Abstract
Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened β-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum β-lactamases. All isolates carried one or more PMQRs; aac(6’)-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-β-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.
Highlights
IntroductionAntimicrobial resistance in Gram-negative bacteria is an emerging and serious global threat to public health
We evaluated the minimum inhibitory concentration (MIC) of levofloxacin, amikacin, imipenem, meropenem, and colistin for strains using 10- and 100-fold of the colony forming units (CFU) in the standard inoculum
We found that blaIMP-6-positive Enterobacteriaceae harbored multiple drug resistant genes including ESBLs and plasmid-mediated quinolone resistance (PMQR)
Summary
Antimicrobial resistance in Gram-negative bacteria is an emerging and serious global threat to public health. Inoculum size effects in IMP-6 Enterobacteriaceae broad resistance to most β-lactam antibiotics including the carbapenems [1,2,3]. The number of CPE infection cases is increasing, the optimal treatment paradigm for CPE infections has not been well defined. There are numerous different types of carbapenemase enzymes, such as the IMP, VIM, KPC, OXA-48-like, and NDM enzymes, each conferring varying spectrums of resistance
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