Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?

We read with interest the excellent letter by HOLTZ and CEGIELSKI [1] contributing to the current discussion on extensively drug-resistant (XDR)-tuberculosis (TB). Several publications have already demonstrated that resistance to fluoroquinolones (FQ) is independently associated with poor outcome and/or that the possibility of including FQ in regimens improves treatment outcomes of multidrug-resistant (MDR)-TB cases [2–4]. This happened before the (recent) description of XDR-TB [1, 5]. We do not know how many of the patients with MDR-TB strains were, in fact, infected with XDR Mycobacterium tuberculosis. We wanted to establish the role of the different XDR-defining components (e.g. isoniazid and rifampicin, FQ and injectable second-line drugs) in determining poor treatment outcomes. Our group has shown for the first time that XDR-TB cases in Italy and Germany have a five-fold increase in the risk of death (relative risk (RR) 5.45; 95% confidence interval (CI) 1.95–15.27; p,0.01), require longer hospitalisation than MDR-TB cases (241.2¡177.0 versus 99.1¡85.9 days; p,0.001), have a longer treatment duration (30.3¡29.4 versus 15.0¡23.8 months; p,0.05) and, for the few cases who converted, need a longer time to smear/culture conversion (p,0.01) [6]. The findings of a second study, which included additional cases from Estonia and the Russian Federation, demonstrated that XDR-TB cases had an RR of 1.58 to achieve death or failure compared with MDR-TB cases resistant to all first-line drugs (95% CI 1.14–2.20; p,0.05) and an RR of 2.61 (95% CI 1.45–4.69; p,0.001) compared with MDR-TB cases in which susceptibility to at least one first-line drug still existed [7]. These data support the observation that the loss of first-line drugs different from rifampicin and isoniazid has a role in worsening prognosis of MDR-TB cases. In order to better understand the role of FQ in determining poor treatment outcomes in MDR-TB cases, we re-analysed data from the four-country study [7] to assess whether there is any difference in death or mortality in MDR-TB cases resistant or susceptible to FQ. The overall sample included 425 MDR-TB cases (361 MDR, 64 XDR). A total of 87 (20%) were resistant to FQ, 23 (26%) being MDR and 64 (74%) XDR. Although the proportion of MDR-TB cases resistant to FQ was similar in the three countries reporting FQ resistance (i.e. 18, 24 and 24% in Italy, Germany and Estonia, respectively), the proportion of XDR-TB cases among FQ-resistant cases was largely different (50, 27 and 88% in Italy, Germany and Estonia, respectively). FQ-resistant MDR-TB cases yielded …