Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria

Abstract

Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.

Keywords: Acinetobacter baumannii; Pseudomonas aeruginosa; carbapenem-resistant Enterobacteriaceae; carbapenemases; gram-negative bacteria.

Figure 1.

Classification of carbapenemases/β-lactamases depending on their central catalytic domain. Adapted from [17]. Abbreviations: ACT, AmpC type β-lactamase; AmpC, ampicillin chromosomal cephalosporinase; CMY, cephamycin-hydrolyzing β-lactamase; CTX-M, cefotaxime-hydrolyzing β-lactamase–Munich; FOX, plasmid-mediated class C β-lactamase; GES, Guiana extended-spectrum β-lactamase; IMI, imipenem-hydrolyzing β-lactamase; IMP, imipenemase metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin carbapenemase/oxacillinase; SHV, sulfhydryl variant of the TEM enzyme; SME, Serratia marcescens enzyme; TEM, Temoneira class A extended-spectrum β-lactamase; VIM, Verona integron-encoded metallo-β-lactamase.

Figure 2.

Number of infections caused by carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli based on the Premier Healthcare Database. Adapted from [3]. Abbreviation: CR, carbapenem resistant.

Figure 3.

Distribution of carbapenem resistance mechanisms in Enterobacteriaceae species in the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. Adapted from [62]. Abbreviations: AmpC, ampicillin chromosomal cephalosporinase β-lactamase; CR, carbapenem resistant; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin carbapenemase/oxacillinase; VIM, Verona integron-encoded metallo-β-lactamase.

Figure 4.

Algorithm to assess potential carbapenem resistance mechanisms in Enterobacteriaceae and nonfermenter species. Abbreviations: CPE, carbapenemase-producing Enterobacteriaceae; CPO, carbapenemase-producing organism; CR, carbapenem resistant; CRE, carbapenem-resistant Enterobacteriaceae; IMP, imipenemase metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; L1, a class B metallo-β-lactamase; MBL, metallo-β-lactamase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillin carbapenemase/oxacillinase; VIM, Verona integron-encoded metallo-β-lactamase.