omadacycline and Soft-Tissue-Infections

Skin and soft tissue infections (SSTIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Although numerous antibiotics are available for this indication, several medical needs remain unmet, especially for treating methicillin-resistant Staphylococcus aureus (MRSA) or mixed infections. This review summarizes the results achieved in the development of omadacycline, a new aminomethylcycline, which could have useful properties for the treatment of SSTIs.. The antimicrobial activity of omadacycline against the micro-organisms most frequently cultured in SSTIs has been confirmed in worldwide panels of clinical isolates, including MRSA, Gram-negative aerobes and some anaerobes. Pharmacokinetic data demonstrate interesting characteristics, allowing intravenous and oral administration. The Phase 3 OASIS-1 trial assessed the clinical efficacy and safety of omadacycline versus linezolid in SSTIs and demonstrated noninferiority and a good safety profile especially with regard to gastrointestinal effects. Analyses of subgroups of patients from this trial showed similar activity to that of the comparator drug, good safety and no dosage adjustments for age, sex or hepatic or renal impairment.. Because of its microbiological activities and pharmacokinetic profile, omadacycline may be particularly suitable for the treatment of SSTIs, whether managed in hospital or on an outpatient basis.

Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Skin Diseases, Infectious; Soft Tissue Infections; Tetracyclines; Treatment Outcome

Within the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent cause of purulent skin and soft tissue infections. New therapeutic options are being investigated for these infections.. We report an integrated analysis of 2 randomized, controlled studies involving omadacycline, a novel aminomethylcycline, and linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Omadacycline in Acute Skin and Skin Structure Infections Study 1 (OASIS-1) initiated patients on intravenous omadacycline or linezolid, with the option to transition to an oral formulation after day 3. OASIS-2 was an oral-only study of omadacycline versus linezolid.. In total, 691 patients received omadacycline and 689 patients received linezolid. Infection types included wound infection in 46.8% of patients, cellulitis/erysipelas in 30.5%, and major abscess in 22.7%. Pathogens were identified in 73.2% of patients. S. aureus was detected in 74.7% and MRSA in 32.4% of patients in whom a pathogen was identified. Omadacycline was noninferior to linezolid using the Food and Drug Administration primary endpoint of early clinical response (86.2% vs 83.9%; difference 2.3, 95% confidence interval -1.5 to 6.2) and using the European Medicines Agency primary endpoint of investigator-assessed clinical response at the posttreatment evaluation. Clinical responses were similar across different infection types and infections caused by different pathogens. Treatment-emergent adverse events, mostly described as mild or moderate, were reported by 51.1% of patients receiving omadacycline and 41.2% of those receiving linezolid.. Omadacycline was effective and safe in ABSSSI.. NCT02378480 and NCT02877927.

Topics: Acute Disease; Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Administration Routes; Female; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Skin; Skin Diseases, Bacterial; Soft Tissue Infections; Tetracyclines; Young Adult

Recent understanding of antimicrobial chemotherapy has expanded to appreciate significant impacts on the host-pathogen relationship by antibiotics. Omadacycline statistically outperformed linezolid in treating acute bacterial skin and skin structure infections in patients with diabetes mellitus in a recent post-hoc analysis of the OASIS-1 and OASIS-2 clinical trials. This difference may speak directly or indirectly to neutrophil dysfunction in diabetes. Neutrophil dysfunction increases the likelihood of Gram-negative bacterial infection, whereby diabetics may benefit from the broader spectrum of omadacycline compared with linezolid. Indirectly, oxazolidinones like linezolid have been shown to be dependent on neutrophil function, potentially compromising the potency of this drug class in diabetics. Finally, tetracyclines like omadacycline have collateral anti-inflammatory properties that have not been seen in other antibiotic drug classes. These differences may impact clinical outcomes in the treatment of infections that are not predicted by their antimicrobial activities alone, as measured in standard susceptibility testing assays.

Topics: Anti-Bacterial Agents; Diabetes Mellitus; Humans; Linezolid; Skin Diseases, Bacterial; Soft Tissue Infections; Tetracyclines