Uropathogenic Escherichia coli are increasingly becoming resistant to flouroquinolones and to other commonly available antimicrobials. We sought to investigate the genetic basis for fluoroquinolone and extended spectrum beta-lactam (ESBL) resistance in 17 fluoroquinolone-resistant (MIC of levofloxacin and ciprofloxacin >32 microg/ml) E. coli isolated from patients with urinary tract infections (UTIs). We applied PCR and Pulsed Field Gel Electrophoresis (PFGE) to characterize resistance genes and to determine clonal relatedness of strains, respectively. Twelve of the 17 E. coli were resistant to multiple drugs, including ampicillin, co-amoxyclav, cefotaxime, ceftriaxone, ceftazidime and gentamicin and nalidixic acid and produced plasmid-mediated CTX-M-15 type ESBLs and CMY-2 AmpC type enzymes. The other 5 E. coli that were non-ESBL-producing were multiply resistant to ampicillin, nitrofurantoin, cefoxitin, nalidixic acid. Resistance to fluoroquinolones resulted from a combination of the presence of qnrA, qnrB, ciprofloxacin acetylating enzyme designated aac(6')-1b-cr, and mutations in the two amino acid substitutions; 83 Serine (TCG) to Leucine (TTG) and 87 Aspartic acid (GAC) to Asparagine (AAC). Antibiogram patterns and PFGE of E. coli showed that these were community acquired UTI caused by pockets of clonally-related and some discreet strain types. Plasmid-mediated CTX-M-15 beta-lactamases and CMY-2 AmpC enzymes and fluoroquinolone resistant E. coli are becoming increasingly prevalent in hospitals in Kenya, posing a major challenge in the management of UTIs.