Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.

[1]  J. Lynch Hospital-acquired pneumonia: risk factors, microbiology, and treatment. , 2001 .

[2]  T. Fabian,et al.  Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group. , 2000, American journal of respiratory and critical care medicine.

[3]  J. Rello,et al.  Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. , 1999, American journal of respiratory and critical care medicine.

[4]  M. Rodnina,et al.  Ribosomal RNA is the target for oxazolidinones, a novel class of translational inhibitors. , 1999, RNA.

[5]  P. Hsueh,et al.  Longitudinal analysis of methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Taiwan. , 1999, Journal of the Formosan Medical Association = Taiwan yi zhi.

[6]  R. Gaynes,et al.  Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. , 1999, Critical care medicine.

[7]  R. Weinstein,et al.  Bird's-eye view of nosocomial infections in medical ICU: blue bugs, fungi, and device-days. , 1999, Critical care medicine.

[8]  T. File,et al.  Overview of resistance in the 1990s. , 1999, Chest.

[9]  R. Baughman,et al.  The diagnosis and treatment challenges in nosocomial pneumonia. , 1999, Diagnostic microbiology and infectious disease.

[10]  G Sherman,et al.  Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. , 1999, Chest.

[11]  R. Wise,et al.  The in-vitro activity of linezolid (U-100766) and tentative breakpoints. , 1998, The Journal of antimicrobial chemotherapy.

[12]  G. Campbell,et al.  Hospital-acquired pneumonia: epidemiology, etiology, and treatment. , 1998, Infectious disease clinics of North America.

[13]  T. Gottlieb,et al.  The independent evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid in methicillin-resistant Staphylococcus aureus in Australian teaching hospitals (1990-1995). Australian Group for Antimicrobial Resistance (AGAR). , 1998, The Journal of antimicrobial chemotherapy.

[14]  J. Maillet,et al.  Hospital-acquired pneumonia: methicillin resistance and intensive care unit admission. , 1998, The American journal of medicine.

[15]  D. Cook,et al.  Risk factors for ICU-acquired pneumonia. , 1998, JAMA.

[16]  L. Dresser,et al.  The Pharmacologic and Bacteriologic Properties of Oxazolidinones, a New Class of Synthetic Antimicrobials , 1998, Pharmacotherapy.

[17]  G. Kaatz,et al.  Comparative In Vitro Activities and Postantibiotic Effects of the Oxazolidinone Compounds Eperezolid (PNU-100592) and Linezolid (PNU-100766) versus Vancomycin against Staphylococcus aureus, Coagulase-Negative Staphylococci, Enterococcus faecalis, and Enterococcus faecium , 1998, Antimicrobial Agents and Chemotherapy.

[18]  A. Vuagnat,et al.  Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. , 1998, American journal of respiratory and critical care medicine.

[19]  M. Kollef,et al.  The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. , 1998, Chest.

[20]  M. Rybak,et al.  In vitro activities of an investigational quinolone, glycylcycline, glycopeptide, streptogramin, and oxazolidinone tested alone and in combinations against vancomycin-resistant Enterococcus faecium , 1997, Antimicrobial agents and chemotherapy.

[21]  L. Nicolle,et al.  Nosocomial Pneumonia on General Medical and Surgical Wards in a Tertiary-Care Hospital , 1997, Infection Control & Hospital Epidemiology.

[22]  K. Marotti,et al.  Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions , 1997, Antimicrobial agents and chemotherapy.

[23]  F. Tenover,et al.  Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. , 1997, The Journal of antimicrobial chemotherapy.

[24]  M. Niederman,et al.  Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. , 1997, Chest.

[25]  J. Jorgensen,et al.  In vitro activities of the oxazolidinone antibiotics U-100592 and U-100766 against Staphylococcus aureus and coagulase-negative Staphylococcus species , 1997, Antimicrobial agents and chemotherapy.

[26]  G. Eliopoulos,et al.  In vitro activities in new oxazolidinone antimicrobial agents against enterococci , 1996, Antimicrobial agents and chemotherapy.

[27]  D. Wilson,et al.  In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections , 1996, Antimicrobial agents and chemotherapy.

[28]  J. Kilburn,et al.  In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents , 1996, Antimicrobial agents and chemotherapy.

[29]  S. J. Brickner,et al.  Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. , 1996, Journal of medicinal chemistry.

