Evaluation of the contemporary occurrence rates of metallo-beta-lactamases in multidrug-resistant Gram-negative bacilli in Japan: report from the SENTRY Antimicrobial Surveillance Program (1998-2002).
Metallo-beta-lactamases (M beta L) 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 M beta L types has increased worldwide, but geographic dissemination within Japan has appeared limited. This study compares baseline levels of M beta L 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, > or =8 microg/mL) were screened for M beta L production by disk approximation tests (EDTA and 2-MPA inhibitors), CARB hydrolysis by enzyme extracts, and selected PCR primers for known M beta L types. All M beta L-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 M beta L strains (1.1% of all PSA tested). M beta L 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 M beta L 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% M beta Ls (IMP-1) overall; it was slightly elevated in this SENTRY Program sample. In conclusion, M beta L-producing strains from several species persist in Japan, but represent a distinct minority of all CARB-resistant strains (1998-2002). Although M beta L 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.
The JONES Group/JMI Laboratories, North Liberty, IA, USA. ronald-jones@jmilabs.com
Ronald N
RN
Jones
Lalitagauri M
LM
Deshpande
Jan M
JM
Bell
John D
JD
Turnidge
Shigeru
S
Kohno
Yoichi
Y
Hirakata
Yasuo
Y
Ono
Yukihisa
Y
Miyazawa
Sayoko
S
Kawakama
Matsuhisa
M
Inoue
Yasuyoshi
Y
Hirata
Mark A
MA
Toleman
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015780:Carbapenems / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011159:Population Surveillance; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases