Evolution of a Plasmid Mediating Resistance to Multiple Antimicrobial Agents During a Prolonged Epidemic of Nosocomial Infections

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Abstract
At the Vanderbilt University Medical Center, Nashville, Tennessee, resistance to gentamicin was encountered with increasing frequency among several species of gramnegative bacilli between 1973 and 1977. Representative strains were screened for plasmid DNA content using agarose gel electrophoresis. In strains of Pseudomonas aeruginosa and Serratia marcescens isolated early in the outbreak, gentamicin resistance was mediated by a common 9.8-megadalton nonconjugative plasmid. Either an 80- or a l00-megadalton transferable plasmid coexisted with the nonconjugative plasmid in the isolates of Serratia. Transposition between the 100-and 9.8-megadalton plasmids in this species resulted in the formation of a 105-megadalton conjugative plasmid that mediated gentamicin resistance; this was observed in strains of Serratia and Klebsiella isolated in 1976–1977. Thus, during this five-year investigation separate outbreaks of nosocomial infections that were caused by different bacterial species were shown to be related by the presence of plasmids that contained a common transposable DNA sequence.