OBJECTIVES: E. coli is the most frequently encountered pathogen in clinical set up causing devastating infections irrespective of age and gender resulting in significant morbidity and mortality. E. coli isolates have been found resistant to variety of antibiotics commonly used in empirical therapy at hospitals and clinics. CTX-M, TEM and SHV type extended spectrum beta-lactamases are mainly responsible for this resistance. The aim of this study was to investigate the prevalence of CTX-M, TEM and SHV beta-lactamases in clinical isolates of E. coli and to assess the resulted economic burden on the poor population. METHODS: E. coliisolates were collected from a tertiary care hospital between 2012 and 2013, and tested against several classes of antibiotics on Kirby- Bauer disk diffusion methods to check their multidrug resistance phenotype. Presence and identification of CTX-M, SHV and TEM beta-lactamases were confirmed on PCR. RESULTS: Overall resistance pattern to the tested antibiotics was amoxicillin(80%), cefazolin(74%), cefotaxime(63%), ceftazidime(58%), gentamycin(58%), ciprofloxacin(89%), levofloxacin(51%), chloramphenicol(38%), erythromycin(83%), amoxicillin/clavulanic acid(82%) and trimethoprim/sulfamethoxazole(91%). The prevalence of different beta-lactamase types in E. coliisolates was CTX-M(72 %), TEM(67%) and SHV(53%). CONCLUSIONS: CTX-M, TEM and SHV beta-lactamases are responsible for such overwhelming resistance in these isolates. These enzymes are present on mobile genetic elements such as plasmids which are readily exchanged between diverse bacterial communities and leading this alarming resistance to epidemic level. More than 50% of population live below the poverty line in Pakistan and cannot afford or have excess to expensive treatments, such resistance is challenging the very health care system of the country. Both rate of infections and resistance to antimicrobials is on the rise and is sped up by the unregulated sub-standard health practice in Pakistan. The current health and economic losses are incalculable but the more devastating consequences to the humanity and economy are not too far from reality.