Dalfopristin

About: Dalfopristin is a research topic. Over the lifetime, 696 publications have been published within this topic receiving 26621 citations. The topic is also known as: RP-54476 & Dalfopristina.

Occurrence of satA and vgb genes in streptogramin-resistant Enterococcus faecium isolates of animal and human origins in the Netherlands.

Abstract: Enteroccocci have emerged as an important cause of nosocomial infections. Infections caused by multiresistant enterococci are treated with vancomycin or another glycopeptide. In recent years the usage of vancomycin and the isolation rate of vancomycin-resistant enterococci (VRE) have steadily increased in both Europe and the United States (8). Despite the fact that VRE infections are a hospital problem and the human usage of glycopeptides is in hospitals, VRE have been isolated from the fecal flora of healthy humans without a known hospital connection, from animals, and from the environment (1, 5, 9). One of the few options for treatment of vancomycin-resistant Enterococcus faecium infection is quinopristin-dalfopristin, a mixture (30:70 ratio) of two streptogramins: dalfopristin (streptogramin A) and quinopristin (streptogramin B) (6). A related mixed compound virginiamycin has been used in Europe for many years as a feed additive to enhance growth in food animals. High numbers of virginiamycin-resistant E. faecium have been isolated from the feces of food animals, and these were also resistant to quinopristin-dalfopristin, indicating cross-resistance between virginiamycin and quinopristin-dalfopristin (2, 13, 15). Two genes, satA and vgb, encoding streptogramin resistance in E. faecium have been detected in clinical isolates. The bacteria were determined to be streptogramin-resistant E. faecium (SREF) by an agar diffusion technique (3, 11). satA encodes resistance to the streptogramin A component (11), while vgb encodes resistance against the streptogramin B component (3). Streptogramin B resistance is also encoded by the erm genes referred to as “MLSB resistance genes” (14). In this study we examined SREF isolates from The Netherlands for resistance to quinopristin-dalfopristin and virginiamycin and for the presence of the two known streptogramin resistance genes in enterococci. In addition, the genotypes were determined by pulsed-field gel electrophoresis (PFGE) after SmaI digestion (12). A total of 51 SREF isolates from fecal samples of healthy (sub)urban residents (n = 5), farmers (n = 19), poultry (n = 22), and pigs (n = 5) were tested. MICs were defined by agar diffusion methods according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) (10). The presence of satA and vgb was established by PCR with specific primers, giving amplicons of 272 bp for satA and 570 bp for vgb. Two isolates (KH 36syn and K 36syn) with identical PFGE patterns were from a poultry farmer (KH 36syn) and his animals (K 36syn). All isolates were resistant to quinopristin-dalfopristin (MIC ≥ 32 mg/liter) and to virginiamycin (MIC ≥ 16 mg/liter). The breakpoint for quinopristin-dalfopristin has been suggested to be 4 mg/liter (7). Since virginiamycin is not used for therapy, no breakpoint has been established by NCCLS, but a breakpoint of 4 mg/liter for virginiamycin has been suggested because of the observed distribution of MICs in an E. faecium population (2). All strains were resistant to both quinopristin-dalfopristin and virginiamycin. The satA gene was detected in 14 (58%) of the SREF isolates of human origin—10 farmers (52%) and 4 suburban residents (80%)—and in 5 (19%) isolates of animal origin—1 porcine isolate (20%) and 4 poultry isolates (18%). The two PFGE-identical SREF isolates both contained the satA gene. The vgb gene was found in a single isolate of human origin (KH 6syn). The study showed that the satA gene encoding streptogramin A resistance was present in SREF isolates of animal and human origins outside hospitals. The vgb gene encoding streptogramin B resistance was found in one human isolate only. These genes have previously been found only in SREF isolates from hospitalized patients (4, 11). satA was more frequently found among isolates from humans than among isolates from animals. The fact that PFGE-identical isolates with the satA genes were found in a farmer and his animals indicates that transfer of SREF between animals and humans occurs. Other resistance genes encoding streptogramin resistance were probably present in the remaining isolates. The erm genes, encoding resistance to streptogramin B compounds, also confer resistance to macrolides and lincosamides. As both groups of antibiotics are widely used in human and veterinary medicine and the macrolide tylosin as growth promoter, the selection for these genes must be high and needs further investigation.

In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.

Abstract: BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of 16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp including C jeikeium (8- to >16-fold) BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S aureus, against which it had equal activity BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml) BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci

Nationwide German Multicenter Study on Prevalence of Antibiotic Resistance in Staphylococcal Bloodstream Isolates and Comparative In Vitro Activities of Quinupristin-Dalfopristin

Abstract: Antibiotic-resistant gram-positive bacteria have become an increasing problem in the last two decades. In order to evaluate the prevalence of antibiotic resistance in staphylococcal bloodstream isolates in Germany, 2,042 staphylococci collected in 21 tertiary-care hospitals were investigated during a 3-year period (March 1996 to March 1999). Altogether, 1,448 S. aureus isolates and 594 coagulase-negative staphylococci (CoNS) that comprised 13 different species were included. Furthermore, the antistaphylococcal activities of quinupristin-dalfopristin were compared with those of eight other compounds by the broth microdilution method. The rates of oxacillin resistance in Staphylococcus aureus, S. epidermidis, S. haemolyticus, and other CoNS were 13.5, 69, 90, and 34%, respectively. In oxacillin-resistant strains high rates of resistance (up to 100%) to erythromycin, clindamycin, ciprofloxacin, and gentamicin were also observed. However, no strain appeared to be resistant to vancomycin or quinupristin-dalfopristin. The streptogramin combination exhibited excellent in vitro activity against all staphylococcal species tested, regardless of the patterns of resistance to other drug classes. In terms of MICs at which 90% of the isolates are inhibited, quinupristin-dalfopristin was 2 times more active against S. aureus isolates, 4 to 16 times more active against S. haemolyticus, and 8 to 32 times more active against S. epidermidis than vancomycin or teicoplanin.

Infection with antimicrobial-resistant microorganisms in dialysis patients.

Abstract: The prevalence of antimicrobial-resistant microorganisms in various health care settings, including outpatient dialysis facilities, has increased dramatically in the last decade. Antimicrobial use and patient-to-patient transmission of resistant strains are the two main factors that have contributed to this rapid increase. Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci are commonly isolated as a cause of hemodialysis (HD) catheter-related bacteremia and peritoneal dialysis (PD)-related catheter infection and peritonitis. The widespread use of vancomycin in dialysis patients is of concern because of an increase in the prevalence of vancomycin-resistant enterococci (VRE) in dialysis patients. Staphylococci with reduced sensitivity to vancomycin have also appeared in dialysis patients. A more recent problem is the appearance of S. aureus isolates with a high degree of resistance to the topical antimicrobial agent mupirocin. This has been seen in PD patients who have received prophylactic application of mupirocin at the peritoneal catheter exit site. Appropriate antimicrobial use will help protect the efficacy of currently used antibiotics, such as vancomycin. Published guidelines for use of vancomycin should be followed. New antimicrobials such as linezolid and quinupristin/dalfopristin have activity against VRE and MRSA, but resistance to these agents has already occurred. Preventing transmission of antimicrobial-resistant microorganisms in health care settings, including outpatient dialysis facilities, is important in limiting the spread of these resistant organisms.