Pak. J. Pharm. Sci., Vol.32, No.2, March 2019, pp.541-546 541 Community onset of CTX-M extended spectrum β-lactamases among uropathogenic E. coli and K. pneumoniae from Karachi, Pakistan Sakina Fatima 1 , Iyad Naeem Muhammad 1 *, Muhammad Naseem Khan 2 , Subia Jamil 3 , Tuba Siddiqui 4 and Humera Khatoon 3 1 Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 2 Microbiology Section, FMRRC, PCSIR Laboratories. Complex Karachi 3 Department of Pharmacology, Faculty of Pharmacy, Jinnah University for Women, Karachi 4 Department of Pharmaceutics, Faculty of Pharmacy, Federal Urdu University of Arts, Science and Technology, Karachi Abstract: Urinary tract infections (UTIs) are major health issue in developing countries like Pakistan, become more complicated with extended spectrum β-lactamase (ESBL) expression in Escherichia coli and Klebsiella pneumoniae. The ground of this present study was to evaluate the incidence of cefotaxime (CTX-M) gene in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. The clinical isolates from various specimens were collected for one-year duration from January till December 2015. After initial screening (n=352) isolates were examined for phenotypic expression of ESBLs by double disc synergy test. Furthermore, eight-four isolates were analyzed by polymerase chain reaction for identification of Cefotaxime (CTX-M), Temoneira (TEM) and Sulfhdryl variable (SHV) genes. Among eighty-four clinical isolates CTX-M was dominant and found positive in 50 isolates (59.5%) followed by TEM in 35 (41.6%) and SHV in 11 (13%). In uropathogenic E. coli and K. pneumoniae, ESBLs gene was found in 50 and 6 isolates out of 57 and 7 respectively. Among uropathogens CTX-M was most prevalent 78% (39/50) in E. coli followed by K. pneumoniae. In uropathogenic E. coli, CTX-M was found dominant in females. The study concluded that ESBL related uropathogenic E. coli were CTX-M dominant, showed community onsets of UTIs that can be preventive and controlled with modified hygienic practices. Keywords: ESBLs, Urinary tract infections (UTIs), CTX-M, E. coli, K. pneumonia INTRODUCTION Extended spectrum β-lactamases (ESBLs) related community acquired infections has increased because of Cefotaxime (CTX-M) variants, a beta-lactamase of molecular class A (Bush et al., 1995) originated from environmental bacteria with highly transferrable plasmid, this link is related in circulation of ESBLs in the community (Pitout et al., 2005). In 1983, first report of CTX-M was published, CTX-M was suggested due to enzymatic activity against cefotaxime by hydrolysis (Knotheet al., 1983). The β-lactamase inhibitors are ineffective against hydrolytic activity of these enzymes (Bradford, 2001). The prevalence of CTX-M enzymes reported from all over the world in both nosocomial and community settings (Cantón and Coque, 2006). E. coli with CTX-M has previously reported from various household animals and different food related products, several reports indicated that stool samples from healthy human subjects and sewage also contained CTX-M producing E. coli. In most regions E. coli has already replaced as the predominant species of ESBLs- Enterobacteriaceae other than Klebsiella spp (Carattoli et al., 2005; Kojima et al., 2005). In Pakistan, recent studies indicated increased prevalence of ESBLs in E. coli (Ali et al., 2016; Rahman et al., 2016) Previously there were several published reports of true community-onset infection or colonization of E. coli with ESBLs (Colodner et al., 2004; Woodford et al., 2004; Rodríguez-Bano et al., 2004; Akram et al., 2007; Laupland et al., 2008; Rodríguez-Baño et al., 2008; Meier et al., 2011; Søraas et al., 2013;). These reports revealed urinary tract infections related with CTX-M positive E. coli from Spain, Turkey, India, Switzerland, Norway, the United Kingdom and Canada. In previous years various reports from Pakistan were published on prevalence of CTXM-ESBLs among E. coli and K. pneumoniae from hospital setups (Habeeb et al., 2014;Rahman et al., 2016; Abrar et al., 2017). This study was designed to determine CTX-M dominance among various Enterobacteriaceae isolates such as E. coli, K. pneumoniae and P. mirabilis reported from non- hospitalized patients. MATERIALS AND METHODS Study layout Over a one-year period (January-December 2015), isolates were collected in cross-sectional manner from various specimens of non-hospitalized patients in Karachi, Pakistan. Total n=352 non-repeated clinical specimens (E. coli, K. pneumoniae and P. mirabilis) were selected for phenotypic investigation of ESBLs. The *Corresponding author: e-mail: iyadnaeem@uok.edu.pk