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.

Quinupristin/dalfopristin attenuates the inflammatory response and reduces the concentration of neuron-specific enolase in the cerebrospinal fluid of rabbits with experimental Streptococcus pneumoniae meningitis

Abstract: The inflammatory response following initiation of antibiotic therapy and parameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous infusion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneumoniae meningitis. With both modes of administration, quinupristin/dalfopristin was less bactericidal than ceftriaxone. However, the concentration of proinflammatory cell wall components (lipoteichoic acid (LTA) and teichoic acid (TA)) and the activity of tumour necrosis factor (TNF) in cerebrospinal fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentrations (25th/75th percentiles) were as follows: (i) 14 h after infection: 133 (72/155) ng/mL for continuous infusion of quinupristin/dalfopristin and 193 (91/308) ng/mL for short duration infusion, compared with 455 (274/2042) ng/mL for ceftriaxone (P = 0.002 and 0.02 respectively); (ii) 17 h after infection: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopristin and 117 (41/247) ng/mL for short duration infusion, compared with 694 (156/2173) ng/mL for ceftriaxone (P = 0.04 and 0.03 respectively). Fourteen hours after infection the median TNF activity (25th/75th percentiles) was 0.2 (0.1/1.9) U/mL for continuous infusion of quinupristin/dalfopristin and 0.1 (0.01/3.5) U/mL for short duration infusion, compared with 30 (4.6/180) U/mL for ceftriaxone (P = 0.02 for each comparison); 17 h after infection the TNF activity was 2.8 (0.2/11) U/mL (continuous infusion of quinupristin/dalfopristin) and 0.1 (0.04/6.1) U/mL (short duration infusion), compared with 48.6 (18/169) U/mL for ceftriaxone (P = 0.002 and 0.001). The concentration of neuron-specific enolase (NSE) 24 h after infection was significantly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) microg/L (continuous infusion) and 3.6 (2.9/4.7) microg/L (short duration infusion) than in those treated with ceftriaxone (17.7 (8.8/78.2) microg/L) (P = 0.03 and 0.009 respectively). In conclusion, antibiotic treatment with quinupristin/dalfopristin attenuated the inflammatory response within the subarachnoid space after initiation of antibiotic therapy. The concentration of NSE in the CSF, taken as a measure of neuronal damage, was lower in quinupristin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits.

Comparative in-vitro activity of quinupristin/dalfopristin against Enterococcus spp.

Abstract: The in-vitro activity of quinupristin/ dalfopristin against Enterococcus spp. was compared with that of amoxycillin, vancomycin, teicoplanin and erythromycin. The susceptibility of 106 vancomycin-susceptible Enterococcus faecalis, 92 vancomycin-susceptible Enterococcus faecium and 14 vancomycin-re sistant enterococci (VRE) was tested. Only one strain of vancomycin-susceptible E. faecium was not susceptible to 0.5 mg/L quinupristin/ dalfopristin; this strain required 4 mg/L. All strains of E. faecalis were inhibited by 8 mg/L quinupristin/dalfopristin and all VRE strains were inhibited by 2 mg/L. In contrast, teicoplanin and vancomycin showed inhibitory activity against E. faecalis and E. faecium but not against VRE. Amoxycillin was active against E. faecalis but not usually against E. faecium and showed variable activity against VRE; 38% of E. faecalis , 84% of E. faecium and 80% of VRE strains were resistant to erythromycin. The bactericidal activity of quinu pristin/dalfopristin against E. faecium exceeded that of the comparator drugs as judged by MIC:MBC ratios and killing curves. The MBC99 of quinupristin/ dalfopristin determined by a microdilution broth technique was 1 mg/L for E. faecium . Four of the five strains of vancomycin-susceptible E. faecium and three of the five VRE strains tested with time‐kill curves showed a 2 log reduction in viable count after exposure to quinupristin/dalfopristin for 6 h.

Nasal and perirectal colonization of vancomycin sensitive and resistant enterococci in patients of paediatrics ICU (PICU) of tertiary health care facilities

Abstract: Enterococci normally inhabit the intestinal tract of humans and are also a potential pathogen in causing nosocomial infections. The increase in antibiotic resistance and transfer of antibiotic resistance gene to Staphylococcus aureus (S. aureus) due to co-colonization has increased its importance in research. The aim of the study was to evaluate local epidemiology of nasal and rectal colonization with Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) in patients of Paediatrics Intensive Care Unit (PICU) and correlation with clinical and socioeconomic factors. The nasal and perirectal swab samples were collected from 110 patients admitted in PICUs of three tertiary care hospitals of Rawalpindi Medical College, Pakistan. The identification of enterococci was done by biochemical tests and by PCR for ddl, vanA and vanB genes. Antibiotic susceptibility testing was performed by disc diffusion and MICs were determined for vancomycin, tetracycline, ciprofloxacin and oxacillin only. Out of 220 nasal and perirectal samples, 09 vancomycin-resistant enterococci (VRE) and 76 vancomycin-susceptible enterococci (VSE), consisting of 40 E. faecalis and 45 E. faecium were isolated. PCR successfully identified both species with ddl primers and VRE with vanA primer. With disc diffusion method, all isolates were resistant to most of the antibiotics tested except linezolid, quinupristin/dalfopristin, teicoplanin and vancomycin. VRE showed resistance to teicoplanin and vancomycin both and none was resistant to linezolid and quinupristin/dalfopristin. Generally, E. faecium isolates were more resistant than E. faecalis. MICs of vancomycin for nasal and perirectal VRE were 512 mg/L and 64 to 512 mg/L respectively. VRE were more in patients with prolonged hospitalization, from urban localities and those having pneumonia. Present study reveals high colonization and antibiotic resistance in enterococcal isolates from nasal and perirectal area. Nasal colonization by enterococci in PICU is more alarming as VRE may cause infection and can transfer this resistance gene to other microorganisms like S. aureus.

Macrolide resistance mechanisms and in vitro susceptibility patterns of viridans group streptococci isolated from blood cultures

Abstract: Objectives Our aim was to study the macrolide resistance mechanisms and antimicrobial susceptibilities of viridans group streptococci (VGS) isolated from blood cultures. Methods In vitro susceptibilities to nine antimicrobials were studied for 85 VGS isolated from blood cultures by agar dilution. Pheno- and genotyping of erythromycin-resistant isolates were studied by the double disc test and PCR. Results Resistance to erythromycin was found in 27% (n = 23) of the isolates. Erythromycin-resistant Streptococcus oralis (n = 13) predominated among the other erythromycin-resistant species isolated. The phenotypes among 23 erythromycin-resistant isolates were as follows: 12 constitutive macrolide-lincosamide-streptogramin (cMLS(B)) resistance phenotype and 11 macrolide (M) resistance phenotype. Of the cMLS(B) isolates 11 had erm(B) genes and 11 of the M phenotype isolates had mef(A) genes. Four of the cMLS(B) isolates had both erm(B) and mef(A) genes. None of the isolates had erm(TR) genes. Combined resistance to erythromycin with penicillin, clindamycin, chloramphenicol, tetracycline and quinupristin/dalfopristin was found in 100, 61, 74, 100 and 100% of the isolates, respectively. No resistance was found for vancomycin, linezolid and levofloxacin. Conclusions The macrolide resistance mechanisms of our VGS isolates revealed that the cMLS(B) phenotype associated with erm(B) and the M phenotype associated with mef(A) genes are found with similar frequencies.