quinupristin and Gram-Positive-Bacterial-Infections

Multi-antibiotic resistant Gram-positive cocci represent emerging pathogens especially in the setting of the immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are of concern, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics and/or immunosuppressive drugs are widely administered. The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds represent an effective response to these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern. The main problems related to the epidemiological and clinical features of multiresistant Gram-positive infection, the potential clinical indications of all recently available compounds compared with the standard of treatment of resistant Gram-positive infections, and updated data on efficacy and tolerability of linezolid have to be clarified.

Topics: Acetamides; Administration, Oral; Anti-Infective Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enterococcus; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Staphylococcus aureus; Streptococcus pneumoniae; Teicoplanin; Tigecycline; Time Factors; Vancomycin; Virginiamycin

Four newer antibiotics are available to treat gram-positive bacterial infections that are resistant to traditional antibiotics and to vancomycin. They should preferably be used with the help of an infectious-disease consultant: specific therapy should be chosen on the basis of the bacteria involved, the site of infection, whether the patient has kidney or liver disease, other medications the patient is taking, and side effects that develop.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Female; Gram-Positive Bacterial Infections; Humans; Middle Aged; Vancomycin; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Proteins; Depression, Chemical; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Virginiamycin

Gram-positive pathogens, primarily Staphylococcus aureus, coagulase-negative staphylococci, viridans group streptococci, and enterococci, are now the predominant causes of infection in neutropenic haematology/oncology patients, but are often resistant to multiple antibiotics. Glycopeptides have been the only alternative antibiotic treatments for multidrug-resistant Gram-positive infections to date. However, glycopeptides are not always effective or well tolerated, and can produce nephrotoxic or ototoxic effects. Quinupristin/dalfopristin is a recently introduced streptogramin antibiotic that is active in vitro against most of the major Gram-positive pathogens causing infection in neutropenic patients. Recent studies of the in vitro susceptibility of clinical isolates of Gram-positive pathogens to quinupristin/dalfopristin are summarized. Pre-clinical and clinical studies of the efficacy and safety of quinupristin/dalfopristin in the treatment of Gram-positive infections are reviewed. Quinupristin/dalfopristin is active in vitro against the vast majority of recent isolates of relevant Gram-positive pathogens, including methicillin-resistant staphylococci, viridans group streptococci, and vancomycin-resistant Enterococcus faecium, but excluding Enterococcus faecalis. Pre-clinical and clinical data indicate the efficacy of quinupristin/dalfopristin in infections caused by these organisms, including bacteraemia and catheter-related infections. Quinupristin/dalfopristin is not associated with nephrotoxicity or ototoxicity. 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.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Neutropenia; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Treatment Outcome; Virginiamycin

The combination of two injectable streptogramins, quinupristin/dalfopristin, provides a new pharmacological choice proven to be therapeutically efficacious against most Gram-positive, multi-resistant microorganisms. They have been shown to be efficacious above all in critically ill patients hospitalized in intensive care who have unique alterations in homeostasis that makes tissue penetration of various pharmacological antimicrobials difficult. In cases of infection localized in difficult-to-treat sites, the combination with other drugs, such as cefepime, a glycopeptide or linezolid, is able to potentiate the action of the streptogramin with positive results which allow resolution of the illness. In this article, we review data from the literature on the use of quinupristin/dalfopristin in the treatment of Gram-positive, multi-resistant infections in critically ill patients.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Streptogramins; Virginiamycin

Quinupristin + dalfopristin* (Synercid -- Aventis Pharma Ltd) is a new combination antibacterial product licensed for treating patients with a variety of Gram-positive infections. Here we assess its place in clinical practice.

Topics: Anti-Bacterial Agents; Drug Costs; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Superinfection; Virginiamycin

Topics: Acetamides; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Child; Cross Infection; Drug Combinations; Gram-Positive Bacterial Infections; Humans; Infant; Infant, Newborn; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Tissue Distribution; Virginiamycin

Vancomycin is a safe, effective antibiotic for a variety of serious gram-positive infections. Because of emerging resistance in enterococci and staphylococci and the emerging threat of spread of vancomycin-resistant genes to other gram-positive organisms, judicious use of vancomycin should be promoted. Quinupristin/dalfopristin, a streptogramin antibiotic, and linezolid, an oxazolidinone, show promise against some strains of gram-positive bacteria that are resistant to vancomycin.

