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Semin Respir Crit Care Med 2006; 27(1): 092-103
DOI: 10.1055/s-2006-933677
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Methicillin-Resistant S. aureus Ventilator-Associated Pneumonia: Strategies to Prevent and Treat

Anna P. Lam1 , Richard G. Wunderink1
  • 1Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Publication History

Publication Date:
01 March 2006 (online)

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ABSTRACT

Ventilator-associated pneumonias (VAPs) due to methicillin-resistant Staphylococcus aureus (MRSA) are rising in incidence and pose unique challenges in their prevention and treatment. Risk factors for the development of MRSA VAP include nasal carriage, prior antibiotic therapy, prolonged mechanical ventilation, poor infection control practices, head trauma/coma, and viral infection. Measures to prevent the development of MRSA VAP include general VAP prevention strategies and reduction of S. aureus nasal carriage. S. aureus possesses a variety of transferable genetic elements that encode proteins conferring resistance to several antibiotics, including β-lactams and glycopeptides. Successful treatment of MRSA VAP with currently available antibiotics has been poor. Current management guidelines recommend glycopeptides as initial therapy for MRSA VAP. However vancomycin success rates are low, ranging from only 35 to 57%. This may be due to the poor penetration of vancomycin into the lung, and alternate dosing regimens to increase tissue levels need to be further studied. Treatment with linezolid, which penetrates well into the lung, is associated with higher cure and survival rates. Further data are needed to evaluate the efficacy of new antibiotics in MRSA VAP.

KEYWORDS

Methicillin-resistance - S. aureus - pneumonia - ventilator-associated pneumonia - vancomycin - linezolid

REFERENCES

  • 1 McGahee W, Lowy F D. Staphylococcal infections in the intensive care unit.  Semin Respir Infect. 2000;  15 308-313
    PubMedGoogle Scholar
  • 2 Noskin G A, Rubin R J, Schentag J J et al.. The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database.  Arch Intern Med. 2005;  165 1756-1761
    CrossrefPubMedGoogle Scholar
  • 3 Chambers H F. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications.  Clin Microbiol Rev. 1997;  10 781-791
    CrossrefPubMedGoogle Scholar
  • 4 Fridkin S K. Increasing prevalence of antimicrobial resistance in intensive care units.  Crit Care Med. 2001;  29 N64-68
    PubMedGoogle Scholar
  • 5 Streit J M, Jones R N, Sader H S, Fritsche T R. Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001).  Int J Antimicrob Agents. 2004;  24 111-118
    CrossrefPubMedGoogle Scholar
  • 6 Fluit A C, Verhoef J, Schmitz F J. Frequency of isolation and antimicrobial resistance of gram-negative and gram-positive bacteria from patients in intensive care units of 25 European university hospitals participating in the European arm of the SENTRY Antimicrobial Surveillance Program 1997-1998.  Eur J Clin Microbiol Infect Dis. 2001;  20 617-625
    PubMedGoogle Scholar
  • 7 Ho P L. Carriage of methicillin-resistant Staphylococcus aureus, ceftazidime-resistant gram-negative bacilli, and vancomycin-resistant enterococci before and after intensive care unit admission.  Crit Care Med. 2003;  31 1175-1182
    PubMedGoogle Scholar
  • 8 Hubmayr R D, Burchardi H, Elliot M et al.. Statement of the 4th International Consensus Conference in Critical Care on ICU-Acquired Pneumonia-Chicago, Illinois, May 2002.  Intensive Care Med. 2002;  28 1521-1536
    CrossrefPubMedGoogle Scholar
