Optimizing Therapy for MRSA Pneumonia

ABSTRACT

With its remarkable armamentarium of resistance and virulence factors, Staphylococcus aureus has emerged as a dominant pathogen causing pneumonia of all classifications. Rates of methicillin resistance are increasing as clinicians struggle to find ways to prevent the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and to effectively treat MRSA pneumonia. Community-associated MRSA has been identified as an important subset of MRSA with unique characteristics. Vancomycin remains a recommended first-line therapy for MRSA pneumonia, but resistance and therapeutic failures with vancomycin are being increasingly reported. Factors associated with vancomycin success or failure have been identified, including the genetics of the MRSA isolate, vancomycin lung penetration, minimum inhibitory concentration, and pharmacokinetic and pharmacodynamic variables. Retrospective analyses suggest that linezolid may provide improved outcomes compared with vancomycin for MRSA pneumonia, but validation in a prospective trial is currently lacking. Other treatment options are limited, but new prospects are being investigated. This paper reviews the epidemiology and pharmacotherapy of MRSA pneumonia.

Methicillin-resistant Staphylococcus aureus - pneumonia - health care-associated

REFERENCES

• 1 Lowy F D. Staphylococcus aureus infections.  N Engl J Med. 1998;  339 520-532
• 2 Archer G L. Staphylococcus aureus: a well-armed pathogen.  Clin Infect Dis. 1998;  26 1179-1181
• 3 Foster T J. The Staphylococcus aureus “superbug”.  J Clin Invest. 2004;  114 1693-1696
• 4 Sakoulas G, Moellering Jr R C, Eliopoulos G M. Adaptation of methicillin-resistant Staphylococcus aureus in the face of vancomycin therapy.  Clin Infect Dis. 2006;  42(Suppl 1) S40-S50
• 5 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
• 6 McDougal L K, Steward C D, Killgore G E, Chaitram J M, McAllister S K, Tenover F C. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database.  J Clin Microbiol. 2003;  41 5113-5120
• 7 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
• 8 Fridkin S K, Hageman J C, Morrison M et al.. Methicillin-resistant Staphylococcus aureus disease in three communities.  N Engl J Med. 2005;  352 1436-1444
• 9 Hidron A I, Kourbatova E V, Halvosa J S et al.. Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage.  Clin Infect Dis. 2005;  41 159-166
• 10 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
• 11 Schramm G E, Johnson J A, Doherty J A, Micek S T, Kollef M H. Increasing incidence of sterile-site infections due to non-multidrug-resistant, oxacillin-resistant Staphylococcus aureus among hospitalized patients.  Infect Control Hosp Epidemiol. 2007;  28 95-97
• 12 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
• 13 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
• 14 Diekema D J, Pfaller M A, Schmitz F J et al.. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999.  Clin Infect Dis. 2001;  32(Suppl 2) S114-S132
• 15 Gaynes R, Edwards J R. Overview of nosocomial infections caused by gram-negative bacilli.  Clin Infect Dis. 2005;  41 848-854
• 16 National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999, issued June 1999.  Am J Infect Control. 1999;  27 520-532
• 17 Fridkin S K, Hill H A, Volkova N V et al.. Temporal changes in prevalence of antimicrobial resistance in 23 US hospitals.  Emerg Infect Dis. 2002;  8 697-701
• 18 Kollef M H. Optimizing antibiotic therapy in the intensive care unit setting.  Crit Care. 2001;  5 189-195
• 19 Iregui M, Ward S, Sherman G, Fraser V J, Kollef M H. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia.  Chest. 2002;  122 262-268
• 20 Cosgrove S E, Qi Y, Kaye K S, Harbarth S, Karchmer A W, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges.  Infect Control Hosp Epidemiol. 2005;  26 166-174
• 21 Mandell L A, Bartlett J G, Dowell S F, File Jr T M, Musher D M, Whitney C. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults.  Clin Infect Dis. 2003;  37 1405-1433
• 22 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
• 23 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
• 24 Zahar J R, Clec'h C, Tafflet M et al.. Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia?.  Clin Infect Dis. 2005;  41 1224-1231
• 25 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
• 26 Micek S T, Dunne M, Kollef M H. Pleuropulmonary complications of Panton-Valentine leukocidin-positive community-acquired methicillin-resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production.  Chest. 2005;  128 2732-2738
• 27 Gonzalez B E, Hulten K G, Dishop M K et al.. Pulmonary manifestations in children with invasive community-acquired Staphylococcus aureus infection.  Clin Infect Dis. 2005;  41 583-590
• 28 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
• 29 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
• 30 Boussaud V, Parrot A, Mayaud C et al.. Life-threatening hemoptysis in adults with community-acquired pneumonia due to Panton-Valentine leukocidin-secreting Staphylococcus aureus .  Intensive Care Med. 2003;  29 1840-1843
• 31 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(12) 1761-1770
• 32 Labandeira-Rey M, Couzon F, Boisset S et al.. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia.  Science. 2007;  315 1130-1133
• 33 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
• 34 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
• 35 Moise P A, Schentag J J. Vancomycin treatment failures in Staphylococcus aureus lower respiratory tract infections.  Int J Antimicrob Agents. 2000;  16(Suppl 1) S31-S34
• 36 Courvalin P. Vancomycin resistance in gram-positive cocci.  Clin Infect Dis. 2006;  42(Suppl 1) S25-S34
• 37 Rybak M J. The pharmacokinetic and pharmacodynamic properties of vancomycin.  Clin Infect Dis. 2006;  42(Suppl 1) S35-S39
