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Oral and intravenous (IV) omadacycline formulations are approved in the United States for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults. Oral omadacycline bioavailability is 34.5%; similar exposures are obtained following 300 mg oral and 100 mg IV doses. Oral administration should be in a fasted state, with dairy products, antacids, or multivitamins avoided for ≥4 hours after dosing. Low protein binding (21%), large volume of distribution (190 L), low systemic clearance (10 L/hour), and long elimination half-life (16–17 hours) support once-daily dosing. Omadacycline is excreted unchanged in feces (81.1%) and urine (14.4%), with low potential for drug–drug interactions. Dose adjustments are unnecessary for age, sex, and renal or hepatic impairment. Pharmacokinetic–pharmacodynamic studies identify fAUC0–24/MIC ratio as the parameter that correlates with in vivo efficacy. Systemic exposure of omadacycline in epithelial lining fluid is greater than/equal to plasma concentrations in healthy adults. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 3% of hospitalized patients with community-acquired bacterial pneumonia (CABP) develop healthcare-associated Clostridioides difficile infection (HCA-CDI). The validated Davis risk score (DRS) indicates that patients with a DRS ≥ 6 are at an increased risk of 30-day HCA-CDI. In the phase 3 OPTIC CABP study, 14% of CABP patients with DRS ≥ 6 who received moxifloxacin developed CDI vs. 0% for omadacycline. This study assessed the potential economic impact of substituting current guideline-concordant CABP inpatient treatments with omadacycline in hospitalized CABP patients with a DRS ≥ 6 across US hospitals. Methods: A deterministic healthcare-decision analytic model was developed. The model population was hospitalized adult CABP patients with a DRS ≥ 6 across US hospitals (100,000 patients). In the guideline-concordant arm, 14% of CABP patients with DRS ≥ 6 were assumed to develop an HCA-CDI, each costing USD 20,100. In the omadacycline arm, 5 days of therapy was calculated for the entire model population. Results: The use of omadacycline in place of guideline-concordant CABP inpatient treatments for CABP patients with DRS ≥ 6 was estimated to result in cost savings of USD 55.4 million annually across US hospitals. Conclusion: The findings of this simulated model suggest that prioritizing the use of omadacycline over current CABP treatments in hospitalized CABP with a DRS ≥ 6 may potentially reduce attributable HCA-CDI costs. The findings are not unique to omadacycline and could be applied to any antibiotic that confers a lower risk of HCA-CDI relative to current CABP inpatient treatments. [ABSTRACT FROM AUTHOR]

Background Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including tetracycline-resistant pathogens. Omadacycline was recently approved in the United States for treatment of adult patients with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections. Analyses were undertaken to determine whether PORT risk class and CURB-65 score influence the pharmacokinetics of omadacycline in patients with CABP. Methods Omadacycline pharmacokinetic data were available from omadacycline-treated patients with CABP enrolled in the Phase 3 OPTIC Study. Patients received omadacycline 100 mg IV q12h on Day 1 followed by 100 mg IV q24h. After Day 3, patients could be switched to 300 mg PO q24h if predefined clinical stability criteria were met. Four pharmacokinetic samples per patient were collected between Days 2 and 5. These data were previously utilized in the development of a population pharmacokinetic model describing the disposition of omadacycline [Microbe 2018; Abstr SAT-628]. Individual post-hoc parameter estimates for patients enrolled in the OPTIC study were utilized to compute Day 1 total-drug plasma area under the concentration-time curve (AUC) values following administration of omadacycline 100 mg IV q12h. Differences among these AUC values by PORT risk class and CURB-65 score were assessed using a one-way ANOVA. Results A total of 187 pharmacokinetic samples were available from 50 patients. Among the patients classified as PORT risk class II, III, and IV (n = 12, 28, and 10, respectively), mean Day 1 omadacycline AUC values were 10.2, 11.0, and 12.0 mg L/h, respectively. Among patients with CURB-65 scores of 0, 1, and 2 (n = 23, 23, and 4, respectively), mean Day 1 omadacycline AUC values were 10.6, 11.6, and 9.7 mg L/h, respectively. The differences in mean AUC values were not statistically significant among patients by PORT risk class (P = 0.248) and CURB-65 score groups (P = 0.745). Moreover, variability was similar across these groups as displayed in Figure 1. Conclusion Omadacycline exposures were similar across PORT risk class and CURB-65 score groups; thus, omadacycline dose adjustments based on these classifications are likely not warranted. