ABSTRACT
AIMS: We report the analysis of genetic determinants conferring resistance to pristinamycin in Staphylococcus epidermidis strains and epidemiology typing of these strains by pulsed-field gel electrophoresis. METHODS AND RESULTS: Staphylococcus epidermidis (346 isolates) were searched for strains with pristinamycin resistance. Pristinamycin-resistant strains (seven isolates) were isolated in five patients with haematological cancer in the Bone Marrow Transplant Centre of Tunisia in 2002. Resistance to pristinamycin was observed in 2% of isolates. The seven pristinamycin-resistant strains shared resistance to oxacillin (MIC = 8-512 microg ml(-1)), gentamicin (MIC = 16-512 microg ml(-1)), erythromycin (MIC > 1024 microg ml(-1)), lincomycin (MIC > 1024 microg ml(-1)), pristinamycin (MIC = 4-16 microg ml(-1)) and rifampin (MIC = 128-256 microg ml(-1)). erm genes were amplified: ermA from six strains and ermC from one. vga gene encoding streptogramins A resistance (pristinamycin résistance) was amplified from all strains and typed as vgaA by analysis after electrophoresis of restriction profiles of vga amplicons (two fragments with Sau3A of 164 and 378 bp; one fragment with EcoRI). Pulsed-field gel electrophoresis (PFGE) of SmaI chromosomal DNA digests of the seven S. epidermidis isolates divided them into two distinct pattern types: pulsed-field type A (classified from A1 to A6 subtypes) and type B. The six strains harbouring ermA genes belonged to the PFGE type A while the strain harbouring ermC genes belonged to the PFGE type B. We characterized an epidemic strain carrying the vgaA and ermA genes responsible for the outbreak. CONCLUSIONS: Two clones of pristinamycin-resistant S. epidermidis were isolated in our patients. One of them, isolated in all patients, had expanded over six months suggesting acquisition by cross-contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Increasing isolation of pristinamycin resistant S. epidermidis strains is an alarming indicator of nosocomial dissemination. The vector will be determined to establish a system of epidemiological surveillance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Hematologic Neoplasms/complications , Pristinamycin/pharmacology , Staphylococcal Infections/epidemiology , Staphylococcus epidermidis/drug effects , Bacterial Proteins/genetics , Bone Marrow Transplantation , DNA Primers , Electrophoresis, Gel, Pulsed-Field , Humans , Microbial Sensitivity Tests , Polymerase Chain Reaction , Sequence Analysis, DNA , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/classification , Staphylococcus epidermidis/genetics , Staphylococcus epidermidis/isolation & purification , TunisiaABSTRACT
The structure-activity relationship study of one of recently described aromatase inhibitors, compound 1 (MR20814), allowed us to design some related derivatives as potential new inhibitors. Among those we synthesized, chlorophenylpyridylmethylenetetrahydroindolizinone 5 (MR20492) exhibited in vitro a ten-fold higher inhibition of the enzyme (IC50 = 0.2 +/- 0.0 microM and Ki = 10.3 +/- 3.3 nM).