  • 9 Fagon J Y, Chastre J, Hance A J, Montravers P, Novara A, Gibert C. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.  Am J Med. 1993;  94 281-288
    CrossrefPubMedGoogle Scholar
  • 10 Heyland D K, Cook D J, Griffith L, Keenan S P, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group.  Am J Respir Crit Care Med. 1999;  159 1249-1256
    CrossrefPubMedGoogle Scholar
  • 11 Torres A, Carlet J. Ventilator-associated pneumonia. European Task Force on ventilator-associated pneumonia.  Eur Respir J. 2001;  17 1034-1045
    CrossrefPubMedGoogle Scholar
  • 12 Trouillet J L, Chastre J, Vuagnat A et al.. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria.  Am J Respir Crit Care Med. 1998;  157 531-539
    CrossrefPubMedGoogle Scholar
  • 13 Rello J, Sa-Borges M, Correa H, Leal S R, Baraibar J. Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices.  Am J Respir Crit Care Med. 1999;  160 608-613
    CrossrefPubMedGoogle Scholar
  • 14 Babcock H M, Zack J E, Garrison T, Trovillion E, Kollef M H, Fraser V J. Ventilator-associated pneumonia in a multi-hospital system: differences in microbiology by location.  Infect Control Hosp Epidemiol. 2003;  24 853-858
    CrossrefPubMedGoogle Scholar
  • 15 Namias N, Samiian L, Nino D et al.. Incidence and susceptibility of pathogenic bacteria vary between intensive care units within a single hospital: implications for empiric antibiotic strategies.  J Trauma. 2000;  49 638-645 discussion 645-646
    CrossrefPubMedGoogle Scholar
  • 16 Ibrahim E H, Ward S, Sherman G, Schaiff R, Fraser V J, Kollef M H. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.  Crit Care Med. 2001;  29 1109-1115
    CrossrefPubMedGoogle Scholar
  • 17 American Thoracic Society/Infactious Diseases Society of America . Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.  Am J Respir Crit Care Med. 2005;  171 388-416
    CrossrefPubMedGoogle Scholar
  • 18 Fagon J Y, Chastre J, Domart Y et al.. Nosocomial pneumonia in patients receiving continuous mechanical ventilation: prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques.  Am Rev Respir Dis. 1989;  139 877-884
    PubMedGoogle Scholar
  • 19 Wunderink R G, Cammarata S K, Oliphant T H, Kollef M H. Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia.  Clin Ther. 2003;  25 980-992
    CrossrefPubMedGoogle Scholar
  • 20 Rello J, Sole-Violan J, Sa-Borges M et al.. Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides.  Crit Care Med. 2005;  33 1983-1987
    CrossrefPubMedGoogle Scholar
  • 21 Rello J, Torres A, Ricart M et al.. Ventilator-associated pneumonia by Staphylococcus aureus: comparison of methicillin-resistant and methicillin-sensitive episodes.  Am J Respir Crit Care Med. 1994;  150 1545-1549
    CrossrefPubMedGoogle Scholar
  • 22 Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo J J. Bacteremic pneumonia due to Staphylococcus aureus: a comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.  Clin Infect Dis. 1999;  29 1171-1177
    CrossrefPubMedGoogle Scholar
  • 23 Cosgrove S E, Sakoulas G, Perencevich E N, Schwaber M J, Karchmer A W, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis.  Clin Infect Dis. 2003;  36 53-59
    PubMedGoogle Scholar
  • 24 Foster T J. The Staphylococcus aureus “superbug”.  J Clin Invest. 2004;  114 1693-1696
    CrossrefPubMedGoogle Scholar
  • 25 Sanford M D, Widmer A F, Bale M J, Jones R N, Wenzel R P. Efficient detection and long-term persistence of the carriage of methicillin-resistant Staphylococcus aureus .  Clin Infect Dis. 1994;  19 1123-1128
    PubMedGoogle Scholar
  • 26 Huang S S, Platt R. Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization.  Clin Infect Dis. 2003;  36 281-285
    CrossrefPubMedGoogle Scholar
