Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment

Abstract

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 nontuberculous 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. @ERSpublications Weak evidence for the efficacy and safety of group 5 drugs for MDR-TB suggests they should be evaluated using RCTs

Comparison of effectiveness and safety of imipenem/clavulanate-versusmeropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

“…The prevalent sex of the cohort was male (105, 58.3%) and the median (IQR) age was 35 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) years (table 1).…”

“…However, the new information provided by this observational study allows clinicians managing difficult-to-treat TB cases to know how to use carbapenems and other repurposed drugs in case the minimum number of active drugs necessary to design an effective regimen is lacking [3,4,9,[44][45][46][47].…”

Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

“…As the future role of carbapenems in the treatment of MDR-and XDR-TB needs further discussion [9,41], the evidence provided by this observational study offers new information to clinicians treating severely resistant TB cases (e.g. those with resistances to six drugs or more or with intolerance to drugs) and lacking the minimum number of active drugs necessary to design an effective regimen [3,4].…”

Population-Based Drug Resistance Surveillance of Multidrug-Resistant Tuberculosis in Taiwan, 2007-2014

“…To further reduce the number of MDR-TB cases, our TB program has implemented priority actions, including preventing transmission, treating drug-susceptible TB cases, scaling up new rapid molecular tests for screening high-risk populations, and making quality treatment and care available for MDR-TB cases. In addition, our drug surveillance system is now expanding to cover more drugs, including group 3–5 drugs (cycloserine, clofazimine and linezolid) and repurposed drugs (oxyphenbutazone, meropenem, potassium clavulanate, amoxicillin, thioridazine, nitazoxanide, trimethoprim and sulfamethoxazole) [18–20] to determine the prevalence of resistance to and the epidemiological cut-off values of these drugs. The findings may be useful to guide clinical trials to develop better treatment regimens for MDR and XDR-TB.…”