aeruginosa.

The biological characteristics of individual colonies of Pseudomonas aeruginosa from 138 specimens were investigated. Of these isolates, 90 (65.2%) formed colonies of similar appearance and morphology, and 48 (34.8%) formed colonies which differed either in appearance or morphology. The individual colonies of 138 isolates were tested for serotype. The former 90 isolates formed only the colonies with one kind of serotype, whereas 17 of the latter 48 isolates formed the colonies with more than one kind of serotype. All the 9 isolates tested also differed in other biochemical characteristics: acid productions from xylose, mannitol and maltose, urease production and gelatin liquefaction. β‐Lactamase activity was investigated in 7 isolates forming colonies with more than one serotype. There were no marked differences in β‐lactamase activity among the different colonies in 5 isolates but marked differences among those in the other 2 isolates.