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Showing papers on "Dalfopristin published in 2006"


Journal ArticleDOI
01 Jan 2006-Drugs
TL;DR: Treatment of infections associated with orthopaedic devices usually requires appropriate surgical intervention combined with prolonged antimicrobial therapy, and the choice of the antimicrobial regimen depends on the duration and pathogenesis of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue.
Abstract: The pathogenesis of implant-associated infection involves interaction between the microorganisms (biofilm formation), the implant and the host. Despite improvement of perioperative prophylaxis, orthopaedic implants still remain highly susceptible to bacterial or fungal contamination, generally resulting in persistent implant-associated infection. Therefore, perioperative and life-long prevention of infection is important. For perioperative prophylaxis, a first- or second-generation cephalosporin is recommended, which should be administered between 60 and 30 minutes before incision. The duration of prophylaxis should not exceed 1 day. In centres with a low incidence of infection, a single dose is sufficient. Treatment of infections associated with orthopaedic devices usually requires appropriate surgical intervention combined with prolonged antimicrobial therapy. The choice of the antimicrobial regimen depends on the duration and pathogenesis of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue. The role of rifampicin (rifampin), which has excellent activity on adherent staphylococci, in combination with β-lactams, glycopeptides, fluoroquinolones, minocycline, cotrimoxazole or fusidic acid, in the treatment of staphylococcal infections is outlined. Increasing antimicrobial resistance requires the use of alternative agents, such as quinupristin/dalfopristin, linezolid and daptomycin, but results of clinical trials with these agents are limited. Also reviewed are potential new antimicrobial agents currently undergoing investigation, such as the novel oxazolidinone RWJ-416457, the new glycopeptide dalbavancin, the glycylcycline compound tigecycline, the new carbacephem BP-102 and novel rifamycin derivatives. Vaccination against Staphylococcus aureus with StaphVAX® induced specific antibodies potentially preventing bacteraemia; however, there are no studies on efficacy in the prophylaxis of device-associated infections with this vaccine.

208 citations


Journal ArticleDOI
Liesbeth Masco1, K. Van Hoorde1, E. De Brandt1, Jean Swings1, Geert Huys1 
TL;DR: The use of the LSM + cysteine medium allowed us to discriminate between intrinsic and atypical resistance properties of bifidobacteria and sets the scene for future definition of epidemiological cut-off values for all important BifidOBacterium species.
Abstract: Objectives: The aim of this study was to assess the antimicrobial susceptibility of a taxonomically diverse set of Bifidobacterium strains to different classes of antimicrobial agents using a recently described medium. Methods: The susceptibility of 100 strains encompassing 11 bifidobacterial species originating from humans, animals and probiotic products to 12 antimicrobial agents was tested by agar overlay disc diffusion. Based on these results, one or two strains per species were selected for susceptibility testing to nine antibiotics by broth microdilution using the Lactic acid bacteria Susceptibility test Medium (LSM) supplemented with cysteine. The genotypic basis of atypical tetracycline resistance was further characterized using PCR, Southern blotting and partial sequencing. Results: Based on the distribution of inhibition zone diameters and MIC values, all strains tested were susceptible to amoxicillin, chloramphenicol, erythromycin, quinupristin/dalfopristin, rifampicin and vancomycin. Our data also reinforce earlier observations indicating that bifidobacteria are intrinsically resistant to gentamicin, sulfamethoxazole and polymyxin B. Susceptibility to trimethoprim, trimethoprim/ sulfamethoxazole, ciprofloxacin, clindamycin, tetracycline and minocycline was variable. The tet(W) gene was responsible for tetracycline resistance in 15 strains including 7 probiotic isolates belonging to the taxa Bifidobacterium animalis subsp. lactis and Bifidobacterium bifidum. This gene was present in a single copy on the chromosome and did not appear to be associated with the conjugative transposon TnB1230 previously found in tet(W)-containing Butyrivibrio fibrisolvens. Conclusions: The use of the LSM + cysteine medium allowed us to discriminate between intrinsic and atypical resistance properties of bifidobacteria and sets the scene for future definition of epidemiological cut-off values for all important Bifidobacterium species. The presence of an acquired tet(W) gene in several probiotic product isolates stresses the need for a minimal safety evaluation during the selection of Bifidobacterium strains for probiotic use.

