Safety and tolerability of clarithromycin in the treatment of multidrug-resistant tuberculosis

Abstract

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are an emerging global threat. An estimated 3.3% of newly diagnosed TB patients and 20% of previously treated patients worldwide have MDR-TB [1]. Moreover, 9.7% of MDR-TB cases are suffering from XDR-TB. Treatment of TB is becoming more difficult since the resistance pattern of Mycobacterium tuberculosis is expanding and treatment success rate is decreasing, with newly emerging drug-resistant strains [2]. Therefore, evaluation of antimicrobial drugs active against M. tuberculosis is necessary. Clarithromycin (CLR) is a macrolide antibiotic previously listed as a World Health Organization (WHO) group 5 drug, but not included in the new WHO classification because it has only modest bacteriostatic effects against M. tuberculosis [3]. However, the in vitro synergy of CLR in combination with linezolid, ethambutol and spectinomycin, and its immunomodulatory effects, hold promise [4-6]. Despite the introduction of newer drugs such as bedaquiline and delamanid, clarithromycin may have added value for the treatment of TB patients in cases of extensive resistance but proven susceptibility to clarithromycin. Unfortunately, real-life data on the use of clarithromycin to guide physicians in the treatment of MDR-TB is scarce. CLR is generally a well-tolerated and safe antimicrobial agent. The most frequently reported adverse reactions were nausea, diarrhoea and abdominal pain. Headache was reported frequently [7], and to a lesser extent hepatotoxicity was observed [8]. For MDR-TB treatment, CLR is used for longer treatment periods than initially intended for its labelled indication. In addition, CLR is used in combination with at least three to five other antimicrobial drugs in an MDR-TB treatment regimen. This may potentially result in drugdrug interactions [9] or aggravation of adverse drug reactions. Long-term safety and tolerability have been assessed in HIV patients with nontuberculous mycobacterial infections, but not in MDR-TB patients [10]. Therefore, we evaluated the safety and tolerability of CLR in patients treated for MDR-TB.

Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169)

“…In cases of MDR-and XDR-TB disease, the use of new anti-TB drugs or repurposed drugs is required (16). Several repurposed drugs, including the antileprosy agent CLO, the macrolide clarithromycin (CLR), the carbapenem meropenem (MEM), and the oxazolidinone linezolid (LZD), are now in trials for the treatment of MDR-TB (17)(18)(19)(20). In addition, new anti-TB compounds are available.…”

Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil

“…those drugs originally designed for indications other than TB which have proved to be useful for treating MDR-TB and XDR-TB. Among these drugs, linezolid [9,10] as well as various carbapenems [11][12][13][14][15] and macrolides [16] have recently raised scientific interest. Furthermore, clofazimine, a fat-soluble riminophenazine dye originally used to treat leprosy, has shown potentiality in vitro and in vivo as a sterilising drug to treat MDR-TB [17,18].…”

Anti-Mycobacterial Antibiotic Therapy Induces Remission in Active Paediatric Crohn’s Disease

“…A sun-tanned appearance, nausea and itchiness are the most common side effects reported in patients treated with AMAT constituents, however no such side effects were reported by our cohort. Notable, yet rarer iatrogenic effects, such as leucopenia and elevated transaminases can occur if a dose escalation model is not employed [ 34 , 35 , 36 ]. However, no significant changes in the WCC and liver function test results ( Figure 1 D–G) in our patients occurred during AMAT, suggesting that the adopted dose escalation model is suitable.…”