virginiamycin and Pneumonia--Bacterial

The proliferation of multidrug-resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium (VREF), has created a pressing need for effective alternative antibiotics. Quinupristin/dalfopristin is a new combination streptogramin product with a selective spectrum of antibacterial activity, mainly against gram-positive aerobic bacteria. It has been assessed primarily in emergency-use protocols, in hospitalized patients with skin and skin-structure infections, and in patients with VREF bacteremia.. The objectives of this review were to summarize important results of in vitro microbiologic studies; to provide information on relevant pharmacokinetic parameters, drug interactions, and Y-site compatibility; and to assess efficacy and safety data from clinical studies of quinupristin/dalfopristin.. Articles included in this review were identified by a MEDLINE search of the literature published between 1966 and September 2000 using the terms Synercid, quinupristin, and dalfopristin. Additional articles were retrieved from the reference lists of articles identified in the MEDLINE search.. In vitro analysis of the spectrum of activity of quinupristin/dalfopristin has confirmed its relatively selective coverage of gram-positive aerobic bacteria. Both quinupristin and dalfopristin undergo hepatic metabolism and are extensively excreted in the feces. Combination quinupristin/dalfopristin inhibits the cytochrome P450 3A4 pathway, and caution is warranted with concomitant use of other medications eliminated via this pathway. In trials in patients with VREF infections, treatment success with quinupristin/dalfopristin varied depending on the site of infection, ranging from 51.9% in bacteremia of unknown origin to 88.9% in urinary tract infections. The results of comparative clinical trials suggest that quinupristin/dalfopristin has similar efficacy to that of commonly used antibiotics, including cefazolin, oxacillin, and vancomycin, in patients with skin and skin-structure infections or nosocomial pneumonia. The most frequently reported adverse effects with administration of quinupristin/dalfopristin were infusion-site inflammation, pain, and edema; other infusion-site reactions; and thrombophlebitis. Arthralgia, myalgia, nausea, diarrhea, vomiting, and rash occurred in 2.5% to 4.6% of patients and were the most frequently reported systemic adverse events.. Outcomes data from clinical trials indicate that quinupristin/dalfopristin has the potential to play an important role in the treatment of bacteremia, complicated skin and skin-structure infections, and nosocomial pneumonia caused by VREF. Issues of bacterial resistance to quinupristin/dalfopristin and other appropriate uses of this combination agent remain to be elucidated.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Interactions; Drug Therapy, Combination; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Skin Diseases, Bacterial; Vancomycin Resistance; Virginiamycin

During the last decade there has been an unexpectedly rapid evolution of antimicrobial resistance in the respiratory pathogens for community- and hospital-acquired pneumonia. In order to choose the most optimal therapy for their patients, it is essential that physicians be aware of the prevalence and mechanisms of resistance and their implications on the effectiveness of the various antimicrobials.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; DNA Topoisomerases, Type II; Drug Resistance, Microbial; Drug Resistance, Multiple; Genes, Bacterial; Gram-Negative Bacterial Infections; Gram-Negative Facultatively Anaerobic Rods; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Mutation; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Staphylococcus aureus; Streptococcus pneumoniae; Virginiamycin

Activity of natural streptogramin (NSG) appears well adapted to pathogens responsible for CAP. The goal of this multicenter pilot study was to bring first data about efficacy of NSG in treatment of CAP. PATIENTS METHOD: Ten days of a NSG (1 gr b.i.d. or t.i.d.) regimen was administered to 46 hospitalized adult patients for CAP defined with fever > 38 degrees C, respiratory symptoms and X-ray opacity. Severely ill patients were excluded. A broncho-pulmonar sample (expectoration or trantracheal aspiration or protected distal sample) was performed in all patients.. two patients were excluded because of pulmonary embolism (n = 1) or tuberculosis (n = 1) and 44 patients were analyzed. 50% of them had associated disease, 20% had failure of prior antibiotherapy. At inclusion, mean fever was 39.2 +/- 0.7 degrees C, respiratory rate was 22 +/- 5/mn, PaO2 was 74 +/- 10 mmHg, chest X-ray showed bilateral opacity in 16%, unilateral in 84% and pleural fluid level in 6 cases. Etiological diagnosis was determined in 70% of cases. Streptococcus pneumoniae (n = 14), Haemophilus influenzae (n = 5), Legionella pneumophila (n = 2), Mycoplasma pneumoniae (n = 2) and Chlamydia psittaci (n = 1) were the most frequent isolated pathogens. 40 patients (91%) were cured with NSG and delay to obtain apyrexia was 4.4 +/- 3.9 days. NSG was stopped in 4 patients: 1 clinical and bacteriological failure (Klebsiella pneumoniae), 2 clinical failures (1 pneumococcus with purulent pleurisy, 1 pneumococcus with worsening of respiratory status), 1 patient with resistant H. influenzae strain in spite of favourable clinical evolution. NSG was well tolerated in 86% of patients.. these data invite to carry on evaluation of first line therapy of CAP with NSG.

Topics: Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome; 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

Quinupristin/dalfopristin (Synercid) is an i.v. antibiotic active against serious Gram-positive infections. Its unique dual mode of action means that the potential for resistance development is expected to be low. To determine the incidence of in vitro emerging resistance in worldwide clinical studies, susceptibility to quinupristin/dalfopristin was measured for baseline pathogens and corresponding on- or post-study isolates from 880 evaluable patients. In comparative studies of community-acquired pneumonia, complicated skin and skin structure infections, and nosocomial pneumonia, the incidence of emerging resistance was low (1 of 453; 0.22%; 95% CI: 0. 01-1.4%). Resistance development occurred in only one pathogen (methicillin-resistant Staphylococcus aureus). In noncomparative studies, six instances (1.8% of 338 evaluable cases; 95% CI: 0.7 to 4.0%) of emerging resistance (all vancomycin-resistant Enterococcus faecium) were confirmed, accompanied by therapeutic failure in four cases. Molecular typing did not confirm the identity of one pair of strains. Overall, the incidence of emerging resistance to quinupristin/dalfopristin was low.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Enterococcus faecium; Global Health; Humans; International Cooperation; Pneumonia, Bacterial; Pneumonia, Staphylococcal; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Virginiamycin