Preliminary, Real-world, Multicenter Experience With Omadacycline for Mycobacterium abscessus Infections

Abstract

Twelve patients were treated with Omadacycline(OMC) as part of a multi-drug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin(7/12;58.3%). The median(IQR) duration of OMC was 6.2(5.0-9.5) months. Clinical success occurred in 9/12(75.0%) of patients. Three patients experienced a possible adverse effect while on therapy.

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

“…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.…”

“…Some advantages of omadacycline compared to tigecycline include (i) that omadacycline is available in both intravenous and oral formulations, making administration simpler for patients and allowing for oral therapy, (ii) that omadacycline has an elevated and sustained concentration in epithelial lining fluid, alveolar cells, and plasma, as well as improved pulmonary pharmacokinetics (PK) compared to those of tigecycline ( 26 ), and (iii) that omadacycline may have better tolerability than tigecycline ( 25 ). In addition, in a recent preliminary, real-world multicenter study, clinical success has been demonstrated with regimens containing omadacycline to treat M. abscessus infections in the majority of patients ( 27 ).…”

Management of Mycobacterium avium complex and Mycobacterium abscessus pulmonary disease: therapeutic advances and emerging treatments

“…In another case series in which seven out of 12 patients had MAB-PD, omadacycline therapy was associated with treatment success in five out of seven MAB-PD patients, while treatment failure in MAB-PD occurred in one patient with fibrocavitary disease and patient with nodular-bronchiectatic disease with dissemination [94]. Gastrointestinal, renal and hepatic adverse effects were reported in one patient each [94]. A phase II clinical trial evaluating the use of omadacycline in treating MAB-PD is currently in progress [95].…”

“…In a case series of four patients who were treated for MAB disease at different sites, omadacycline was tolerated for >7 months in a patient with MAB-PD, although they required a lobectomy 5 months into omadacycline treatment [93]. In another case series in which seven out of 12 patients had MAB-PD, omadacycline therapy was associated with treatment success in five out of seven MAB-PD patients, while treatment failure in MAB-PD occurred in one patient with fibrocavitary disease and patient with nodular-bronchiectatic disease with dissemination [94]. Gastrointestinal, renal and hepatic adverse effects were reported in one patient each [94].…”

“…Fragment-based screening approaches have been used to identify potential therapeutic target sites in M. abscessus [123]. In vitro inhibitors have Adding clofazimine to bedaquiline in vitro improves bacteriostatic effect of bedaquiline against M. abscessus (but promotes bedaquiline resistance); has modest effect on bactericidal effect of bedaquiline against M. avium (and slows emergence of bedaquiline resistance) [82] Tedizolid Concentration-dependent activity in vitro against M. avium; enhanced when combined with ethambutol Weak bacteriostatic activity in vitro against MAB; enhanced when combined with amikacin [85] Well-tolerated and efficacious in patient with pulmonary TB and liver transplant due to hepatic failure secondary to anti-TB medications [87] No significant difference in safety profile between tedizolid and linezolid when used to treat NTM infections in solid-organ transplant recipients [86] Probably contributed to anaemia in patient with pulmonary mycobacterial infection, and thrombocytopenia in patient with disseminated mycobacterial infection [88] Omadacycline Potent activity against rapid-growing NTM in vitro; similar activity to tigecycline against MAB, M. chelonae and M. fortuitum [89][90][91] Symptomatic improvement and radiographic stability at 1-month follow-up in a patient who had previously failed NTM-PD treatment following treatment with 4-week course of omadacycline plus amikacin and aztreonam [92] Tolerated for >7 months in a patient with MAB-PD; lobectomy required 5 months into omadacycline treatment [93] Associated with treatment success in five out of seven patients with MAB-PD; treatment failure in MAB-PD in one patient with fibrocavitary disease and one patient with nodular-bronchiectatic disease with dissemination [94] Eravacycline Inhaled imipenem-cilastatin well-tolerated and resulted in lung function stability in two paediatric MAB-PD patients [104] Inhaled high-dose tigecycline effective in a dose-dependent manner at reducing pulmonary bacterial load in a GM-CSF knockout model of MAB infection [105] Clofazimine inhalation suspension achieved four-fold higher concentration in the lungs than oral clofazimine and was well-tolerated in a mouse model of NTM lung disease [106] IFN-γ Inhaled IFN-γ improves NTM clearance in patients with IFN-γ deficiency [107] Inhaled IFN-γ poor at promoting sputum culture conversion among those with cavitary disease [108] Adjuvant intramuscular IFN-γ associated with higher treatment response rates relative to placebo and fewer disease-related deaths in MAC-PD [109] GM-CSF Adjuvant inhaled GM-CSF associated with improved lung function and culture conversion in two patients with CF and MAB-PD [112] Inhaled NO 160 ppm inhaled NO for 21 days fo...…”