Direct Testing for KPC-Mediated Carbapenem Resistance from Blood Samples Using a T2 Magnetic Resonance Based Assay.

Giulia De Angelis,Giulia Menchinelli,Maurizio Sanguinetti,Jessica L Snyder,Riccardo Paggi,Thomas J Lowery,Brunella Posteraro,Antonella Mencacci

doi:10.3390/antibiotics10080950

Abstract

Molecular-based carbapenem resistance testing in Gram-negative bacterial bloodstream infections (BSIs) is currently limited because of the reliance on positive blood culture (BC) samples. The T2Resistance™ panel may now allow the detection of carbapenemase- and other β-lactamase encoding genes directly from blood samples. We detected carbapenem resistance genes in 11 (84.6%) of 13 samples from patients with BC-documented BSIs (10 caused by KPC-producing Klebsiella pneumoniae and 1 caused by VIM/CMY-producing Citrobacter freundii). Two samples that tested negative for carbapenem resistance genes were from patients with BC-documented BSIs caused by KPC-producing K. pneumoniae who were receiving effective antibiotic therapy. In conclusion, our findings suggest that the T2Resistance™ panel can be a reliable tool for diagnosing carbapenem-resistant Gram-negative bacterial BSIs.

Highlights

Bacterial bloodstream infection (BSI) continues to represent a major public health concern [1], in the case of infection-associated sepsis [2], leading to high morbidity and mortality rates around the world [3]
In addition to identifying the most common pathogens isolated from blood culture (BC) (e.g., Enterobacterales) within few hours, these assays can detect antimicrobial resistance determinants, such as the Klebsiella pneumoniae carbapenemase (KPC), which is encoded by the blaKPC gene [9]
With multidrug-resistant Gram-negative BSIs [13], the molecular assays’ turnaround time—if compared to the phenotypic or genotypic antimicrobial resistance detection methods performed on the bacterial isolates grown from BCs [14]—would allow guiding the therapeutic decisions some days before culture-based antimicrobial susceptibility testing (AST) results are available [6]

Summary

Introduction

Bacterial bloodstream infection (BSI) continues to represent a major public health concern [1], in the case of infection-associated sepsis [2], leading to high morbidity and mortality rates around the world [3]. With multidrug-resistant Gram-negative BSIs [13], the molecular assays’ turnaround time—if compared to the phenotypic or genotypic antimicrobial resistance detection methods performed on the bacterial isolates grown from BCs [14]—would allow guiding the therapeutic decisions some days before culture-based antimicrobial susceptibility testing (AST) results are available [6]. Due to their reliance on positive BCs, these assays lead so far to delays in appropriate antimicrobial therapy [13] that may translate to increases in Gram-negative BSI associated morbidity and mortality [15]

Objectives

Methods

Results