g determined by a number of additional strain-dependent factors. The TEM-1 enzyme has been found in many E. coli isolates including commensal strains isolated from the faeces of healthy volunteers.
Strains of antibiotic resistant E. coli isolated from children in a children's day care centre, had frequently acquired trimethoprim resistance compared to isolates from children not attending such centres. According to plasmid profile analyses, these isolates were unique to each day care centre. These children then become the focus spreading the strains to other members of the households and into the community. Such spread is highest to mothers, then siblings and least to fathers. It is noteworthy that no link between antibiotic use and the spread of trimethoprim-resistant strains of E. coli within the household was observed. In Nigeria a study on E. coli isolated from children with diarrhoea found high levels of trimethoprim resistance. Over half the isolates were able to transfer their resistance and many of the enterotoxigenic strains were able to transfer the drug resistance as well as their toxigenic characteristics. A similar transferability of drug resistance linked to enterotoxigenicity plasmids was found among animal strains in India.
Two major mechanisms of resistance to the quinolone drugs have been observed. E. coli have been shown to develop a DNA gyrase with altered subunit structure or by reducing the number of porins, giving a decreased permeability through the outer membrane. As rough mutants, deficient in the lipopolysaccharide structures, are more susceptible to hydrophobic quinolones than the smooth wild-type strains, it is suggested that the porins are not the only mechanism by which these drugs may enter E. coli cells. Tosufloxacin and sparfloxacin are more efficiently accumulated by E. coli porin-deficient mutants also indicating another mechanism of uptake. It has been suggested that these drugs may permeate through the phospholipid bilayers. There is no evidence of specific porin pathways for imipenem and the related drug meropenem. Meropenem penetrates E. coli cells more slowly than imipenem, but is significantly more active against E. coli strains.
E. coli can readily become resistant to Zidovidine (AZT), a thimine analogue, which is active against the human immunodeficiency virus. This is associated with the loss of thimidine kinase, which converts AZT to the active triphosphate form. Selective advantage for the E. coli must be provided in the natural environment, so that such plasmids are maintained in their host bacterium. An example is the great diversity, of plamids conferring b-lactam resistance found among hospital isolates of E. coli, suggesting a wide distribution of such strains in nature. The observations made with trimethoprim resistant E. coli carried by children in day care centres and their family members demonstrate the extensive interchange of plasmids and other genetic material among E. coli in nature.