Empiric Therapy of Gram-positive Bloodstream Infections and Pneumonia

  • M. Bassetti
  • G. Villa
Part of the Annual Update in Intensive Care and Emergency Medicine book series (AUICEM, volume 2012)


Intensive care units (ICUs) represent high-risk areas for nosocomial infections. One third of hospital-acquired infections are related to the ICU, where a patient has a 5- to 7-fold greater risk of nosocomial infection compared to another hospitalized in a different ward [1]. Gram-positive organisms play an important part in this setting, being a leading cause of morbidity and mortality in ICUs [2]; moreover, several reports have shown an increase in antimicrobial resistance for these isolates in recent years [3].


Bloodstream Infection Antimicrob Agent Nosocomial Pneumonia Vancomycin Minimum Inhibitory Concentration Vancomycin MICs 
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  1. 1.
    Chen YY, Wang FD, Liu CY, Chou P (2009) Incidence rate and variable cost of nosocomial infections in different types of intensive care units. Infect Control Hosp Epidemiol 30: 39–46PubMedCrossRefGoogle Scholar
  2. 2.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39: 309–317PubMedCrossRefGoogle Scholar
  3. 3.
    Wise R (2003) Introduction: treatment of Gram-positive infections. J Antimicrob Chemother 51 (Suppl 2): ii5–ii7PubMedGoogle Scholar
  4. 4.
    Bassetti M, Ginocchio F, Giacobbe DR (2011) New approaches for empiric therapy in Gram-positive sepsis. Minerva Anestesiol 77: 821–827PubMedGoogle Scholar
  5. 5.
    Sakoulas G, Moellering RC, Eliopoulos GM (2006) Adaptation of methicillin-resistant Staphylococcus aureus in the face of vancomycin therapy. Clin Infect Dis 42 (Suppl 1): S40–S50PubMedCrossRefGoogle Scholar
  6. 6.
    Moise PA, Sakoulas G, Forrest A, Schentag JJ (2007) Vancomycin in vitro bactericidal activity and its relationship to efficacy in clearance of methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 51: 2582–2586PubMedCrossRefGoogle Scholar
  7. 7.
    Rodríguez-Baño J, Millán AB, Domínguez MA, et al (2009) Impact of inappropriate empirical therapy for sepsis due to health care-associated methicillin-resistant Staphylococcus aureus. J Infect 58: 131–137PubMedCrossRefGoogle Scholar
  8. 8.
    Moreno R, Afonso S, Fevereiro T (2006) Incidence of sepsis in hospitalized patients. Curr Infect Dis Rep 8: 346–350PubMedCrossRefGoogle Scholar
  9. 9.
    Vallés J, Ferrer R (2009) Bloodstream infection in the ICU. Infect Dis Clin North Am 23: 557–569PubMedCrossRefGoogle Scholar
  10. 10.
    Luzzaro F, Ortisi G, Larosa M, Drago M, Brigante G, Gesu G (2011) Prevalence and epidemiology of microbial pathogens causing bloodstream infections: results of the OASIS multicenter study. Diagn Microbiol Infect Dis 69: 363–369PubMedCrossRefGoogle Scholar
  11. 11.
    Albrecht SJ, Fishman NO, Kitchen J, et al (2006) Reemergence of gram-negative health care-associated bloodstream infections. Arch Intern Med 166: 1289–1294PubMedCrossRefGoogle Scholar
  12. 12.
    Vergidis PI, Falagas ME (2008) New antibiotic agents for bloodstream infections. Int J Antimicrob Agents 32 (Suppl 1): S60–S65PubMedCrossRefGoogle Scholar
  13. 13.
    Adam HJ, DeCorby M, Rennie R, et al (2011) Prevalence of antimicrobial resistant pathogens from blood cultures from Canadian hospitals: results of the CANWARD 2007-2009 study. Diagn Microbiol Infect Dis 69: 307–313PubMedCrossRefGoogle Scholar
  14. 14.
