**5. Epidemiology**

*E.coli* are responsible for various infections like urinary tract infection, diarrhoea, pneumonia, bacteremia, upper respiratory tract infections, wound infections, osteomyelitis and neonatal meningitis [73,74].

The successful outcome of clinical use of 3rd generation cephalosporines unfortunately led to the increased use and emergence of ESBL producing Enterobacteriaceae. With the emergence of ESBL and Amp C β – lactamase production in *E.coli*, *Klebsiella pneumoniae* and other Enterobacteriaceae, Carbapenems were used as last resort to treat those infections. Because of selective pressure of Carbapenems, even carbapenemases producing Enterobacteriaceae (CRE) has emerged.

Most common MBL found worldwide in Enterobacteriaceae were VIM (Verona integron encoded MBL) and IMP (active on imipenem). Multidrug resistant *E.coli* harboring New Delhi metallobetalactamase - 1 (NDM-1) isolated from a patient returned to Canada from India [75], was reported first in 2009. NDM -1 was also recognized among Enterobacteriaceae 32 from Mumbai, 13 from Varanasi and 3 from Guwahati in India and 25 isolates from eight different cities in Pakistan. These isolates were from cases of bacteraemia, ventilator associated pneu‐ monia and community acquired urinary tract infections [76].

NDM - 1 spread largely to different countries like Australia, Japan, Brazil, Belgium, Canada, Germany etc [77]. The gene encoding NDM – 1is called blaNDM-1, located on transmissible plasmid which may include other antibiotic resistance genes also leading to extensive drug resistant phenotypes (so called 'superbugs'). A recent report from ICU and wards of Sir Gangaram hospital Delhi, India showed 8.1% NDM – 1 positive E.coli [78]. In January 2011, the name of NDM–1 was changed to PCM (Plasmid encoding Carbapenem resistant metallo‐ betalactamases) [79].

Metallobatalactamases are also found in Carbapenem susceptible organisms. This hidden MBL gene can spread unnoticed in hospitals if isolates are reported sensitive without screening for presence of MBL [48].

The prevalence of ESBL and Amp C beta lactamases in a single isolate reduces effectiveness of beta – lactam and beta - lactamase inhibitor combinations while MBLs and Amp C beta– lactamases confer resistance to carbapenems and Cephamycin. Unfortunatenly thses enzymes usually co-exist in same isolate.
