P-1528. <i>In Vitro</i> Activity of Omadacycline and Comparator Agents against a Collection of <i>Neisseria Gonorrhoeae</i> Urine Isolates Collected from the United States During 2018-2020

Abstract Background Omadacycline (OMC) is a third-generation tetracycline (TET) class antibacterial approved for treatment of adults with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia caused by indicated organisms. OMC is active against bacterial isolates expressing common TET resistance mechanisms and strains resistant (R) to other drug classes. In this study, the in vitro activity of OMC and comparator agents was evaluated against a contemporary collection of N. gonorrhoeae clinical isolates. In addition, analysis of publicly available genomic sequences for these isolates was performed to determine the molecular mechanisms of TET resistance. Antimicrobial activity of omadacycline and comparators tested against 100 Neisseria gonorrhoeae isolates Methods The modal minimal inhibitory concentration (MIC) of OMC and comparator agents was determined by testing in triplicate by agar dilution for 100 N. gonorrhoeae clinical isolates (BEI Resources) collected from the urethra of patients with urethritis within the US (2018-2020). R or non-susceptible (NS) phenotypes were interpreted using breakpoints published by Clinical and Laboratory Standards Institute. Resistance genes were identified from genome sequences using ResFinder 4.0. Cumulative distribution of omadacycline MIC values tested against comparator-resistant or non-susceptible N. gonorrhoeae subsets Results OMC displayed activity against N. gonorrhoeae isolates (MIC50/90, 2/4 µg/mL) that had limited susceptibility (S) to TET (13%), ciprofloxacin (CIP) (60%) and penicillin (PEN) (4%) but high S to azithromycin (AZM), cefixime (CFX), and ceftriaxone (CFN) (Table 1). Among isolates with NS or R phenotypes for comparators, the OMC MIC50/90 (when calculated) were generally not impacted, although some of these subsets had very low numbers (Table 2). The rpsJ mutation was widespread among TET-R isolates, including those with additional mutations in porB, the mtrR promoter and tet(M) (Table 3). The highest OMC MIC (8 µg/mL) correlated with combined mutations in porB and rpsJ. OMC had MICs &amp;lt; 1 µg/mL among isolates (n=3) with high level TET-R (MIC&amp;gt; 16 µg/mL), including those with tet(M). Tetracycline resistance mechanisms among tetracycline resistant Neisseria gonorrhoeae isolates Conclusion OMC MICs were 0.12-8 µg/mL against this set of N. gonorrhoeae clinical isolates and the MIC distribution was minimally impacted by isolates NS/R to AZM, CFX, CFN, CIP, PEN, or TET. These results support the further research of OMC for N. gonorrhoeae infections, especially for those with high level TET-R. Disclosures J.V. Pierce, PhD, Paratek Pharmaceuticals: Employee Alisa W. Serio, PhD, Paratek Pharmaceuticals: Employee