Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan

Background: Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan\u27s first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country.Findings: In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin.Conclusion: Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required

Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries

Mycobacterium tuberculosis (MTB) is the causative agent of TB. TB incidence is high in many low resource settings where limited health systems make it difficult for screening of co-morbid conditions. Susceptibility to TB is increased with coincident diabetes mellitus (DM) or prediabetes. DM leads to chronic, subclinical inflammation in the host leading to compromised protective immunity against MTB, impacting TB treatment. This review focuses on the immunological impact of DM and prediabetes on TB infections, highlighting the importance of having effective diagnostic, treatment and management programs for early identification of hyperglycemia in TB patients to improve treatment outcomes. Further, it describes challenges in monitoring of TB and DM co-morbidity in a high-burden setting