Quinupristin-dalfopristin resistance in gram-positive bacteria: mechanism of resistance and epidemiology.

Antimicrobial resistance in gram-positive bacteria is a continuing problem resulting in significant morbidity, mortality, and cost. Because of this resistance, new antimicrobial agents have been needed. Quinupristin-dalfopristin is a recently approved agent for treatment of these infections. Shortly after its introduction into clinical medicine, resistance was reported. Resistance can occur by one or more of several mechanisms, including enzymatic modification, active transport of efflux mediated by an adenosine triphosphate-binding protein, and alteration of the target site. Resistance is rare in isolates of staphylococci and Enterococcus faecium from humans. Resistance is common in isolates recovered from food animals and is related to the use of virginiamicin as a feed additive. Considering the effect antimicrobial resistance has on human health, as well as its economic impact, measures to preserve the usefulness of these agents and delay the development of resistance are urgently needed.

[1]  R. Leclercq,et al.  Nonsense Mutations in the lsa-Like Gene in Enterococcus faecalis Isolates Susceptible to Lincosamides and Streptogramins A , 2003, Antimicrobial Agents and Chemotherapy.

[2]  Fred C Tenover,et al.  Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. , 2003, The New England journal of medicine.

[3]  Marilyne Davi,et al.  Clonal Diversity among Streptogramin A-Resistant Staphylococcus aureus Isolates Collected in French Hospitals , 2003, Journal of Clinical Microbiology.

[4]  P. McDermott,et al.  Prevalence of streptogramin resistance genes among Enterococcus isolates recovered from retail meats in the Greater Washington DC area. , 2002, The Journal of antimicrobial chemotherapy.

[5]  P. McDermott,et al.  Identification of vat(E) in Enterococcus faecalis Isolates from Retail Poultry and Its Transferability to Enterococcus faecium , 2002, Antimicrobial Agents and Chemotherapy.

[6]  B. Fantin,et al.  Resistance to Quinupristin-Dalfopristin Due to Mutation of L22 Ribosomal Protein in Staphylococcus aureus , 2002, Antimicrobial Agents and Chemotherapy.

[7]  G. Weinstock,et al.  An Enterococcus faecalis ABC Homologue (Lsa) Is Required for the Resistance of This Species to Clindamycin and Quinupristin-Dalfopristin , 2002, Antimicrobial Agents and Chemotherapy.

[8]  L. Jensen,et al.  Indication of Transposition of a Mobile DNA Element Containing the vat(D) and erm(B) Genes inEnterococcus faecium , 2001, Antimicrobial Agents and Chemotherapy.

[9]  L. McDonald,et al.  Quinupristin-dalfopristin-resistant Enterococcus faecium on chicken and in human stool specimens. , 2001, The New England journal of medicine.

[10]  T. Mukhtar,et al.  Vgb from Staphylococcus aureus inactivates streptogramin B antibiotics by an elimination mechanism not hydrolysis. , 2001, Biochemistry.

[11]  Frank Møller Aarestrup,et al.  Effect of Abolishment of the Use of Antimicrobial Agents for Growth Promotion on Occurrence of Antimicrobial Resistance in Fecal Enterococci from Food Animals in Denmark , 2001, Antimicrobial Agents and Chemotherapy.

[12]  F. Aarestrup,et al.  Linkage of vat(E) and erm(B) in Streptogramin-Resistant Enterococcus faecium Isolates from Europe , 2000, Antimicrobial Agents and Chemotherapy.

[13]  F. Aarestrup.  Characterization of Glycopeptide-Resistant Enterococcus faecium (GRE) from Broilers and Pigs in Denmark: Genetic Evidence that Persistence of GRE in Pig Herds Is Associated with Coselection by Resistance to Macrolides , 2000, Journal of Clinical Microbiology.

[14]  F. Aarestrup,et al.  Comparison of antimicrobial resistance phenotypes and resistance genes in Enterococcus faecalis and Enterococcus faecium from humans in the community, broilers, and pigs in Denmark. , 2000, Diagnostic microbiology and infectious disease.

