Carbapenemase kpc is an emerging resistance mechanism for a broad range of Gram-negative bacteria including Klebsiella pneumonia.carbapenemase kpc Detection of the gene encoding for this carbapenemase enables the clinician to identify resistant strains in patients with suspected GNB infections. Various diagnostic platforms based on molecular methods can rapidly identify the presence of blaKPC in positive blood cultures and rectal swabs. Some of these are able to detect blaKPC and other clinically relevant resistance genes in as little as 1 hour compared to conventional microbiological methods that can take up to 72 hours.
The occurrence of resistance mechanisms such as carbapenemases is a major challenge to the effectiveness of antibiotic therapy in hospitalised patients.carbapenemase kpc Rapid detection of the blaKPC gene in such strains is important to ensure early initiation of appropriate and targeted therapies. There are several diagnostic platforms that can detect the presence of blaKPC in a single reaction with lysates from gram-negative bacteria. These include a commercial real-time polymerase chain reaction (PCR) system called Xpert Carba-R which can identify blaKPC and other resistance genes from positive blood cultures or swabs in a single assay, and a mass spectrometry-based system such as FilmArray BC-ID that can detect the presence of blaKPC and other resistance genes in a blood culture within 6 hours.
KPC-2 is an ATP-dependent class A b-lactamase that produces a wide-spectrum hydrolysis of carbapenems and other -lactams.carbapenemase kpc The stability and resistance phenotype of this enzyme can be reduced by the use of inhibitors such as avibactam, aztreonam or diazabicyclooctane (DBO) bifidamycin oxime. However, a number of variants of the blaKPC-2 gene have been reported worldwide suggesting that resistance to these inhibitors is continuing to evolve.
Using enhanced sampling computational approaches together with structural studies and site-directed mutagenesis, we have identified two hydrophobic networks in the structure of the KPC-2 protein that are responsible for its overall stability and allosteric signaling.carbapenemase kpc Disruption of these networks restores sensitivity to carbapenems and cephalosporins, including the IMP-type metallo-b-lactamases, indicating that these proteins are susceptible to allosteric modulation.
The occurrence of blaKPC-producing organisms in Japan is of concern, as these enzymes can confer resistance to a broad range of -lactam antimicrobial agents.carbapenemase kpc This is especially true for the IMP-type metallo-b-lactamases, which can also degrade carbapenems. To date, blaKPC-producing organisms in Japanese patients have been reported only in those with a history of foreign travel. We report a case of a patient admitted for aspiration pneumonia with a blaKPC-producing isolate detected in his sputum. This patient did not have a history of foreign travel, and the clinical improvement without the need for susceptible antimicrobial therapy suggests that the spread of this resistance mechanism may already be occurring in Japan. This is an urgent issue that needs to be addressed.