    Wilson J, Elgohari S, Livermore DM, et al (2011) Trends among pathogens reported as causing bacteraemia in England, 2004–2008. Clin Microbiol Infect 17: 451–458PubMedCrossRefGoogle Scholar
  15. 15.
    Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y (2003) Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36: 53–59PubMedCrossRefGoogle Scholar
  16. 16.
    Nicoletti G, Schito G, Fadda G, et al (2006) Bacterial isolates from severe infections and their antibiotic susceptibility patterns in Italy: a nationwide study in the hospital setting. J Chemother 18: 589–602PubMedGoogle Scholar
  17. 17.
    Soriano A, Marco F, Martínez JA, et al (2008) Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 46: 193–200PubMedCrossRefGoogle Scholar
  18. 18.
    Bassetti M, Mesini, A, Molinari MP, Viscoli C (2011) Vancomycin susceptibility of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia isolates in an Italian hospital. Int J Antimicrob Agents 38: 453–454PubMedCrossRefGoogle Scholar
  19. 19.
    Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC, Eliopoulos GM (2004) Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 42: 2398–2402PubMedCrossRefGoogle Scholar
  20. 20.
    Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH (2007) A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Clin Ther 29: 1107–1115PubMedCrossRefGoogle Scholar
  21. 21.
    Patel N, Lubanski P, Ferro S, et al (2009) Correlation between vancomycin MIC values and those of other agents against gram-positive bacteria among patients with bloodstream infections caused by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53: 5141–5144PubMedCrossRefGoogle Scholar
  22. 22.
    Watanabe Y, Neoh HM, Cui L, Hiramatsu K (2008) Improved antimicrobial activity of linezolid against vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 52: 4207–4208PubMedCrossRefGoogle Scholar
  23. 23.
    DiazGranados CA, Zimmer SM, Klein M, Jernigan JA (2005) Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 41: 327–333PubMedCrossRefGoogle Scholar
  24. 24.
    Hawkey PM (2008) Pre-clinical experience with daptomycin. J Antimicrob Chemother 62 (Suppl 3): iii7–ii14PubMedCrossRefGoogle Scholar
  25. 25.
    Streit JM, Jones RN, Sader HS (2004) Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms. J Antimicrob Chemother 53: 669–674PubMedCrossRefGoogle Scholar
  26. 26.
    Smith K, Perez A, Ramage G, Gemmell CG, Lang S (2009) Comparison of biofilm-associated cell survival following in vitro exposure of meticillin-resistant Staphylococcus aureus biofilms to the antibiotics clindamycin, daptomycin, linezolid, tigecycline and vancomycin. Int J Antimicrob Agents 33: 374–378PubMedCrossRefGoogle Scholar
  27. 27.
    Hanberger H, Nilsson LE, Maller R, Isaksson B (1991) Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2+ and albumin on these drugs. Antimicrob Agents Chemother 35: 1710–1716PubMedCrossRefGoogle Scholar
  28. 28.
    Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI, Daptomycin 98-01 and 99-01 Investigators (2004) The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 38: 1673–1681PubMedCrossRefGoogle Scholar
  29. 29.
    Fowler VG, Boucher HW, Corey GR, et al (2006) Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 355: 653–665PubMedCrossRefGoogle Scholar
  30. 30.
    Rose WE, Leonard SN, Rybak MJ (2008) Evaluation of daptomycin pharmacodynamics and resistance at various dosage regimens against Staphylococcus aureus isolates with reduced susceptibilities to daptomycin in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 52: 3061–3067PubMedCrossRefGoogle Scholar
  31. 31.
    Boucher HW, Sakoulas G (2007) Perspectives on daptomycin resistance, with emphasis on resistance in Staphylococcus aureus. Clin Infect Dis 45: 601–608PubMedCrossRefGoogle Scholar
  32. 32.
