zithromax and Tuberculosis--Multidrug-Resistant

The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated. We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5). We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) -0.13, 95% CI -0.40-0.14) and amoxicillin-clavulanate had no efficacy in two other studies (RD 0.07, 95% CI -0.21-0.35). The largest number of studies described prolonged use for treatment of non-tuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI -0.02-0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs (proportion 0.20, 95% CI 0.12-0.27). For most group 5 drugs we found inadequate evidence of safety for prolonged use or for efficacy for MDR-TB, although macrolides appeared to be safe in prolonged use.

Topics: Amoxicillin; Antitubercular Agents; Azithromycin; Cilastatin; Clarithromycin; Clavulanic Acid; HIV Infections; Humans; Imipenem; Isoxazoles; Macrolides; Meropenem; Mycobacterium tuberculosis; Oxazolidinones; Randomized Controlled Trials as Topic; Thienamycins; Thioridazine; Treatment Outcome; Tuberculosis, Multidrug-Resistant; World Health Organization

Many drugs with potential QT prolongation effects (QT drugs) have already been used for decades in patients with multidrug-resistant TB (MDR-TB) or non-tuberculous mycobacterial (NTM) disease, but without a common consensus.. To investigate the effects of QT drugs on cardiac events in patients with MDR-TB or NTM disease.. We retrospectively reviewed 373 patients (mean age: 56.4 years) with MDR-TB or NTM disease treated for >1 month with clofazimine (CFZ), moxifloxacin (MFX), bedaquiline (BDQ), delamanid (DLM) or macrolides (clarithromycin or azithromycin). Adverse cardiac events, death and QTcF changes were evaluated.. Forty-four per cent had MDR-TB; 165 (44%), 315 (85%), 10 (3%), 229 (61%) and 1 patient received CFZ, MFX, BDQ, macrolides and DLM, respectively. Except for three patients (0.8%) lost to follow-up with unknown cause of death, 3 (0.8%, 95%CI 0.2-2.4) adverse cardiac events were documented: atrial fibrillation, cardiac tamponade due to TB pericarditis and cardiac arrest, which was determined to not have been caused by QT drugs. Clinically significant QTcF changes (QTcF > 500 msec or an increase > 60 msec) were observed in 10/60 patients (17%, 95%CI 8.0-30.7) without clinical events.. The use of QT drugs, alone or in combination, in the treatment of MDR-TB or NTM disease is relatively safe.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Azithromycin; Child; Clarithromycin; Clofazimine; Diarylquinolines; Female; Fluoroquinolones; Follow-Up Studies; Humans; Lost to Follow-Up; Macrolides; Male; Middle Aged; Moxifloxacin; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nitroimidazoles; Nontuberculous Mycobacteria; Oxazoles; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Young Adult