In Vitro Activity of omadacycline against Chlamydia pneumoniae S. Kohlhoff# , N.A. Huerta, M.R. Hammerschlag Department of Pediatrics, Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn , NY # Corresponding author: Stephan A. Kohlhoff, MD Poster # SATURDAY-626 Tel: 718-270-2271 Email: [email protected]

Abstract: Introduction Results Discussion Background: Omadacycline (PTK 0796) is a new • The MICs and MBCs of Omadacycline and in vitro • Omadacycline (PTK 0796) is a new • The in vitro activity of omadacycline is aminomethylcycline with potent comparators for 15 isolates of C. pneumoniae antibacterial activity against a broad range of aminomethylcycline with potent in vitro comparable to that of several antibiotics bacteria causing respiratory infections, including antibacterial activity against a broad range of are shown in Table 1 and 2, respectively below. with proven clinical efficacy. Chlamydia spp.. C. pneumoniae is a frequent bacteria causing respiratory infections • Omadacycline achieves high, sustained cause of community-acquired respiratory • We compared the in vitro activity of Table 1 concentrations in plasma, epithelial lining infections, including pneumonia and bronchitis, omadacycline, azithromycin, levofloxacin, MIC (μg/ml) fluid and alveolar cells suggesting that it in adults. moxifloxacin and doxycycline against clinical will be effective in the treatment of Method: 15 respiratory isolates of C. and laboratory isolates of C. pneumoniae. Drug Range 50% 90% pulmonary infections, including those due pneumoniae were tested against omadacycline, C. Methods Omadacycline 0.03-0.5 0.06 0.25 to intracellular organisms, including azithromycin, doxycycline, moxifloxacin and pneumoniae 2 levofloxacin. Susceptibility testing of C. • C. pneumoniae isolates tested were: 2 isolates Azithromycin 0.03-0.06T 0.06 0.06 • Omadacycline has received qualified pneumoniae was performed in cell culture using from ATCC® (Manassas, VA): TW-183 (VR-2282), infectious disease product status from the HEp-2 cells grown in supplemented DMEM CM-1 (VR-1360), and 13 human isolates from Levofloxacin 0.25-0.5 0.5 0.5 US Food and Drug Administration for the 3 4 media followed by infection with 10 – 10 patients with community-acquired pneumonia treatment of CAP IFU/ml and included both MIC and MBC (CAP) including BAL specimens from the United Moxifloxacin 0.25-1.0 0.5 1.0 • In a phase 3 study omadacycline was non- determinations. States. Doxycycline 0.06-0.25 0.125 0.125 inferior to moxifloxacin in the treatment of Background: The activities of omadacycline and • Susceptibility testing was done in tissue culture community-acquired bacterial pneumonia 3 comparator antibacterials against 15 isolates of 1 as previously described . • The role of omadacycline in the treatment C. pneumoniae are shown in the table below. • HEp-2 cells were grown in 96-well microtiter Table 2 of C. pneumoniae infections will depend on Drug MIC range MIC50 MIC90 MBC range MBC90 plates and infected with 104 IFU/ml of the (μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml) the results of clinical studies that assess 4 Omadacycline 0.03-0.5 0.06 0.25 0.06-0.5 0.5 chlamydia isolate. MBC (μg/ml) microbiologic efficacy • After 72 hrs incubation cultures were fixed and References Azithromycin 0.03-0.06 0.06 0.06 0.06-0.25 0.25 stained with a fluorescein-conjugated anti- Drug Range 90% 1. Kohlhoff SA, Huband MD, Hammerschlag MR. In vitro activity of AZD0914, a novel DNA gyrase inhibitor, against Chlamydia Levofloxacin 0.25-0.5 0.5 0.5 0.25-2 2 chlamydia LPS antibody and examined for the Omadacycline 0.06-0.5 0.5 trachomatis and Chlamydia pneumoniae. Antimicrob Agents presence of inclusions. Chemother 2014; 58:7595-7596. Moxifloxacin 0.25-1 0.5 1 0.5-1 1 2. Gotfried MH, Horn K, Garrity-Ryan L, et al. Comparison of • The MIC was lowest antibiotic concentration Azithromycin 0.06-0.25 0.25 omadacycline and tygecycline pharmacokinetics in the plasma, epithelial lining fluid and alveolar cells of healthy adults. Antimicrob Doxycycline 0.06-0.25 0.125 0.125 0.25-0.5 0.5 without visible inclusions Levofloxacin 0.25-2 2 Agents Chemother 2018; 61:e01135-17. • MBC was determined by removing antibiotic- 3. R. Stets, M. Popescu, J. Gonong, et al (2017) A Phase 3, Randomized, Double-Blind, Multi-Center Study to Compare the Conclusions: Omadacycline had potent in vitro containing medium and adding antibiotic-free Moxifloxacin 0.5-1.0 1.0 Safety and Efficacy of IV to Oral Omadacycline to Moxifloxacin for activity against C. pneumoniae. The high in vitro medium; infected cells were frozen at -70°C, the Treatment of Adult Patients With CABP (The OPTIC Study). activity supports further clinical investigations Poster 1883. IDWeek 2017, San Diego, CA.] thawed, passed onto new cells, incubated for Doxycycline 0.25-0.5 0.5 4. Kohlhoff SA, Hammerschlag MR. Treatment of chlamydial with omadacycline against C. pneumoniae 72h, and then fixed and stained as described infections: 2014 update. Expert Opin Pharmacother 2014;16:2015- especially community-acquired bacterial 21. above; the MBC was the lowest antibiotic Acknowledgments C. pneumonia including infections due to concentration that resulted in no inclusions after This study was supported in part by a grant from Paratek pneumoniae. passage. Pharmaceuticals, Inc.