130 citations


Journal ArticleDOI
TL;DR: Telavancin demonstrated concentration-dependent bactericidal activity against GISS, hGISS and VRSA at concentrations equal to or above 4x MIC, which corresponds to therapeutic levels against Giss and clinically achieved concentrations against the VRSA.
Abstract: Background: Telavancin, a new multifunctional lipoglycopeptide antibiotic, exhibits broad-spectrum Gram-positive activity against a variety of pathogens. We examined the effects of human serum and antimicrobial concentrations on the activity of telavancin against glycopeptide-intermediate staphylococcal species (GISS), heteroresistant GISS (hGISS) and three vancomycin-resistant Staphylococcus aureus (VRSA) compared with vancomycin, quinupristin/dalfopristin, linezolid and daptomycin. Methods:MICandMBCswereperformedagainstallantimicrobials.Time–killexperimentswereperformed usingtwostrainsofGISS(Mu50;NJ992)andVRSA(VRSAMI;VRSAPA)at1,2,4,8,16and32·MIC.Telavancin and daptomycin were evaluated in the presence and absence of serum. Results: All GISS and hGISS were susceptible to the tested agents with telavancin and quinupristin/ dalfopristin demonstrating the lowest MIC, followed by daptomycin, linezolid and vancomycin. Against VRSA, daptomycin and quinupristin/dalfopristin had the lowest MIC, followed by linezolid, telavancin and vancomycin. In the presence of serum, telavancin and daptomycin MICs increased 1- to 4-fold. Concentration-dependent activity was demonstrated by telavancin and daptomycin, in the presence and absence of serum. Telavancin and daptomycin were bactericidal against GISS and performed similarly in the presence of serum. Quinupristin/dalfopristin demonstrated bactericidal activity at clinically achievable concentrations, whereas linezolid was bacteriostatic. Conclusions:Telavancindemonstratedconcentration-dependentbactericidalactivityagainstGISS,hGISS andVRSAatconcentrationsequaltoorabove4·MIC,whichcorrespondstotherapeuticlevelsagainstGISS and clinically achieved concentrations against the VRSA. Similar to daptomycin, telavancin activity was diminished in the presence of serum but bactericidal activity was maintained. Further investigation with telavancin against GISS, hGISS and VRSA is warranted.

120 citations


Journal ArticleDOI
TL;DR: The aac(6')-aph(2''), aph(3')-IIIa, erm(B) and tet(M) genes were demonstrated in most of the gentamicin-, kanamycin-, erythromycin- and tetracycline-resistant isolates, respectively.

99 citations


Journal ArticleDOI
TL;DR: Tigecycline, the first antimicrobial of the oxazolidinone class, is bacteriostatic against most pathogens but has a broad spectrum of antimicrobial activity and has enhanced penetration into many tissues.

60 citations


Journal ArticleDOI
TL;DR: Dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptide, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI.

53 citations



Journal ArticleDOI
TL;DR: The Etest method appears promising, and further investigations are warranted, after a number of combinations demonstrated either synergistic or additive effects against hGISA SA118 and GISA SA179.

46 citations


Journal ArticleDOI
TL;DR: Analysis of 247 faecal enterococcal isolates from 99 healthy Portuguese individuals during 2001 revealed the presence of enterococci resistant to vancomycin and highly resistant to streptomycin, kanamycin or gentamicin, which were related to Portuguese poultry isolates described previously.

40 citations


Journal ArticleDOI
TL;DR: All isolates were resistant to rifampicin, erythromycin and ciprofloxacin, and some were also resistant to quinupristin/dalfopristin, tetracycline, levofloxacIN, gentamicin and streptomycin, while vancomycin resistance was not detected.

40 citations


Journal ArticleDOI
TL;DR: The results of the present study suggest that subinhibitory quinupristin/dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S.aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.
Abstract: Objectives: The semi-synthetic streptogramin quinupristin/dalfopristin antibiotic exerts potent bactericidal activity against Staphylococcus aureus. We investigated whether, like other bactericidal antibiotics used at subinhibitory concentrations, quinupristin/dalfopristin enhances release of toxins by Grampositive cocci. Methods: The activity of quinupristin/dalfopristin on exotoxin release by S. aureus was investigated by 2D SDS–PAGE combined with MALDI-TOF/MS analysis and by western blotting. Results: We show that quinupristin/dalfopristin at subinhibitory concentrations reduces the release of S. aureus factors that induce tumour necrosis factor secretion in macrophages. Furthermore, quinupristin/dalfopristin but not linezolid attenuated S. aureus-mediated killing of infected host cells. When added to S. aureus cultures at different stages of bacterial growth, quinupristin/dalfopristin reduced in a dose-dependent manner the release of specific virulence factors (e.g. autolysin, protein A, aand b-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins remained unchanged. Conclusions: The results of the present study suggest that subinhibitory quinupristin/dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S. aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.