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Microbial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazoles; Oxazolidinones; Teicoplanin; Vancomycin; Virginiamycin

Gram-positive bacteria (e.g. Staphylococcus aureus and Streptococcus pyogenes) are the main cause of skin and skin structure infections (SSSI). Treatment presents a clinical challenge to the physician, particularly with the increase in multidrug-resistant strains and widespread cross-resistance to antibiotic treatment. Initial treatment of SSSI involves the use of fluoroquinolones or penicillinase-resistant penicillins. If infection is caused by methicillin-resistant staphylococci, therapy with glycopeptides is warranted. However, in the last few years several cases of infection caused by strains of S. aureus with reduced susceptibility to glycopeptides have been reported. Quinupristin/dalfopristin is a new streptogramin that has shown efficacy in the management of multidrug-resistant gram-positive infections. Two major studies suggest that in the treatment of complicated SSSI, the clinical efficacy of quinupristin/dalfopristin is equivalent to that of vancomycin and/or oxacillin and vancomycin and/or cefazolin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Fluoroquinolones; Gram-Positive Bacterial Infections; Humans; Skin Diseases, Bacterial; Virginiamycin

To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction.. We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy.. Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05).. Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate.

Topics: Aged; Alkaline Phosphatase; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Arthralgia; Biliary Tract Diseases; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Immunosuppressive Agents; Liver Function Tests; Male; Methotrexate; Middle Aged; Muscular Diseases; Neoplasms; Pain; Recurrence; Risk Factors; Tacrolimus; Virginiamycin

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Child; Drug Therapy, Combination; Enterococcus; Enterococcus faecalis; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Immunity; Male; Middle Aged; Minocycline; Neoplasms; Pain; Vancomycin Resistance; Virginiamycin

To find a therapeutic alternative for the treatment of skin and soft tissue infections, we evaluated the effects of combinations of retapamulin with macrolide, lincosamide, and streptogramin (MLS) antibiotics against Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecium, and Enterococcus faecalis. Using both the disk diffusion test and checkerboard assay, we initially examined the effects of combinations of retapamulin with MLS antibiotics against standard strains of these species. Combinations of retapamulin with erythromycin, quinupristin/dalfopristin and quinupristin showed synergistic activity against E. faecalis only. Synergy of retapamulin with clindamycin and dalfopristin was not observed. Then, a checkerboard assay was performed to evaluate the effects of the combinations against 15 clinical strains of E. faecalis. Retapamulin and quinupristin, the most synergistic combination, showed activity against all erythromycin-susceptible, -intermediate, and -resistant strains tested. Among the eight strains with high-level erythromycin resistance, five strains were synergistically inhibited in the presence of only 1 μg of retapamulin per ml. Time-kill assay revealed that combinations of retapamulin with erythromycin and quinupristin were bacteriostatic. These results suggest that combinations of retapamulin with erythromycin and quinupristin have in vitro synergistic activity against E. faecalis, including strains with high-level erythromycin resistance.

Topics: Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Drug Synergism; Enterococcus faecalis; Enterococcus faecium; Erythromycin; Gram-Positive Bacterial Infections; Humans; Macrolides; Microbial Sensitivity Tests; Staphylococcus aureus; Streptococcus pyogenes; Virginiamycin

The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacterial Infections; Computational Biology; Daptomycin; Drug Delivery Systems; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Forecasting; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Minocycline; Oxazolidinones; Pharmacogenetics; Systems Biology; Tigecycline; Virginiamycin

VanA glycopeptide resistance has persisted on broiler farms in the UK despite the absence of the antimicrobial selective pressure, avoparcin. This study aimed to investigate the contribution of horizontal gene transfer of Tn1546 versus clonal spread in the dissemination of the resistance.. One hundred and one vancomycin-resistant Enterococcus faecium isolated from 19 unrelated farms have been investigated. Tn1546 characterization by long PCR and ClaI-digestions of amplicons showed a very low diversity of Tn types (n=4) in comparison to the high genotypic diversity demonstrated by PFGE (n=62). Conjugation experiments were carried out to assess the transfer of vancomycin resistance. Co-transfer of vanA together with erm(B) positioned on the same conjugative plasmid containing a replicon similar to pRE25 was demonstrated and also the presence of different plasmid replicons, associated with antimicrobial resistance on several unrelated farms.. Horizontal transfer of vancomycin resistance may play a more important role in the persistence of antimicrobial resistance than clonal spread. The presence of different plasmid replicons, associated with antimicrobial resistance on several unrelated farms, illustrates the ability of these enterococci to acquire and disseminate mobile genetic elements within integrated livestock systems.

