Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors

David, Susana; Barros, Vanessa; Verde, Sandra Cabo; Portugal, Clara; David, Hugo L.

doi:10.1093/jac/46.3.391

Cited by 43 publications

(26 citation statements)

References 34 publications

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“…Most studies performed drug susceptibility testing against M. tuberculosis by determining the MIC using the radiometric BACTEC 460 method [36][37][38][39][40][41][44][45][46]. Often a concentration range up to 16 μg·mL −1 was used [36,37,39,41].…”

Section: Resultsmentioning

confidence: 99%

“…Often a concentration range up to 16 μg·mL −1 was used [36,37,39,41]. Overall, studies have shown no susceptibility of MDR-TB strains to CLR, with all studies reporting high MIC values [36][37][38][39][40][41]. This was also observed for roxithromycin, azithromycin (AZI) [41] and the metabolite of CLR 14-hydroxyclarithromycin [36].…”

Section: Resultsmentioning

confidence: 99%

“…Macrolides have high MIC values in M. tuberculosis isolates when evaluated in vitro [36][37][38][39][40][41][42][43][44][45][47][48][49]. However, some studies reported promising results that might contribute to clinical activity in the sense of macrolides exerting bacteriostatic effects in vitro [39,45,48,49] and in vivo [39,47,59].…”

Section: Discussionmentioning

confidence: 99%

“…However, some studies reported promising results that might contribute to clinical activity in the sense of macrolides exerting bacteriostatic effects in vitro [39,45,48,49] and in vivo [39,47,59]. Furthermore, a decrease in mortality in murine infection models [39,60] and synergistic effects when CLR was combined in vitro with second-line anti-TB drugs [36,37,40,57,73] were seen. Also, an interaction was reported in a clinical study [61], suggesting an increase of LZD serum concentration when combined with CLR.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of CLR and rifabutin resulted in a FIC of 1-2, suggesting indifference [38]. When CLR was combined with ethambutol (EMB) a synergistic effect was observed [36,40]. CLR and AZI also acted synergistically with spectinomycin against the drug susceptible H37Rv strain, FICs were all ⩽0.5.…”

Section: Synergy Testingmentioning

confidence: 99%

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Evaluation of macrolides for possible use against multidrug-resistant Mycobacterium tuberculosis

et al. 2015

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Multidrug-resistant tuberculosis (MDR-TB) is a major global health problem. The loss of susceptibility to an increasing number of drugs behoves us to consider the evaluation of non-traditional anti-tuberculosis drugs.Clarithromycin, a macrolide antibiotic, is defined as a group 5 anti-tuberculosis drug by the World Health Organization; however, its role or efficacy in the treatment of MDR-TB is unclear. A systematic review of the literature was conducted to summarise the evidence for the activity of macrolides against MDR-TB, by evaluating in vitro, in vivo and clinical studies. PubMed and Embase were searched for English language articles up to May 2014.Even though high minimum inhibitory concentration values are usually found, suggesting low activity against Mycobacterium tuberculosis, the potential benefits of macrolides are their accumulation in the relevant compartments and cells in the lungs, their immunomodulatory effects and their synergistic activity with other anti-TB drugs.A future perspective may be use of more potent macrolide analogues to enhance the activity of the treatment regimen. @ERSpublications Macrolides deserve more research interest for use against MDR-TB as results appear to be more promising than thought http://ow.ly/LDFjp

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