Objective: To assess fluoroquinolone and clarithromycin susceptibility pattern along with the types of genomic mutations involved in the resistance of Helicobacter pylori isolates.Methods: The cross-sectional study was conducted at the Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, from June 2009 to July 2010, and comprised 162 gastric biopsy samples which were tested with GenoTypeHelicoDR (Hain Lifescience GmbH, Germany), a reverse hybridisation multiplex polymerase chain reaction (PCR) line probe assay (LiPA). Also, 23S rRNA (ribosomal ribonucleic acid) gene was analysed with three-point mutations at A2146G, A2146C and A2147G for clarithromycin, and gyrA gene was analyzed at two codon positions 87 and 91 for fluoroquinolone susceptibility testing. SPSS 19 was used for statistical analyses.Results: Clarithromycin resistance was seen in 60 (37.0%) of the isolates mainly involving mutation at A2147G (85%) followed by A2146G (n=35; 21.6%) and A2146C (n=19; 11.6%). Fluoroquinolone resistance was noted in 101(62.3%) isolates, while gyrA mutations at codon 87 was seen in 64 (39.6%) and at codon 91 in 66 (40.6%). Isolates showing combined resistance to both antibiotics were 44 (26.9%).Conclusion: High rate of resistance to fluoroquinolones was seen despite the fact that the drug was not part of the first-line anti-helicobacter therapy. There was moderate increase of clarithromycin resistance beyond the cutoff rates where empirical use of this antibiotic is abandoned. The findings warrant the need for pre-treatment susceptibility testing in Helicobacter pylori infections, especially in Pakistan where burden of disease is high and very limited data is available, to improve patient care by providing targeted therapy
