The Role of MRSA in Healthcare-Associated Pneumonia

ABSTRACT

An important continued trend in healthcare-associated infection, including healthcare-associated pneumonia (HCAP), is the rise of methicillin-resistant Staphylococcus aureus (MRSA). The emergence of community-acquired strains of MRSA has complicated the management further. We review likely risk factors for MRSA HCAP, which include prior antibiotic therapy, nasal colonization, poor infection control practices, and antecedent viral infection. The multiple mechanisms of antibiotic resistance are also described, and virulence factors that may affect antibiotic choices are discussed. The limitations of vancomycin and evidence for superior outcomes with linezolid are reviewed. Alternatives for community-acquired strains and future options are mentioned.

Staphylococcus aureus - methicillin-resistant S. aureus - vancomycin - linezolid - Panton-Valentine leukocidin (PVL)

REFERENCES

• 1 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
• 2 Chambers H F. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications.  Clin Microbiol Rev. 1997;  10 781-791
• 3 Fridkin S K. Increasing prevalence of antimicrobial resistance in intensive care units.  Crit Care Med. 2001;  29(4, Suppl) N64-N68
• 4 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
• 5 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
• 6 Kollef M H, Shorr A, Tabak Y P, Gupta V, Liu L Z, Johannes R S. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia.  Chest. 2005;  128 3854-3862
• 7 Richards M J, Edwards J R, Culver D H, Gaynes R P. Nosocomial infections in combined medical-surgical intensive care units in the United States.  Infect Control Hosp Epidemiol. 2000;  21 510-515
• 8 Micek S T, Kollef K E, Reichley R M, Roubinian N, Kollef M H. Healthcare-associated pneumonia and community-acquired pneumonia: a single-center experience.  Antimicrob Agents Chemother. 2007;  51 3568-3573
• 9 Carratala J, Mykietiuk A, Fernandez-Sabe N et al.. Healthcare-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes.  Arch Intern Med. 2007;  167 1393-1399
• 10 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
• 11 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
• 12 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
• 13 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(6 Pt 1) 1545-1549
• 14 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
• 15 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
• 16 Athanassa Z, Siempos I I, Falagas M E. Impact of methicillin resistance on mortality in Staphylococcus aureus VAP: a systematic review.  Eur Respir J. 2008;  31 625-632
• 17 Shorr A F, Combes A, Kollef M H, Chastre J. Methicillin-resistant Staphylococcus aureus prolongs intensive care unit stay in ventilator-associated pneumonia, despite initially appropriate antibiotic therapy.  Crit Care Med. 2006;  34 700-706
• 18 Vidaur L, Planas K, Sierra R et al.. Ventilator-associated pneumonia: impact of organisms on clinical resolution and medical resources utilization.  Chest. 2008;  133 625-632
• 19 Miller L G, Perdreau-Remington F, Rieg G et al.. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles.  N Engl J Med. 2005;  352 1445-1453
• 20 Adem P V, Montgomery C P, Husain A N et al.. Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children.  N Engl J Med. 2005;  353 1245-1251
• 21 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
• 22 LaPlante K L, Rybak M J, Amjad M, Kaatz G W. Antimicrobial susceptibility and staphylococcal chromosomal cassette mec type in community- and hospital-associated methicillin-resistant Staphylococcus aureus .  Pharmacotherapy. 2007;  27 3-10
• 23 Herold B C, Immergluck L C, Maranan M C et al.. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk.  JAMA. 1998;  279 593-598
• 24 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
• 25 Panton P NV. FCO. Staphylococcal toxin.  Lancet. 1931;  1 506-508
• 26 Voyich J M, Otto M, Mathema B et al.. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?.  J Infect Dis. 2006;  194 1761-1770
• 27 Labandeira-Rey M, Couzon F, Boisset S et al.. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia.  Science. 2007;  315 1130-1133
• 28 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
• 29 Daum R S, Ito T, Hiramatsu K et al.. A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds.  J Infect Dis. 2002;  186 1344-1347
• 30 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
• 31 Gillet Y, Vanhems P, Lina G et al.. Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin.  Clin Infect Dis. 2007;  45 315-321
• 32 Centers for Disease Control and Prevention (CDC) . Methicillin-resistant Staphylococcus aureus infections in correctional facilities—Georgia, California, and Texas, 2001–2003.  MMWR Morb Mortal Wkly Rep. 2003;  52 992-996
• 33 Hageman J C, Uyeki T M, Francis J S et al.. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003–04 influenza season.  Emerg Infect Dis. 2006;  12 894-899
• 34 Centers for Disease Control and Prevention (CDC) . Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections—Los Angeles County, California, 2002–2003.  MMWR Morb Mortal Wkly Rep. 2003;  52 88
