quinupristin and Staphylococcal-Infections

Research efforts to discover new compounds active against staphylococci are more than ever justified today. The incidence of methicillin-resistant staphylococci remains very high in hospitals, and the solution provided by glycopeptides is far from being satisfactory. These compounds exhibit mediocre pharmacokinetic and pharmacodynamic properties. Their ease and safety of use are poor. Finally, strains with diminished sensitivity to these antibiotics are beginning to appear. This article examines the opportunities offered by two new anti-staphylococcal agents: quinupristine-dalfopristine (Synercid) and linezolide (not marketed in France).

Topics: Acetamides; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Linezolid; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Virginiamycin

Safety and efficacy of quinupristin-dalfopristin (an injectable streptogramin antibiotic) were evaluated in the treatment of a variety of infections due to methicillin-resistant Staphylococcus aureus (MRSA) in patients either intolerant of or failing prior therapy. The influence of resistance phenotypes on treatment outcome was also assessed. This worldwide, multicentre, open-label, non-comparative, emergency-use clinical study enrolled patients with one or more of nine predefined, culture-confirmed infections with MRSA, who had no clinically appropriate alternative antibiotic therapy. The recommended quinupristin-dalfopristin dose was 7.5 mg/kg administered iv every 8 h for a duration judged appropriate by the investigator. There were no restrictions on prior or concomitant treatment with other antibiotics. Clinical, microbiological and laboratory assessments were performed at baseline, during study drug treatment, within 24 h after the last dose, and 7-21 days post-therapy. Ninety patients [age (mean +/- S.D.) 57.4 +/- 18.5 years] with significant underlying medical illnesses were treated at 63 centres in five countries. The most common indications were bone and joint infection (44.4% of patients) and skin and skin structure infection (16.7%). The mean (+/- S.D.) daily dose and treatment duration was 20.2 +/- 2.9 mg/kg/day for 28.5 +/- 22.3 days, most frequently administered every 8 h. The overall success rate (defined as a clinical outcome of either cure or improvement and a bacteriological outcome of eradication or presumed eradication) was 71.1% in the all-treated population (n = 90) and 66.7% in patients who were both clinically and bacteriologically evaluable (n = 27). Success rates for endocarditis, respiratory tract infection and bacteraemia of unknown source were below the population mean. The macrolide-lincosamide-streptogramin type B resistance phenotype did not appear to alter the response rate. The most common non-venous adverse events related to study medication were arthralgias (10.8%), myalgias (8.6%) and nausea (8.6%). Quinupristin-dalfopristin should be considered as a treatment option for infections caused by MRSA, especially in patients intolerant of or failing alternate therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Confidence Intervals; Drug Therapy, Combination; Emergency Treatment; Female; Humans; Male; Methicillin Resistance; Middle Aged; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Virginiamycin

Two different doses of quinupristin/dalfopristin were compared with intravenous vancomycin with regard to the efficacy and safety in the treatment of catheter-related staphylococcal bacteremia. A total of 39 patients were enrolled from 13 centers. For all treated patients with a baseline pathogen, outcome was comparable for all antibiotic study regimens. Discontinuation of the antibiotic for an adverse clinical event occurred in 12% of patients receiving quinupristin/dalfopristin and in 15% of those receiving vancomycin. Quinupristin/dalfopristin may have the potential to serve as an alternative agent in the treatment of catheter-related staphylococcal bacteremia. However, larger prospective randomized trials are required.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Catheterization; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Single-Blind Method; Staphylococcal Infections; Vancomycin; Virginiamycin

Topics: Aged; Bacteremia; Catheterization, Central Venous; Chronic Disease; Daptomycin; Discitis; Humans; Jugular Veins; Male; Methicillin-Resistant Staphylococcus aureus; Pancreatitis; Rifampin; Staphylococcal Infections; Vancomycin; Virginiamycin

We report here a 34-year-old woman with complicated severe opportunistic pulmonary infection, who was treated with the newly developed antibiotics quinupristin/dalfopristin (QPR/DPR) and voriconazole. She had received repeated chemotherapy, irradiation of the left lung, autologous and allogeneic bone marrow transplantation (BMT), and segmentectomy of the base of the left lung as treatments for Hodgkin's lymphoma. Although she had been in complete remission (CR), the structure of the left lung was severely degraded. Four years after achieving CR, she developed complicated life-threatening pulmonary infections with methicillin-resistant Staphylococcus epidermidis and Aspergillus niger during outpatient care. Chemotherapies with QPR/DPR for S. epidermidis pneumonia and voriconazole for chronic necrotizing pulmonary aspergillosis (CNPA) improved her symptoms rapidly without any major complications. 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.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Aspergillus niger; Chronic Disease; Drug Therapy, Combination; Female; Hodgkin Disease; Humans; Lung Diseases, Fungal; Lymphatic Irradiation; Necrosis; Pneumonia, Bacterial; Pyrimidines; Radiation Injuries; Radiography; Staphylococcal Infections; Staphylococcus epidermidis; Triazoles; Virginiamycin; Voriconazole

Topics: Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Greece; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus hominis; Virginiamycin

The growing incidence of infections due to Gram-positive multiresistant germs has stimulated research into new drugs endowed with broader activity, that are useful in case of infections unresponsive to common antibiotics. The case of a 28-year-old man infected with a methicillin resistant Staphylococcus aureus non responder to therapy with glycopeptide antibiotics is reported. At admission the patient presented a septic condition and required mechanical ventilation. Antibiotic therapy was immediately started with teicoplanin+meropenem. Blood culture and bronchial aspirate evidenced a methicillin resistant Staphylococcus aureus with high sensibility to glycopeptide antibiotics. Although this therapy produced a slight improvement in clinical condition and the patient was extubated, fever and leucocytosis associated with a BAL positive to methicillin resistant Staphylococcus aureus, in vitro susceptible to glycopeptides, persisted. Considering the possibility of a non-responder condition of the patient to glycopeptide antibiotics, quinupristin/dalfopristin was added. The streptogramin produced a quick improvement in clinical condition with resolution of sepsis and culture sterilization. The patient improved progressively and was discharged. In conclusion, in our experience the association quinupristin/dalfopristin was effective in the resolution of a critical methicillin resistant Staphylococcus aureus infection non responder to classical treatment with glycopeptide antibiotics that showed a high sensibility in vitro.

