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Objective: This clinical trial, carried out among injection drug users and the HIV-infected with tuberculin skin test ≥ 5 mm, aimed to evaluate the compliance and tolerability of two preventive strategies against tuberculosis (TB). Methods: Study protocol prospectively compares adherence to nine months of daily therapy with isoniazid (9H) versus two months of daily therapy with rifampin plus pyrazinamide (2RZ) administered randomly. All patients were concurrently admitted to a methadone maintenance programme. To assess toxicity, liver function was monitored monthly. Results: From 305 assessable patients, those in 2RZ arm showed better adherence (84% vs. 59%, p < 0.0001). Results on liver toxicity did not show significant differences between 9H and 2RZ (4.5% vs. 6.9%; odds ratio = 1.58, 95% confidence interval = 0.42—7.24). Conclusion: 2RZ should be considered an option to prevent TB in selected groups of patients infected with HIV, such as injection drug users on methadone treatment.

An unexplained resurgence of Group A streptococci (GAS) infections has been observed since the mid-1980s in the United States and Europe, particularly among intravenous drug users (IDUs). Several risk factors have been identified. Mutations in the capsule synthesis regulator genes (csrRS) have been associated with an increase in virulence. From January 1998 to December 2003, we conducted a prospective and retrospective descriptive analysis of invasive GAS soft-tissue infections in IDUs in Barcelona, Spain. Clinical features were collected, and we conducted a surveillance study to identify risk factors associated with GAS soft-tissue infections. We analyzed chromosomal DNA by low cleavage restriction enzymes and used pulsed-field gel electrophoresis (PFGE) and variable gene sequence typing (VGST) of the emm gene to disclose the epidemiologic relationship between the strains. We analyzed the influence of clonality (M-type) and mutations in csrRS genes of these strains on clinical features. We identified 44 cases, all of which were grouped in 3 clusters: fall 2000, fall 2002, and fall 2003. Cellulitis with or without abscesses (75%) and fever (90.9%) were the most common clinical manifestations. Distant septic complications were infrequent (18.2%). Although all patients had severe infections (mainly bacteremic needle abscesses), their outcome with antibiotic therapy, usually beta-lactam, was successful in all cases. However, surgery was needed in 40.9% of patients. Through the surveillance study we found that infected patients had a higher number of drug injections per day (odds ratio [OR], 18.84; 95% confidence interval [CI], 4.83-79.4; p

Available data on anti-tuberculosis drug research reveal different properties of the agents and provoke speculation about future directions. Higher doses of the rifamycins are promising and are currently being evaluated in regimens of shorter duration that the isoniazid plus rifampin-based, six-to-nine month-course therapy. Moxifloxacin and gatifloxacin might shorten tuberculosis treatment as well, possibly in combination with rifapentine, while SQ109 could enhance the activity of rifampin-containing regimens. On the other hand, co-administration of moxifloxacin and PA-824 could be active against latent tuberculosis, whereas linezolid, PA-824 and TMC207 are candidates for a rifampin-free regimen in multidrug-resistant and extensively-resistant tuberculosis. Unfortunately, shorter than existent treatment regimens based on the new agents discussed here are likely to take at least another decade to be fully developed and implemented in clinical practice.