Disseminated actinomycetoma due to Nocardia wallacei.

BACKGROUND: Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge. AIMS: Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma. MATERIALS AND METHODS: We evaluated the medical management of an 18-year-old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique. RESULTS: The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found. DISCUSSION: Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma. CONCLUSION: Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei.

Emergence of mmpT5 Variants during Bedaquiline Treatment of Mycobacterium intracellulare Lung Disease.

Bedaquiline (BDQ), a diarylquinoline antibiotic that targets ATP synthase, is effective for the treatment of Mycobacterium tuberculosis infections that no longer respond to conventional drugs. While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with Mycobacterium intracellulare lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of M. intracellulare uncovered mutations in a previously uncharacterized locus, mmpT5 Preliminary analysis suggested similarities between mmpT5 and the mmpR5 locus, which is associated with low-level BDQ resistance in M. tuberculosis Both genes encode transcriptional regulators and are adjacent to orthologs of the mmpS5-mmpL5 drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous mmpT5 mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (atpE), the primary target of BDQ. Susceptibility testing indicated that mmpT5 mutations are associated with modest 2- to 8-fold increases in MICs for BDQ and clofazimine, whereas one atpE mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of M. intracellulare lung disease, but optimization of treatment regimens is required to prevent the emergence of mmpT5 variants and microbiological relapse.

Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria.

Within the past 10 years, treatment and diagnostic guidelines for nontuberculous mycobacteria have been recommended by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA). Moreover, the Clinical and Laboratory Standards Institute (CLSI) has published and recently (in 2011) updated recommendations including suggested antimicrobial and susceptibility breakpoints. The CLSI has also recommended the broth microdilution method as the gold standard for laboratories performing antimicrobial susceptibility testing of nontuberculous mycobacteria. This article reviews the laboratory, diagnostic, and treatment guidelines together with established and probable drug resistance mechanisms of the nontuberculous mycobacteria.

Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water.

BACKGROUND: Hypersensitivity pneumonitis has been described with exposure to aerosolized Mycobacterium avium complex (MAC) in indoor hot tubs (hot tub lung). OBJECTIVES: To describe a case of MAC-associated hypersensitivity pneumonitis-like reaction possibly from showering and review previous hot tub lung reports. METHODS: For the case report, we investigated a patient with histologically diagnosed hypersensitivity pneumonitis and MAC-positive sputum culture findings. Mycobacterial cultures were obtained from his home and workplace. Isolates were typed using pulsed-field gel electrophoresis. For the review, MEDLINE and EMBASE were searched for hot tub lung reports, which were reviewed and summarized. RESULTS: A 50-year-old man had progressive dyspnea and episodic fever and myalgias. Pulmonary function testing results revealed obstruction and impaired diffusion; a chest CT scan found diffuse, centrilobular, ground-glass nodules, and air trapping, and a lymphocytic alveolitis with an elevated CD4/CD8 ratio. Transbronchial biopsy showed multiple well-formed nonnecrotizing granulomas. Multiple respiratory samples and shower and bathtub specimens grew MAC, with matching pulsed-field gel electrophoresis patterns. The patient changed from showering to tub bathing. Prednisone and antimycobacterial drugs were administered for approximately 1 year. His symptoms, pulmonary function abnormalities, and CT scan findings resolved. The literature review yielded 36 cases of hot tub lung. Clinical features included dyspnea (97%), cough (78%), and fever (58%). Pulmonary function testing showed obstruction (67%), restriction (55%), and impaired diffusion (75%). A chest CT scan showed ground-glass opacification (95%) and nodules (67%). Granulomas were well-formed in 95%. Treatments included discontinuation of hot tub use and prednisone, antimycobacterial drugs, or both. Outcomes were favorable. CONCLUSIONS: A hypersensitivity pneumonitis-like reaction to mycobacteria can occur from exposures other than hot tubs. There are key differences between classic hypersensitivity pneumonitis and MAC-associated hypersensitivity pneumonitis. Antimycobacterial therapy may be required. The possibility of MAC hypersensitivity pneumonitis from showering raises potential implications in the investigation of patients with hypersensitivity pneumonitis.