Strategies for Treating Latent Multiple-Drug Resistant Tuberculosis: A Decision Analysis

BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice

Preoperative therapeutic considerations in chronic suppurative otitis media

The present randomized, prospective study of 119 cases of chronic suppurative otitis media compares the effectiveness of inexpensive, atoxic, nonallergenic disinfectants applied locally, to that of a number of occasionally toxic antimicrobial chemo-therapeutic agents, administered systemically. Systemic treatment resulted in a cure rate of 53.5% (SEp=5.9%) while ototopical treatment resulted in a 39.5% cure rate (SEp=7%). Eradication of pathogens or colonization by a nonpathogen occurred in 50.7% (SEp=5.9%) with systemic treatment, and in 39.5% (SEp=7%) with ototopical treatment. Bacteriological modification was 2.5 times more frequent with systemic treatment than with ototopical treatment. No recurrences were noted with ototopical treatment, while 13% to 36% recurrence rates were noted in various subgroups of cases treated systemically. Cure rates achieved with particular drug regimens (administration based on sensitivity tests in vitro) were: Azactam 25% (5%–57% confidence limits), sulfamethoxazole plus trimethoprim 58.6% (38%–76%), ciprofloxacin 87.5% (47%–99%), ciprofloxacin plus metronidazole 90% (55%–99%). Cure rates with other drugs were inconclusive because of the limited number of observations. © The American Laryngological, Rhinological & Otological Society, Inc

Role of aerobic and anaerobic microorganisms in chronic suppurative otitis media

This study reports resuRs of cultures of drainage from 119 cases with chronic otitis media. Mixed infections were found to occur 30 times more frequently among cholesteatomatous cases compared to noncholesteatomatous. A significant association was found between prior use of gentamicin ear drops and bacterial resistance to the drug. The role of aerobes and anaerobes in mixed infections of cholesteatomatous ears is discussed. The relevant literature is critically reviewed and the mechanisms of synergistic anaerobic infections of the ear are summarized. The need for animal studies of bacterial pathogenicity and parallel human studies of response to rational medicinal treatment is stressed. © The American Laryngological, Rhinological & Otological Society, Inc