Molecular analysis of the integrons of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates collected by nationwide surveillance programs across Japan

Abstract

BackgroundWe investigate the evolving molecular epidemiology of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates collected in a 100 institution, nationwide surveillance study in Japan from 2004 to 2006.ResultsMBL-producers were detected in 23/996 isolates (2.3%) in 2004 and 21/992 (2.1%) in 2006. Antimicrobial resistance (specifically, carbapenem resistance) rates between two periods did not differ significantly. MBL-producers were more prevalent in urinary tract isolates. blaIMP-1 group was the most predominant (38 isolates, 80%), followed by 3 blaIMP-7, 2 blaIMP-11 group, and 1 blaVIM-1. All MBL genes were identified in 16 different class 1 integrons, most of which were novel to INTEGRALL database. A total of 17 isolates of sequence type (ST) 235, a recognized worldwide drug-resistant lineage, were distributed in 5 geographic regions across Japan. ST235 isolates included a sublineage associated with In113-like integron. ST357 was identified in 14 isolates, 9 of which harboring a sole blaIMP-1 gene cassette (In994) were recovered from Chugoku region in 2004. ST357 isolates with blaIMP-11 group or ST235 with blaIMP-7 emerged in 2006. We also report for the first time the presence of novel fosI gene cassette in strains other than Mycobacterium spp.ConclusionsOur data give an important “snapshot” of the molecular characteristics and dynamics of MBL-producing lineages in P. aeruginosa in Japan. The significant association of specific genotypes and integrons implies that dissemination and transmission of the preexisting resistant lineage, rather than horizontal gene transfer in situ, might largely explain their endemicity.

Molecular characteristics of carbapenem‐resistant Pseudomonas aeruginosa isolated from urine in Hyogo, Japan

“…We found these MBL‐producing P. aeruginosa isolates were highly resistant to most antibiotics examined, except CL. In the relationship between P. aeruginosa and MBL genes, IMP‐1 isolated in Japan were highly resistant to all β‐lactams, aminoglycoside and fluoroquinolones; however, the present data showed that AMK had some possibility as a therapeutic strategy for this (susceptibility rate: 18/21, 85.7%). In addition, CL was also added as a therapeutic strategy for carbapenem‐resistant Gram‐negative bacteria infections .…”

“…Our MBL‐producing P. aeruginosa isolates were typed into IMP‐1, IMP‐7 or VIM‐1, and those with IMP‐1 were first discovered worldwide in the late 1980s and spread to Japan in 1991 . To date, the isolates with IMP‐1 have mainly spread in Asian regions . P. aeruginosa with VIM‐1 or IMP‐7 was also first found in 1999 or 2002, respectively, and has been found in Asian regions (isolated in Japan in 2010) and European regions as well .…”

“…Whereas, KPC and OXA types as other types of carbapenemase are rarely detected in P. aeruginosa . Previous Japanese studies have reported that the most prevalent type of MBL‐producing P. aeruginosa was the IMP type, particularly the IMP‐1 type …”

“…In particular, production of MBLs as the main types of carbapenemases hydrolyzes almost all β‐lactams, including penicillins, cephalosporins and carbapenems, and importantly, the bacteria with MBLs are not often inhibited by β‐lactamase inhibitors . MBLs found from P. aeruginosa are mainly typed as the IMP type ( bla IMP‐1 and bla IMP‐2 ) and VIM type ( bla VIM‐1 and bla VIM‐2 ) . Whereas, KPC and OXA types as other types of carbapenemase are rarely detected in P. aeruginosa .…”

“…As a molecular epidemiological technique: MLST, based on nucleotide sequencing of seven housekeeping genes in the bacterial chromosome, provides information as the STs on bacterial phylogeny, and has been increasingly applied to compare with worldwide strains by observation of the same STs . Then, MLST analysis revealed that P. aeruginosa clones, such as ST235, ST244, ST175 and ST357, have spread worldwide . Furthermore, the rep‐PCR, based on the differences of repetitive extragenic palindromic DNA sequence alignments in the bacterial chromosome, is mainly used to characterize the genetic diversity for confirming an outbreak in a hospital or region by grouping strains belonging to the same ST isolates …”