title: Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and in vitro synergy of the colistin-meropenem combination.
abstract: In this prospective study, consecutive isolates of Klebsiella pneumoniae were tested for different mechanisms of carbapenem resistance using the modified Hodge test (MHT), Rosco Neo-Sensitabs (ROSCO). Phenylalanine arginine beta-naphthylamide assay (PABN) inhibitor-based test was done on isolates in which the mechanism of resistance was not identifiable by the ROSCO. Among 105 selected isolates, carbapenemase production was noted in 100 (95%) by MHT and ROSCO showed 97 (92·4%) inhibition with dipicolinic acid signifying the production of MBL. PCR amplification was positive in 90 (86%) isolates for bla(NDM-1) and 46 (44%) isolates for bla(OXA-48). 54 (51%) isolates were positive for bla(CTX-M) and all belonged to bla(CTX-M) group 1. Isolates co produced bla(OXA-48) (31/105, 30%) and bla(CTX-M) (40/105, 38%) in combination with the carbapenemase (bla(NDM-1)) gene. Five colistin-resistant isolates were positive for bla(OXA-48). Eight isolates did not show inhibition with any of the inhibitor containing disks and found to be positive for bla(OXA-48). Isolates were tested for colistin-meropenem synergy and detection rate was higher by the checkerboard (48%) than E-test method (35%). Our study necessitates continuous surveillance to recognize the predominant machinery of resistance in a particular geographical region to formulate effective control measures.
authors.forename: Lakshmana Gowda
authors.initials: LG
authors.lastname: Krishnappa
authors.forename: Mohammed Ali M
authors.initials: MA
authors.lastname: Marie
authors.forename: Yazeed A
authors.initials: YA
authors.lastname: Al Sheikh
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D013845:Thienamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D003091:Colistin
keywords: Carbapenem-resistant Klebsiella pneumoniae (CRKP),; Colistin-meropenem,; In vitro synergy,; Modified Hodge test (MHT)