Topics: Adult; Anti-Bacterial Agents; Critical Illness; Humans; Male; Methicillin Resistance; Staphylococcal Infections; Thoracic Injuries; Tomography, X-Ray Computed; Virginiamycin; Wounds, Stab

We report our experience with quinupristin/ dalfopristin in combination with a glycopeptide in the treatment of severe staphylococcal infections failing previous glycopeptide regimens.. Five patients, affected by persistent bacteremia (n = 2), post-cardiothoracic surgery infection (n = 2) and post-traumatic bone infection (n = 1) due to methicillin-resistant Staphylococcus aureus (MRSA, n = 4) methicillin-resistant coagulase-negative Staphylococcus (MRCNS, n = 1) and unsuccessfully treated with antibiotics including a glycopeptide, were treated with a quinupristin/ dalfopristin and glycopeptide combination.. Three patients were clinically cured; one patient with MRSA thoracic aorta prosthetic infection relapsed after 3 months; one patient was lost to follow-up.. Quinupristin/dalfopristin, in combination with a glycopeptide, is an effective treatment option for severe methicillin-resistant staphylococcal infections failing previous glycopeptide regimens.

Topics: Adult; Aged; Anti-Bacterial Agents; Colony Count, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Staphylococcal Infections; Teicoplanin; Treatment Outcome; Vancomycin; Virginiamycin

To describe the efficacy and safety of quinupristin-dalfopristin (Q-D) as rescue therapy in critically ill patients with severe infections caused by methicillin-resistant staphylococci unresponsive to vancomycin treatment.. Observational study in the context of the compassionate use programme for Q-D.. Twelve mechanically ventilated patients suffering from severe staphylococcal infections, pretreated unsuccessfully with vancomycin despite in vitro sensitivity, were included. Patients received, intravenously, Q-D 7.5 mg/kg body weight 3 times daily. The duration of Q-D therapy averaged 11.8 days (range: 1-26 days). The outcome variables were clinical efficacy and bacteriological eradication.. Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were isolated in three patients each, and both bacteria were isolated from six patients. Eradication of pathogen(s) was achieved in 7 of 12 patients (66%). Five patients (42%) died due to severe co-morbidity. Adverse events related to Q-D were not observed and neither renal nor liver function was adversely affected.. Quinupristin-dalfopristin appears to be an efficient and safe antimicrobial drug for the rescue treatment of staphylococcal infections in critically ill patients. It may be considered as a treatment option in cases of vancomycin treatment failure.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Care; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Middle Aged; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; 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

We compared the efficacies of quinupristin-dalfopristin (Q-D; 30 mg/kg of body weight every 8 h) and vancomycin (60 mg/kg twice daily), alone or in combination with rifampin (10 mg/kg twice daily), in a rabbit model of methicillin-resistant Staphylococcus aureus knee prosthesis infection. In contrast to vancomycin, Q-D significantly reduced the mean log(10) CFU per gram of bone versus that for the controls. The combination of rifampin with either Q-D or vancomycin was significantly more effective than monotherapy.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Synergism; Drug Therapy, Combination; Joint Prosthesis; Methicillin Resistance; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Tissue Distribution; Vancomycin; Virginiamycin

We evaluated the activity of quinupristin-dalfopristin (Q-D) against three clinical strains of Staphylococcus aureus susceptible to Q (MIC, 8 microg/ml) and Q-D (MICs, 0.5 to 1 microg/ml) but displaying various levels of susceptibility to D. D was active against S. aureus HM 1054 (MIC, 4 microg/ml) and had reduced activity against S. aureus RP 13 and S. aureus N 95 (MICs, 32 and 64 microg/ml, respectively). In vitro, Q-D at a concentration two times the MIC (2xMIC) produced reductions of 4.3, 3.9, and 5.8 log(10) CFU/ml after 24 h of incubation for HM 1054, RP 13, and N 95, respectively. Comparable killing was obtained at 8xMIC. Q-D-resistant mutants were selected in vitro at a frequency of 2 x 10(-8) to 2 x 10(-7) for the three strains on agar containing 2xMIC of Q-D; no resistant bacteria were detected at 4xMIC. Rabbits with aortic endocarditis were treated for 4 days with Q-D at 30 mg/kg of body weight intramuscularly (i.m.) three times a day (t.i.d.) or vancomycin at 50 mg/kg i.m. t.i.d. In vivo, Q-D and vancomycin were similarly active and bactericidal against the three tested strains compared to the results for control animals (P < 0.01). Among animals infected with RP 13 and treated with Q-D, one rabbit retained Q-D-resistant mutants that were resistant to Q and to high levels of D (MICs, 64, >256, and 8 microg/ml for Q, D, and Q-D, respectively). We conclude that the bactericidal activity of Q-D against strains with reduced susceptibility to D and susceptible to Q-D is retained and is comparable to that of vancomycin. Acquisition of resistance to both Q and D is necessary to select resistance to Q-D.

Topics: Animals; Disease Models, Animal; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Microbial Sensitivity Tests; Mutation; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Virginiamycin