[30]  D. Craven,et al.  Epidemiology of nosocomial pneumonia. New perspectives on an old disease. , 1995, Chest.

[31]  A. J. Block,et al.  HMOs and CEOs. , 1995, Chest.

[32]  H. Lode,et al.  Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  Ge Dl Epidemiology of nosocomial pneumonia in intensive care unit patients. , 1995 .

[34]  J. Rello,et al.  Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. , 1994, American journal of respiratory and critical care medicine.

[35]  L. Anderson,et al.  Guideline for Prevention of Nosocomial Pneumonia , 1994, Infection Control & Hospital Epidemiology.

[36]  L. Anderson,et al.  Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. , 1994, American journal of infection control.

[37]  A. D. Nogare Nosocomial pneumonia in the medical and surgical patient: Risk Factors and Primary Management , 1994 .

[38]  Jerome J. Schentag,et al.  Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group , 1994, Antimicrobial Agents and Chemotherapy.

[39]  E. Bergogne-Bérézin,et al.  Opportunistic nosocomial multiply resistant bacterial infections--their treatment and prevention. , 1993, The Journal of antimicrobial chemotherapy.

[40]  W J Martone,et al.  Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975-1991. , 1992, Infection control and hospital epidemiology.

[41]  D. Craven,et al.  Preventing nosocomial pneumonia: state of the art and perspectives for the 1990s. , 1991, The American journal of medicine.

[42]  S. Solomon,et al.  Nosocomial pneumonia in Medicare patients. Hospital costs and reimbursement patterns under the prospective payment system. , 1991, Archives of internal medicine.

[43]  G. Baum Textbook of Pulmonary Diseases , 1989 .

[44]  H. Lode,et al.  Prospective randomized controlled study of ciprofloxacin versus imipenem-cilastatin in severe clinical infections , 1987, Antimicrobial Agents and Chemotherapy.

[45]  L. Cone,et al.  Ceftazidime versus tobramycin-ticarcillin in the treatment of pneumonia and bacteremia , 1985, Antimicrobial Agents and Chemotherapy.

[46]  C. Craig,et al.  Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. , 1984, American journal of infection control.

[47]  E. Wong,et al.  Guideline for Prevention of Nosocomial Pneumonia , 1982, Infection Control.

[48]  Elder Ha,et al.  Nosocomial infection surveillance. , 1979 .

[49]  N. Anthonisen Steroids in COPD: the nearly eternal question. , 1999, Chest.

[50]  A. King,et al.  Incidence of antibiotic resistance in blood and urine isolates from hospitalized patients. Report from a European collaborative study. European Study Group on Antibiotic Resistance (ESGAR). , 1998, Scandinavian journal of infectious diseases.

[51]  M. Fine,et al.  Variations in antimicrobial use and cost in more than 2,000 patients with community-acquired pneumonia. , 1998, The American journal of medicine.

[52]  J. Dorca,et al.  Clinical and epidemiological findings in mechanically-ventilated patients with methicillin-resistant Staphylococcus aureus pneumonia. , 1998, European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology.

[53]  C. Campbell,et al.  Update: Staphylococcus aureus with reduced susceptibility to vancomycin--United States, 1997. , 1997, Canada communicable disease report = Releve des maladies transmissibles au Canada.

[54]  L. Mandell,et al.  Hospital-acquired pneumonia in adults: Diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: A consensus statement , 1996 .

[55]  D. George Epidemiology of nosocomial pneumonia in intensive care unit patients. , 1995, Clinics in chest medicine.

[56]  R. D. McCormick,et al.  Guideline for prevention of nosocomial pneumonia. Part I. Issues on prevention of nosocomial pneumonia - 1994 , 1994 .

[57]  D. Banker,et al.  Nosocomial infection. , 1994, Indian journal of medical sciences.

[58]  A. D. Dal Nogare,et al.  Nosocomial pneumonia in the medical and surgical patient. Risk factors and primary management. , 1994, The Medical clinics of North America.

[59]  K. Tipton,et al.  Interactions of monoamine oxidase with substrates and inhibitors , 1989, Medicinal research reviews.

[60]  J. Hughes,et al.  Nosocomial infection surveillance, 1984. , 1986, MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries.

[61]  H. Elder,et al.  Nosocomial infection surveillance. , 1979, QRB. Quality review bulletin.