• 38 Sakoulas G, Eliopoulos G M, Moellering Jr R C et al.. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin.  Antimicrob Agents Chemother. 2002;  46 1492-1502
• 39 Cruciani M, Gatti G, Lazzarini L et al.. Penetration of vancomycin into human lung tissue.  J Antimicrob Chemother. 1996;  38 865-869
• 40 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
• 41 Geisel R, Schmitz F J, Fluit A C, Labischinski H. Emergence, mechanism, and clinical implications of reduced glycopeptide susceptibility in Staphylococcus aureus .  Eur J Clin Microbiol Infect Dis. 2001;  20 685-697
• 42 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
• 43 Tenover F C, Weigel L M, Appelbaum P C et al.. Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania.  Antimicrob Agents Chemother. 2004;  48 275-280
• 44 Vancomycin-resistant Staphylococcus aureus-New York, 2004.  MMWR Morb Mortal Wkly Rep. 2004;  53 322-323
• 45 Diep B A, Gill S R, Chang R F et al.. Complete genome sequence of USA300, an epidemic clone of community-acquired methicillin-resistant Staphylococcus aureus .  Lancet. 2006;  367 731-739
• 46 Hidayat L K, Hsu D I, Quist R, Shriner K A, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity.  Arch Intern Med. 2006;  166 2138-2144
• 47 Tenover F C, Moellering Jr R C. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus .  Clin Infect Dis. 2007;  44 1208-1215
• 48 Jones R N. Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains.  Clin Infect Dis. 2006;  42(Suppl 1) S13-S24
• 49 Rhee K Y, Gardiner D F, Charles M. Decreasing in vitro susceptibility of clinical Staphylococcus aureus isolates to vancomycin at the New York Hospital: quantitative testing redux.  Clin Infect Dis. 2005;  40 1705-1706
• 50 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
• 51 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
• 52 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
• 53 Farber B F, Moellering Jr R C. Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981.  Antimicrob Agents Chemother. 1983;  23 138-141
• 54 Jeffres M N, Isakow W, Doherty J A, Micek S T, Kollef M H. A retrospective study of possible renal toxicity in patients with healthcare-associated Staphylococcus aureus pneumonia treated with vancomycin.  Clin Ther. 2007;  29 1107-1115
• 55 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
• 56 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
• 57 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
• 58 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
• 59 Lawrence K R, Adra M, Gillman P K. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data.  Clin Infect Dis. 2006;  42 1578-1583
• 60 Taylor J J, Wilson J W, Estes L L. Linezolid and serotonergic drug interactions: a retrospective survey.  Clin Infect Dis. 2006;  43 180-187
• 61 Lin Y H, Wu V C, Tsai I J et al.. High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency.  Int J Antimicrob Agents. 2006;  28 345-351
• 62 Wu V C, Wang Y T, Wang C Y et al.. High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease.  Clin Infect Dis. 2006;  42 66-72
• 63 Senneville E, Legout L, Valette M et al.. Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study.  Clin Ther. 2006;  28 1155-1163
• 64 Palenzuela L, Hahn N M, Nelson Jr R P et al.. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis?.  Clin Infect Dis. 2005;  40 e113-e116
• 65 Rodvold K A, Gotfried M H, Cwik M, Korth-Bradley J M, Dukart G, Ellis-Grosse E J. Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose.  J Antimicrob Chemother. 2006;  58 1221-1229
• 66 Rose W E, Rybak M J. Tigecycline: first of a new class of antimicrobial agents.  Pharmacotherapy. 2006;  26 1099-1110
• 67 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
• 68 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
• 69 Chambers H F. Ceftobiprole: in-vivo profile of a bactericidal cephalosporin.  Clin Microbiol Infect. 2006;  12(Suppl 2) 17-22
• 70 Livermore D M. Can beta-lactams be re-engineered to beat MRSA?.  Clin Microbiol Infect. 2006;  12(Suppl 2) 11-16
• 71 Lodise T PJP, Pypstra R MD, Kahn J MD et al.. Probability of target attainment for ceftobiprole as derived from a population pharmacokinetic analysis of 150 subjects.  Antimicrob Agents Chemother. 2007;  51 2378-2387
• 72 Pankuch G A, Appelbaum P C. Postantibiotic effect of ceftobiprole against 12 gram-positive organisms.  Antimicrob Agents Chemother. 2006;  50 3956-3958
• 73 Van Bambeke F. Glycopeptides and glycodepsipeptides in clinical development: a comparative review of their antibacterial spectrum, pharmacokinetics and clinical efficacy.  Curr Opin Investig Drugs. 2006;  7 740-749
• 74 Stryjewski M E, O'Riordan W D, Lau W K et al.. Telavancin versus standard therapy for treatment of complicated skin and soft-tissue infections due to gram-positive bacteria.  Clin Infect Dis. 2005;  40 1601-1607
• 75 Stryjewski M E, Chu V H, O'Riordan W D et al.. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study.  Antimicrob Agents Chemother. 2006;  50 862-867
• 76 Reyes N, Skinner R, Kaniga K et al.. Efficacy of Telavancin (TD-6424), a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action, in a murine model of pneumonia induced by methicillin-resistant Staphylococcus aureus .  Antimicrob Agents Chemother. 2005;  49 4344-4346
• 77 Pope S D, Roecker A M. Dalbavancin: a novel lipoglycopeptide antibacterial.  Pharmacotherapy. 2006;  26 908-918
• 78 Ward K E, Mersfelder T L, LaPlante K L. Oritavancin: an investigational glycopeptide antibiotic.  Expert Opin Investig Drugs. 2006;  15 417-429
• 79 Bhavnani S M, Passarell J A, Owen J S, Loutit J S, Porter S B, Ambrose P G. Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia.  Antimicrob Agents Chemother. 2006;  50 994-1000