Showing papers on "Dalfopristin published in 2003"
TL;DR: Enterococci are the second to third most important bacterial genus in hospital infections and their transferable resistance genes are of special interest from medical point of view and across the food chain (by GREF-contaminated meat products), these multiple-resistant bacteria or their vanA gene clusters can reach humans.
248 citations
TL;DR: Staphylococcus aureus strain HMC3, was resistant to vancomycin (VRSA) through the presence of the vanA resistance gene; it also contained mecA, erm(A), erM(B), tet(K) and aac(6')-aph(2), conferring resistance to licensed beta-lactams, macrolides, tetracycline and aminoglycosides.
Abstract: Staphylococcus aureus strain HMC3 isolated at the Hershey Medical Center, was resistant to vancomycin (VRSA) through the presence of the vanA resistance gene; it also contained mecA, erm(A), erm(B), tet(K) and aac(6')-aph(2"), conferring resistance to licensed β-lactams, macrolides, tetracycline and aminoglycosides. HMC3 also had alterations in GyrA and GrlB and was resistant to available quinolones. Experimental drugs with low MICs (<2 mg/L) for VRSA HMC3 included cephalosporins BAL9141 and RWJ-54428; glycopeptides oritavancin and dalbavancin; the lipopeptide daptomycin; the glycolipodepsipeptide ramoplanin; new fluoroquinolones WCK 771 A, WCK 1153, DK-507k and sitafloxacin; and the DNA nanobinder GS02-02. These agents were all bactericidal as were trimethoprim/sulfamethoxazole and teicoplanin (MIC 4 mg/L). Oxa- zolidinones linezolid and ranbezolid; the injectable streptogramin quinupristin/dalfopristin; DNA nanobinders GS2-10547 and GS02-104; peptide deformylase inhibitors NVP-PDF713 and GS02-12; tetracycline derivative tigecycline; the antifolate iclaprim; mupirocin and fusidic acid were all active in vitro but bacteriostatic.
213 citations
TL;DR: Two- or three-agent combination regimens may be required with greater frequency, especially to cover the more prevalent resistances among both gram-positive cocci and gram-negative nonfermentative rods.
Abstract: Resistance to antimicrobial agents among clinically important pathogens in the community and hospital settings has compromised therapy and requires constant monitoring of emerging patterns. Although local information indexed by hospital service or ward remains preferred, the initiation of several comprehensive surveillance programs (SENTRY Antimicrobial Surveillance Program, MYSTIC Programme, ICARE, EARSS, etc.) offers quality susceptibility testing results to guide empirical treatment regimens. Enterococci and staphylococci with novel resistance mechanisms to glycopeptides (vancomycin, teicoplanin) require greater use of quinupristin/dalfopristin and linezolid. For streptococci, recent modifications of laboratory interpretive criteria for cefotaxime, ceftriaxone, and cefepime indicates that coverage remains at > or = 95%. Extended-spectrum beta-lactamases in Enterobacteriaceae and multidrug resistance in Acinetobacter spp. and Pseudomonas aeruginosa most challenge our choices of effective agents for nosocomial infections. Few new drugs have surfaced for therapy of these gram-negative bacilli, and two- or three-agent combination regimens may be required with greater frequency, especially to cover the more prevalent resistances among both gram-positive cocci and gram-negative nonfermentative rods.
174 citations
TL;DR: Quinupristin-dalfopristin and linezolid demonstrate in vitro activity against a wide range of gram-positive bacteria, including many isolates resistant to earlier antimicrobials.
Abstract: Quinupristin-dalfopristin and linezolid demonstrate in vitro activity against a wide range of gram-positive bacteria, including many isolates resistant to earlier antimicrobials Quinupristin-dalfopristin is inactive against Enterococcus faecalis but has been effective for treatment of infections due to vancomycin-resistant Enterococcus faecium associated with bacteremia In comparative trials, linezolid proved to be equivalent to comparator agents, resulting in its approval for several clinical indications The almost-complete bioavailability of linezolid permits oral administration Each agent can cause adverse effects that may limit use in individual patients Resistance to these drugs has been encountered infrequently among vancomycin-resistant E faecium Resistance to quinupristin-dalfopristin is rare among staphylococci in the United States, and resistance to linezolid is very rare Whether there is any benefit to use of these agents in combination regimens, and whether there are circumstances in which they might be alternatives to cell-wall active antibiotics for treatment of bone or endovascular infections, are questions that deserve further study
162 citations
TL;DR: An awareness of the prevalence and patterns of resistance among gram-positive nosocomial pathogens is vital for the appropriate treatment of hospitalized patients and efforts must be made to minimize the selection and spread of these organisms.
