The genetics of bacterial trimethoprim resistance in tropical areas

Resistance to trimethoprim in Gram-negative bacteria is largely manifested by two trimethoprim resistant dihydrofolate reductases (types I and II) encoded by genes originally located on resistance plasmids. Although trimethoprim resistance increased markedly after the clinical introduction of trimethoprim in the West, its spread has slowed and, in Edinburgh at least, has actually been declining. This reduction has been accompanied by the migration of a transposon, encoding the type I plasmid resistance gene, into the bacterial chromosome. In tropical areas, the incidence of trimethoprim resistance is very much higher. In Tanzania, it has spilled over into other bacteria outside the Enterobacteriaceae, but it was in India where the major problem existed. The majority (64%) of the Indian Enterobacteriaceae studied were resistant to the drug and most of the resistance genes were located on very large plasmids which also conferred resistance to many other antibacterial drugs. Some Indian plasmids carried a new trimethoprim resistance gene which is not detectable by conventional sensitivity tests and may be spreading unnoticed elsewhere. The proportion of trimethoprim resistance has been related to the volume of antibacterial drugs used.