• 35 Centers for Disease Control and Prevention (CDC) . 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
• 36 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
• 37 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
• 38 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 951-943
• 39 Kazakova S V, Hageman J C, Matava M et al.. A clone of methicillin-resistant Staphylococcus aureus among professional football players.  N Engl J Med. 2005;  352 468-475
• 40 Lobo L J, Wunderink R G. Low mortality in necrotizing CA-MRSA CAP [abstract].  Am J Respir Crit Care Med. 2008;  177 A286
• 41 Saiman L, O'Keefe M, Graham III P L et al.. Hospital transmission of community-acquired methicillin-resistant Staphylococcus aureus among postpartum women.  Clin Infect Dis. 2003;  37 1313-1319
• 42 Seybold U, Kourbatova E V, Johnson J G et al.. Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections.  Clin Infect Dis. 2006;  42 647-656
• 43 Benoit S R, Estivariz C, Mogdasy C et al.. Community strains of methicillin-resistant Staphylococcus aureus as potential cause of healthcare-associated infections, Uruguay, 2002–2004.  Emerg Infect Dis. 2008;  14 1216-1223
• 44 David M D, Kearns A M, Gossain S, Ganner M, Holmes A. Community-associated methicillin-resistant Staphylococcus aureus: nosocomial transmission in a neonatal unit.  J Hosp Infect. 2006;  64 244-250
• 45 Gonzalez B E, Rueda A M, Shelburne III S A, Musher D M, Hamill R J, Hulten K G. Community-associated strains of methicillin-resistant Staphylococcus aureus as the cause of healthcare-associated infection.  Infect Control Hosp Epidemiol. 2006;  27 1051-1056
• 46 Maree C L, Daum R S, Boyle-Vavra S, Matayoshi K, Miller L G. Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections.  Emerg Infect Dis. 2007;  13 236-242
• 47 Neofytos D, Kuhn B, Shen S, Hua Zhu X, Jungkind D, Flomenberg P. Emergence of staphylococcal cassette chromosome mec type IV methicillin-resistant Staphylococcus aureus as a cause of ventilator-associated pneumonia.  Infect Control Hosp Epidemiol. 2007;  28 1206-1209
• 48 Rossney A S, Shore A C, Morgan P M, Fitzgibbon M M, O'Connell B, Coleman D C. The emergence and importation of diverse genotypes of methicillin-resistant Staphylococcus aureus (MRSA) harboring the Panton-Valentine leukocidin gene (pvl) reveal that pvl is a poor marker for community-acquired MRSA strains in Ireland.  J Clin Microbiol. 2007;  45 2554-2563
• 49 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
• 50 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
• 51 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
• 52 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
• 53 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
• 54 Foster T J. The Staphylococcus aureus “superbug”.  J Clin Invest. 2004;  114 1693-1696
• 55 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
• 56 Huang S S, Platt R. Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization.  Clin Infect Dis. 2003;  36 281-285
• 57 Garrouste-Orgeas M, Timsit J F, Kallel H et al.. Colonization with methicillin-resistant Staphylococcus aureus in ICU patients: morbidity, mortality, and glycopeptide use.  Infect Control Hosp Epidemiol. 2001;  22 687-692
• 58 von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study group.  N Engl J Med. 2001;  344 11-16
• 59 Safdar N, Bradley E A. The risk of infection after nasal colonization with Staphylococcus aureus .  Am J Med. 2008;  121 310-315
• 60 Davis K A, Stewart J J, Crouch H K, Florez C E, Hospenthal D R. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection.  Clin Infect Dis. 2004;  39 776-782
• 61 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
• 62 McGahee W, Lowy F D. Staphylococcal infections in the intensive care unit.  Semin Respir Infect. 2000;  15 308-313
• 63 Zinderman C E, Conner B, Malakooti M A, LaMar J E, Armstrong A, Bohnker B K. Community-acquired methicillin-resistant Staphylococcus aureus among military recruits.  Emerg Infect Dis. 2004;  10 941-944
• 64 Oztoprak N, Cevik M A, Akinci E et al.. Risk factors for ICU-acquired methicillin-resistant Staphylococcus aureus infections.  Am J Infect Control. 2006;  34 1-5
• 65 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
• 66 Clancy M, Graepler A, Wilson M, Douglas I, Johnson J, Price C S. Active screening in high-risk units is an effective and cost-avoidant method to reduce the rate of methicillin-resistant Staphylococcus aureus infection in the hospital.  Infect Control Hosp Epidemiol. 2006;  27 1009-1017
• 67 Kallen A J, Brunkard J, Moore Z et al.. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season.  Ann Emerg Med. 2008 Jun 3;  , [Epub ahead of print]
• 68 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
• 69 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
• 70 Lowy F D. Staphylococcus aureus infections.  N Engl J Med. 1998;  339 520-532
• 71 Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance.  Lancet Infect Dis. 2001;  1 147-155
• 72 Cosgrove S E, Carroll K C, Perl T M. Staphylococcus aureus with reduced susceptibility to vancomycin.  Clin Infect Dis. 2004;  39 539-545
• 73 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
