High moxifloxacin cross-resistance levels among “newly identified” ofloxacin-resistant multidrug-resistant tuberculosis patients from South India: A ticking bomb or a tricky challenge?

Abstract

Background: Fluoroquinolones (FQs) are among the most important second-line anti-tuberculosis (TB) drugs, of which 8-methyl FQs; moxifloxacin (MFX) and gatifloxacin are considered to have the most mycobactericidal and “sterilizing action.” Because of the wide and often illogical usage, FQ resistance has evolved and challenged the multidrug-resistant (MDR)/extensively drug-resistant TB (XDRTB) control activities worldwide. We have compared the baseline ofloxacin (OFX) resistance among MDR/rifampicin-resistant (RR) TB cases identified from South Tamil Nadu and Kerala states in India and then assessed the cross-resistance with different concentrations of MFX using MGIT 960. Methods: Bactec MGIT 960 method and the standard protocol as per the manufacturer modified for the multiple concentrations of the drugs were used for the susceptibility testing. Results: We found that samples from newly identified MDR/RR cases of both states have baseline OFX resistance at 16–17%. MFX cross-resistance was 33%–35% (2 mg/L), 59%–70% (1 mg/L), and 87%–93% (0.5 mg/L). Conclusions: As the cross-resistances to MFX 1 mg/L (minimum inhibitory concentration between 1 and 2 mg/L) and 2 mg/L are very high, 59%–70% and 33%–35%, respectively, among newly identified OFX-resistant MDRTB cases, we assume the sterilizing activity of MFX-containing regimens may be seriously compromised leading to higher relapse rates despite having decent cure rates. This may pose considerable technical as well as cost-wise challenges for TB control program in the future.

Keywords

• Cross-resistance
• extensively drug-resistant tuberculosis
• fluoroquinolones
• MGIT 960
• minimum inhibitory concentration
• multidrug-resistant tuberculosis
• relapses