Utilizing the Promise of Omadacycline in a Resistant, Non-tubercular Mycobacterial Pulmonary Infection

Minhas, Ramandeep; Sharma, Shaurya; Kundu, Suhali

doi:10.7759/cureus.5112

Cited by 20 publications

(19 citation statements)

References 9 publications

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“…In the past few years, in vitro studies of omadacycline have reported low MICs against M. abscessus and therefore offer promising potential against this bacterium ( 21 – 23 , 25 ). Additionally, recent real-world case reports and case series have reported promising clinical outcomes with regimens containing omadacycline in treating M. abscessus lung disease ( 27 , 59 – 61 ). These observations have warranted evaluation in a preclinical model that permits efficacy determination of omadacycline alone against multiple M. abscessus isolates in a controlled laboratory setting.…”

Section: Discussionmentioning

confidence: 99%

Potency of Omadacycline against Mycobacteroides abscessus Clinical Isolates In Vitro and in a Mouse Model of Pulmonary Infection

Nicklas

Maggioncalda

Story-Roller

et al. 2022

Antimicrob Agents Chemother

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The incidence of nontuberculous mycobacterial diseases in the US is rising and has surpassed tuberculosis. Most notable among the nontuberculous mycobacteria is Mycobacteroides abscessus , an emerging environmental opportunistic pathogen capable of causing chronic infections. M. abscessus disease is difficult to treat and the current treatment recommendations include repurposed antibiotics, several of which are associated with undesirable side effects. In this study, we have evaluated the activity of omadacycline, a new tetracycline derivative, against M. abscessus using in vitro and in vivo approaches. Omadacycline exhibited an MIC 90 of 0.5 μg/ml against a panel of 32 contemporary M. abscessus clinical isolates several of which were resistant to antibiotics that are commonly used for treatment of M. abscessus disease. Omadacycline when combined with clarithromycin, azithromycin, cefdinir, rifabutin or linezolid also exhibited synergism against several M. abscessus strains and did not exhibit antagonism when combined with an additional nine antibiotics also commonly considered to treat M. abscessus disease. Concentration-dependent activity of omadacycline was observed in time-kill assessments. Efficacy of omadacycline was evaluated in a mouse model of lung infection against four M. abscessus strains. A dose equivalent to the 300 mg standard oral human dose was used. Compared to the untreated control group, within four weeks of treatment, 1 to 3 log 10 fewer M. abscessus colony forming units were observed in the lungs of mice treated with omadacycline. Treatment outcome was biphasic, with bactericidal activity observed after the first two weeks of treatment against all four M. abscessus strains.

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Section: Discussionmentioning

confidence: 99%

Potency of Omadacycline against Mycobacteroides abscessus Clinical Isolates In Vitro and in a Mouse Model of Pulmonary Infection

Nicklas

Maggioncalda

Story-Roller

et al. 2022

Antimicrob Agents Chemother

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“…In the first 3 studies discussed above, omadacycline MICs correlated well with tigecycline MICs. Despite the growing literature of favorable in vitro data for M abscessus , there has been only 1 report of omadacycline clinical use in this situation [ 29 ]. This case series provides the most clinical data published on the use of omadacycline for M abscessus disease to date.…”

Section: Discussionmentioning

confidence: 99%

Omadacycline for the Treatment of Mycobacterium abscessus Disease: A Case Series

Pearson

Dionne

Richterman

et al. 2020

Open Forum Infectious Diseases

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Background Omadacycline is an aminomethylcycline antimicrobial approved by the United States Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking. Methods Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M. abscessus disease in 2019. Results Four patients received omadacycline for the treatment of culture-positive M. abscessus disease in 2019. Two patients had cutaneous disease, one had pulmonary disease, and one had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range 104-227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in three of four patients, with one patient improving on ongoing treatment. Omadacycline’s tolerability was acceptable for patients with M. abscessus disease, with one patient discontinuing therapy in month six due to nausea. Conclusions Omadacycline is a novel oral option for the treatment of Mycobacterium abscessus disease, for which safe and effective options are needed. While this case series is promising, further data are required to determine omadacycline’s definitive role in the treatment of Mycobacterium abscessus disease.

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“…Based on available evidence to date, oral omadacycline thus represents an attractive option for replacement of intravenous tigecycline in drug regimens to treat M. abscessus pulmonary infections. However, since the clinical efficacy of omadacycline in M. abscessus infections is limited to a single case report to date, 130 further studies are required to test this hypothesis.…”

Section: Repurposable Drugs Versus M Abscessus Complex: Play To Losementioning

confidence: 99%

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

Egorova¹,

Jackson

Gavrilyuk³

et al. 2021

Medicinal Research Reviews

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The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti‐M. abscessus small‐molecule drug development process can be enhanced by two parallel strategies—discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small‐molecule agents, and more particularly focuses on the activity, mode of action and structure–activity relationship of promising inhibitors from five different chemical classes—benzimidazoles, indole‐2‐carboxamides, benzothiazoles, 4‐piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessus that may be worthy of future drug and adjunct therapeutic development.

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Utilizing the Promise of Omadacycline in a Resistant, Non-tubercular Mycobacterial Pulmonary Infection

Cited by 20 publications

References 9 publications

Potency of Omadacycline against Mycobacteroides abscessus Clinical Isolates In Vitro and in a Mouse Model of Pulmonary Infection

Potency of Omadacycline against Mycobacteroides abscessus Clinical Isolates In Vitro and in a Mouse Model of Pulmonary Infection

Omadacycline for the Treatment of Mycobacterium abscessus Disease: A Case Series

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

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