  • 27 Naimi T S, LeDell K H, Como-Sabetti K et al.. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.  JAMA. 2003;  290 2976-2984
    CrossrefPubMedGoogle Scholar
  • 28 Tobin-D Anglo M, Arnold K, Lance-Park . Methicillin-resistant Staphylococcus aureus infections in correctional facilities-Georgia, California, and Texas, 2001-2003.  MMWR Morb Mortal Wkly Rep. 2003;  52 992-996
    PubMedGoogle Scholar
  • 29 Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections-Los Angeles County, California, 2002-2003.  MMWR Morb Mortal Wkly Rep. 2003;  52 88
    PubMedGoogle Scholar
  • 30 Gantz N, Harmon H, Hondy H et al.. Methicillin-resistant Staphylococcus aureus infections among competitive sports participants-Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003.  MMWR Morb Mortal Wkly Rep. 2003;  52 793-795
    PubMedGoogle Scholar
  • 31 Kaplan S L, Hulten K G, Gonzalez B E et al.. Three-year surveillance of community-acquired Staphylococcus aureus infections in children.  Clin Infect Dis. 2005;  40 1785-1791
    CrossrefPubMedGoogle Scholar
  • 32 Frazee B W, Lynn J, Charlebois E D, Lambert L, Lowery D, Perdreau-Remington F. High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections.  Ann Emerg Med. 2005;  45 311-320
    CrossrefPubMedGoogle Scholar
  • 33 Young D M, Harris H W, Charlebois E D et al.. An epidemic of methicillin-resistant Staphylococcus aureus soft tissue infections among medically underserved patients.  Arch Surg. 2004;  139 947-951 discussion 951-953
    PubMedGoogle Scholar
  • 34 Deryke C A, Lodise Jr T P, Rybak M J, McKinnon P S. Epidemiology, treatment, and outcomes of nosocomial bacteremic Staphylococcus aureus pneumonia.  Chest. 2005;  128 1414-1422
    CrossrefPubMedGoogle Scholar
  • 35 MacDougall C, Powell J P, Johnson C K, Edmond M B, Polk R E. Hospital and community fluoroquinolone use and resistance in Staphylococcus aureus and Escherichia coli in 17 US hospitals.  Clin Infect Dis. 2005;  41 435-440
    CrossrefPubMedGoogle Scholar
  • 36 Monnet D L, MacKenzie F M, Lopez-Lozano J M et al.. Antimicrobial drug use and methicillin-resistant Staphylococcus aureus, Aberdeen, 1996-2000.  Emerg Infect Dis. 2004;  10 1432-1441
    PubMedGoogle Scholar
  • 37 El-Solh A A, Pietrantoni C, Bhat A et al.. Microbiology of severe aspiration pneumonia in institutionalized elderly.  Am J Respir Crit Care Med. 2003;  167 1650-1654
    CrossrefPubMedGoogle Scholar
  • 38 Drinka P J, Gauerke C, Le D. Antimicrobial use and methicillin-resistant Staphylococcus aureus in a large nursing home.  J Am Med Dir Assoc. 2004;  5 256-258
    CrossrefPubMedGoogle Scholar
  • 39 Mendelson G, Yearmack Y, Granot E, Ben-Israel J, Colodner R, Raz R. Staphylococcus aureus carrier state among elderly residents of a long-term care facility.  J Am Med Dir Assoc. 2003;  4 125-127
    CrossrefPubMedGoogle Scholar
  • 40 Pujol M, Corbella X, Pena C et al.. Clinical and epidemiological findings in mechanically ventilated patients with methicillin-resistant Staphylococcus aureus pneumonia.  Eur J Clin Microbiol Infect Dis. 1998;  17 622-628
    PubMedGoogle Scholar
  • 41 Lucet J C, Paoletti X, Lolom I et al.. Successful long-term program for controlling methicillin-resistant Staphylococcus aureus in intensive care units.  Intensive Care Med. 2005;  31 1051-1057
    CrossrefPubMedGoogle Scholar
  • 42 Hsieh A H, Bishop M J, Kubilis P S, Newell D W, Pierson D J. Pneumonia following closed head injury.  Am Rev Respir Dis. 1992;  146 290-294
    PubMedGoogle Scholar
  • 43 Rello J, Ausina V, Ricart M, Puzo C, Net A, Prats G. Nosocomial pneumonia in critically ill comatose patients: need for a differential therapeutic approach.  Eur Respir J. 1992;  5 1249-1253
