Atypical mycobacterial infections – management and when to treat

Abstract

Purpose of review Infections caused by nontuberculous mycobacteria (NTM) are increasing for several reasons, including diagnostic advances, increased awareness and a larger at-risk population. NTM pulmonary disease is surpassing tuberculosis (TB) in some low incidence areas. This review summarizes the latest literature and guidelines and aims to be a concise source outlining treatment and management of NTM lung infections, integrating established treatment paradigms with novel pharmacological interventions. Recent findings Recent additions to NTM treatment are inhaled liposomal amikacin and the anti-TB drug bedaquiline. Several other new or repurposed treatments are being explored in vitro, in animal models and in clinical trials, including novel beta-lactamase inhibitor/lactam combinations, dual-lactam combinations, efflux pump inhibitors, novel antimicrobials, inhaled clofazimine suspension and bacteriophages. Summary Patients with NTM pulmonary disease are mainly female and older with significant delay between diagnosis and treatment being common. Treatment varies according to causative organism, drug susceptibilities, radiological type and disease severity. Underlying chronic conditions, drug intolerances and interactions require careful consideration. In all cases, at least three drugs should be used to minimize acquisition of drug resistance, and all patients should receive a minimum of 12 months of treatment. Expert advice should be taken. NTM treatment is longer than TB treatment, more likely to fail and more likely to cause toxicity. The relatively small numbers of patients affected by each NTM species has limited research. Novel treatments hold promise; nevertheless, it is likely that new solutions for NTM management will stem from the TB pipeline for the foreseeable future.

Efficacy of PBTZ169 and pretomanid against Mycobacterium avium, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum in BALB/c mice models

“…Treatment regimens of NTM lung disease often require long-term therapy with multiple antimicrobial drug combinations ( Gill et al., 2021 ). Even so, the global cure rate for NTM infection is comparable to or worse than that for multidrug-resistant TB, and recurrence or reinfection is common ( Daley et al., 2020 ; Dartois and Dick, 2022 ).…”

Antimicrobial susceptibility testing using MYCO test-system and MIC distribution of 8 drugs against clinical isolates from Shanghai of Nontuberculous Mycobacteria

“…Infections caused by non-tuberculous mycobacteria (NTM) are increasing worldwide, which is becoming a major new global health issue. NTM has its natural drug resistance, and treating them involves a complex approach, requiring a combination of multiple drugs administered for a long time (1)(2)(3)(4). There are no specific drugs to treat these infections, and the recommended regimens generally lack efficacy, emphasizing the need for novel antibacterial compounds.…”

Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways.

“…The prevalence and incidence of NTM pulmonary infections are increasing worldwide and often intractable to treat (7)(8)(9). NTM treatment with standard antimicrobial regimens is challenging, takes longer than TB treatment, and has a low cure rate because of antibiotic resistance and toxicity (10)(11)(12). There is an urgent need for innovative host-directed therapeutics (HDT) based on deciphering an in-depth molecular mechanisms underlying host-pathogen interactions that could be geared for e cient protective responses against TB and NTM infections.…”