Topics: Animals; Blotting, Southern; Chickens; DNA Primers; DNA Transposable Elements; Enterococcus faecium; Gene Transfer, Horizontal; Gram-Positive Bacterial Infections; Lincosamides; Macrolides; Plasmids; Poultry Diseases; Replicon; Reverse Transcriptase Polymerase Chain Reaction; Streptogramin B; United Kingdom; Vancomycin Resistance; Virginiamycin

Enterococcus faecalis strains with multiple antibiotic resistances can cause infections that are difficult to treat. The microbial flora in treatment-resistant apical periodontitis is dominated by E. faecalis, and is a potential source of infections at other sites.. Sensitivities to a range of antibiotics were determined for 59 endodontic E. faecalis isolates from Finland and Lithuania. The DNA sequence of the gene responsible for the species' intrinsic quinupristin-dalfopristin resistance, lsa, was determined from two isolates with diminished resistance. Four pairs of isolates from the same root canal were typed by pulsed-field gel electrophoresis.. A high prevalence of resistance to rifampicin was found, whereas all isolates were susceptible or showed intermediate susceptibility to penicillin and ampicillin and four isolates were unusually susceptible to cefotaxime. No vancomycin or high-level gentamicin resistance was detected. Nine of 59 isolates were susceptible to quinupristin-dalfopristin. A fully quinupristin-dalfopristin-susceptible isolate also susceptible to clindamycin produced a truncated Lsa polypeptide, and an isolate with borderline quinupristin-dalfopristin-susceptibility had mutations proximal to the predicted ribosomal binding site. Pulsed-field gel electrophoresis showed that the same root canal could harbor two different strains of E. faecalis during the course of the same infection.. Despite the differing antibiotic usage in Finland and Lithuania, E. faecalis from endodontic infections in these countries showed similar susceptibility patterns with levels of resistance considered typical for the species, and decreased resistance to clindamycin and quinupristin-dalfopristin as well as lesions in the lsa gene which were similar to those described in other clinical isolates.

Topics: Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Base Sequence; Dental Pulp Cavity; DNA Mutational Analysis; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecalis; Finland; Genes, Bacterial; Gram-Positive Bacterial Infections; Humans; Latvia; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Periapical Periodontitis; Virginiamycin

To evaluate the antibiotic susceptibilities of Propionibacterium acnes isolates from central nervous system (CNS) infections to agents used in current treatment regimens.. MICs of 16 reference antibiotics were determined by an agar dilution method for 24 consecutive strains of P. acnes isolated from individual patients with intracranial empyema or brain abscess. Bactericidal activities of antibiotics against P. acnes PAN14 were studied at 0.25-2 x MIC using a time-kill method.. All of the isolates were resistant to fosfomycin, intermediate or resistant to metronidazole and susceptible to all the other antibiotics tested, except for nine strains, which were intermediate to ofloxacin. Among antibiotics tested alone in time-kill experiments, vancomycin was the most effective drug and exhibited bactericidal activity after 24 h at 1x and 2 x MIC, whereas cefotaxime and ciprofloxacin were bactericidal after 48 h at 2 x MIC. No significant bactericidal activity could be demonstrated with the other antibiotics tested alone. The addition of cefotaxime to vancomycin resulted in bactericidal activity at lower concentrations (0.5 x MIC), whereas synergy was observed between quinupristin/dalfopristin and cefotaxime at 2 x MIC. In contrast, antagonism was observed between cefotaxime and linezolid, and ciprofloxacin and clindamycin.. Our data suggest that P. acnes isolates causing CNS infections remain highly susceptible to most antibiotics used for the treatment of such infections. Moreover, we showed that cefotaxime, vancomycin and ciprofloxacin possess good bactericidal activities against P. acnes, and that these activities may be enhanced when vancomycin is combined with cefotaxime or when cefotaxime is combined with quinupristin/dalfopristin.