    PubMedGoogle Scholar
  • 44 Berrouane Y, Daudenthun I, Riegel B et al.. Early onset pneumonia in neurosurgical intensive care unit patients.  J Hosp Infect. 1998;  40 275-280
    CrossrefPubMedGoogle Scholar
  • 45 Bronchard R, Albaladejo P, Brezac G et al.. Early onset pneumonia: risk factors and consequences in head trauma patients.  Anesthesiology. 2004;  100 234-239
    CrossrefPubMedGoogle Scholar
  • 46 Campbell W, Hendrix E, Schwalbe R, Fattom A, Edelman R. Head-injured patients who are nasal carriers of Staphylococcus aureus are at high risk for Staphylococcus aureus pneumonia.  Crit Care Med. 1999;  27 798-801
    PubMedGoogle Scholar
  • 47 Ewig S, Torres A, El-Ebiary M et al.. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury: incidence, risk factors, and association with ventilator-associated pneumonia.  Am J Respir Crit Care Med. 1999;  159 188-198
    CrossrefPubMedGoogle Scholar
  • 48 Sirvent J M, Torres A, Vidaur L, Armengol J, de Batlle J, Bonet A. Tracheal colonisation within 24 h of intubation in patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia.  Intensive Care Med. 2000;  26 1369-1372
    PubMedGoogle Scholar
  • 49 Gillet Y, Issartel B, Vanhems P et al.. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients.  Lancet. 2002;  359 753-759
    CrossrefPubMedGoogle Scholar
  • 50 Bassetti S, Bischoff W E, Walter M et al.. Dispersal of Staphylococcus aureus into the air associated with a rhinovirus infection.  Infect Control Hosp Epidemiol. 2005;  26 196-203
    PubMedGoogle Scholar
  • 51 Fagon J Y, Chastre J, Wolff M et al.. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: a randomized trial.  Ann Intern Med. 2000;  132 621-630
    PubMedGoogle Scholar
  • 52 Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet D. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus .  Antimicrob Agents Chemother. 1999;  43 1412-1416
    PubMedGoogle Scholar
  • 53 Parras F, Guerrero M C, Bouza E et al.. Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus .  Antimicrob Agents Chemother. 1995;  39 175-179
    PubMedGoogle Scholar
  • 54 Krueger W A, Lenhart F P, Neeser G et al.. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.  Am J Respir Crit Care Med. 2002;  166 1029-1037
    CrossrefPubMedGoogle Scholar
  • 55 de Jonge E, Schultz M J, Spanjaard L et al.. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.  Lancet. 2003;  362 1011-1016
    CrossrefPubMedGoogle Scholar
  • 56 de Jonge E. Effects of selective decontamination of digestive tract on mortality and antibiotic resistance in the intensive-care unit.  Curr Opin Crit Care. 2005;  11 144-149
    CrossrefPubMedGoogle Scholar
  • 57 Verwaest C, Verhaegen J, Ferdinande P et al.. Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.  Crit Care Med. 1997;  25 63-71
    CrossrefPubMedGoogle Scholar
  • 58 Leone M, Albanese J, Antonini F, Nguyen-Michel A, Martin C. Long-term (6-year) effect of selective digestive decontamination on antimicrobial resistance in intensive care, multiple-trauma patients.  Crit Care Med. 2003;  31 2090-2095
    CrossrefPubMedGoogle Scholar
  • 59 Lingnau W, Berger J, Javorsky F, Fille M, Allerberger F, Benzer H. Changing bacterial ecology during a five-year period of selective intestinal decontamination.  J Hosp Infect. 1998;  39 195-206
    CrossrefPubMedGoogle Scholar
  • 60 Silvestri L, Milanese M, Oblach L et al.. Enteral vancomycin to control methicillin-resistant Staphylococcus aureus outbreak in mechanically ventilated patients.  Am J Infect Control. 2002;  30 391-399
    CrossrefPubMedGoogle Scholar
