Omadacycline and <i>Clostridioides difficile</i>: A Systematic Review of Preclinical and Clinical Evidence

Garey, Kevin W.; Rose, Warren E.; Gunter, Kyle; Serio, Alisa W.; Wilcox, Mark H.

doi:10.1177/10600280221089007

Cited by 8 publications

(5 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A retrospective study of 50 patients receiving eravacycline as an inpatient or outpatient parenteral antibiotic therapy reported only one case of post-treatment CDI, where 40% of these patients had experienced CDI in the 12 months before receiving eravacycline [ 78 ]. While the mechanism of decreased risk of CDI with tetracycline-class drugs remains unclear, high drug concentrations in the bowel, less disruption to the gut microbiota than observed with other antibiotics, and in vitro and in vivo activity against C. difficile may all play a role [ 75 , 79 , 80 ].…”

Section: Clinical Data On Third-generation Tetracycline-class Antibio...mentioning

confidence: 99%

Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance

et al. 2022

View full text Add to dashboard Cite

The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select appropriate treatments with the goal of minimising further emergence of resistance and to optimise clinical outcomes. Three new tetracycline-class antibiotics, eravacycline, omadacycline, and tigecycline, have been approved within the past 15 years, and represent a new era in the use of tetracyclines. These drugs overcome the two main mechanisms of acquired tetracycline-class resistance and exhibit a broad spectrum of in vitro activity against gram-positive, gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains. We provide an overview of the three generations of tetracycline-class drugs, focussing on the efficacy, safety, and clinical utility of these three new third-generation tetracycline-class drugs. We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known β-lactam antibiotic allergy, reducing the risk of Clostridioides difficile infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGES The long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents. The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms. Based on in vitro characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs – including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent Clostridioides difficile infection, or polymicrobial infections, and those at risk of drug–drug interactions.

show abstract

Section: Clinical Data On Third-generation Tetracycline-class Antibio...mentioning

confidence: 99%

Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Tetracycline-class drugs are associated with lower rates of C. difficile infection compared with other classes of antibiotics, such as fluoroquinolones and third-generation cephalosporins. 54 Similar to other tetracyclines, omadacycline has potent in vitro activity against C. difficile . 54 The potential mechanisms by which tetracyclines confer a lower risk of C. difficile infection may include high drug concentrations in the bowel or reduced disruption to gut microbiota compared with other antibiotics.…”

Section: Discussionmentioning

confidence: 99%

“… 54 Similar to other tetracyclines, omadacycline has potent in vitro activity against C. difficile . 54 The potential mechanisms by which tetracyclines confer a lower risk of C. difficile infection may include high drug concentrations in the bowel or reduced disruption to gut microbiota compared with other antibiotics. 55 …”

Section: Discussionmentioning

confidence: 99%

A Review of Omadacycline for Potential Utility in the Military Health System for the Treatment of Wound Infections

Zurawski,

Serio,

Black

et al. 2023

Military Medicine

View full text Add to dashboard Cite

Introduction Combat-related wound infections complicate the recovery of wounded military personnel, contributing to overall morbidity and mortality. Wound infections in combat settings present unique challenges because of the size and depth of the wounds, the need to administer emergency care in the field, and the need for subsequent treatment in military facilities. Given the increase in multidrug-resistant pathogens, a novel, broad-spectrum antibiotic is desired across this continuum of care when the standard of care fails. Omadacycline was FDA-approved in 2018 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSI), as well as community-acquired bacterial pneumonia (CABP). It is a broad-spectrum antibiotic with activity against gram-positive, gram-negative, and atypical bacterial pathogens, including multidrug-resistant species. Omadacycline can overcome commonly reported tetracycline resistance mechanisms, ribosomal protection proteins, and efflux pumps, and is available in once-daily intravenous or oral formulations. In this review, we discuss the potential role of omadacycline, which is included in the Department of Defense Formulary, in the context of combat wound infections. Materials and Methods A literature review was undertaken for manuscripts published before July 21, 2023. This included a series of publications found via PubMed and a bibliography made publicly available on the Paratek Pharmaceuticals, Inc. website. Publications presenting primary data published in English on omadacycline in relation to ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter species) pathogens and Clostridioides difficile, including in vitro, in vivo, and clinical data were included. Results Of 260 identified records, 66 were included for evidence review. Omadacycline has in vitro activity against almost all the ESKAPEE pathogens, apart from P. aeruginosa. Importantly, it has activity against the four most prevalent bacterial pathogens that cause wound infections in the military healthcare system: S. aureus, including methicillin-resistant S. aureus, A. baumannii, K. pneumoniae, and E. coli. In vivo studies in rats have shown that omadacycline is rapidly distributed in most tissues, with the highest tissue-to-blood concentration ratios in bone mineral. The clinical efficacy of omadacycline has been assessed in three separate Phase 3 studies in patients with ABSSSI (OASIS-1 and OASIS-2) and with CABP (OPTIC). Overall, omadacycline has an established safety profile in the treatment of both ABSSSI and CABP. Conclusions Omadacycline has broad-spectrum activity, the option to be orally administered and an established safety profile, making it a potentially attractive replacement for moxifloxacin in the military individual first aid kit, especially when accounting for the increasing resistance to fluoroquinolones. Further studies and clinical evaluation are warranted to support broader use of omadacycline to treat combat wound infections in the military healthcare system.

show abstract

“…Conversely, ceftobiprole and ceftaroline, with an ELF/plasma ratio of around 20–25%, may require optimized dosing regimens [ 44 , 194 , 195 ]. On the same line, dalbavancin and oritavancin, given their optimal penetration in bone structures and their long half-life, are ideal candidates for the long-term treatment of osteoarticular or prosthetic joint infections [ 96 , 97 , 127 , 128 ].…”

Section: Discussionmentioning

confidence: 99%

“…Omadacycline is available as IV and oral formulations, the latter being characterized by poor bioavailability (35%), which can be significantly decreased under well-fed conditions (especially when dairy is included in the meal) [ 127 , 128 ]. The terminal half-life for omadacycline is about 16 h and, in order to achieve therapeutic concentration by day 2, loading doses of omadacycline are used [ 129 ].…”

Section: Tetracyclinesmentioning

confidence: 99%

New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians

Carcione,

Intra,

Andriani

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including ceftobiprole, ceftaroline, dalbavancin, oritavancin, omadacycline, tedizolid, and delafloxacin. From a methodological standpoint, a comprehensive analysis on clinical trials, molecular structure, mechanism of action, microbiological targeting, clinical use, pharmacokinetic/pharmacodynamic features, and potential for therapeutic drug monitoring will be addressed. Each antibiotic paragraph is divided into specialized microbiological, clinical, and pharmacological sections, including detailed and appropriate tables. A better understanding of the latest promising advances in the field of therapeutic options could lead to the development of a better approach in managing antimicrobial therapy for multidrug-resistant Gram-positive pathogens, which increasingly needs to be better stratified and targeted.

show abstract

Omadacycline and Clostridioides difficile: A Systematic Review of Preclinical and Clinical Evidence

Cited by 8 publications

References 116 publications

Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance

Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance

A Review of Omadacycline for Potential Utility in the Military Health System for the Treatment of Wound Infections

New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians

Contact Info

Product

Resources

About