Evaluation of the contemporary occurrence rates of metallo-β-lactamases in multidrug-resistant Gram-negative bacilli in Japan: Report from the SENTRY Antimicrobial Surveillance Program (1998–2002)

Abstract

Metallo-β-lactamases (MβL) were initially characterized in Japan, usually of the IMP-type, and found in Pseudomonas aeruginosa (PSA), Acinetobacter spp. (ACB), or Serratia marcescens (SM). The number of MβL types has increased worldwide, but geographic dissemination within Japan has appeared limited. This study compares baseline levels of MβL resistance from two 22-center studies (1996–1997) to the longitudinal sample (3 sites) of Japanese isolates from the SENTRY Antimicrobial Surveillance Program (1998–2002). All minimal inhibitory concentration results were determined by reference methods. A total of 26.8% PSA, 3.4% ACB, and 3.1% Enterobacteriaceae (enterobacters and SM) with resistance to monitored carbapenems (CARB) (minimal inhibitory concentration, ≥8 μg/mL) were screened for MβL production by disk approximation tests (EDTA and 2-MPA inhibitors), CARB hydrolysis by enzyme extracts, and selected PCR primers for known MβL types. All MβL-positive strains (10) were sequenced to determine enzyme identification. Clonality in each center was determined by automated ribotyping and PFGE. The CARB susceptibility rates in PSA decreased (80.7% to 62.0%) over the monitored interval (1998–2002), but varied by medical center location. Among CARB-resistant isolates, 10.8% were attributed to MβL strains (1.1% of all PSA tested). MβL identification showed the following: five PSA (three IMP-1, two IMP-2), four SM (one IMP-1, two IMP-1 + OXA-1, and one IMP-11). Also a single ACB had an IMP-1. Eight of 10 MβL isolations occurred between 2000 and 2002; four occurred in 2002. BRL42715, an AMP-C inhibitor, confirmed AMP-C–mediated resistance in 87.3% of PSA, and outer membrane protein changes were also discovered by membrane studies. Prior results (22 sites, 1997–1998) showed CARB resistance at 22.4–25.6% and 0.5–0.9% MβLs (IMP-1) overall; it was slightly elevated in this SENTRY Program sample. In conclusion, MβL-producing strains from several species persist in Japan, but represent a distinct minority of all CARB-resistant strains (1998–2002). Although MβL rates appear generally stable in Japan, continued surveillance for these mechanisms seems to be a prudent practice, because of the mobility of the genetic determinants and the emergence of novel enzyme types, especially among the Enterobacteriaceae.