Abstract: Purpose of review The epidemiology of gram-positive pathogens in the intensive care unit are reviewed, recent trends in antimicrobial resistance among these organisms are discussed, and the significance of these data with respect to treatment are considered. Recent findings Results of surveillance studies published in 2001 and 2002 have demonstrated that gram-positive organisms such as Staphylococcus aureus, coagulase-negative staphylococci, and enterococci are among the most common bacteria infecting patients in intensive care units. Furthermore, these organisms are becoming increasingly resistant to available antimicrobial agents, and 2002 has ushered in worrisome developments such as the appearance of vancomycin-resistant S. aureus. Community-acquired methicillin-resistant S. aureus and the rise in incidence of vancomycin-resistant enterococci are other problems of great concern. Novel antibiotics such as quinupristin/dalfopristin and linezolid have activity against these agents, but resistance may develop to these agents as well. Studies have shown that infections caused by antibiotic-resistant organisms may be associated with increased morbidity, mortality, and costs. Exposure to antibiotics is a major risk factor for producing antibiotic resistance in patients, and methods to limit the spread of these organisms include restriction of antibiotic use, infection control, surveillance programs, and isolation procedures. Summary An awareness of the prevalence and patterns of resistance among gram-positive nosocomial pathogens is vital for the appropriate treatment of hospitalized patients. In addition, efforts must be made to minimize the selection and spread of these organisms.
140 citations
TL;DR: The mutations and epidemiology associated with fluoroquinolone-resistant pneumococci collected as part of the PROTEKT global surveillance programme during 1999-2000 were analyzed to conclude most levofloxacin-resistant isolates possess two mutations.
Abstract: Results: Levofloxacin resistance was low overall (1% worldwide), with higher rates in: Hong Kong (14.3%), South Korea (2.9%), USA (1.8%), Mexico (1.5%), Canada (1.4%) and Japan (1.3%). Levofloxacin resistance was very low or absent in European countries, and absent in Australia. Worldwide, there was a total of 35 levofloxacin-resistant isolates, of which 22 (63%) were resistant and 10 (29%) were intermediate to moxi- floxacin. All levofloxacin-resistant isolates were susceptible to telithromycin (≤0.5 mg/L), linezolid (≤2 mg/L) and quinupristin/dalfopristin (≤1 mg/L). One or more mutations in the topoisomerase genes were identified in all levofloxacin-resistant isolates; most of these isolates (33/35) had a mutation in one of the DNA gyrase encoding genes (gyrA, gyrB) and one of the topoisomerase IV encoding genes (parC, parE). Eighteen (51%) isolates carried the same combination of amino acid substitutions: Ser-81→Phe in GyrA and Ser-79→Phe in ParC. Isolates displaying a levofloxacin MIC of 2-4 mg/L generally had no mutation or one mutation in either a DNA gyrase or a topoisomerase IV gene, although most mutations were in parC.
126 citations
TL;DR: Only one E. faecium strain was resistant to penicillin, while all strains were sensitive to the glycopeptide antibiotics, vancomycin and teicoplanin, which are causes for concern.
125 citations
TL;DR: The emergence of SREF is likely to be the result of an interaction between QD use in medicine and the long-term use of virginiamycin for animal growth promotion, which has created a credible threat to the efficacy of QD.
Abstract: Vancomycin-resistant enterococci (VRE) are an important cause of hospital-acquired infections and an emerging infectious disease. VRE infections were resistant to standard antibiotics until quinupristin/dalfopristin (QD), a streptogramin antibiotic, was approved in 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections in people. After that decision, the practice of using virginiamycin in agriculture for animal growth promotion came under intense scrutiny. Virginiamycin, another streptogramin, threatens the efficacy of QD in medicine because streptogramin resistance in enterococci associated with food animals may be transferred to E faecium in hospitalised patients. Policy makers face an unavoidable conundrum when assessing risks for pre-emergent pathogens; good policies that prevent or delay adverse outcomes may leave little evidence that they had an effect. To provide a sound basis for policy, we have reviewed the epidemiology of E faecium and streptogramin resistance and present qualitative results from mathematical models. These models are based on simple assumptions consistent with evidence, and they establish reasonable expectations about the population-genetic and population-dynamic processes underlying the emergence of streptogramin-resistant E faecium (SREF). Using the model, we have identified critical aspects of SREF emergence. We conclude that the emergence of SREF is likely to be the result of an interaction between QD use in medicine and the long-term use of virginiamycin for animal growth promotion. Virginiamycin use has created a credible threat to the efficacy of QD by increasing the mobility and frequency of high-level resistance genes. The potential effects are greatest for intermediate rates of human-to-human transmission (R0 approximately equal 1).