    Benvenuto M, Benziger DP, Yankelev S, Vigliani G (2006) Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Agents Chemother 50: 3245–3249PubMedCrossRefGoogle Scholar
  33. 33.
    Figueroa DA, Mangini E, Amodio-Groton M, et al (2009) Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis 49: 177–180PubMedCrossRefGoogle Scholar
  34. 34.
    Bassetti M, Nicco E, Elena Nicco, et al (2010) High-dose daptomycin in documented Staphylococcus aureus infections. Int J Antimicrob Agents 36: 459–461PubMedCrossRefGoogle Scholar
  35. 35.
    Wilcox M, Nathwani D, Dryden M (2004) Linezolid compared with teicoplanin for the treatment of suspected or proven Gram-positive infections. J Antimicrob Chemother 53: 335–344PubMedCrossRefGoogle Scholar
  36. 36.
    Stevens DL, Herr D, Lampiris H, Hunt JL, Batts DH, Hafkin B (2002) Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 34: 1481–1490PubMedCrossRefGoogle Scholar
  37. 37.
    Shorr AF, Kunkel MJ, Kollef M (2005) Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies. J Antimicrob Chemother 56: 923–929PubMedCrossRefGoogle Scholar
  38. 38.
    American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Am J Respir Crit Care Med 171: 388–416CrossRefGoogle Scholar
  39. 39.
    Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165: 867–903PubMedCrossRefGoogle Scholar
  40. 40.
    Richards MJ, Edwards JR, Culver DH, Gaynes RP (1999) Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 27: 887–892PubMedCrossRefGoogle Scholar
  41. 41.
    Safdar N, Dezfulian C, Collard HR, Saint S (2005) Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 33: 2184–2193PubMedCrossRefGoogle Scholar
  42. 42.
    Kollef MH, Sherman G, Ward S, Fraser VJ (1999) Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115: 462–474PubMedCrossRefGoogle Scholar
  43. 43.
    Zahar JR, Clec’h C, Tafflet M, et al (2005) Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia? Clin Infect Dis 41: 1224–1231PubMedCrossRefGoogle Scholar
  44. 44.
    Lodise TP, McKinnon PS, Swiderski L, Rybak MJ (2003) Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis 36: 1418–1423PubMedCrossRefGoogle Scholar
  45. 45.
    Rello J, Ausina V, Ricart M, Castella J, Prats G (2009) Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 136: e30PubMedCrossRefGoogle Scholar
  46. 46.
    Franzetti F, Antonelli M, Bassetti M, et al (2010) Consensus document on controversial issues for the treatment of hospital-associated pneumonia. Int J Infect Dis 14 (Suppl 4): S55–S65PubMedCrossRefGoogle Scholar
  47. 47.
    Hidron AI, Edwards JR, Patel J, et al (2008) NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 29: 996–1011PubMedCrossRefGoogle Scholar
  48. 48.
    Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS (2005) Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 128: 3854–3862PubMedCrossRefGoogle Scholar
  49. 49.
    Welte T, Pletz MW (2010) Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. Int J Antimicrob Agents 36: 391–400PubMedCrossRefGoogle Scholar
  50. 50.
    Gotfried MH, Shaw JP, Benton BM, et al (2008) Intrapulmonary distribution of intravenous telavancin in healthy subjects and effect of pulmonary surfactant on in vitro activities of telavancin and other antibiotics. Antimicrob Agents Chemother 52: 92–97PubMedCrossRefGoogle Scholar
  51. 51.
    Hegde SS, Reyes N, Wiens T, et al (2004) Pharmacodynamics of telavancin (TD-6424), a novel bactericidal agent, against gram-positive bacteria. Antimicrob Agents Chemother 48: 3043–3050PubMedCrossRefGoogle Scholar
  52. 52.
    Jung YJ, Koh Y, Hong SB, et al (2010) Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia. Crit Care Med 38: 175–180PubMedCrossRefGoogle Scholar
  53. 53.