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Omadacycline is a broad-spectrum aminomethylcycline approved in October 2018 by the U.S. Food and Drug Administration for treating acute bacterial skin and skin structure infections and community-acquired pneumonia as both an oral and intravenous once-daily formulation. In this report, the activities of omadacycline and comparators were tested against 49,000 nonduplicate bacterial isolates collected prospectively during 2016 to 2018 from medical centers in Europe (24,500 isolates, 40 medical centers [19 countries]) and the United States (24,500 isolates, 33 medical centers [23 states and all 9 U.S. census divisions]). Omadacycline was tested by broth microdilution following the methods in Clinical and Laboratory Standards Institute document M07 ( Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard , 11th ed., 2018). Omadacycline (MIC 50/90 , 0.12/0.25 mg/liter) inhibited 98.6% of Staphylococcus aureus isolates at ≤0.5 mg/liter, including 96.3% of methicillin-resistant S. aureus isolates and 99.8% of methicillin-susceptible S. aureus isolates. Omadacycline potency was comparable for Streptococcus pneumoniae (MIC 50/90 , 0.06/0.12 mg/liter), viridans group streptococci (MIC 50/90 , 0.06/0.12 mg/liter), and beta-hemolytic streptococci (MIC 50/90 , 0.12/0.25 mg/liter), regardless of species and susceptibility to penicillin, macrolides, or tetracycline. Omadacycline was active against all Enterobacterales tested (MIC 50/90 , 1/8 mg/liter; 87.5% of isolates were inhibited at ≤4 mg/liter) except Proteus mirabilis (MIC 50/90 , 16/>32 mg/liter) and indole-positive Proteus spp. (MIC 50/90 , 8/32 mg/liter) and was most active against Escherichia coli (MIC 50/90 , 0.5/2 mg/liter), Klebsiella oxytoca (MIC 50/90 , 1/2 mg/liter), and Citrobacter spp. (MIC 50/90 , 1/4 mg/liter). Omadacycline inhibited 92.4% of Enterobacter cloacae species complex and 88.5% of Klebsiella pneumoniae isolates at ≤4 mg/liter. Omadacycline was active against Haemophilus influenzae (MIC 50/90 , 0.5/1 mg/liter), regardless of β-lactamase status, and against Moraxella catarrhalis (MIC 50/90 , ≤0.12/0.25 mg/liter). The potent activity of omadacycline against Gram-positive and -negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative bacterial infections may be a concern., (Copyright © 2020 American Society for Microbiology.)

Objectives: Omadacycline is an aminomethylcycline antibacterial (oral and intravenous once-daily formulation) that recently (October 2018) received United States Food and Drug Administration (FDA) approval for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP) against selected organism groups. This study tested omadacycline and comparators against 14 000 non-duplicate bacterial isolates that were prospectively collected during 2017 from medical centres in Europe (EUR; 7000 isolates) and the United States (USA; 7000 isolates)., Methods: Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A11 (2018) methods., Results: A total of 98.7% ofStaphylococcus aureus isolates were susceptible to omadacycline (MIC 50/90 , 0.12/0.25mg/L; ABSSSI breakpoints) including 96.5% of methicillin-resistant Staphylococcus aureus (MRSA), 99.8% of methicillin-susceptible Staphylococcus aureus, and 93.9% of tetracycline-resistant strains. Omadacycline activity was similar for Streptococcus pneumoniae (MIC 50/90 0.06/0.12mg/L; 98.6% susceptible [CABP breakpoints]), Streptococcus anginosus group (MIC 50/90 0.06/0.06mg/L; 100.0% susceptible [ABSSSI breakpoints]), and Streptococcus pyogenes (MIC 50/90 0.06/0.12mg/L; 97.7% susceptible [ABSSSI breakpoints]). Omadacycline demonstrated activity against Enterobacter cloacae species complex isolates (MIC 50/90 , 2/4mg/L; 91.2% susceptible [ABSSSI breakpoints]), Klebsiella pneumoniae (MIC 50/90 , 2/8mg/L; 87.5% susceptible [CABP and ABSSSI breakpoints]), and inhibited 99.1% of Escherichia coli (MIC 50/90 , 0.5/2mg/L) isolates at ≤ 4mg/L. Omadacycline was active against Haemophilus influenzae (MIC 50/90 , 0.5/1mg/L; 99.8% susceptible [CABP breakpoints]), including all β-lactamase positive isolates, and inhibited 100.0% of Moraxella catarrhalis isolates at ≤ 0.25mg/L., Conclusions: The potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be of concern., (Copyright © 2019 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Omadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active against Staphylococcus aureus (MIC 50 /MIC 90 , 0.12/0.25 mg/liter), including methicillin-resistant S. aureus (MRSA); streptococci (MIC 50 /MIC 90 , 0.06/0.12 mg/liter), including Streptococcus pneumoniae , viridans group streptococci, and beta-hemolytic streptococci; Enterobacteriaceae , including Escherichia coli (MIC 50 /MIC 90 , 0.5/2 mg/liter); Haemophilus influenzae (MIC 50 /MIC 90 , 1/1 mg/liter); and Moraxella catarrhalis (MIC 50 /MIC 90 , 0.25/0.25 mg/liter). Omadacycline merits further study in serious infections where resistant pathogens may be encountered., (Copyright © 2018 Pfaller et al.)