78 citations
TL;DR: A 19,398-bp plasmid (pLME300), present in several erythromycin-resistant strains of Lb.
76 citations
TL;DR: Ramoplanin is a new glycolipodepsipeptide antibiotic that has features that particularly suit it for decolonization, and has potent bactericidal activity against Gram-positive organisms and limited side effects, which suggest that ramoplanin may have a role in future gastrointestinal decolonized regimens.
Abstract: Enterococci are naturally resistant to a wide range of antimicrobial agents. In addition, some enterococci, known as vancomycin-resistant enterococci (VRE) have become resistant to glycopeptide antibiotics. The therapeutic options for VRE infections are therefore very limited. New antimicrobials have been developed that are active against VRE, such as linezolid and quinupristin/dalfopristin. Others, e.g. tigecycline, daptomycin and oritavancin, are in the later stages of development. However, resistance has already been detected to some of these agents. Some success has been enjoyed through the application of older antibiotics against VRE. The lack of therapeutic options has led to the consideration of measures to prevent infection with VRE. In addition to standard infection control procedures such as isolation and hand washing, decolonization of the gastrointestinal tract has been investigated as a method for the prevention of VRE infection in vulnerable patient groups. Several decolonization regimens have been investigated. These include the use of ramoplanin, a new glycolipodepsipeptide antibiotic that has features that particularly suit it for decolonization. Ramoplanin is not absorbed from the gastrointestinal tract, has potent bactericidal activity against Gram-positive organisms and limited side effects. These features and current clinical evidence suggest that ramoplanin may have a role in future gastrointestinal decolonization regimens.
74 citations
TL;DR: resistances in enterococci continue to be documented worldwide, but rates within endemic areas like NA appears to be stabilizing, although some of the older agents remain usable as primary therapy or as alternatives to the newer agents such as the oxazolidinones.
TL;DR: An in vitro pharmacodynamic model with simulated endocardial vegetations incorporating protein and a high inoculum was used to simulate daptomycin, linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA strain.
Abstract: In search of treatment alternatives against vancomycin-resistant S. aureus (VRSA), an in vitro pharmacodynamic model with simulated endocardial vegetations incorporating protein and a high inoculum was used to simulate daptomycin, linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA strain. Daptomycin and quinupristin-dalfopristin exhibited the greatest bacterial reductions, and all tested agents except vancomycin exhibited bactericidal activity against the VRSA.
TL;DR: The magnitude of antibiotic resistance in bloodstream isolates, in particular Gram-positive bacteria, emphasizes the importance of hospital control measures, rational prescribing policies and new vaccine strategies.
Abstract: All bloodstream strains, total 1463, isolated during a 1 month period in 105 hospitals representing all geographical areas in France were collected to study their antimicrobial susceptibility. The three major species were Escherichia coli, Staphylococcus aureus and coagulase-negative staphylococci. Among the 242 S. aureus, 87 were resistant to methicillin and among those 99% were resistant to ciprofloxacin, 11.5% to gentamicin, 1% to quinupristin/dalfopristin and 8% were heterogeneously resistant to vancomycin. Study of the methicillin-resistant S. aureus indicated that 12 clones had disseminated in French hospitals, six being heterogeneously resistant to vancomycin. Among the Streptococcus pneumoniae, 43% showed decreased susceptibility to the penicillins and 42% to erythromycin. One isolate was highly resistant to fluoroquinolones. Gentamicin, cefotaxime, ciprofloxacin and gatifloxacin resistance was rare in Enterobacteriaceae with 95% of strains susceptible. The incidence of extended-spectrum beta-lactamases was quite low. Moreover more than 25% of Pseudomonas aeruginosa strains were resistant to ciprofloxacin and gentamicin. The magnitude of antibiotic resistance in bloodstream isolates, in particular Gram-positive bacteria, emphasizes the importance of hospital control measures, rational prescribing policies and new vaccine strategies.
TL;DR: The use of vancomycin in dialysis patients is of concern because of an increase in the prevalence of vancombycin-resistant enterococci (VRE) in kidney patients and S. aureus isolates with a high degree of resistance to topical antimicrobial agent mupirocin this article.
