Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018

Abstract

The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase-producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention's Antibiotic Resistance Laboratory Network. The aim of the study was to determine the susceptibility of these isolates against 32 currently available antibiotics using reference broth microdilution and explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretative criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretative criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible) 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug-resistant, and 116 isolates were extensively drug-resistant (42.2%) 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.

Therapeutic Options for Metallo-β-Lactamase-Producing Enterobacterales

“…of Isolates %S (MIC 50/90 [mg/L]) Ref. PLZ AMK TOB GENT MBL 37 a,b 42.1 (128/>128) 13.5 (>32/>32) NR (>8/>8) 21.6 (>8/>8) 108 552 c N/A 32.6 (N/A) N/A 27.7 (N/A) 156 NDM 282 d 22.7 (N/A) N/A N/A N/A 115 42 e 35.7 (>128/>128) 38.1 (>128/>128) 9.5 (>128/>128) 14.3 (>128/>128) 111 277 f 52.7 (2/>128) 52.7 (2/>64) 20 (>16/>16) 32 (>16/>16) 112 VIM 182 d 89.6 (N/A) N/A N/A N/A 115 20 g 95 (0.5/0.5) 90 (16/16) 0 (16/64) …”

“… 122 In a large surveillance study of MBL-producing Enterobacterales isolates collected in the US between 2017 and 2018, tetracycline susceptibilities are illustrated. 112 Among 275 Enterobacterales isolates harboring bla NDM tigecycline was the most active tetracycline agent followed by eravacycline ( Table 5 ). In another susceptibility study, tigecycline, eravacycline, and minocycline susceptibilities were evaluated against NDM (n=42), VIM (n=44), and IMP-producing (n=15) Enterobacterales isolates.…”

Peritoneal Dialysis-Related Peritonitis With Carbapenem-Resistant Klebsiella pneumoniae and Vancomycin-Resistant Enterococcus faecium

“…Bla NDM-1 was identified in our patient and renders all beta-lactams besides aztreonam inactive (including novel beta-lactam/beta-lactamase inhibitor combinations) [ 8 ]. Due to additional resistance genes, high rates of aztreonam and aminoglycoside resistance have also been noted in bla NDM-1 -carrying isolates [ 8 , 9 ]. In contrast, tigecycline and colistin usually retain activity [ 8 , 9 ].…”

“…Due to additional resistance genes, high rates of aztreonam and aminoglycoside resistance have also been noted in bla NDM-1 -carrying isolates [ 8 , 9 ]. In contrast, tigecycline and colistin usually retain activity [ 8 , 9 ]. In our case, tigecycline had the added advantage of activity against VRE.…”

“…Our case demonstrates that tigecycline remains a viable option for the treatment of nonbacteremic infections, including PD-related peritonitis with difficult-to-treat organisms such as CRE and VRE. The role of novel antimicrobials in this setting remains to be determined, but several agents such as plazomicin, eravacycline, omadacycline, and cefiderocol represent promising additions to the armamentarium [ 9 ].…”