Activity of Omadacycline and Other Tetracyclines Against Contemporary Gram-Negative Pathogens from New York City Hospitals

Abstract

Antibiotic-resistant Enterobacteriaceae and Acinetobacter baumannii are problematic pathogens, with few treatment options for multidrug-resistant (MDR)-A. baumannii and few oral options for extended spectrum β-lactamase (ESBL)-producing and MDR-Enterobacteriaceae. Omadacycline, a newer tetracycline derivative, has activity against some of these pathogens. We tested the in vitro activity of omadacycline against a contemporary collection of over 2,600 consecutive unique clinical isolates of Enterobacteriaceae and A. baumannii, a previous collection of carbapenem-resistant Klebsiella pneumoniae and A. baumannii from a surveillance study in 2013–2014, and a group of K. pneumoniae and A. baumannii isolates with previously defined resistance mechanisms. For the contemporary collection, over 96% of Escherichia coli and 70% of K. pneumoniae isolates were inhibited by omadacycline at ≤4 μg/mL including 95% of E. coli and 49% of K. pneumoniae with presumptive ESBLs. Nearly 90% of A. baumannii were inhibited by omadacycline at ≤4 μg/mL. The omadacycline MIC_50/90 was 1/4 μg/mL, 4/>8 μg/mL, and 0.5/8 for E. coli, K. pneumoniae, and A. baumannii, respectively. For the carbapenem-resistant collection of isolates, 56% of A. baumannii were inhibited by omadacycline at ≤4 μg/mL, but only 30% of Klebsiella pneumoniae carbapenemase (KPC)-possessing K. pneumoniae were susceptible. Expression of the efflux gene adeB appeared to affect the activity of omadacycline against A. baumannii, but could not fully explain resistance to this agent. Omadacycline may prove to be a parenteral or oral option for some infections due to ESBL-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, and clinical studies are warranted.