[15]  R. Leclercq,et al.  Characterization of isolates associated with emerging resistance to quinupristin/dalfopristin (Synercid) during a worldwide clinical program. , 2000, Diagnostic microbiology and infectious disease.

[16]  B. Fantin,et al.  Influence of Resistance to Streptogramin A Type Antibiotics on the Activity of Quinupristin-Dalfopristin In Vitro and in Experimental Endocarditis Due toStaphylococcus aureus , 2000, Antimicrobial Agents and Chemotherapy.

[17]  J. Martínez,et al.  Macrolide Resistance Genes inEnterococcus spp , 2000, Antimicrobial Agents and Chemotherapy.

[18]  N. Woodford,et al.  Mechanisms of Resistance to Quinupristin-Dalfopristin among Isolates of Enterococcus faecium from Animals, Raw Meat, and Hospital Patients in Western Europe , 2000, Antimicrobial Agents and Chemotherapy.

[19]  R. Leclercq,et al.  Effects of Genes Encoding Resistance to Streptogramins A and B on the Activity of Quinupristin-Dalfopristin against Enterococcus faecium , 1999, Antimicrobial Agents and Chemotherapy.

[20]  N. Solh,et al.  Comparative analysis of staphylococcal plasmids carrying three streptogramin-resistance genes: vat-vgb-vga. , 1999, Plasmid.

[21]  G. Talbot,et al.  The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium , 1999 .

[22]  W. Witte,et al.  Characterization of a New Enterococcal Gene, satG, Encoding a Putative Acetyltransferase Conferring Resistance to Streptogramin A Compounds , 1999, Antimicrobial Agents and Chemotherapy.

[23]  L. Jensen,et al.  Horizontal Transfer of the satA Gene Encoding Streptogramin A Resistance Between Isogenic Enterococcus faecium Strains in the Gastrointestinal Tract of Gnotobiotic Rats , 1999 .

[24]  F. Aarestrup,et al.  Occurrence of satA and vgb Genes in Streptogramin-Resistant Enterococcus faecium Isolates of Animal and Human Origins in The Netherlands , 1998, Antimicrobial Agents and Chemotherapy.

[25]  F. Aarestrup,et al.  Detection of the satA gene and transferability of virginiamycin resistance in Enterococcus faecium from food-animals. , 1998, FEMS microbiology letters.

[26]  M. Zervos,et al.  Treatment of Vancomycin-Resistant Enterococcus faeciumwith RP 59500 (Quinupristin-Dalfopristin) Administered by Intermittent or Continuous Infusion, Alone or in Combination with Doxycycline, in an In Vitro Pharmacodynamic Infection Model with Simulated Endocardial Vegetations , 1998, Antimicrobial Agents and Chemotherapy.

[27]  J J Schentag,et al.  Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada. , 1998, Diagnostic microbiology and infectious disease.

[28]  N. Liassine,et al.  Characterization of a Staphylococcal Plasmid Related to pUB110 and Carrying Two Novel Genes, vatC andvgbB, Encoding Resistance to Streptogramins A and B and Similar Antibiotics , 1998, Antimicrobial Agents and Chemotherapy.

[29]  N. Solh,et al.  Characterization of a new staphylococcal gene, vgaB, encoding a putative ABC transporter conferring resistance to streptogramin A and related compounds. , 1997, Gene.

[30]  P. Mertens,et al.  High prevalence of colonization with vancomycin- and pristinamycin-resistant enterococci in healthy humans and pigs in The Netherlands: is the addition of antibiotics to animal feeds to blame? , 1997, The Journal of antimicrobial chemotherapy.

[31]  P. Vannuffel,et al.  Inhibition of protein synthesis by streptogramins and related antibiotics. , 1997, The Journal of antimicrobial chemotherapy.

[32]  S. Aubert,et al.  Distribution of genes encoding resistance to streptogramin A and related compounds among staphylococci resistant to these antibiotics , 1996, Antimicrobial agents and chemotherapy.

[33]  N. Solh,et al.  Diversity among the gram-positive acetyltransferases inactivating streptogramin A and structurally related compounds and characterization of a new staphylococcal determinant, vatB , 1995, Antimicrobial agents and chemotherapy.

