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Ventilator-Associated Pneumonia (VAP) with Multidrug-Resistant (MDR) Pathogens: Optimal Treatment?

  • Sepsis and ICU (L Napolitano, Section Editor)
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Abstract

Ventilator-associated pneumonia (VAP) due to multidrug-resistant bacteria (MDR) is an emerging problem worldwide. Both gram-negative and gram-positive microorganisms are associated with VAP. We first describe the magnitude of the problem of MDR VAP followed by its clinical impact on survival outcomes, with the primary aim to review the optimal antibiotic choices to treat patients with MDR VAP. We discuss the challenges of intravenous and inhaled antibiotic treatments, as well as of monotherapy and combination antimicrobial therapies.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Bercault N, Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case–control study. Crit Care Med. 2001;29(12):2303–9.

    Article  CAS  PubMed  Google Scholar 

  2. Martin-Loeches I, et al. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms. J Infect, 2014.

  3. Peres-Bota D et al. Are infections due to resistant pathogens associated with a worse outcome in critically ill patients? J Infect. 2003;47(4):307–16.

    Article  PubMed  Google Scholar 

  4. Tedja R et al. The impact of multidrug resistance on outcomes in ventilator-associated pneumonia. Am J Infect Control. 2014;42(5):542–5. This article suggests increased mortality in patients with VAP due to multidrug resistance.

    Article  PubMed  Google Scholar 

  5. Zheng Y-I et al. Risk factors and mortality of patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia. Am J Infect Control. 2013;41(7):e59–63.

    Article  PubMed  Google Scholar 

  6. Magiorakos AP et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–81. This article provides a potential definition for multi-drug bacterial resistance.

    Article  CAS  PubMed  Google Scholar 

  7. Hidron AI et al. 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. 2008;29(11):996–1011.

    Article  PubMed  Google Scholar 

  8. Rosenthal VD et al. International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004–2009. Am J Infect Control. 2012;40(5):396–407.

    Article  PubMed  Google Scholar 

  9. Sievert DM et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect Control Hosp Epidemiol. 2013;34(1):1–14.

    Article  PubMed  Google Scholar 

  10. Soriano A et al. Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia. Clin Infect Dis. 2000;30(2):368–73.

    Article  CAS  PubMed  Google Scholar 

  11. Cosgrove SE et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36(1):53–9.

    Article  PubMed  Google Scholar 

  12. Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006;42(Supplement 2):S82–9.

    Article  PubMed  Google Scholar 

  13. Cardoso T et al. Additional risk factors for infection by multidrug-resistant pathogens in healthcare-associated infection: a large cohort study. BMC Infect Dis. 2012;12:375.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Dias M, Marçal P, Amaro P. Ventilator-associated pneumonia (VAP)—early and late-onset differences. Eur Respir J. 2013;42 Suppl 57:P2457.

    Google Scholar 

  15. Restrepo MI et al. Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies. Respir Care. 2013;58(7):1220–5.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med, 2005. 171(4): p. 388–416.

  17. Berton DC et al. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev. 2008;4, CD006482.

    PubMed  Google Scholar 

  18. Berton DC, Kalil AC, Teixeira PJ. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev. 2014;10, CD006482.

    PubMed  Google Scholar 

  19. Rello J 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):1545–9.

    Article  CAS  PubMed  Google Scholar 

  20. Parker CM et al. Ventilator-associated pneumonia caused by multidrug-resistant organisms or Pseudomonas aeruginosa: prevalence, incidence, risk factors, and outcomes. J Crit Care. 2008;23(1):18–26.

    Article  PubMed  Google Scholar 

  21. Depuydt P et al. Systematic surveillance cultures as a tool to predict involvement of multidrug antibiotic resistant bacteria in ventilator-associated pneumonia. Intensive Care Med. 2008;34(4):675–82.

    Article  CAS  PubMed  Google Scholar 

  22. Thomson KS, Moland ES. Cefepime, piperacillin-tazobactam, and the inoculum effect in tests with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2001;45(12):3548–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Pop-Vicas A, Opal SM. The clinical impact of multidrug-resistant gram-negative bacilli in the management of septic shock. Virulence. 2014;5(1):206–12.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Kollef MH et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care. 2012;16(6):R218.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Florescu DF et al. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis. 2012;54(5):670–80.

    Article  CAS  PubMed  Google Scholar 

  26. Curcio D et al. Late onset ventilator-associated pneumonia due to multidrug-resistant Acinetobacter spp. experience with tigecycline. J Chemother. 2009;21(1):58–62.

  27. Conde-Estévez D et al. Off-label prescription of tigecycline: clinical and microbiological characteristics and outcomes. Int J Antimicrob Agents. 2010;36(5):471–2.

    Article  PubMed  Google Scholar 

  28. Freire AT et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis. 2010;68(2):140–51.

    Article  CAS  PubMed  Google Scholar 

  29. Chuang Y-C et al. Effectiveness of tigecycline-based versus colistin-based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis. 2014;14(1):102.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Ramirez J et al. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013;57(4):1756–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care. 2009;15(5):413–8.

