Rifabutin

About: Rifabutin is a research topic. Over the lifetime, 1072 publications have been published within this topic receiving 29513 citations. The topic is also known as: LM-427 & Ansamicin.

Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.

Abstract: In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacterium avium were determined in the microplate Alamar blue assay (MABA) with both visual and fluorometric readings and compared to MICs determined in the BACTEC 460 system. For all three mycobacterial strains, there was < or = 1 dilution difference between MABA and BACTEC median MICs in four replicate experiments for 25 to 27 of the 30 antimicrobics. Significant differences between MABA and BACTEC MICs were observed with 0, 2, and 5 of 30 antimicrobial agents against H37Rv, H37Ra, and M. avium, respectively. Overall, MICs determined either visually or fluorometrically in MABA were highly correlated with those determined in the BACTEC 460 system, and visual MABA and fluorometric MABA MICs were highly correlated. MICs of rifampin, rifabutin, minocycline, and clarithromycin were consistently lower for H37Ra compared to H37Rv in all assays but were similar for most other drugs. M. tuberculosis H37Ra may be a suitable surrogate for the more virulent H37Rv strain in primary screening of compounds for antituberculosis activity. MABA is sensitive, rapid, inexpensive, and nonradiometric and offers the potential for screening, with or without analytical instrumentation, large numbers of antimicrobial compounds against slow-growing mycobacteria.

Two Controlled Trials of Rifabutin Prophylaxis against Mycobacterium avium Complex Infection in AIDS

Abstract: Background Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months. Methods We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts ≤ 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival. Results In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P<0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in th...

A Multi-institutional Outbreak of Highly Drug-Resistant Tuberculosis: Epidemiology and Clinical Outcomes

Abstract: Objective. —To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome. Design. —Epidemiologic investigation of every tuberculosis case reported in New York City. Setting. —Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months). Patients. —We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W. Main Outcome Measures. —Patient survival and the conversion of sputum cultures from positive to negative. Results. —Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who recieved medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+T-lymphocyte count greater than 0.200×109/L (200/μL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival. Conclusions. —This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.

Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates.

Abstract: Background Mycobacterium marinum is a nontuberculous mycobacterium responsible for skin infections. Although cases have been seldom reported, no series of M marinum infection has been recently reported and the treatment is not standardized. Methods A national survey was conducted on culture-confirmed M marinum infections that occurred in France from January 1, 1996, to December 31, 1998. Clinical characteristics and therapeutic data were analyzed, and the minimum inhibitory concentrations of 11 antibiotics were determined against the causative isolates. Results Sixty-three cases of M marinum infection were studied. In 53 (84%) of the patients, inoculation was related to fish tank exposure. The site of infection was mainly the upper limb (in 60 [95%] of the 63 patients), and infection was spread to deeper structures in 18 (29%) of the patients. All patients were treated with antibiotics (median time, 3½ months), and 30 (48%) underwent surgery. Various antibiotic regimens were prescribed, and the initial regimen was modified in 22 (35%) of the patients. Clarithromycin, cyclines, and rifampin were the most commonly prescribed antibiotics. Cure was observed for 55 (87%) of the patients. Failure was related to deep structure involvement (3 of 45 vs 5 of 18 patients; P = .04) but not to any antibiotic regimen. All strains showed the same susceptibility pattern without acquired resistance. The 90% minimum inhibitory concentrations of rifampin and rifabutin were far lower (0.5 and 0.06 µg/mL, respectively) than the 90% minimum inhibitory concentrations of clarithromycin (2 µg/mL) and the cyclines (minocycline, 4 µg/mL; and doxycycline, 8 µg/mL). Conclusions Mycobacterium marinum infections are emerging infections related to fish tank hobby. Because of the severity of the cases with spread of infection, clinical awareness of M marinum infection and its associated risk factors is important so that the diagnosis can be made and therapy can be initiated promptly.