[34]  H. Claus,et al.  vanA-mediated high-level glycopeptide resistance in Enterococcus faecium from animal husbandry. , 1995, FEMS microbiology letters.

[35]  R. Gaynes,et al.  Addressing emerging infectious disease threats; a prevention strategy for the United States : executive summary , 1994 .

[36]  R. Gaynes,et al.  An overview of nosocomial infections, including the role of the microbiology laboratory , 1993, Clinical Microbiology Reviews.

[37]  J. Duval,et al.  Identification of the satA gene encoding a streptogramin A acetyltransferase in Enterococcus faecium BM4145 , 1993, Antimicrobial Agents and Chemotherapy.

[38]  M. Delepierre,et al.  Sequence of a staphylococcal gene, vat, encoding an acetyltransferase inactivating the A-type compounds of virginiamycin-like antibiotics. , 1993, Gene.

[39]  N. Solh,et al.  Sequence of a staphylococcal plasmid gene, vga, encoding a putative ATP-binding protein involved in resistance to virginiamycin A-like antibiotics. , 1992, Gene.

[40]  D. Baldwin,et al.  Concentrations of cefpodoxime in serum and bronchial mucosal biopsies. , 1992, The Journal of antimicrobial chemotherapy.

[41]  K. Towner.  Detection of antibiotic resistance genes with DNA probes. , 1992, The Journal of antimicrobial chemotherapy.

[42]  R. Leclercq,et al.  Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification , 1991, Antimicrobial Agents and Chemotherapy.

[43]  R. Leclercq,et al.  Intrinsic and unusual resistance to macrolide, lincosamide, and streptogramin antibiotics in bacteria , 1991, Antimicrobial Agents and Chemotherapy.

[44]  J. Wootton,et al.  Inducible erythromycin resistance in staphlyococci is encoded by a member of the ATP‐binding transport super‐gene family , 1990, Molecular microbiology.

[45]  P. Mazodier,et al.  Nucleotide sequence of a staphylococcal plasmid gene, vgb, encoding a hydrolase inactivating the B components of virginiamycin-like antibiotics. , 1988, Plasmid.

[46]  J. Duval,et al.  Plasmid mediated pristinamycin resistance: PH 1A, a pristinamycin 1A hydrolase. , 1977, Annales de microbiologie.

[47]  S. Levy,et al.  Spread of antibiotic-resistant plasmids from chicken to chicken and from chicken to man , 1976, Nature.

[48]  B. Weisblum,et al.  Altered methylation of ribosomal RNA in an erythromycin-resistant strain of Staphylococcus aureus. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[49]  W. Witte,et al.  Quinupristin/dalfopristin-resistant enterococci of the satA (vatD) and satG (vatE) genotypes from different ecological origins in Germany. , 2000, Microbial drug resistance.

[50]  G. Talbot,et al.  The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Synercid Emergency-Use Study Group. , 1999, The Journal of antimicrobial chemotherapy.

[51]  F M Aarestrup,et al.  Occurrence of glycopeptide resistance among Enterococcus faecium isolates from conventional and ecological poultry farms. , 1995, Microbial drug resistance.

[52]  Nosocomial enterococci resistant to vancomycin--United States, 1989-1993. , 1993, MMWR. Morbidity and mortality weekly report.

[53]  J. Duval,et al.  Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics. , 1992, The Journal of antimicrobial chemotherapy.

[54]  D. Bouanchaud,et al.  Antimicrobial activity against Staphylococcus aureus of semisynthetic injectable streptogramins: RP 59500 and related compounds. , 1992, The Journal of antimicrobial chemotherapy.

[55]  F. Goffic.  Structure activity relationships in lincosamide and streptogramin antibiotics. , 1985, The Journal of antimicrobial chemotherapy.

[56]  B. Weisblum.  Inducible resistance to macrolides, lincosamides and streptogramin type B antibiotics: the resistance phenotype, its biological diversity, and structural elements that regulate expression--a review. , 1985, The Journal of antimicrobial chemotherapy.