Data for this review were identified by searches of PubMed and references from relevant articles. Search terms were “tuberculosis”, “Mycobacterium tuberculosis”, “quinolones”, “fluoroquinolones”, “activity”, “safety”, “use”, “treatment”, “resistance”, “mechanism”, “gyrase”, “quinolone resistance-determining region”, “human immunodeficiency virus”, and “acquired immunodeficiency syndrome”. English language papers were reviewed.
ReviewFluoroquinolones, tuberculosis, and resistance
Section snippets
In vitro activity
Fluoroquinolones have in vitro activity against M tuberculosis.15, 16 The newer fluoroquinolones, sparfloxacin, gatifloxacin, and moxifloxacin, have lower minimum inhibitory concentrations (MICs) than levofloxacin, ciprofloxacin, and ofloxacin (table 1).17“24 Against rifampicin-tolerant persistent organisms–bacilli that survive and persist despite chemotherapy–in an in-vitro model examining sterilising activity, gatifloxacin and moxifloxacin had the greatest bactericidal activities of the
Fluoroquinolones in the treatment of tuberculosis
There is a need for more clinical trials evaluating fluoroquinolones as part of first-line therapy against M tuberculosis.16,77,81,82 In a clinical trial from India, patients with drug-susceptible and drug-resistant pulmonary tuberculosis were treated for 4–5 months with an ofloxacin-containing regimens under direct observation.62 Patients were randomly assigned to one of four treatment arms: (1) isoniazid, rifampicin, pyrazinamide, and ofloxacin daily for 3 months; (2) isoniazid, rifampicin,
Mechanism of fluoroquinolone resistance
As the only presently licensed antibiotics that directly inhibit DNA synthesis, fluoroquinolones target bacterial topoisomerases II and IV. Unlike most other bacterial species, M tuberculosis lacks topoisomerase IV and includes only topoisomerase II or DNA gyrase, a tetramer consisting of two A and two B subunits, encoded by the genes gyrA (2517 bp) and gyrB (2060 bp), respectively.89 The primary target of fluoroquinolones in Staphylococcus aureus is topoisomerase IV, whereas in Escherichia coli
Conclusions
Fluoroquinolones are rapidly emerging as important drugs for the treatment of tuberculosis. With most of their current use in multidrug-resistant tuberculosis, fluoroquinolones are also under investigation for first-line treatment of pulmonary tuberculosis. There is concern about the rapid development of resistance particularly when fluoroquinolones are administered as the only active agent in a failing multidrug regimen, and treatment failures as well as relapses have been documented under
Search strategy and selection criteria
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