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.
TL;DR: These data show routes of dissemination of resistance to multiple antibiotics including streptogramins and glycopeptides in E. faecium via vertical and/or horizontal gene transfer.
Abstract: Objectives: To demonstrate nosocomial transmission of Enterococcus faeclum resistant to quinupristin/ dalfopristin and vancomycin/teicoplanin among paediatric patients in a German hospital ward. Materials and methods: Multiply-resistant E. faecium were isolated from three female patients aged 9 months, 2 and 15 years during a 10 day time span. Antibiotic susceptibilities were determined by microbroth dilution. Clonal relatedness among the isolates was investigated via Smal-macrorestriction analysis by PFGE, multilocus sequence typing (MLST), and plasmid profiling. Presence of virulence and resistance determinants was tested by polymerase chain reaction (PCR). Selected resistance genes were localized by Southern hybridizations. Results: A single E. faecium Isolate per patient was investigated. All exhibited resistances to quinupristin/ dalfopristin, vancomycin/teicoplanin, streptomycin (high-level), penicillin/ampicillin, erythromycin, oxytetracycline, chloramphenicol, rifampicin and fusidic acid. The isolates were susceptible to linezolid only and intermediately resistant to fluoroquinolones Including moxifloxacin. PFGE revealed identical patterns for all three Isolates. PCRs for virulence determinants hyaluronidase and enterococcal surface protein, esp, were negative, whereas PCR for the enterocin A gene was positive. MLST identified clonal type [8-5-1-1-1-1-1] belonging to a clonal subgroup C1 of hospital- and outbreak-related E. faecium. Southern hybridizations located several resistance genes (erm(B), va(D), vanA) on a large plasmid, which was transferable in mating experiments with an E. faecium recipient. Conclusions: These data show routes of dissemination of resistance to multiple antibiotics including streptogramins and glycopeptides in E. faecium via vertical and/or horizontal gene transfer. The isolates spread in the absence of a direct selective pressure, as none of the patients had received earlier streptogramin or glycopeptide therapy.
TL;DR: The newest antimicrobials reviewed herein are not a significant improvement upon older agents in the treatment of SSSIs, and perhaps this assessment will change if the penetrance of the antimicrobial resistance patterns described above reach a critical threshold and clinical failures become more widespread.
Abstract: Bacterial skin and skin structure infections (SSSIs) are among the most frequently seen infectious entities in the community setting and occasionally in the institutional setting. A wide variety of SSSIs exist, with cellulitis, impetigo and folliculitis being the most common. Most SSSIs are caused by aerobic staphylococci and streptococci, with aerobic Gram-negative bacilli and anaerobes being involved in more complicated infections. Systemic therapy with a variety of beta-lactams, macrolides and lincosamides (clindamycin) have been the cornerstone of SSSI therapy for many years. With the exception of mupirocin, topical therapy occupies a small therapeutic niche. Despite the emergence of antimicrobial resistance among the pathogens most commonly associated with SSSIs (for example, Streptococcus pyogenes and macrolides; Staphylococcus aureus and methicillin, vancomycin, penicillin and mupirocin), few treatment failures have been reported. The newest antimicrobials reviewed herein (linezolid, quinupristin/dalfopristin, gatifloxacin, gemifloxacin and moxifloxacin) are not a significant improvement upon older agents in the treatment of SSSIs. Perhaps this assessment will change if the penetrance of the antimicrobial resistance patterns described above reach a critical threshold and clinical failures become more widespread.
TL;DR: Findings confirm that the newer cephalosporins (cefepime and ceftriaxone) among broad-spectrum beta-lactam agents have a spectrum of activity that remains comprehensive for the commonly isolated Gram-positive pathogens.
TL;DR: The lsa gene confers intrinsic resistance to lincosamides and streptogramins A in Enterococcus faecalis, probably by active efflux and obtained by selection on agar plates containing clindamycin.
Abstract: The lsa gene confers intrinsic resistance to lincosamides and streptogramins A in Enterococcus faecalis, probably by active efflux. The lsa-like genes of two clinical isolates of E. faecalis susceptible to lincosamides and dalfopristin contained mutations that produced premature termination codons. Revertant mutants were obtained by selection on agar plates containing clindamycin.
TL;DR: Macrolide resistance has remained stable over the last five years and M-phenotypes are the most prevalent expression of MLS(B) resistance in North America, compared to previous SENTRY Program analysis.
TL;DR: The association between erythromycin and tetracycline resistance was common and the erm(B) and tet(M) determinants seem to be associated in the authors' VGS.
