Table 5.
Efficacy of Omadacycline in Animal Models
| Study | Animal Model | Strain | Antimicrobial | Result | |
|---|---|---|---|---|---|
| Lepak et al [41] | Neutropenic mouse pneumonia model (female ICR/Swiss mice, 3 mice/group) |
Streptococcus pneumoniae
a
1293 ATCC 10813 |
SC administrationb | Plasma AUC/MIC | |
| Omadacycline | Emax, 4.85 ED50, 15.60 r2, 0.74 |
||||
| 140 ATCC 49619 |
Omadacycline | Epithelial lining fluid AUC/MIC Emax, 4.91 ED50, 15.11 r2, 0.75 |
|||
| Lepak et al [42] | Mouse neutropenic thigh infection model (4 thigh infections/group) |
SC administrationc Omadacycline |
|||
| Staphylococcus aureus MSSA | Thigh bacterial burden | ||||
| Reduction of 4–5 log10 CFU/thigh compared with untreated controls | |||||
| S. aureus MRSA | Omadacycline | Plasma AUC/MIC | |||
| Emax, 4.62 | |||||
| ED50, 21.7 | |||||
| r 2, 0.92 | |||||
| Macone et al [8] | Mouse IP infection model (male CD-1 mice, 5 mice/group) |
IV administrationd | MIC (μg/mL) | ED50e (mg/kg [95% CI]) |
|
| S. pneumoniae PBS1339 | Omadacycline Tigecycline |
0.125 0.125 |
3.34 ± 1.56 4.13 (2.46 to 5.79) |
||
| S. pneumoniae 700905 | Omadacycline Tigecycline |
≤0.06 0.125 |
0.45 (0.32 to 0.58) 1.72 (0.6 to 2.82) |
||
| S. aureus 29213 | Omadacycline Tigecycline |
0.25 0.125 |
1.74 (0.91 to 2.58) 0.73 (0.69 to 0.76) |
||
| S. aureus USA300 | Omadacycline Tigecycline |
0.25 0.125 |
0.90 (0.33 to 1.46) 0.58 (0.40 to 0.75) |
||
| S. aureus MRSA5 | Omadacycline Tigecycline |
0.25 ≤0.06 |
0.30 (0.295 to 0.305) 1.74 (0.91 to 2.57) |
||
| Escherichia coli PBS1478 | Omadacycline Tigecycline |
1 ≤0.06 |
2.02 (1.09 to 2.96) 1.75 (1.12 to 2.38) |
||
| Endermann et al [44] | Mouse postoperative polymicrobial peritonitis model (female CFW-1 mice, 10 mice/group) | Enterococcus faecalis TR | IV administrationf | 10-day survival | |
| Omadacycline | 80% | ||||
| Enterococcus faecium VR | Imipenem | 70% | |||
| Linezolid | 30% | ||||
| McKenney et al [45] | Mouse urinary tract infection model (male CD-1 mice) | E. coli C189P4 | IV administrationg | MIC (μg/mL) | Kidney bacterial burden |
| (ED50, mg/kg) | |||||
| Omadacycline | 0.5 | 4.3 | |||
| Minocycline | 0.5 | 4.5 <1.0 |
|||
| Ciprofloxacin | ≤0.06 | ||||
| Steenbergen et al [16] | Mouse whole-body aerosol infection model, delayed treatment exposure (female BALB/c mice, 9 or 10 mice/group) | Bacillus anthracis Ames | IP administrationh | 40-day survival | |
| Omadacycline | 60% | ||||
| Doxycycline | 70% | ||||
| Ciprofloxacin | 80% | ||||
| Vehicle | 0% | ||||
| Mouse whole-body aerosol infection model, postexposure prophylaxis (female BALB/c mice, 10 mice/group) | Yersinia pestis CO92 | IP administrationi | 40-day survival | ||
| Omadacycline | 90% (40 mg/kg dose group) | ||||
| Doxycycline | 90% (40 mg/kg dose group) | ||||
| Ciprofloxacin | 100% | ||||
| Vehicle | 0% | ||||
| Kim et al [46] | Hamster C. difficile infection model (male LGV Golden Syrian hamsters, 10 hamsters/group) | Clostridioides difficile ATCC 43596 | Oral administrationj | Median survival (days) | |
| Omadacycline | 12 (P = .0004) | ||||
| Vancomycin | 2 (P = .0293) |
Abbreviations: AUC, area under the plasma concentration–time curve; CFU, colony-forming units; CI, confidence interval; ED50, 50% effective dose; Emax, maximum effect; IP, intraperitoneal; IV, intravenous; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; SC, subcutaneous; TR, tetracycline-resistant; VR, vancomycin-resistant.
aThere were 4 strains examined, with varying susceptibility to tetracyclines, β-lactams, and macrolides.
bThere were 4-fold increasing doses examined, from 0.1 to 25.6 mg/kg.
cDoses increased 4-fold every 12 hours, from 0.25 to 64 mg/kg.
dAt least 4 dose levels per experiment, with doses typically ranging from 0.11 to 18 mg/kg (dose minimum–maximum, 0.08–54 mg/kg); only tigecycline comparator is shown.
eData are represented as means ± standard deviations from 7 independent experiments.
fTwo doses of 10 mg/kg administered at 4 hours and 18 hours postsurgery.
gIncreasing single doses on day 4 postinfection.
hOmadacycline: 15 mg/kg; doxycycline: 15 mg/kg; ciprofloxacin: 30 mg/kg; vehicle: 0.2 mL saline. All treatments began 48 ± 1 hours postinfection, and were given twice daily for 14 days.
iOmadacycline: 5, 10, 20, or 40 mg/kg; doxycycline: 5, 10, 20, or 40 mg/kg; ciprofloxacin: 15 mg/kg; vehicle: 0.2 mL saline. All treatments began 24 ± 1 hours postinfection, and were given twice daily for 7 days.
jGiven for 5 days at 50 mg/kg/day.