Surveillance of Omadacycline Activity against Clinical Isolates from a Global Collection (North America, Europe, Latin America, Asia-Western Pacific), 2010-2011

Abstract

Omadacycline is a broad-spectrum aminomethylcycline in late-stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia as an oral and an intravenous oncedaily formulation. In this study, omadacycline and comparators were tested against 69,246 nonduplicate bacterial isolates collected prospectively during 2010 and 2011 from medical centers in Asia-Pacific (11,397 isolates), Europe (23,490 isolates), Latin America (8,038 isolates), and North America (26,321 isolates). Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A10 (2015) methods. A total of 99.9% of Staphylococcus aureus isolates were inhibited by Յ2 g/ml of omadacycline (MIC 50/90 , 0.12/0.25 g/ml), including 100.0% of methicillin-susceptible S. aureus isolates and 99.8% of methicillin-resistant S. aureus isolates. Omadacycline potencies were comparable for Streptococcus pneumoniae (MIC 50/90 , 0.06/0.06 g/ml), viridans group streptococci (MIC 50/90 , 0.06/0.12 g/ml), and beta-hemolytic streptococci (MIC 50/90 , 0.06/0.12 g/ml) regardless of species and susceptibility to penicillin. Omadacycline was active against Enterobacteriaceae and was most active against Escherichia coli (MIC 50/90 , 0.5/2 g/ml), Enterobacter aerogenes (MIC 50/90 , 2/4 g/ml), Klebsiella oxytoca (MIC 50/90 , 1/4 g/ml), and Citrobacter spp. (MIC 50/90 , 1/4 g/ml). Omadacycline was active against Haemophilus influenzae (MIC 50/90 , 1/1 g/ml) regardless of ␤-lactamase status and against Moraxella catarrhalis (MIC 50/90 , 0.12/0.25 g/ml). The potent activity of omadacycline against Gram-positive and Gramnegative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.KEYWORDS aminomethylcycline, omadacycline, resistance, surveillance A ntimicrobial resistance (AMR) is a global problem that requires a coordinated response to prevent further erosion of the ability to address established and emerging threats to human health (1). In the United States, AMR infections cost an estimated additional $20 billion annually and associated production losses of $35 billion per year (2). In the United Kingdom, it is estimated that drug-resistant infections might account for 10 million deaths per year by 2050, with total costs of $100 trillion in lost output (1). Collection of AMR surveillance and antibiotic consumption data is an essential approach to both defining the scope of the resistance problem and developing interventions that improve appropriate use of antibiotics and decrease resistance selection pressure (1, 3). Another important effort is to understand the mechanisms of resistance whereby bacteria avoid the effects of antibiotics and to use this information to develop new agents, or modify older agents, such that potent activity is retained against the key target pathogens (4-6). Downloaded fromTetracyclines are broad-spectrum age...

Omadacycline Enters the Ring: A New Antimicrobial Contender

“…Similarly, in a global surveillance study including roughly 70,000 isolates, 99.9% of all S. aureus and Enterococcus spp. were inhibited by omadacycline concentrations less than or equal to 2 mg/L …”

“…complex (n=2101) and other Acinetobacter spp. (n=292) was assessed, and omadacycline inhibited growth of 91.5% and 95.5% of the isolates at less than or equal to 4 mg/L, respectively . Against 315 Stenotrophomonas maltophilia isolates, omadacycline inhibited growth of 82.2% of the organisms evaluated .…”

“…(n=292) was assessed, and omadacycline inhibited growth of 91.5% and 95.5% of the isolates at less than or equal to 4 mg/L, respectively . Against 315 Stenotrophomonas maltophilia isolates, omadacycline inhibited growth of 82.2% of the organisms evaluated . Against other multidrug‐resistant Enterobacteriaceae, omadacycline inhibited 85.3% of non–ceftazidime‐susceptible (n=1439) and 52.7% of non–imipenem‐susceptible isolates (n=277) …”

“…The two minor mechanisms of resistance include modification of the ribosomal target and enzymatic inactivation . Omadacycline retains activity for organisms with these resistance genes and does not appear to be affected by resistance to other antimicrobials . No strains with induced resistance have been reported.…”

“…6,7,16 Omadacycline retains activity for organisms with these resistance genes and does not appear to be affected by resistance to other antimicrobials. 7,8,10 No strains with induced resistance have been reported.…”