virginiamycin and Skin-Diseases--Bacterial

With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multidrug-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 those presently in clinical development for the treatment of skin and skin structure infections. Linezolid, quinupristin-dalfopristin, and daptomycin have been approved by the Food and Drug Administration for the treatment of skin and skin structure infections. Two newer compounds, oritavancin and dalbavancin, are in clinical development for this indication. In addition, the quinolones moxifloxacin and gatifloxacin recently were approved for cutaneous infections.. At the conclusion of this learning activity, participants should be familiar with the modes of action, clinical indications, dosage regimens, and contraindications and cautions for several novel antibacterial agents for skin and skin structure infections.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Humans; Linezolid; Oxazolidinones; Quinolones; Skin Diseases, Bacterial; Soft Tissue Infections; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Half-Life; Humans; Linezolid; Metabolic Clearance Rate; Oxazolidinones; Skin Diseases, Bacterial; Virginiamycin

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.

Topics: Acetamides; Anti-Bacterial Agents; Biological Availability; Drug Therapy, Combination; Gram-Positive Bacterial Infections; Half-Life; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Virginiamycin

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

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

This study was aimed to compare the clinical and antibacterial efficacy of fusidic acid 500 mg twice a day, per os, over 7.5 days) to pristinamycin 1 g twice a day, per os, over 10 days).. Patients aged over 18, suffering from a superficial pyoderma requiring antibiotherapy and having given their informed consent were enrolled in a controlled, multicentre, double blind double dummy, parallel groups study. From day 0 to day 10, the patients received the randomised treatment. Those who were cured at day 11 had a visit at day 25 without any treatment between day 11 and day 25. A swab was performed on days 0, 11 and 25. The two treatment groups were compared in terms of efficacy, safety and global cost.. 334 patients seen in dermatologic consultation were included in the study. 313 patients were analysed on an intent-to-treat basis. 158 received fusidic acid (FA) and 155 were treated with pristinamycin (P). At D11, 126 patients were cured in the FA group (79.7%) and 118 in the P group (76.1%) (p = 0.44). The bacteriological success rate was 85.2% in the FA group and 82.7 in the P group (p = 0.67). The recovery was confirmed in 92.6% of the FA patients and 90.4% of the P patients at D25 (p = 0.56). Digestive tolerance was better with fusidic acid than with pristinamycin. In economic terms, fusidic acid was cheaper than pristinamycin: 443 French francs in the FA group versus 545 FF in the P group.. Therefore we conclude that an oral course of 7.5 days with fusidic acid is an efficient and cheaper alternative to a treatment with pristinamycin over 10 days.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Costs and Cost Analysis; Data Interpretation, Statistical; Double-Blind Method; Female; Fusidic Acid; Humans; Male; Middle Aged; Placebos; Pyoderma; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Streptococcal Infections; Time Factors; Virginiamycin

Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the treatment of severe gram-positive infections. The purpose of this open, nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics after single and repeated doses under the two different dosing regimens corresponding to the effective doses and to evaluate tolerability. Two groups of 10 healthy volunteers received multiple 1-hour intravenous infusions of 7.5 mg/kg Q/D either every 8 or 12 hours for 4 or 5 days, respectively. Plasma concentrations of Q, D, and metabolites were determined using high-performance liquid chromatography and selective microbiological assays. The two regimens q8h and q12h lead to the same disposition profile after single and repeated administration. Single-dose data confirmed the high plasma clearances of Q and D (about 0.90 l/h/kg) obtained previously. Unchanged drugs were the main components in plasma, with each of the three metabolites representing about 20% (in terms of the AUC ratio) of the parent drugs. Comparable steady-state concentrations were reached from day 2 of both regimens. A similar moderate increase in Cmax and AUC (about 20%) of parent drugs was observed between the first and last day of treatment. This phenomenon, which was also observed for the metabolites, was not expected considering the short terminal disposition half-lives of the parent drugs and trough plasma concentrations of all components mostly below the limits of quantitation at steady state, whatever the dosing regimen. The clearances of parent drugs at steady state were about 20% lower as compared with that observed following the first drug administration (statistically significant difference). No trend suggesting a treatment effect on any laboratory parameter, vital signs, or electrocardiographic parameters was identified. However, 80% of subjects reported venous adverse events probably related to treatment.

Topics: Adolescent; Adult; Area Under Curve; Biological Assay; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Half-Life; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Skin Diseases, Bacterial; Time Factors; Virginiamycin

Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), w

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cefazolin; Cephalosporins; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitalization; Humans; Male; Middle Aged; Oxacillin; Penicillins; Skin Diseases, Bacterial; Vancomycin; Virginiamycin

We recently demonstrated that oral roxithromycin is as effective as intravenous penicillin G in adults with erysipelas. We therefore evaluated the effectiveness of pristinamycin, an antibiotic which is very active on streptococci and Staphylococcus aureus, in non-necrotizing bacterial dermohypodermitis in adults.. This prospective open study was conducted in one center and included immunocompetent patients with bacterial dermophypodermitis without signs of toxicity or local manifestations suggesting necrotizing fasciitis. Bacteriology tests included direct immunofluorescence for streptococcus (groups A, C, G) on skin biopsies of the lesion before treatment. Patients were treated with pristinamycin (Pyostacine 500, 3 g/day until 10 days after apyrexia), and evaluated clinically on day 0, 2, 6, 8, and 15. Overall treatment effect was assessed on day 15.. The study group included 42 adults (23 woman and 19 men; mean age 64 +/- 3.5 yr). In 39 cases (93%), the bacterial dermohypodermitis was localized on the lower limb. The inflammatory lesion was well delimited, a characteristic feature of erysipelas, in 32 cases (76%). Sample culture, direct immunofluorescence or serology findings demonstrated presence of streptococci in 33 cases (79%). A single treatment with pristinamycin was successful in 36 patients, giving an overall rate of 86%. Drainage of a localized abscess was successful in 5 of 6 patients after initial failure of antibiotic treatment.. This prospective study demonstrated the effectiveness of pristinamycin in non-necrotizing bacterial dermohypodermitis in the adult, especially in erysipelas. Overall effectiveness was comparable with that reported for penicillin G or macrolides in erysipelas.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Erysipelas; Female; Humans; Male; Middle Aged; Prospective Studies; Skin Diseases, Bacterial; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome; Virginiamycin

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