Topics: Acetamides; Cefotaxime; Central Nervous System Infections; Drug Therapy, Combination; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Propionibacterium acnes; Vancomycin; Virginiamycin

The susceptibility of 135 vancomycin-resistant Enterococcus faecium bacteremic isolates to linezolid and quinupristin-dalfopristin was determined. All were susceptible to linezolid, while 88% were susceptible to quinupristin-dalfopristin prior to the clinical use of the drugs at our hospital. More than 6 months after their clinical use, a decrease in susceptibility was noted for only linezolid at 83%. This was related in part to a single G2576U gene mutation in domain V of the 23S rRNA gene.

Topics: Acetamides; Anti-Bacterial Agents; Drug Utilization; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Point Mutation; RNA, Bacterial; RNA, Ribosomal, 23S; Vancomycin Resistance; Virginiamycin

Enterococci are uncommon causes of CNS infection. We describe a case of ventriculitis and Ommaya reservoir infection due to vancomycin-resistant Enterococcus faecium successfully treated with the combination of i.v. quinupristin/dalfopristin and i.v. linezolid. The patient deteriorated after receiving three dosages of intraventricular quinupristin/dalfopristin. He recovered after discontinuation of intraventricular quinupristin/dalfopristin.

Topics: Aged; Brain Neoplasms; Central Nervous System Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterococcus faecium; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Injections, Intralesional; Lymphoma; Male; Opportunistic Infections; Risk Assessment; Treatment Outcome; Vancomycin; Virginiamycin

To demonstrate nosocomial transmission of Enterococcus faecium resistant to quinupristin/dalfopristin and vancomycin/teicoplanin among paediatric patients in a German hospital ward.. 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 SmaI-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.. 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), vat(D), vanA) on a large plasmid, which was transferable in mating experiments with an E. faecium recipient.. 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.

Topics: Anti-Bacterial Agents; Child; Cross Infection; Drug Resistance; Enterococcus faecium; Female; Genes, Bacterial; Gram-Positive Bacterial Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests; Phylogeny; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Vancomycin Resistance; Virginiamycin

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.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Diabetes Mellitus, Type 1; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gentamicins; Gram-Positive Bacterial Infections; Humans; Immunocompromised Host; Kidney Transplantation; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Recurrence; Treatment Outcome; Vancomycin Resistance; Virginiamycin

Life-threatening infections with multiresistant gram-positive bacteria are increasing. Treatment with quinupristin/dalfopristin (Q-D) has turned out to be effective against such resistant pathogens.. We report on treatment of six patients on dialysis (four with additional liver injury) and of one renal graft recipient with normal renal function who had severe infections caused by multiresistant Staphylococus epidermidis (1/7), methicillin-resistant Staphylococcus aureus (4/7) and vancomycin-resistant Enterococcus faecium (2/7).. Six out of seven patients were cured by therapy with Q-D in adjusted doses lasting for 10 to 34 days. Pharmacokinetics of Q-D and its metabolites were determined and remained within the therapeutic range, despite a modest increase of all compounds at the presumed steady state. The concentrations of the metabolites of Q-D were clearly lower than the parent drugs, including those of quinupristin-conjugated derivatives, which has not been reported previously.. These preliminary results suggest that: a) neither quinupristin nor dalfopristin or its metabolites accumulated despite the long duration of treatment; b) no adjustment of the standard dosage regimen (three times 7.5 mg/kg/day) is necessary in end-stage renal disease.

Topics: Aged; Aged, 80 and over; Bacteremia; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecium; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Kidney Failure, Chronic; Male; Methicillin Resistance; Middle Aged; Prospective Studies; Risk Assessment; Sampling Studies; Staphylococcal Infections; Treatment Outcome; Vancomycin Resistance; Virginiamycin