  • 61 Bergmans D C, Bonten M J, Gaillard C A et al.. Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.  Am J Respir Crit Care Med. 2001;  164 382-388
    PubMedGoogle Scholar
  • 62 Pugin J, Auckenthaler R, Lew D P, Suter P M. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia: a randomized, placebo-controlled, double-blind clinical trial.  JAMA. 1991;  265 2704-2710
    CrossrefPubMedGoogle Scholar
  • 63 Silvestri L, van Saene H K, Milanese M et al.. Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial.  Eur Respir J. 2004;  23 921-926
    PubMedGoogle Scholar
  • 64 Lindsay J A, Holden M T. Staphylococcus aureus: superbug, super genome?.  Trends Microbiol. 2004;  12 378-385
    CrossrefPubMedGoogle Scholar
  • 65 Melles D C, Gorkink R F, Boelens H A et al.. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus .  J Clin Invest. 2004;  114 1732-1740
    CrossrefPubMedGoogle Scholar
  • 66 Feil E J, Cooper J E, Grundmann H et al.. How clonal is Staphylococcus aureus? .  J Bacteriol. 2003;  185 3307-3316
    CrossrefPubMedGoogle Scholar
  • 67 Lowy F D. Staphylococcus aureus infections.  N Engl J Med. 1998;  339 520-532
    CrossrefPubMedGoogle Scholar
  • 68 Fedtke I, Gotz F, Peschel A. Bacterial evasion of innate host defenses: the Staphylococcus aureus lesson.  Int J Med Microbiol. 2004;  294 189-194
    CrossrefPubMedGoogle Scholar
  • 69 de Haas C J, Veldkamp K E, Peschel A et al.. Chemotaxis inhibitory protein of Staphylococcus aureus: a bacterial antiinflammatory agent.  J Exp Med. 2004;  199 687-695
    CrossrefPubMedGoogle Scholar
  • 70 Panton P NV. FCO. Staphylococcal toxin.  Lancet. 1931;  1 506-508
    PubMedGoogle Scholar
  • 71 Lina G, Piemont Y, Godail-Gamot F et al.. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia.  Clin Infect Dis. 1999;  29 1128-1132
    CrossrefPubMedGoogle Scholar
  • 72 Francis J S, Doherty M C, Lopatin U et al.. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes.  Clin Infect Dis. 2005;  40 100-107
    PubMedGoogle Scholar
  • 73 Vandenesch F, Naimi T, Enright M C et al.. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.  Emerg Infect Dis. 2003;  9 978-984
    CrossrefPubMedGoogle Scholar
  • 74 Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance.  Lancet Infect Dis. 2001;  1 147-155
    PubMedGoogle Scholar
  • 75 de Lencastre H, de Jonge B L, Matthews P R, Tomasz A. Molecular aspects of methicillin resistance in Staphylococcus aureus .  J Antimicrob Chemother. 1994;  33 7-24
    PubMedGoogle Scholar
  • 76 Ma X X, Ito T, Tiensasitorn C et al.. Novel type of staphylococcal cassette chromosome mec identified in community-acquired methicillin-resistant Staphylococcus aureus strains.  Antimicrob Agents Chemother. 2002;  46 1147-1152
    CrossrefPubMedGoogle Scholar
  • 77 Sakoulas G, Eliopoulos G M, Fowler Jr V G et al.. Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function.  Antimicrob Agents Chemother. 2005;  49 2687-2692
    CrossrefPubMedGoogle Scholar
  • 78 Moise-Broder P A, Sakoulas G, Eliopoulos G M, Schentag J J, Forrest A, Moellering Jr R C. Accessory gene regulator group II polymorphism in methicillin-resistant Staphylococcus aureus is predictive of failure of vancomycin therapy.  Clin Infect Dis. 2004;  38 1700-1705
    CrossrefPubMedGoogle Scholar
  • 79 Sakoulas G, Eliopoulos G M, Moellering Jr R C et al.. Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance?.  J Infect Dis. 2003;  187 929-938
    CrossrefPubMedGoogle Scholar
  • 80 Fowler Jr V G, Sakoulas G, McIntyre L M et al.. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein.  J Infect Dis. 2004;  190 1140-1149
    CrossrefPubMedGoogle Scholar
