The emergence of multidrug resistance to antimicrobial agents for the treatment of typhoid fever

Abstract
Resistance to chloramphenicol was reported in Salmonella Typhi in 1950 but it was not until 22 years later that the first outbreaks of chloramphenicol-resistant typhoid fever occurred. Multidrug-resistant (MDR) Salmonella Typhi emerged in the 1980s and today has an almost worldwide distribution. Genome analysis of Salmonella Typhi strain CT18, an MDR isolate from a patient admitted to The Centre for Tropical Diseases, Ho Chi Minh City, Viet Nam, in December 1993 revealed that the resistance plasmid pHCM1 is very closely related to plasmid R27 which was first isolated in 1961. There is a core region shared by the two plasmids with five regions of variation. Two of these regions contain the genes encoding resistance. The largest region is 34.955 kbp in length, is bordered by two almost identical IS10 elements and contains several integron-like structures including a truncated Tn10 element. The second region is 14.75I kbp and encodes a trimethoprim-resistance gene, dfrA14, associated with a class one integrase. Restriction enzyme analysis has shown that the variation in Salmonella Typhi plasmids, collected during the emergence of resistant Salmonella Typhi in Viet Nam, maps to five variable regions. These regions appear to be hot spots for DNA acquisition in IncHI1 plasmids.