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

Antibiotic-resistant Enterobacteriaceae andAcinetobacter baumanniiare problematic pathogens, with few treatment options for multidrug-resistant (MDR)-A. baumanniiand few oral options for extended spectrum beta-lactamase (ESBL)-producing and MDR-Enterobacteriaceae. Omadacycline, a newer tetracycline derivative, has activity against some of these pathogens. We tested thein vitroactivity of omadacycline against a contemporary collection of over 2,600 consecutive unique clinical isolates of Enterobacteriaceae andA. baumannii, a previous collection of carbapenem-resistantKlebsiella pneumoniaeandA. baumanniifrom a surveillance study in 2013-2014, and a group ofK. pneumoniaeandA. baumanniiisolates with previously defined resistance mechanisms. For the contemporary collection, over 96% ofEscherichia coliand 70% ofK. pneumoniaeisolates were inhibited by omadacycline at <= 4 mu g/mL including 95% ofE. coliand 49% ofK. pneumoniaewith presumptive ESBLs. Nearly 90% ofA. baumanniiwere inhibited by omadacycline at <= 4 mu g/mL. The omadacycline MIC(50/90)was 1/4 mu g/mL, 4/>8 mu g/mL, and 0.5/8 forE. coli,K. pneumoniae, andA. baumannii, respectively. For the carbapenem-resistant collection of isolates, 56% ofA. baumanniiwere inhibited by omadacycline at <= 4 mu g/mL, but only 30% ofKlebsiella pneumoniaecarbapenemase (KPC)-possessingK. pneumoniaewere susceptible. Expression of the efflux geneadeB appeared to affect the activity of omadacycline againstA. 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-resistantA. baumannii, and clinical studies are warranted.