quinupristin-dalfopristin and Pneumonia--Staphylococcal

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Topics: Adult; Aged; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Prospective Studies; Treatment Outcome; Vancomycin; Virginiamycin

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pneumonia, Staphylococcal; Tigecycline; Vancomycin; Virginiamycin

Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively.. We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA).. Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 2.99 +/- 0.44, 6.38 +/- 0.32, 5.75 +/- 0.43 and 8.40 +/- 0.14 log10 CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean +/- SEM): 5.17 +/- 0.52, 7.03 +/- 0.11, 7.10 +/- 0.49 and 7.18 +/- 0.36 log10 CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D.. Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.

Topics: Animals; Bacteremia; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Japan; Lung; Male; Methicillin Resistance; Mice; Mice, Inbred Strains; Pneumonia, Staphylococcal; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus; Vancomycin Resistance; 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