Abstract

Use of Mass Spectrometry for Rapid Detection of Carbapenem Resistant Gram Negative Hospital Acquired Infections

Mandar Kulkarni, Chief Technology Officer, Bioserve Biotechnologies

The practice of modern medicine relies heavily on effective antibiotic therapy to combat bacterial infections. In their absence, many surgeries and chemotherapeutic regimens used to combat cancer and suppress chronic inflammatory conditions would simply not be possible. Development of multidrug-resistant (MDR) bacterial strains threatens to undermine these advances and represents a major global health challenge. A common resistance mechanism in “gram negative rod” (GNR) bacteria is secretion of a ß-lactamase that hydrolyzes the ß-lactam ring common to all members of the penicillin class. Hundreds of diverse ß-lactamases, which vary in their catalytic mechanism and substrate specificity, have evolved in response to treatment of infections with multiple antibiotics. Carbapenems represent the last line of effective defense against MDR GNRs expressing extended spectrum ß-lactamases (ESBLs) capable of hydrolyzing all non-carbapenem ß-lactams. However, their effectiveness has been compromised by the recent emergence of plasmid-encoded carbapenemases. To effectively contain and/or prevent outbreaks of carbapenem resistant bacterial infections and to offer optimal patient care, rapid detection of carbapenemase activity in clinical specimens is imperative. We have pioneered a rapid, phenotypic method relying on mass spectrometry to detect carbapenemase activity, by selectively monitoring for the appearance of carbapenem hydrolysis products. Application of the methodology to the detection of carbapenemase activity in critical patient specimens: positive blood cultures and urine samples, respectively, is a potential path forward for this assay.