[A pharmacologic approach to treatment of Mycobacterium abscessus pulmonary disease]. / Analyse pharmacologique du traitement des pneumopathies à Mycobacterium abscessus.

Mycobacterium abscessus is a fast-growing non-tuberculous mycobacteria complex causing pulmonary infections, comprising the subspecies abscessus, massiliense and bolletii. Differences are based predominantly on natural inducible macrolide resistance, active in most Mycobacterium abscessus spp abscessus species and in Mycobacterium abscessus spp bolletii but inactive in Mycobacterium abscessus spp massiliense. Therapy consists in long-term treatment, combining multiple antibiotics. Prognosis is poor, as only 40% of patients experience cure. Pharmacodynamic and pharmacokinetic data on M. abscessus have recently been published, showing that therapy ineffectiveness might be explained by intrinsic bacterial resistance (macrolides…) and by the unfavorable pharmacokinetics of the recommended antibiotics. Other molecules and inhaled antibiotics are promising.

[R207910 (TMC207): a new antibiotic for the treatment of tuberculosis]. / R207910 (TMC207): un nouvel antibiotique pour le traitement de la tuberculose.

A new class of antibacterials, diarylquinolines, was identified. The lead compound, R207910 (TMC207), was able to inhibit Mycobacterium tuberculosis in vitro, in mice and in patients. R207910 targets the mycobacterial ATP synthase. In vitro, it displayed potent activities against both drug-sensitive and multidrug-resistant strains of M. tuberculosis. It was also strongly active against dormant bacilli in the Wayne's dormancy culture system, hypoxia and nitric oxide models. In the murine model, when used alone, it was as active as the triple combination of rifampicin+isoniazid+pyrazinamide. When added to the previous combination or substituted for isoniazid or rifampicin, the treatment including the combinations containing R207910 led to culture conversion after 2 months of therapy. When added to the combination used to treat MDR-TB or substituted for moxifloxacin or ethionamide, the combinations containing R207910 led to culture conversion after 2 months of therapy. In MDR-TB infected patients, R207910 combined with second line drugs was able to convert more sputum cultures (47.6%) than the placebo combined to second line drugs regimen (8.7%).

[Treatment of cutaneous infections due to Mycobacterium fortuitum: two cases]. / Traitement des infections cutanées àMycobacterium fortuitum : deux cas.

INTRODUCTION: Cutaneous infections due to Mycobacterium fortuitum, a rapidly growing environmental mycobacteria, are often iatrogenic, resulting from surgery or injection. We report two cases following plastic surgery and describe the outcome after surgery and antibiotics. CASE REPORTS: Two immunocompetent women underwent abdominal plastic surgery and liposuction, which were complicated with recurrent abscesses one and 13 months later respectively. Cultures of bacteriologic samples isolated M. fortuitum in the two patients. The two strains exhibited different antibiotic sensibility profiles. The initial antibiotic therapy consisted of combined amikacin and moxifloxacin in both patients plus imipenem in one, followed by oral doxycycline and clarithromycin in one and moxifloxacin in the other for a total duration of nine and five months, respectively. In both cases, surgical treatment was also given before, during and after antibiotic therapy. No new lesions had appeared six months after the end of antibiotic therapy. DISCUSSION: Cutaneous infections due to M. fortuitum are rare and secondary to iatrogenic skin wounds. The clinical appearance is not specific, accounting for delayed diagnosis. Treatment is difficult and there is no consensus. According to our experience, surgical treatment is essential whereas the efficacy of antibiotics, even involving multiple agents, seems more doubtful.

Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.

Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.