Fluoroquinolone Resistance in Patients with Newly Diagnosed Tuberculosis

Abstract

Fluoroquinolones are widely used for the treatment of bacterial infections and are also second-line therapy for tuberculosis. However, fluoroquinolone resistance in patients with newly diagnosed cases of tuberculosis is not routinely assessed. We performed in vitro susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones for all culture-confirmed tuberculosis cases in adults that were diagnosed at Johns Hopkins Hospital (Baltimore) between January 1998 and March 2002. Fifty-five patients were included in the study; 19 received fluoroquinolone monotherapy before the initiation of antituberculosis therapy. Two of 55 M. tuberculosis isolates (4%; 95% CI, 1%-13%) had decreased susceptibility to fluoroquinolones, including 2 of 19 of those from patients who had received fluoroquinolones (11%; 95% CI, 1%-33%) and 0 of 36 isolates from those who had not (95% CI, 0%-10%). The 2 fluoroquinolone-resistant M. tuberculosis strains were both from patients with acquired immunodeficiency syndrome and a CD4+ lymphocyte count of <50 cells/mm3. The incidence of M. tuberculosis fluoroquinolone resistance in this small sample of patients with newly diagnosed tuberculosis was high, particularly among patients with prior fluoroquinolone exposure.

Rapid Detection of Ofloxacin Resistance in Mycobacterium tuberculosis by Two Low-Cost Colorimetric Methods: Resazurin and Nitrate Reductase Assays

“…However, it is well known that DST on Löwenstein Jensen (LJ) medium or Middlebrook agar is very slow, requiring at least 4 to 6 weeks to produce the first results (5, 6). The development of rapid DST that is simple to use and affordable for low-resource countries is a priority (20, 24), since there are already reports of OFX-resistant strains of M. tuberculosis or the creation of OFX resistance during treatment (14,15,16,18,31,34,38). Some efforts have already been made to perform second-line DST by the radiometric BACTEC TB-460 system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.)…”

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

“…Some quinolones (Ciprofloxacin, levofloxacinetc) inhibit strains of Mtb at concentrations less than 2 g/mL. Indeed, cross-resistance has been reported within the FQ class such that reduced susceptibility to one FQs likely confers reduced susceptibility to all FQs [66], [67]. The major concern is that widespread use of FQs for treatment of other bacterial infections may select for resistant strains of Mtb.…”

“…In contrast, the incidence of Mtb FQ resistance in a small sample of patients with newly diagnosed TB was found to be high among patients with prior FQ exposure. Cross-resistance was observed among the different FQs tested (ofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and ciprofloxacin) [67]. There are reasons for concerns about the rapid development of resistance particularly when FQs are administered as the only active agent in a failing multi-drug regimen.…”

New treatment options for multidrug-resistant tuberculosis

“…Fluoroquinolone resistance can develop during treatment and patients not previously treated for TB may acquire fluoroquinolone-resistant strains because of their widespread use to treat other infections [Devasia et al 2009;Ginsburg et al 2003;Liu et al 2011]. Cross resistance can develop between the drugs in this class [Ginsburg et al 2003]. Another concern is that coadministration of moxifloxacin with R reduces moxifloxacin AUC by 27% [Weiner et al 2007].…”