Carbapenemases in Gram-Negative Bacteria: Laboratory Detection and Clinical Significance

Carbapenems are potent -lactam antibiotics used to treat serious infections in hospital settings.In comparison to penicillins, cephalosporins, or -lactam/-lactamase inhibitor, they have broad antimicrobial spectrum that includes Gram-positive (e.g., imipenem, doripenem) and Gramnegative bacteria (e.g., meropenem, ertapenem).Imipenem and meropenem have better activity against P. aeruginosa, while imipenem and doripenem have better activity than meropenem against Acinetobacter baumannii.Doripenem has the lowest MIC against P. aeruginosa and A. baumannii in comparison to imipenem and meropenem, and it is least susceptible to hydrolysis by carbapenemases.To act on PBPs, carbapenems have to enter the wall of Gram-negative bacteria through outer membrane proteins (porins).Binding to different PBPs, they inhibit the synthesis of cell wall finally leading to the death of bacterium [1].Carbapenem resistance in Gram-negative bacteria can be the consequence of the production of a -lactamase, expression of efflux pumps, porin loss, and alterations in PBPs.Since -lactams, including carbapenem-like compounds, are natural products of several environmental bacteria and fungi, it is supposed that other bacteria started to produce their intrinsic -lactamase to give them selective advantage for survival.Thus, several genes encoding different carbapenemases can be found in environmental bacteria like Bacillus anthracis, Serratia fonticola, Pseudomonas cepacia, or Acinetobacter spp. as part of their chromosome [1,2].Further step in