Dissemination of trimethoprim-resistant clones of Shigella sonnei in Bulgaria.

Bacterial dysentery due to Shigella sonnei remains a serious public health problem in developed countries, including Bulgaria. At the National Shigella Reference Laboratory in Sofia, 17,126 strains of S. sonnei from epidemics and sporadic cases collected from 1973 to 1987 were studied. Antibiotic susceptibility testing, phage typing, colicin typing, and biotyping were performed for all strains to allow intraspecies differentiation and to track any clonal distribution. Of all strains, 84.3% were resistant to one or more antimicrobials, the most frequent being tetracycline (Tet), streptomycin (Str), sulfonamide (Sul), chloramphenicol (Chl), ampicillin (Amp), and trimethoprim (Tmp). Resistance patterns most prevalent for successive 5-y periods included Tet, StrSulTet, and AmpChlStrSulTet, respectively. For the final 5 y, a new pattern (AmpKanStrSulTetTm [Kan = kanamycin]) was spread throughout the country by two trimethoprim-resistant clones. High-level resistance to trimethoprim (MIC greater than 1500 micrograms/mL) in both clones was determined by dihydrofolate reductase type I. The genes for trimethoprim resistance were located on a conjugative R-plasmid of approximately 145 kilobases which cotransferred all other antimicrobial resistances. A similar-sized R-plasmid had been found in earlier isolates of Bulgarian S. sonnei, suggesting that new antimicrobial resistance genes had been sequentially added to an ancestral R-plasmid. Controlling the expression of these new as well as older antimicrobial resistances, particularly for enteric pathogens, must involve reduction in usage of generic antimicrobial agents.