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Results of retrospective studies have suggested clofazimine as an alternative for rifampicin in the treatment of Mycobacterium aviumcomplex pulmonary disease (MAC-PD).

ABSTRACTIntroduction: Guidelines recommend the use of amikacin in the treatment of nontuberculous mycobacterial (NTM) disease. The authors have evaluated the evidence for the position of amikacin in NTM disease treatment.Areas covered: The authors performed a literature search for original research on amikacin in NTM disease, including its mechanism of action, emergence of resistance, pre-clinical and clinical investigations.Expert opinion: Amikacin shows moderate in vitroactivity against the clinically most relevant NTM species (M. aviumcomplex and M. abscessus). It is synergistic with ethambutol, clofazimine, and macrolides and these combinations are effective in animal models. Liposomal encapsulation increases amikacin efficacy. Clinically, the recommended dose of 15 mg/kg intravenous amikacin does not lead to PK/PD target attainment in all patients and a positive impact on long-term treatment outcomes remains unproven in both M. aviumcomplex and M. abscessusdisease. Adding the amikacin liposome inhalation suspension did prove to be effective in short and long term in patients not responding to recommended treatment for M. aviumcomplex pulmonary disease. Its optimal use in M. aviumcomplex and M. abscessuspulmonary disease warrants further evaluation.

The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.

Aim:Antibiotic resistance in Mycobacterium abscessusrenders treatment poorly effective. Despite erm(41)-gene-mediated macrolide resistance, treatment with azithromycin or clarithromycin is recommended. It is contested whether macrolides differ in erm(41) induction. We determine whether this is the case. Methods: M. abscessusCIP104536 was used. Minimum inhibitory concentrations of clarithromycin and azithromycin were determined. Time-kill kinetics of M. abscessusexposed to azithromycin or clarithromycin were performed and RNA was isolated at predetermined intervals for erm(41)quantification. Results:Minimum inhibitory concentrations increased >30-fold. Time-kill kinetics showed a temporary bacteriostatic effect, abrogated by induced resistance. Erm(41)expression was increased following exposure to either macrolide for 7 days. Conclusion:Both macrolides induce resistance similarly, and this should not be an argument in choosing either macrolide for therapy.

Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice.

For Mycobacterium aviumcomplex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitroactivity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium aviumand studied the contributions of individual antibiotics to efficacy.

In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium aviumcomplex (MAC) lung disease (ALIS+GBT, 29% [65/224] vs GBT-alone, 8.9% [10/112], P<.0001).

A symptomatic patient had repeatedly positive cultures of Mycobacterium aviumsubsp. hominissuisafter exposure to a hot tub contaminated with M. aviumsubsp. hominissuis. The pulmonary and tub water isolates were indistinguishable by IS1245RFLP as well as rep-PCR typing. Discontinued use of the hot tub resulted in culture conversion.

Treatment of Mycobacterium aviumcomplex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore the efficacy of thioridazine against M. aviumisolates using MICs, time-kill combination assays, ex vivomacrophage infection assays, and efflux assays. Thioridazine is bactericidal against M. avium, inhibits intracellular growth at 2× MIC, and blocks ethidium bromide efflux.

Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for Mycobacterium abscessus. New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for Mycobacterium tuberculosis. Here, we test auranofin against NTM in vitroand ex vivo. We tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution.

Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs).

Mycobacterium abscessuscauses a difficult-to-treat pulmonary disease (MAb-PD). After initial intravenous treatment, minocycline is recommended in the oral continuation phase of treatment.