Carbapenemases are enzymes that break down carbapenems by hydrolyzing the beta-lactam ring of these antibiotics, thus rendering them ineffective for treating infections.imp carbapenemase The development of newer metallo-beta-lactamases has led to an increase in resistance to many previously effective antimicrobial agents, and their prevalence appears to be increasing worldwide (1). Carbapenemases also render novel beta-lactam combination drugs (such as ceftazidime-avibactam and meropenem-vaborbactam) less effective (2). Therefore, identification of a carbapenemase gene is critical for infection prevention and control (IPAC) practices as well as for treatment considerations (3).
The IMP carbapenemase is an emerging member of the family of metallo-beta-lactamases.imp carbapenemase It has been found in a few clinical isolates of K. pneumoniae and has been linked to the spread of carbapenem non-susceptible K. pneumoniae (CPE) in a hospital in China (4). This enzyme exhibits a high level of activity against a wide range of aminoglycosides and carbapenems, including imipenem, clofidone, ertapenem, and aztreonam. It also has low activity against erythromycin and reduced catalytic efficiency against penicillins (5). The IMP gene is usually located on large plasmids, and multiple bla IMP variants have been reported with different kinetic parameters and substrate specificities (6).
Recently, three IMP-producing Enterobacteriaceae were identified in the United States.imp carbapenemase These isolates were related to each other by pulsed-field gel electrophoresis and shared a common plasmid containing the bla IMP gene. PCR and sequencing analysis confirmed that these isolates produced IMP-4, an MBL carbapenemase not previously reported among enterobacteriaceae in the United States. IMP-4 produces a carbapenemase with substrate selectivity in favor of oxyinosine and sulfadiazine over urea, amikacin and ceftazidime and increased hydrolysis efficiency against doripenem and meropenem compared to IMP-1.
All three IMP-6-CPE isolates came from patients hospitalized at ONH for severe sepsis.imp carbapenemase They were related to each other by PFGE and multilocus sequence typing and did not belong to contemporary carbapenemase-positive isolates from the same institution or to carbapenem non-susceptible Enterobacteriaceae in the NCTC database (8). The isolates were recovered from abdominal surgical wounds or drains and urine. Antimicrobial susceptibility testing and characterization by PFGE, VITEK 2 AST Kit, MLST and PCR amplification of the bla IMP genes indicated that they were members of the CCUG 44386 clade (9).
The IMP-6-producing strains were resistant to multiple antibiotics including the carbapenems and aztreonam.imp carbapenemase They had similar MICs to ceftazidime-avibactam, and exhibited heterogeneous resistance patterns against meropenem, amikacin and ciprofloxacin. In addition, they were susceptible to the newer IMP-1- and MBL-based interpretive criteria for carbapenem resistance (Table 1), suggesting that these strains may have been acquired outside of the hospital, possibly by patients whose infections were treated with carbapenem-resistant strains in the community. Several independent predictors of CPE colonization were noted including previous hospitalizations, residence in long-term care or nursing facilities and the use of a urinary catheter or nasogastric tube. This report highlights the emergence of a new IMP-producing MBL in the United States and the need for hospitals to adopt recommended interventions. These include the implementation of standardized patient isolation protocols and increased use of alternatives to CPE-resistant antibiotics.