Journal ArticleDOI
TL;DR: Known streptogramin resistance genes were absent in the majority of isolates, suggesting the presence of other, as-yet-undetermined, mechanisms of Q-D resistance.
Abstract: Three hundred sixty-one quinupristin-dalfopristin (Q-D)-resistant Enterococcus faecium (QDREF) isolates were isolated from humans, turkeys, chickens, swine, dairy and beef cattle from farms, chicken carcasses, and ground pork from grocery stores in the United States from 1995 to 2003. These isolates were evaluated by pulsed-field gel electrophoresis (PFGE) to determine possible commonality between QDREF isolates from human and animal sources. PCR was performed to detect the streptogramin resistance genes vatD, vatE, and vgbA and the macrolide resistance gene ermB to determine the genetic mechanism of resistance in these isolates. QDREF from humans did not have PFGE patterns similar to those from animal sources. vatE was found in 35%, 26%, and 2% of QDREF isolates from turkeys, chickens, and humans, respectively, and was not found in QDREF isolates from other sources. ermB was commonly found in QDREF isolates from all sources. Known streptogramin resistance genes were absent in the majority of isolates, suggesting the presence of other, as-yet-undetermined, mechanisms of Q-D resistance.

Journal ArticleDOI
TL;DR: Ribosomal mutations were associated with resistance to macrolides and related antibiotics in M. hominis and some mutants showed a loss of the intrinsic resistance to erythromycin and azithromycin.
Abstract: Objectives: Mycoplasma hominis is intrinsically resistant to 14- and 15-membered macrolides and to the ketolide telithromycin but is susceptible to josamycin, a 16-membered macrolide, and lincosamides. The aim of our study was to investigate the in vitro development of macrolide resistance in M. hominis and to study the impact of ribosomal mutations on MICs of various macrolides and related antibiotics. Methods: Selection of macrolide-resistant mutants was performed by serial passages of M. hominis PG21 in broth medium containing subinhibitory concentrations of clindamycin, pristinamycin, quinupristin/ dalfopristin and telithromycin. Stepwise selection of josamycin-resistant mutants was performed onto agar medium containing increasing inhibitory concentrations of josamycin. Resistant mutants were characterized by PCR amplification and DNA sequencing of 23S rRNA, L4 and L22 ribosomal protein genes. Results: Various mutations in domain II or V of 23S rRNA were selected in the presence of each selector antibiotic and were associated with several resistance phenotypes. Josamycin was the sole antibiotic that selected for single amino acid changes in ribosomal proteins L4 and L22. Unexpectedly, the C2611U transition selected in the presence of clindamycin and the quinupristin/dalfopristin combination was associated with decreased MICs of erythromycin, azithromycin and telithromycin, leading to a loss of the intrinsic resistance of M. hominis to erythromycin and azithromycin. Conclusions: Ribosomal mutations were associated with resistance to macrolides and related antibiotics in M. hominis. Some mutants showed a loss of the intrinsic resistance to erythromycin and azithromycin.

Journal ArticleDOI
TL;DR: Resistance to linezolid and quinupristin/dalfopristin appears to be independent of reduced susceptibility to daptomycin, which had potent activity against all strains.

Journal ArticleDOI
TL;DR: The macrolide resistance mechanisms of the VGS isolates revealed that the cMLS(B) phenotype associated with erm(B), and the M phenotypeassociated with mef(A) genes are found with similar frequencies.
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.

Journal ArticleDOI
TL;DR: An intergeneric conjugal system in B. burgdorferi suggests that horizontal gene transfer may play a role in its evolution and is a potential tool for developing new genetic systems to study the pathogenesis of Lyme disease.

Journal ArticleDOI
TL;DR: It is indicated that antibiotics with a high potential for local cytotoxicity may cause an inflammatory response by endothelial cells even at rather low concentrations and the increase in expression of cell surface markers involved in cell-cell interaction could be an important mechanism in the development of infusion phlebitis.

Journal ArticleDOI
TL;DR: Streptococcus pneumoniae isolates from Sydney are commonly resistant to &bgr;‐lactams and available non‐& bgr;-lactam agents, especially if they are penicillin non‐susceptible.

Journal ArticleDOI
TL;DR: It is shown that the vat(E) gene, conferring resistance to Q/D, was carried on different plasmids in a heterogeneous group of E. faecium, some of which may be acquired by E. Faecium capable of infecting humans.