    Article  PubMed  Google Scholar 

  32. Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med. 2014;189(10):1225–33. This study provides evidence on the potential benefits of inhaled antibiotics.

    Article  PubMed  Google Scholar 

  33. Hallal A et al. Aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect. 2007;8(1):73–82.

    Article  Google Scholar 

  34. Niederman MS et al. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with gram-negative pneumonia. Intensive Care Med. 2012;38(2):263–71.

    Article  CAS  PubMed  Google Scholar 

  35. Lu Q, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med, 2012. 184(1).

  36. Durante-Mangoni E, et al. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii. A multicentre, randomised, clinical trial. Clin Infect Dis, 2013: p. cit253.

  37. Aydemir H et al. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. Epidemiol Infect. 2013;141(06):1214–22.

    Article  CAS  PubMed  Google Scholar 

  38. Tascini C et al. Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2013;57(8):3990–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Pachón-Ibáñez ME et al. Efficacy of rifampin and its combinations with imipenem, sulbactam, and colistin in experimental models of infection caused by imipenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2010;54(3):1165–72.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Motaouakkil S et al. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii. J Infect. 2006;53(4):274–8.

    Article  PubMed  Google Scholar 

  41. Bassetti M et al. Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2008;61(2):417–20.

    Article  CAS  PubMed  Google Scholar 

  42. Garnacho-Montero J et al. Clinical efficacy and safety of the combination of colistin plus vancomycin for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii. Chemotherapy. 2013;59(3):225–31.

    Article  CAS  PubMed  Google Scholar 

  43. Petrosillo N et al. Clinical experience of colistin-glycopeptide combination in critically ill patients infected with Gram-negative bacteria. Antimicrob Agents Chemother. 2014;58(2):851–8.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Kalin G et al. Comparison of colistin and colistin/sulbactam for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. Infection. 2014;42(1):37–42.

    Article  CAS  PubMed  Google Scholar 

  45. Qureshi ZA et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56(4):2108–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Jernigan MG et al. The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2012;56(6):3395–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Pontikis K et al. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents. 2014;43(1):52–9.

    Article  CAS  PubMed  Google Scholar 

  48. Guner R et al. Outcomes in patients infected with carbapenem-resistant Acinetobacter baumannii and treated with tigecycline alone or in combination therapy. Infection. 2011;39(6):515–8.

    Article  CAS  PubMed  Google Scholar 

  49. Michalopoulos A et al. Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin Microbiol Infect. 2010;16(2):184–6.

    Article  CAS  PubMed  Google Scholar 

  50. Safarika A, et al. Time-kill effect of levofloxacin on multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: synergism with imipenem and colistin. Eur J Clin Microbiol Infect Dis, 2014: p. 1–7.

  51. Tumbarello M et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55(7):943–50.

    Article  CAS  PubMed  Google Scholar 

  52. Rubinstein E et al. Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis. 2011;52(1):31–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Kalil AC et al. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med. 2010;38(9):1802–8.

    Article  CAS  PubMed  Google Scholar 

  54. Walkey AJ, O’Donnell MR, Wiener RS. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials. CHEST J. 2011;139(5):1148–55.

    Article  CAS  Google Scholar 

  55. Kalil AC. Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis. BMJ Open. 2013;3(10):e003912. This study provides further evidence on the similar efficacy between linezolid and vancomycin.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Wang Y et al. Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis. Eur J Clin Pharmacol. 2015;71(1):107–15.

    Article  CAS  PubMed  Google Scholar 

  57. Sun C et al. In vitro activity of minocycline combined with fosfomycin against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiotics. 2011;64(8):559–62.

    Article  CAS  Google Scholar 

  58. Xu-hong Y et al. In vitro activity of fosfomycin in combination with linezolid against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiotics. 2014;67(5):369–71.

    Article  Google Scholar 

  59. Jung YJ et al. Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia. Crit Care Med. 2010;38(1):175–80.

    Article  CAS  PubMed  Google Scholar 

  60. Pugh R, et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev, 2011. 10.

  61. Clancy CJ et al. Emerging and resistant infections. Ann Am Thorac Soc. 2014;11(Supplement 4):S193–200.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Kristina Bailey and Andre Kalil have no relevant disclosures to report.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

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Authors and Affiliations

  1. Pulmonary, Critical Care Allergy and Sleep Medicine Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Kristina L. Bailey

  2. Infectious Diseases Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Andre C. Kalil

  3. VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA

    Kristina L. Bailey

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  1. Kristina L. Bailey
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  2. Andre C. Kalil
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Correspondence to Andre C. Kalil.

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Bailey, K.L., Kalil, A.C. Ventilator-Associated Pneumonia (VAP) with Multidrug-Resistant (MDR) Pathogens: Optimal Treatment?. Curr Infect Dis Rep 17, 39 (2015). https://doi.org/10.1007/s11908-015-0494-5

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