Biology subjects

Kayama, S.

Publications and source records attributed to Kayama, S..

3 recordsLinked to original sources

bioRxiv2024

In vitro activity of cefiderocol against carbapenemase-producing and meropenem-nonsusceptible gram-negative bacteria collected in the Japan Antimicrobial Resistant Bacterial Surveillance (JARBS-GNR)

The treatment options available for infections caused by multidrug-resistant gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against multidrug-resistant gram-negative pathogens. Several studies have reported the in vitro activity of CFDC using clinical isolates from Europe, the United States, and China. However, no large-scale studies on the in vitro activities of CFDC have been conducted using all isolates with available genomic backgrounds based on whole-genome sequencing (WGS). We evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-nonsusceptible Enterobacterales, and carbapenemase-producing non-fermentative bacteria. We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from the recent surveillance of clinical isolates in Japan using WGS data. Among these, 97.7% (300/307 strains) of carbapenemase-producing Enterobacterales, 100% (18/18 strains) of carbapenemase-producing P. aeruginosa, and 91.2% (52/57 strains) of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. In addition, CFDC was highly effective against class A, B, and D {beta}-lactamase harboring isolates when compared to the other antimicrobial agents in this study. While {beta}-lactam antibiotics were essentially ineffective against CFDC-resistant Enterobacterales, minocycline was the most effective, and gentamicin and amikacin were also effective. This is the first large-scale study to systematically demonstrate the efficacy of CFDC using carbapenemase-producing strains with transparent genomic backgrounds.

microbiology↗

bioRxiv2023

Nationwide genome surveillance of carbapenem-resistant Pseudomonas aeruginosa in Japan

Japan is a country with an approximate 10 % prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates were classified as difficult-to-treat resistance P. aeruginosa. Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs (P = 0.0056, chi-square test). Only 4.1% of CRPA isolates carried the carbapenemase genes: blaGES (2) and blaIMP (13). One ST235 isolate carried the novel blaIMP variant blaIMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD, and 28.8% showed mutations in the regulatory genes (mexR, nalC, and nalD) for the MexAB-OprM effux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI. The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable dataset that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.

microbiology↗

bioRxiv2022

Isolation and characterization of bacteriophages against IMP-6-producing Klebsiella pneumoniae isolated from clinical settings in Japan

Carbapenemase-producing Enterobacteriaceae (CPE) are one of the most detrimental species of antibiotic-resistant bacteria worldwide. Phage therapy has emerged as an effective strategy for the treatment of infections caused by CPE pathogens. In west Japan, the increasing occurrence of Klebsiella pneumoniae harboring the pKPI-6 plasmid, which encodes blaIMP-6, is a growing concern. To manage such major antimicrobial-resistant pathogens, we isolated 29 novel phages from sewage in Japan, targeting 31 strains of K. pneumoniae and one strain of Escherichia coli harboring the pKPI-6 plasmid. Electron microscopy analysis indicated that of the 29 isolated phages, 21 (72.4%), 5 (17.2%), and 3 (10.3%) belonged to Myoviridae, Siphoviridae, and Podoviridae, respectively. Host range analysis revealed that 20 Myoviridae members in isolated phages infected 25-26 strains of K. pneumoniae, indicating that most of the isolated phages have a broad host range. The K. pneumoniae Kp21 can only be infected by phage oKp_21, while Kp22 can be infected by more than 20 phages. We applied a phage cocktail, which consists of 10 phages, against Kp21 and Kp22 and found that the phage cocktail delayed the emergence of phage-resistant bacteria for Kp21 strain but not for the Kp22 strain. Furthermore, phage-resistant Kp21 (Kp21r) became prone to be infected from other bacteriophages as a "trade-off" of resistance to phage oKp_21. Our proposed phage set has an adequate number of phages to combat the K. pneumoniae strain isolated in Japan. Notably, our work demonstrates how a suitable phage cocktail diminishes the occurrence of phage-resistant bacteria. ImportanceKlebsiella pneumoniae harboring the plasmid carrying blaIMP-6 is becoming an increasingly hazardous species in Japan. We collected and characterized 29 novel bacteriophages that infect K. pneumoniae carrying the pKPI-6 plasmid, isolated in clinical settings of west Japan. Our phages showed broad host ranges. We applied a phage cocktail treatment constructed from 10 phages against two host strains, Kp21 and Kp22, which show different phage susceptibility patterns each other. Although the phage cocktail delayed phage-resistant Kp21 emergence, the emergence of phage-resistant Kp22 could not be delayed. Moreover, phage-resistant Kp21 became sensitive to other phages, which did not originally infect wild-type Kp21. Our study demonstrates how a suitable phage cocktail can diminish the occurrence of phage-resistant bacteria.

microbiology↗