Journal Article
TL;DR: The results confirm the superior performance of cefoxitin disk test to detect methicillin resistance in heterogenous population of CoNS and confirm the presence of macrolides and streptogramines type A efflux pump in PFGE patterns.
Abstract: Coagulase-negative staphylococci (CoNS) are often responsible for cases of chronic ostitis and osteomyelitis, especially in patients with orthopedic prosthesis/implants. The aim of this study was to characterize CoNS isolated from ambulatory patients with chronic ostitis/osteomyelitis and to compare them by PFGE (pulsed-field gel electrophoresis). Out of 263 bacterial strains isolated from wounds/sinuses of patients with chronic ostitis/osteomylitis, 41 were identified as CoNS. Twenty methicillin-resistant strains were selected for this study. Our results confirm the superior performance of cefoxitin disk test to detect methicillin resistance in heterogenous population of CoNS. High level of antibiotic resistance was observed among the studied strains: majority of CoNS were resistant to tetracycline and erythromycin and also to clindamycin and ciprofloxacin. Importantly, in 15 out of 20 studied CoNS different phenotypes of macrolides, lincosamides and streptogramin--MLS resistance was suggested. Eight strains demonstrated resistance to both erythromycin and clindamycin, suggesting constitutive MLS(B) phenotype. Seven remaining strains presented resistance to erythromycin and susceptibility to clindamycin with negative D-test results, suggesting the presence of macrolides and streptogramines type A efflux pump. All studied strains were sensitive to vancomycin (MIC 0.75-2.0 microg/ml), teicoplanin (MIC 0.125-8.0 microg/ml), and quinupristin/dalfopristin (MIC 0.19-1.0 microg/ml). No clonal relatedness was observed in PFGE patterns.

Journal ArticleDOI
TL;DR: Quinupristin/dalfopristin (QPR/DPR) and voriconazole are considered effective for patients with life-threatening opportunistic pulmonary infections who have previously been treated with intensive regimens including radiotherapies to the lung.

Journal ArticleDOI
TL;DR: The nuances of AMP not addressed by current guidelines can be highlighted by asking the basic questions of “Who, What, When, Where, Why, and How?”
Abstract: Prevention of surgical site infections (SSIs) has long been a quality measure of surgical practice, and a cornerstone of SSI prevention is the appropriate and timely administration of antimicrobial prophylaxis (AMP). Guidelines for prevention of SSI are available from multiple specialty groups, as well as national agencies of various countries. These guidelines contain extensive reviews of the literature that support their recommendations. Even so, interpretation of guidelines can seem arbitrary even among experienced physicians. Due to inconclusive data, the evolution of microorganisms, and the continuous advancement of surgical techniques, guidelines are unable to answer several key questions regarding surgical AMP. The nuances of AMP not addressed by current guidelines can be highlighted by asking the basic questions of “Who, What, When, Where, Why, and How?”

Journal Article
TL;DR: The MICs and MBCs of quinupristin/dalfopristin were determined for 22 clinical strains MRSA with inducible type of resistance to MLS-B and for 15 of their derivatives with constitutive resistance toMLS-B.
Abstract: The MICs and MBCs of quinupristin/dalfopristin were determined for 22 clinical strains MRSA with inducible type of resistance to MLS-B and for 15 of their derivatives with constitutive resistance to MLS-B. For MRSA strains with inducible resistance to MLS-B the obtained results for quinupristin/ dalfopristin were: MIC50 = 0.25, MIC90 = 0.5, MBC50 = 1.0 and MBC90 = 1.0. Mutants of the same strains characterized with the following values for quinopristin/dalfopristin: MIC50 = 0.5, MIC90 = 1.5, MBC50 = 4.0 and MTC90 = 8.0.

01 Jan 2006
TL;DR: In this study, the in vitro activities of ampici llin, ciprofloxacin, vancomycin, teicoplanin, linezolid and Q/D and high level resistance to gentamycin were determined for 137 Enterococcus species isolated from the intensive care unit.
Abstract: Objective: Recently, there has been a dramatic increase in the number of nosocomial infections caused by enterococci. Intensive care unit is the part of the hospital with the highest frequency of nosocomial enterococcal infections. Since enterococci are i ntrinsically resistant to �-lactams and aminoglycosides and they acquired high-level resistance to many other antimicrobial agents, new classes of antimicrobial agents became available in several countries. Material and Methods: In this study, the in vitro activities of ampici llin, ciprofloxacin, vancomycin, teicoplanin, linezolid and qui nupristin/dalfopristin (Q/D) and high level resistance to gentam ycin were determined for 137 Enterococcus species (96 E. faeca lis and 41 E. faecium ) isolated from our intensive care unit. Results: MICs of vancomycin, teicoplanin, linezolid and Q/D were determined by E-test. All enterococcal isolates were susceptible to vancomycin, teicoplanin and linezolid. High- level resistanc e to gentamycin was observed in 21.9% of E. faecalis and 26.8% of E. faecium isolates. While ampicillin resistance rate was 16.7% for E. faecalis isolates, it was 73.2% for E. faecium strains. Ninety percent of E. faecalis and 100% E. faecium is olates with high-level resistance to gentamycin were also resi stant to ciprofloxacin. Conclusions: Although Q/D is not available in clinical settings in our country, 7.3% of E. Faecium and 72.9% of E. faecalis isolates were resistant to this drug.