Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis
Abstract:OBJECTIVE: To evaluate the early bactericidal activity (EBA) of the new fluoroquinolones levofloxacin, gatifloxacin and moxifloxacin in patients with pulmonary tuberculosis (PTB).
DESIGN: Randomized, open-label trial. Forty adults with newly diagnosed smear-positive PTB (10 per arm) were assigned to receive isoniazid (INH) 300 mg, levofloxacin 1000 mg, gatifloxacin 400 mg, or moxifloxacin 400 mg daily for 7 days. Sputum for quantitative culture was collected for 2 days before and daily during 7 days of monotherapy. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (EBA 0–2) and last 5 days of monotherapy (extended EBA, EBA 2–7). Laboratory staff were blinded to treatment assignment.
RESULTS: The EBA 0–2 of INH (0.67 log10 cfu/ml/day) was greater than that of moxifloxacin and gatifloxacin (0.33 and 0.35 log10 cfu/ml/day, respectively), but not of levofloxacin 1000 mg daily (0.45 log10 cfu/ml/day) (P = 0.14). Bactericidal activity between days 2 and 7 was similar for all three fluoroquinolones. In a pooled comparison, the EBA 2–7 of the fluoroquinolones was greater than for INH.
CONCLUSION: Moxifloxacin, gatifloxacin, and high-dose levofloxacin have excellent EBA, only slightly less than for INH, and greater extended EBA. These drugs warrant further study in the treatment of drug-susceptible TB.
Document Type: Regular Paper
Affiliations: 1: Department of Medicine, Division of Infectious Diseases, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA 2: Núcleo de Doenças Infecciosas, Centro Biomédico, Universidade Federal do Espírito Santo, Vitória, Brazil 3: Division of Mycobacterial and Respiratory Infections, National Jewish Medical and Research Center, Denver, Colorado, USA 4: Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, Colorado, USA; and Schools of Pharmacy and Medicine, University of Colorado, Denver, Colorado, USA 5: University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA 6: Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA 7: AIDS Research Institute, University of California–San Francisco, San Francisco, California, USA
Publication date: June 1, 2006
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