• 74 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
• 75 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
• 76 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
• 77 Fedtke I, Gotz F, Peschel A. Bacterial evasion of innate host defenses–the Staphylococcus aureus lesson.  Int J Med Microbiol. 2004;  294(2–3) 189-194
• 78 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
• 79 Supersac G, Prevost G, Piemont Y. Sequencing of leucocidin R from Staphylococcus aureus P83 suggests that staphylococcal leucocidins and gamma-hemolysin are members of a single, two-component family of toxins.  Infect Immun. 1993;  61 580-587
• 80 Prevost G, Cribier B, Couppie P et al.. Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities.  Infect Immun. 1995;  63 4121-4129
• 81 Prevost G, Couppie P, Prevost P et al.. Epidemiological data on Staphylococcus aureus strains producing synergohymenotropic toxins.  J Med Microbiol. 1995;  42 237-245
• 82 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
• 83 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
• 84 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
• 85 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
• 86 Wang R, Braughton K R, Kretschmer D et al.. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA.  Nat Med. 2007;  13 1510-1514
• 87 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
• 88 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
• 89 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
• 90 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
• 91 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
• 92 Jeffres M N, Isakow W, Doherty J A et al.. Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices.  Chest. 2006;  130 947-955
• 93 Jeffres M N, Isakow W, Doherty J A, Micek S T, Kollef M H. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia.  Clin Ther. 2007;  29 1107-1115
• 94 Moise P A, Smyth D S, El-Fawal N et al.. Microbiological effects of prior vancomycin use in patients with methicillin-resistant Staphylococcus aureus bacteraemia.  J Antimicrob Chemother. 2008;  61 85-90
• 95 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
• 96 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
• 97 Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections.  Antimicrob Agents Chemother. 2005;  49 2260-2266
• 98 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
• 99 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
• 100 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
• 101 Conte Jr J E, Golden J A, Kipps J, Zurlinden E. Intrapulmonary pharmacokinetics of linezolid.  Antimicrob Agents Chemother. 2002;  46 1475-1480
• 102 Honeybourne D, Tobin C, Jevons G, Andrews J, Wise R. Intrapulmonary penetration of linezolid.  J Antimicrob Chemother. 2003;  51 1431-1434
• 103 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
• 104 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
• 105 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
• 106 Stevens D L, Ma Y, Salmi D B, McIndoo E, Wallace R J, Bryant A E. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus .  J Infect Dis. 2007;  195 202-211
• 107 Dumitrescu O, Boisset S, Badiou C et al.. Effect of antibiotics on Staphylococcus aureus producing Panton-Valentine leukocidin.  Antimicrob Agents Chemother. 2007;  51 1515-1519
• 108 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(3 Pt 1) 753-762
• 109 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
• 110 Pertel P E, Bernardo P, Fogarty C et al.. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia.  Clin Infect Dis. 2008;  46 1142-1151
• 111 Fenton C, Keating G M, Curran M P. Daptomycin.  Drugs. 2004;  64 445-455 discussion 457-458
• 112 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
• 113 Silverman J A, Mortin L I, Vanpraagh A D, Li T, Alder J. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact.  J Infect Dis. 2005;  191 2149-2152
• 114 Zhanel G G, Homenuik K, Nichol K et al.. The glycylcyclines: a comparative review with the tetracyclines.  Drugs. 2004;  64 63-88
• 115 Zhang K, McClure J A, Elsayed S, Tan J, Conly J M. Coexistence of Panton-Valentine leukocidin-positive and -negative community-associated methicillin-resistant Staphylococcus aureus USA400 sibling strains in a large Canadian health-care region.  J Infect Dis. 2008;  197 195-204
• 116 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
• 117 Patel M, Waites K B, Moser S A, Cloud G A, Hoesley C J. Prevalence of inducible clindamycin resistance among community- and hospital-associated Staphylococcus aureus isolates.  J Clin Microbiol. 2006;  44 2481-2484
• 118 Van Bambeke F, Van Laethem Y, Courvalin P, Tulkens P M. Glycopeptide antibiotics: from conventional molecules to new derivatives.  Drugs. 2004;  64 913-936
• 119 Iizawa Y, Nagai J, Ishikawa T et al.. In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599.  J Infect Chemother. 2004;  10 146-156
• 120 Anderson S D, Gums J G. Ceftobiprole: an extended-spectrum anti-methicillin-resistant Staphylococcus aureus cephalosporin.  Ann Pharmacother. 2008;  42 806-816
• 121 Patti J M. A humanized monoclonal antibody targeting Staphylococcus aureus .  Vaccine. 2004;  22(Suppl 1) S39-S43