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

Abstract

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/ clavulanate to treat multidrug-and extensively drug-resistant tuberculosis (MDR-and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR-and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9) versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR-and XDR-TB cases. @ERSpublications Meropenem/clavulanate is effective and safe to treat MDR-and XDR-TB in comparison with controls

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…However, a lack of an active oral formulation and the necessity of combining amoxicillin-clavulanate (to protect it from ß-lactamases) renders these compounds less appealing, even though some appear very active with excellent tolerability and safety. [80][81][82] Linezolid, an oxazolidinone, has demonstrated anti-mycobacterial efficacy and is included in many drug trial regimens; 83 however, its toxicity profile does not allow for its use beyond drug-resistant TB. Sutezolid and delpazolid are two newer generation oxazolidinones in early clinical trials which are hoped to be just as effective as linezolid but less toxic.…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…The potential usefulness of meropenem plus clavulanate or imipenem plus clavulanate has been highlighted, but it is expensive, requires long-term intravenous access, and insufficient clinical evidence of its usefulness or effectiveness exists. 287,288 Use of linezolid, bedaquiline, and delamanid…”

Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

“…Imipenem/cilastatin and meropenem, combined with clavulanic acid, seem to have a promising activity, while being well tolerated (34)(35)(36)(37). In the direct comparison meropenem performs better than imipenem (37).…”

“…Imipenem/cilastatin and meropenem, combined with clavulanic acid, seem to have a promising activity, while being well tolerated (34)(35)(36)(37). In the direct comparison meropenem performs better than imipenem (37). Initial clinical experience with ertapenem suggests that it can be a valid drug for the home-care phase of MDR-TB treatment, as it can be administered intramuscularly once a day (38).…”