Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 753-762

Treatment of Gram-positive Nosocomial Pneumonia
Prospective Randomized Comparison of Quinupristin/Dalfopristin versus Vancomycin

J.-Y. FAGON, H. PATRICK, D. W. HAAS, A. TORRES, C. GIBERT, W. G. CHEADLE, R. E. FALCONE, J. D. ANHOLM, F. PAGANIN, T. C. FABIAN, F. LILIENTHAL, and the Nosocomial Pneumonia Group

Department of Intensive Care, Hopital Européen Georges Pompidou, Paris; Department of Intensive Care, Bichat Hospital, Paris; Intensive Care Unit, Felix Guyon Hospital, Saint Denis de la Reunion, and Rhône-Poulenc Rorer, Antony, France; Department of Pneumology, Hospital Clinic, Barcelona, Spain; Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; Vanderbilt University School of Medicine, Nashville; Department of Surgery, University of Tennessee, Memphis, Tennessee; Department of Surgery, University of Louisville, Kentucky; Grant Memorial Hospital, Columbus, Ohio; and Pulmonary Service, J. L. Pettis Veterans Affairs Medical Center, Loma Linda, California

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. Fagon J-Y, Patrick H, Haas DW, Torres A, Gibert C, Cheadle WG, Falcone RE, Anholm JD, Paganin F, Fabian TC, Lilienthal F, and the Nosocomial Pneumonia Group.

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