Antibiotic-resistant Gram-positive pathogens are an increasingly common cause of serious pediatric infections. Although quinupristin/dalfopristin demonstrates favorable activity against resistant Gram-positive pathogens (including many vancomycin-resistant and methicillin-resistant staphylococci), published experience in the pediatric patient population is limited.. We retrospectively analyzed data from the global quinupristin/dalfopristin Emergency-Use Program, which enrolled patients with serious Gram-positive infections who had no further therapy options because of resistance to, failure on or intolerance to standard antibiotic treatments. Our subset included safety and efficacy data from pediatric patients (age <18 years). There were no restrictions on underlying diseases, severity of illness or prior/concomitant antimicrobial use.. Between May 1995 and October 1999, 127 pediatric patients with 131 infections were enrolled. Microbiologic confirmation of etiology was available in 124 patients. All patients had 1 or more concomitant conditions, including malignancy and solid organ or bone marrow transplantation. The most frequent causative pathogens were vancomycin-resistant (80%), spp. (7%), methicillin-resistant (6%) and (4%). All but 21 patients received intravenous quinupristin/dalfopristin 7.5 mg/kg every 8 h. The favorable clinical response rate of quinupristin/dalfopristin was 86 of 124 (69%); the favorable microbiologic response rate was 97 of 124 (78%). Eleven patients (8%) had nonvenous adverse events classified as possibly or probably related to quinupristin/dalfopristin.. Quinupristin/dalfopristin demonstrated favorable response rates and was reasonably well-tolerated in pediatric patients with serious Gram-positive infections unable to receive alternative therapy. In our opinion quinupristin/dalfopristin is a therapeutic option for the management of such infections.

Topics: Adolescent; Bacteremia; Child; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Probability; Prognosis; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Virginiamycin

Data regarding clinical administration, outcomes, and costs of quinupristin-dalfopristin treatment in 48 patients with serious gram-positive infections in a large teaching hospital were analyzed retrospectively. Thirty-six patients had vancomycin-resistant Enterococcus faecium (VREF) infections, 10 had methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE) infections, and 2 were treated empirically Overall, 67% of the patients were clinically cured, and 56% had bacteriologic eradication; overall response rate was 48%. Patients with VREF bacteremia had the highest clinical cure (82%) and bacteriologic eradication (73%) rates. Mortality rate was 31%, but 6 of 15 patients who died were treated successfully with quinupristin-dalfopristin. Length of hospital stay was significantly shorter among patients who lived versus those who died (p<0.05). Similarly, the mean hospital cost/patient was significantly lower in patients who lived than in those who died ($35,244 vs $122,922). Quinupristin-dalfopristin is effective in the treatment of both VREF and MRSA or MRSE infections in patients who fail to respond to, or are intolerant of, vancomycin.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cost-Benefit Analysis; Drug Resistance, Microbial; Female; Gram-Positive Bacterial Infections; Humans; Length of Stay; Male; Middle Aged; Retrospective Studies; Vancomycin Resistance; Virginiamycin

The emergence and spread of vancomycin-resistant Enterococcus faecium (VREF) has presented serious therapeutic difficulties because of the lack of reliably active antibiotics. Quinupristin/dalfopristin is a new injectable streptogramin antibiotic that is active against most strains of VREF. Experience with this agent in adults with VREF infections is well-documented; however, there are few reports of its use in children. We report on eight children with VREF infections who received quinupristin/dalfopristin under a compassionate use protocol.. Quinupristin/dalfopristin was administered according to the manufacturer's recommendations. Clinical and laboratory data were recorded for each patient.. The infections treated comprised six cases of bacteremia and two of peritonitis. All patients had serious underlying conditions. Seven patients recovered fully. One patient died, having experienced a relapse of his infection after quinupristin/dalfopristin was discontinued. None of the patients experienced side effects or other adverse events.. Quinupristin/dalfopristin was well-tolerated and generally effective in children with infections caused by VREF. There is increasing evidence that it may be more effective than other currently available antibiotics in some such patients.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Infant; Male; Treatment Outcome; Vancomycin Resistance; Virginiamycin

Central nervous system infections involving vancomycin-resistant Enterococcus faecium (VREF) are infrequently described and pose significant therapeutic difficulties, because these organisms are intrinsically resistant to many antibiotics. We describe the use of intrathecal quinupristin/dalfopristin to treat a VREF-associated infection in a neuro--surgical patient.

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Enterococcus faecium; Fatal Outcome; Female; Gram-Positive Bacterial Infections; Humans; Hydrocephalus; Injections, Intravenous; Injections, Intraventricular; Injections, Spinal; Linezolid; Middle Aged; Oxazoles; Oxazolidinones; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Vancomycin; Ventriculoperitoneal Shunt; Virginiamycin

Topics: Adult; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Injections, Intraventricular; Male; Vancomycin; Ventriculoperitoneal Shunt; Virginiamycin

Topics: Anti-Bacterial Agents; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Meningitis, Bacterial; Virginiamycin