  • 81 Tomasz A, Drugeon H B, de Lencastre H M, Jabes D, McDougall L, Bille J. New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity.  Antimicrob Agents Chemother. 1989;  33 1869-1874
    PubMedGoogle Scholar
  • 81a Hiramatsn K, Hanaki H, Ino T, Yabnta K, Oguri T, Tenover F C. Methicillin-resistance Staphylococcus aureus clinical strain with reduced suscaptibility.  J Antimicrob Chemother. 1987;  40 135-136
    PubMedGoogle Scholar
  • 82 Chang S, Sievert D M, Hageman J C et al.. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene.  N Engl J Med. 2003;  348 1342-1347
    CrossrefPubMedGoogle Scholar
  • 83 Cosgrove S E, Carroll K C, Perl T M. Staphylococcus aureus with reduced susceptibility to vancomycin.  Clin Infect Dis. 2004;  39 539-545
    CrossrefPubMedGoogle Scholar
  • 84 Fridkin S K, Hageman J, McDougal L K et al.. Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997-2001.  Clin Infect Dis. 2003;  36 429-439
    CrossrefPubMedGoogle Scholar
  • 85 Sieradzki K, Roberts R B, Haber S W, Tomasz A. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection.  N Engl J Med. 1999;  340 517-523
    CrossrefPubMedGoogle Scholar
  • 86 Howe R A, Wootton M, Bennett P M, MacGowan A P, Walsh T R. Interactions between methicillin and vancomycin in methicillin-resistant Staphylococcus aureus strains displaying different phenotypes of vancomycin susceptibility.  J Clin Microbiol. 1999;  37 3068-3071
    PubMedGoogle Scholar
  • 87 Climo M W, Patron R L, Archer G L. Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin.  Antimicrob Agents Chemother. 1999;  43 1747-1753
    PubMedGoogle Scholar
  • 88 Bozdogan B, Esel D, Whitener C, Browne F A, Appelbaum P C. Antibacterial susceptibility of a vancomycin-resistant Staphylococcus aureus strain isolated at the Hershey Medical Center.  J Antimicrob Chemother. 2003;  52 864-868
    CrossrefPubMedGoogle Scholar
  • 89 Handwerger S, Skoble J, Discotto L F, Pucci M J. Heterogeneity of the vanA gene cluster in clinical isolates of enterococci from the northeastern United States.  Antimicrob Agents Chemother. 1995;  39 362-368
    PubMedGoogle Scholar
  • 90 Arthur M, Molinas C, Depardieu F, Courvalin P. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147.  J Bacteriol. 1993;  175 117-127
    PubMedGoogle Scholar
  • 91 Arthur M, Courvalin P. Genetics and mechanisms of glycopeptide resistance in enterococci.  Antimicrob Agents Chemother. 1993;  37 1563-1571
    PubMedGoogle Scholar
  • 92 Leclercq R, Dutka-Malen S, Brisson-Noel A et al.. Resistance of enterococci to aminoglycosides and glycopeptides.  Clin Infect Dis. 1992;  15 495-501
    PubMedGoogle Scholar
  • 93 Arthur M, Reynolds P E, Depardieu F et al.. Mechanisms of glycopeptide resistance in enterococci.  J Infect. 1996;  32 11-16
    CrossrefPubMedGoogle Scholar
  • 94 Evers S, Courvalin P. Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR(B) two-component regulatory system in Enterococcus faecalis V583.  J Bacteriol. 1996;  178 1302-1309
    PubMedGoogle Scholar
  • 95 Dutka-Malen S, Molinas C, Arthur M, Courvalin P. Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance.  Gene. 1992;  112 53-58
    CrossrefPubMedGoogle Scholar
  • 96 Panesso D, Abadia-Patino L, Vanegas N, Reynolds P E, Courvalin P, Arias C A. Transcriptional analysis of the vanC cluster from Enterococcus gallinarum strains with constitutive and inducible vancomycin resistance.  Antimicrob Agents Chemother. 2005;  49 1060-1066
    CrossrefPubMedGoogle Scholar
  • 97 Billot-Klein D, Gutmann L, Sable S, Guittet E, van Heijenoort J. Modification of peptidoglycan precursors is a common feature of the low-level vancomycin-resistant VANB-type Enterococcus D366 and of the naturally glycopeptide-resistant species Lactobacillus casei, Pediococcus pentosaceus, Leuconostoc mesenteroides, and Enterococcus gallinarum .  J Bacteriol. 1994;  176 2398-2405
