A structural, epidemiological & genetic overview of Klebsiella pneumoniae carbapenemases (KPCs).

Abstract

Klebsiella pneumoniae carbapenemases (KPCs) are plasmid encoded carbapenem hydrolyzing enzymes which have the potential to spread widely through gene transfer. The instability of upstream region of blaKPC accelerates emergence of different isoforms. Routine antibiotic susceptibility testing failed to detect KPC producers and some commercial kits have been launched for early identification of KPC producers. Notable among the drugs under development against KPC are mostly derivatives of polymixin; β-lactamase inhibitor NXL104 with combination of oxyimino cephalosporin as well as with ceftazidime; a novel tricyclic carbapenem, LK-157, potentially useful against class A and class C enzymes; BLI-489-a bicyclic penem derivative; PTK-0796, a tetracycline derivative and ACHN-490. Combination therapy might be preferable to control KPC infections in immediate future. Clinicians are likely to opt for unconventional combinations of antibiotics to treat KPC infections because of unavailability of alternative agents. The KPCs have become endemic in many countries but there is no optimal treatment recommendation available for bacteria expressing KPCs. Reports of outbreaks involving KPCs have focused mainly on laboratory identification, empirical treatment outcomes and molecular epidemiology. This review includes information on the emergence of KPC variants, limitations of phenotyping methods, available molecular methods for identification of the KPC variants and treatment options highlighting the drugs under development.