TL;DR: The structure of the VatD-dalfopristin complex can be used to predict positions where further structural modification of the drug might preclude enzyme binding and thereby circumvent Synercid® resistance.
TL;DR: A spectrum of pneumococci with varying susceptibilities to beta-lactams, macrolides and quinolones was tested for susceptibility to nine antibiotics, including the novel lipopeptide daptomycin, which demonstrated bactericidal activity in seven of eight strains tested.
Abstract: A spectrum of pneumococci with varying susceptibilities to β-lactams, macrolides and quinolones was tested for susceptibility to nine antibiotics, including the novel lipopeptide daptomycin. Daptomycin was active against all strains (MIC range ≤0.5 mg/L; MIC 50 0.125 mg/L; MIC 90 0.25 mg/L). All pneumococci were susceptible to vancomycin, teicoplanin, linezolid and quinupristin/dalfopristin, with MICs 90% killing at 1 h.
TL;DR: A limited number of new antimicrobial agents have been introduced with activity against the resistant gram-positive organisms that are responsible for problematic cardiovascular infections, including quinupristin/dalfopristin and linezolid.
TL;DR: A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resistant Enterococcus faecium tricuspid valve endocarditis and therapy with this combination of quinupristin/dalfopristin plus high-dose ampicillin achieved cure and later confirmed at 2-year follow-up.
Abstract: A 56-year-old man with diabetes mellitus and cadaveric renal transplantation had vancomycin-resistant Enterococcus faecium tricuspid valve endocarditis. Relapse followed 6 weeks of treatment with intravenous gentamicin and high-dose ampicillin. On the basis of previous data suggesting the potential for synergistic activity of quinupristin/dalfopristin plus high-dose ampicillin, therapy with this combination was administered for 63 days. Cure was achieved and later confirmed at 2-year follow-up.
TL;DR: There was no correlation between receipt of virginiamycin or weight gain and presence of quinupristin/dalfopristin-resistant strains.
TL;DR: XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents, and all compounds tested had unimodal MIC distributions.
Abstract: MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC50], 0.25 μg/ml; MIC90, 0.5 μg/ml), while quinupristin/dalfopristin had MICs which were 1 to 2 dilutions higher. Single components of both XRP 2868 and quinupristin/dalfopristin had higher MICs. Erythromycin A, azithromycin, clarithromycin, and clindamycin MICs were higher for penicillin G-intermediate and -resistant than -susceptible pneumococci. Against 150 H. influenzae strains, all compounds tested had unimodal MIC distributions. XRP 2868 had an overall MIC50 of 0.25 μg/ml and an MIC90 of 1.0 μg/ml, with no differences between β-lactamase-positive, β-lactamase-negative, and β-lactamase-negative ampicillin-resistant strains. Of note was the similarly low activity of one of its components, RPR 132552A. Pristinamycin and quinupristin/dalfopristin had MICs of 0.125 to 8.0 μg/ml; quinupristin alone had MICs of 8.0 to >64.0 μg/ml, and dalfopristin had MICs of 1.0 to >64.0 μg/ml. Erythromycin A, azithromycin, and clarithromycin had modal MICs of 4.0, 1.0, and 8.0 μg/ml, respectively. MICs of all compounds against H. parainfluenzae were 1 to 2 dilutions higher than against H. influenzae. XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents.
TL;DR: A rapid and specific high-performance liquid chromatography-mass spectrometry was developed for the determination of quinupristin and dalfopristin using positive electrospray tandem mass spectromaetry (+ESI-MS/MS) and the ratio of the slopes of the calibration curves was found to be 0.425, which matches the nominal ratio composition of the antimicrobial compounds in Synercid.
TL;DR: A case of ventriculitis and Ommaya reservoir infection due to vancomycin-resistant Enterococcus faecium successfully treated with the combination of i.
TL;DR: Quinupristin/dalfopristin is a potential alternative to glycopeptides in haematology or oncology patients with multidrug-resistant Gram-positive infections, especially those who are unresponsive to, or intolerant of, glycopePTides.
Journal Article•
TL;DR: This review focuses on agents newly introduced and FDA-approved for the treatment of skin and skin structure infections: linezolid and quinupristin/dalfopristin.
Abstract: With the continuing development of clinical drug resistance among bacteria, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important. With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives. This review focuses on agents newly introduced and FDA-approved for the treatment of skin and skin structure infections: linezolid and quinupristin/dalfopristin.