    PubMedGoogle Scholar
  • 98 Moise P A, Forrest A, Bhavnani S M, Birmingham M C, Schentag J J. Area under the inhibitory curve and a pneumonia scoring system for predicting outcomes of vancomycin therapy for respiratory infections by Staphylococcus aureus .  Am J Health Syst Pharm. 2000;  57(Suppl 2) S4-S9
    PubMedGoogle Scholar
  • 99 Cui L, Ma X, Sato K et al.. Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus .  J Clin Microbiol. 2003;  41 5-14
    CrossrefPubMedGoogle Scholar
  • 100 Levine D P, Fromm B S, Reddy B R. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis.  Ann Intern Med. 1991;  115 674-680
    CrossrefPubMedGoogle Scholar
  • 101 Moise-Broder P A, Forrest A, Birmingham M C, Schentag J J. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections.  Clin Pharmacokinet. 2004;  43 925-942
    CrossrefPubMedGoogle Scholar
  • 102 Moise P A, Forrest A, Birmingham M C, Schentag J J. The efficacy and safety of linezolid as treatment for Staphylococcus aureus infections in compassionate use patients who are intolerant of, or who have failed to respond to, vancomycin.  J Antimicrob Chemother. 2002;  50 1017-1026
    CrossrefPubMedGoogle Scholar
  • 103 Fagon J, Patrick H, Haas D W et al.. Treatment of gram-positive nosocomial pneumonia: prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.  Am J Respir Crit Care Med. 2000;  161 753-762
    CrossrefPubMedGoogle Scholar
  • 104 Rubinstein E, Cammarata S, Oliphant T, Wunderink R. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.  Clin Infect Dis. 2001;  32 402-412
    CrossrefPubMedGoogle Scholar
  • 105 Baughman R P, Kerr M A. Ventilator-associated pneumonia patients who do not reduce bacteria from the lungs have a worse prognosis.  J Intensive Care Med. 2003;  18 269-274
    CrossrefPubMedGoogle Scholar
  • 106 Cruciani M, Gatti G, Lazzarini L et al.. Penetration of vancomycin into human lung tissue.  J Antimicrob Chemother. 1996;  38 865-869
    PubMedGoogle Scholar
  • 107 Lamer C, de Beco V, Soler P et al.. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.  Antimicrob Agents Chemother. 1993;  37 281-286
    PubMedGoogle Scholar
  • 108 Georges H, Leroy O, Alfandari S et al.. Pulmonary disposition of vancomycin in critically ill patients.  Eur J Clin Microbiol Infect Dis. 1997;  16 385-388
    CrossrefPubMedGoogle Scholar
  • 109 Sakoulas G, Moise-Broder P A, Schentag J, Forrest A, Moellering Jr R C, Eliopoulos G M. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia.  J Clin Microbiol. 2004;  42 2398-2402
    CrossrefPubMedGoogle Scholar
  • 110 Wysocki M, Delatour F, Faurisson F et al.. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study.  Antimicrob Agents Chemother. 2001;  45 2460-2467
    CrossrefPubMedGoogle Scholar
  • 111 Cepeda J A, Whitehouse T, Cooper B et al.. Linezolid versus teicoplanin in the treatment of gram-positive infections in the critically ill: a randomized, double-blind, multicentre study.  J Antimicrob Chemother. 2004;  53 345-355
    CrossrefPubMedGoogle Scholar
  • 112 Sgarabotto D, Cusinato R, Narne E et al.. Synercid plus vancomycin for the treatment of severe methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections: evaluation of 5 cases.  Scand J Infect Dis. 2002;  34 122-126
    CrossrefPubMedGoogle Scholar
  • 113 Anstead G M, Owens A D. Recent advances in the treatment of infections due to resistant Staphylococcus aureus .  Curr Opin Infect Dis. 2004;  17 549-555
    CrossrefPubMedGoogle Scholar