    Haraga I, Nomura S, Fukamachi S, et al (2002) Emergence of vancomycin resistance during therapy against methicillin-resistant Staphylococcus aureus in a burn patient—importance of low-level resistance to vancomycin. Int J Infect Dis 6: 302–308PubMedCrossRefGoogle Scholar
  54. 54.
    Hanaki H, Yamaguchi Y, Barata K, Sakai H and Sunakawa K (2004) Improved method of detection of beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). Int J Antimicrob Agents 23: 311–313PubMedGoogle Scholar
  55. 55.
    Kollef MH, Rello J, Cammarata SK, Croos-Dabrera RV, Wunderink RG (2004) Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med 30: 388–394PubMedCrossRefGoogle Scholar
  56. 56.
    Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH (2003) Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 124: 1789–1797PubMedCrossRefGoogle Scholar
  57. 57.
    Rubinstein E, Cammarata S, Oliphant T, Wunderink R (2001) Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis 32: 402–412PubMedCrossRefGoogle Scholar
  58. 58.
    Wunderink RG, Cammarata SK, Oliphant TH, Kollef MH (2003) Linezolid Nosocomial Pneumonia Study Group. Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia. Clin Ther 25: 980–992PubMedCrossRefGoogle Scholar
  59. 59.
    Conte JE, Golden JA, Kipps J, Zurlinden E (2002) Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother 46: 1475–1480PubMedCrossRefGoogle Scholar
  60. 60.
    Powers JH, Ross DB, Lin D, Soreth J (2004) Linezolid and vancomycin for methicillinresistant Staphylococcus aureus nosocomial pneumonia: the subtleties of subgroup analyses. Chest 126: 314–315PubMedCrossRefGoogle Scholar
  61. 61.
    Wunderink RG, Mendelson MH, Somero MS, et al (2008) Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus. Chest 134: 1200–1207PubMedCrossRefGoogle Scholar
  62. 62.
    Kunkel M, Chastre JE, Kollef M, et al (2010) Linezolid vs vancomycin in the treatment of nosocomial pneumonia proven due to methicillin-resistant Staphylococcus aureus. IDSA 48th Annual Meeting, Vancouver Abstract LB49Google Scholar
  63. 63.
    Wong A, Reddy SP, Smyth DS, Aguero-Rosenfeld ME, Sakoulas G, Robinson DA (2010) Polyphyletic emergence of linezolid-resistant staphylococci in the United States. Antimicrob Agents Chemother 54: 742–748PubMedCrossRefGoogle Scholar
  64. 64.
    Bassetti M, Farrel PA, Callan DA, Topal JE, Dembry LM (2003) Emergence of linezolidresistant Enterococcus faecium during treatment of enterococcal infections. Int J Antimicrob Agents 2003 6: 593–594CrossRefGoogle Scholar
  65. 65.
    Attassi K, Hershberger E, Alam R, Zervos MJ (2002) Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 34: 695–698PubMedCrossRefGoogle Scholar
  66. 66.
    Azamfirei L, Copotoiu SM, Branzaniuc K, Szederjesi J, Copotoiu R, Berteanu C (2007) Complete blindness after optic neuropathy induced by short-term linezolid treatment in a patient suffering from muscle dystrophy. Pharmacoepidemiol Drug Saf 16: 402–404PubMedCrossRefGoogle Scholar
  67. 67.
    Wilcox M, Nathwani D, Dryden M (2004) Linezolid compared with teicoplanin for the treatment of suspected or proven Gram-positive infections. J Antimicrob Chemother 53: 335–344PubMedCrossRefGoogle Scholar
  68. 68.
    Tascini C, Gemignani G, Doria R, et al (2009) Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin. J Chemother 21: 311–316PubMedGoogle Scholar
  69. 69.
    Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T (2009) Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint. Int J Antimicrob Agents 34: 101–102PubMedCrossRefGoogle Scholar
  70. 70.
    Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E (2008) Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis 46: 567–570PubMedCrossRefGoogle Scholar

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  • M. Bassetti
  • G. Villa

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