Long-term Follow-up of Mycobacterium avium Complex Lung Disease in Patients Treated With Regimens Including Clofazimine and/or Rifampin.

BACKGROUND: Mycobacterium avium complex (MAC) lung disease requires prolonged treatment with multiple antibiotics. Drug intolerances and interactions are common with the current recommended treatment. There is limited information on outcomes with alternative medications. METHODS: Retrospective review including adult patients with MAC lung disease who were treated and monitored for at least 6 months posttreatment. The aim was to evaluate the clinical and microbiologic outcomes in patients treated with regimens including clofazimine and/or rifampin. RESULTS: One hundred and seven patients were included (79% were female; mean age, 67 years). Sputum samples were smear positive in 54% of patients. The majority (84%) were treated with clofazimine in combination with a macrolide and ethambutol. Fourteen patients (13%) were treated with rifampin, macrolide, and ethambutol. Most patients (95%) converted from positive to negative sputum culture results in an average of 4.5 ± 4.2 months (range, 0-30 months). A significantly greater proportion of patients treated with clofazimine converted to negative culture results compared with those treated with rifampin (100% vs 71%; P = .0002). Microbiologic relapse occurred in 52 of 107 patients (49%). Thirty-six percent of patients required retreatment. There was no difference in microbiologic relapse or re-treatment rates between the two treatment groups. CONCLUSIONS: The majority of patients with MAC lung disease achieve negative sputum culture results. Re-treatment is needed in approximately one-third of patients. In this cohort, both initial outcomes and re-treatment rates were at least as good in patients treated with clofazimine-containing regimens as in patients receiving rifampin-containing regimens. Clofazimine should be considered as an alternative drug for the treatment of MAC lung disease.

Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.