title: Fluoroquinolone resistance in Mycobacterium tuberculosis isolates from Pakistan 2010-2014: Implications for disease control.
abstract: Fluoroquinolones (FQ) are an essential component of current and new regimens for the treatment of tuberculosis (TB). The 2014 Global TB report indicates a FQ resistance rate of 17% amongst multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) tested in 2013. There is, however, a paucity of FQ-resistance data from high burden countries. In this study the trend of FQ-resistance amongst MDR-MTB and non-MDR-MTB is analyzed over a four-and-a-half-year period (January 2010-July 2014).
  
  
  
  This study was conducted at the Aga Khan University laboratory, a technical partner of the Pakistan National TB Program and part of the World Health Organization (WHO) Supra-national Laboratory Network for TB. The laboratory receives specimens from across the country through its peripheral collection units. MTB was isolated using standard methods. Susceptibility testing was performed using the agar proportion method with drug concentrations as recommended by Clinical Laboratory Institute Standards (CLSI). FQ susceptibilities were determined using ofloxacin (2μg/ml). MTB H37Rv was used as a control with each batch of susceptibility testing. MDR was defined as resistance to both isoniazid (0.2μg/ml) and rifampicin (1.0μg/ml).
  
  
  
  During the study period 14,711 MTB strains were isolated. Of these, 6403 (43.5%) were MDR and 8308 were non-MDR. FQ resistance in MDR strains ranged between 54% and 58%. Amongst non-MDR MTB strains, FQ resistance increased from 214/2059 (10.3%) in 2010 to 180/1049 (17.1%) in 2014. The proportion of FQ mono-resistant TB strains averaged at 10.5% of the non-MDR isolates during this period.
  
  
  
  FQ resistance in non-MDR-MTB strains with a considerable proportion of FQ mono-resistant strains in Pakistan is alarming. These data highlight the limited potential of empirical FQ usage for TB treatment in both MDR and non-MDR cases and the need to implement regular surveillance for FQ-resistance in MTB in the country. High FQ resistance amongst MTB isolates further emphasizes the importance of stewardship and the responsible use of FQs in particular, and antimicrobials in general in the country.
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
authors.forename: Kausar
authors.initials: K
authors.lastname: Jabeen
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Shakoor
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
authors.forename: Faisal
authors.initials: F
authors.lastname: Malik
authors.affiliation: Department of Pathology & Microbiology, Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
authors.forename: Rumina
authors.initials: R
authors.lastname: Hasan
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D062665:Epidemiological Monitoring; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D010154:Pakistan / Q000453:epidemiology; D015995:Prevalence; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones
keywords: Fluoroquinolone; Pakistan; Resistance