Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin-Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis

Abstract

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment ( < 0.001) and cavitary lesions on chest radiography ( < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide ( = 0.003), streptomycin ( = 0.015), prothionamide ( < 0.001), and para-aminosalicylic acid ( < 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [ < 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group ( < 0.001) to have favorable outcomes. Despite moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

Multidrug-resistant strains of Mycobacterium complex species in Egyptian farm animals, veterinarians, and farm and abattoir workers

“…MBTC isolates were highly resistant to the second-line drugs, kanamycin 82.3% and amikacin 80.7%, but were sensitive to ciprofloxacin and clarithromycin, 71.1 and 73.3%, respectively (Table - 5). Results are consistent with reports by other investigators who indicate that ciprofloxacin and the fluoroquinolones, in general, are the most active antituberculosis drugs [34][35][36]. In contrast, other studies reported that amikacin was a significantly more effective drug when tested against M. avium [37].…”

Analysis of Serial Multidrug-Resistant Tuberculosis Strains Causing Treatment Failure and Within-Host Evolution by Whole-Genome Sequencing

“…Our study reemphasized the importance of the usage of FQ in treatment ( 31 ), as the success rate of treatment was significantly higher in FQ-S patients effectively treated with FQ, in accordance with previously reported conclusions ( 32 , 33 ). The usage of MFX to treat LFX-resistant MDR-TB patients, regardless of the effectiveness of the treatment combination, resulted in the evolution of a higher level of resistance to FQ ( 34 ), a finding that merits serious attention.…”

Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching

“…We speculate that these results might be attributed to OFX-resistant and LFX/MFX-susceptible patients. Although there is controversy regarding the impact of using later-generation FQs in cases where there is a discrepancy in DST results between OFX and LFX/MFX and how it may affect the treatment outcomes [ 23 , 24 ], our results support the use of later-generation FQs against susceptible strains in patients with FQr-MDR-TB. However, in the absence of clear evidence on the efficacy of FQs for treating FQr-MDR-TB, FQs should be used with caution and should not be considered “effective” in patients with FQr-MDR-TB.…”