  • 114 Eliopoulos G M. Quinupristin-dalfopristin and linezolid: evidence and opinion.  Clin Infect Dis. 2003;  36 473-481
    CrossrefPubMedGoogle Scholar
  • 115 Wunderink R G, Rello J, Cammarata S K, Croos-Dabrera R V, Kollef M H. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia.  Chest. 2003;  124 1789-1797
    CrossrefPubMedGoogle Scholar
  • 116 Kollef M H, Rello J, Cammarata S K, Croos-Dabrera R V, Wunderink R G. Clinical cure and survival in gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin.  Intensive Care Med. 2004;  30 388-394
    PubMedGoogle Scholar
  • 117 Stevens D L, Herr D, Lampiris H, Hunt J L, Batts D H, Hafkin B. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.  Clin Infect Dis. 2002;  34 1481-1490
    CrossrefPubMedGoogle Scholar
  • 118 Gee T, Ellis R, Marshall G, Andrews J, Ashby J, Wise R. Pharmacokinetics and tissue penetration of linezolid following multiple oral doses.  Antimicrob Agents Chemother. 2001;  45 1843-1846
    CrossrefPubMedGoogle Scholar
  • 119 Honeybourne D, Tobin C, Jevons G, Andrews J, Wise R. Intrapulmonary penetration of linezolid.  J Antimicrob Chemother. 2003;  51 1431-1434
    CrossrefPubMedGoogle Scholar
  • 120 Conte Jr J E, Golden J A, Kipps J, Zurlinden E. Intrapulmonary pharmacokinetics of linezolid.  Antimicrob Agents Chemother. 2002;  46 1475-1480
    CrossrefPubMedGoogle Scholar
  • 121 Boselli E, Breilh D, Rimmele T et al.. Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia.  Crit Care Med. 2005;  33 1529-1533
    CrossrefPubMedGoogle Scholar
  • 122 Bernardo K, Pakulat N, Fleer S et al.. Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression.  Antimicrob Agents Chemother. 2004;  48 546-555
    CrossrefPubMedGoogle Scholar
  • 123 Ohlsen K, Ziebuhr W, Koller K P, Hell W, Wichelhaus T A, Hacker J. Effects of subinhibitory concentrations of antibiotics on alpha-toxin (hla) gene expression of methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates.  Antimicrob Agents Chemother. 1998;  42 2817-2823
    PubMedGoogle Scholar
  • 124 Nasraway S A, Shorr A F, Kuter D J, O'Grady N, Le V H, Cammarata S K. Linezolid does not increase the risk of thrombocytopenia in patients with nosocomial pneumonia: comparative analysis of linezolid and vancomycin use.  Clin Infect Dis. 2003;  37 1609-1616
    CrossrefPubMedGoogle Scholar
  • 125 Shopsin B, Zhao X, Kreiswirth B N, Tillotson G S, Drlica K. Are the new quinolones appropriate treatment for community-acquired methicillin-resistant Staphylococcus aureus? .  Int J Antimicrob Agents. 2004;  24 32-34
    PubMedGoogle Scholar
  • 126 Sander A, Beiderlinden M, Schmid E N, Peters J. Clinical experience with quinupristin-dalfopristin as rescue treatment of critically ill patients infected with methicillin-resistant staphylococci.  Intensive Care Med. 2002;  28 1157-1160
    CrossrefPubMedGoogle Scholar
  • 127 Fenton C, Keating G M, Curran M P. Daptomycin.  Drugs. 2004;  64 445-455 discussion 457-458
    PubMedGoogle Scholar
  • 128 Zhanel G G, Homenuik K, Nichol K et al.. The glycylcyclines: a comparative review with the tetracyclines.  Drugs. 2004;  64 63-88
    PubMedGoogle Scholar
  • 129 Van Bambeke F, Van Laethem Y, Courvalin P, Tulkens P M. Glycopeptide antibiotics: from conventional molecules to new derivatives.  Drugs. 2004;  64 913-936
    PubMedGoogle Scholar
  • 130 Tsiodras S, Gold H S, Sakoulas G et al.. Linezolid resistance in a clinical isolate of Staphylococcus aureus .  Lancet. 2001;  358 207-208
    PubMedGoogle Scholar

Richard G WunderinkM.D. 

Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine

676 North St. Clair, Ste. 14-044, Chicago, IL 60611

Email: r-wunderink@northwestern.edu