omadacycline and Bacterial-Infections

This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections.. A search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs).. A total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I. Omadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Staphylococcal Infections; Tetracyclines; Treatment Outcome

This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections in adult patients through meta-analysis.. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated omadacycline and other comparators for treating acute bacterial infections in adult patients were included. The primary outcome was the clinical response rate at the posttreatment evaluation, whereas the secondary outcomes were risk of an adverse event (AE) and mortality.. Four RCTs were included. Overall, omadacycline had a clinical response rate noninferior to comparators in the treatment of acute bacterial infection in the modified intent-to-treat population (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04-1.65; I = 0%) and in the clinically evaluable population (OR, 1.53; 95% CI, 1.11-2.11; I = 0%). Furthermore, no significant differences were found between omadacycline and comparators for the risk of treatment-emergent AEs (OR, 1.13; 95% CI, 0.60-2.14; I = 93%), treatment-related AEs (OR, 0.70; 95% CI, 0.46-1.04; I = 56%), serious AEs (OR, 1.01; 95% CI, 0.64-1.58; I = 0%), and discontinuation of study drug due to an AE (OR, 0.78; 95% CI, 0.47-1.29; I = 0%). However, in the clinical trial, NCT02877927, in which omadacycline was used in only oral form, the reported incidence of nausea and vomiting were 30.2% (111/368) and 16.9% (62/368), respectively. Finally, the mortality rate was similar between omadacycline and comparator in the treatment of acute bacterial infection (OR, 1.32; 95% CI, 0.47-3.67; I = 0%).. The clinical efficacy of omadacycline is not inferior to that of comparators in the treatment of acute bacterial infections in adult patients, and this antibiotic is also well tolerated.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Randomized Controlled Trials as Topic; Tetracyclines

Omadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the US Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad-spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains, like methicillin-resistant Staphylococcus aureus, as well as Yersinia pestis and Bacillus anthracis, organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms.

Topics: Administration, Intravenous; Administration, Oral; Bacteria; Bacterial Infections; Clinical Trials as Topic; Drug Compounding; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Tetracyclines

To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic.. A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer's website were reviewed.. Preclinical data and published phase 1, 2, and 3 studies were evaluated.. Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP.. Omadacycline is an alternative treatment option for ABSSSI and CABP.

Topics: Acute Disease; Administration, Intravenous; Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Community-Acquired Infections; Dose-Response Relationship, Drug; Humans; Skin Diseases, Bacterial; Tetracyclines; Treatment Outcome

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

Omadacycline is a novel aminomethylcycline antimicrobial agent that is available in both oral and intravenous formulations. The distinguishing structural characteristics of omadacycline from other tetracyclines allow for its continued antimicrobial activity in the presence of traditional tetracycline resistance mechanisms (efflux pumps and ribosomal protection proteins). Omadacycline has been found to have potent activity against antibiotic-resistant pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended spectrum beta-lactamase-producing Escherichia coli and multidrug-resistant Streptococcus pneumoniae. Currently available data indicate that omadacycline is generally well tolerated with the most common adverse effects being gastrointestinal symptoms. Omadacycline seems to be a promising new agent for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Studies for the treatment of cystitis in adult females are currently underway, and future results of these studies will further help delineate the antibacterial role of omadacycline.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Interactions; Humans; Tetracyclines; Treatment Outcome

Paratek Pharmaceuticals are developing omadacycline (NUZYRA™), a first-in-class orally active aminomethylcycline antibacterial, as a treatment for various bacterial infections. The drug, which is available in intravenous and oral formulations, has a broad spectrum of antibacterial activity and was recently approved in the USA as a treatment for the treatment of community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This article summarizes the milestones in the development of omadacycline leading to this first global approval for the treatment of CABP and ABSSSI.

Topics: Anti-Bacterial Agents; Bacterial Infections; Community-Acquired Infections; Drug Approval; Humans; Skin Diseases, Bacterial; Tetracyclines; United States

Omadacycline is a first-in-class aminomethylcycline antibiotic that circumvents common tetracycline resistance mechanisms. In vitro omadacycline has potent activity against Gram-positive aerobic bacteria including methicillin-resistant Staphylococcus aureus, penicillin-resistant and multidrug-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus spp. It is also active against common Gram-negative aerobes, some anaerobes and atypical bacteria including Legionella spp. and Chlamydia spp. Ongoing Phase III clinical trials with omadacycline are investigating once daily doses of 100 mg intravenously followed by once-daily doses of 300 mg orally for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This paper provides an overview of the microbiology, nonclinical evaluations, clinical pharmacology and initial clinical experience with omadacycline.

Topics: Bacteria; Bacterial Infections; Chlamydia; Community-Acquired Infections; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Gram-Negative Aerobic Bacteria; Gram-Positive Bacteria; Legionella; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Skin; Skin Diseases, Bacterial; Streptococcus pneumoniae; Tetracyclines; Vancomycin-Resistant Enterococci

Topics: Bacteria; Bacterial Infections; Humans; Tetracyclines

Topics: Bacteria; Bacterial Infections; Humans; Tetracyclines

Topics: Bacterial Infections; Humans; Tetracyclines

Omadacycline is the first intravenous and oral 9-aminomethylcycline in clinical development for use against multiple infectious diseases including acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), and urinary tract infections (UTI). The comparative in vitro activity of omadacycline was determined against a broad panel of Gram-positive clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Lancefield groups A and B beta-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae (PRSP), and Haemophilus influenzae (H. influenzae). The omadacycline MIC90s for MRSA, VRE, and beta-hemolytic streptococci were 1.0 μg/ml, 0.25 μg/ml, and 0.5 μg/ml, respectively, and the omadacycline MIC90s for PRSP and H. influenzae were 0.25 μg/ml and 2.0 μg/ml, respectively. Omadacycline was active against organisms demonstrating the two major mechanisms of resistance, ribosomal protection and active tetracycline efflux. In vivo efficacy of omadacycline was demonstrated using an intraperitoneal infection model in mice. A single intravenous dose of omadacycline exhibited efficacy against Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, including tet(M) and tet(K) efflux-containing strains and MRSA strains. The 50% effective doses (ED50s) for Streptococcus pneumoniae obtained ranged from 0.45 mg/kg to 3.39 mg/kg, the ED50s for Staphylococcus aureus obtained ranged from 0.30 mg/kg to 1.74 mg/kg, and the ED50 for Escherichia coli was 2.02 mg/kg. These results demonstrate potent in vivo efficacy including activity against strains containing common resistance determinants. Omadacycline demonstrated in vitro activity against a broad range of Gram-positive and select Gram-negative pathogens, including resistance determinant-containing strains, and this activity translated to potent efficacy in vivo.

Topics: Animals; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Enterococcus; Escherichia coli; Gene Expression; Haemophilus influenzae; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Peritoneum; Ribosomes; Staphylococcus aureus; Streptococcus pneumoniae; Tetracyclines