Download PDF
Semin Respir Crit Care Med 2022; 43(02): 229-233
DOI: 10.1055/s-0041-1740584
Review Article

Defining Clinical and Microbiological Nonresponse in Ventilator-Associated Pneumonia

Adrian Ceccato
1   August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona; Biomedical Research Networking Centres in Respiratory Diseases (CIBERES), Barcelona, Spain
2   Intensive Care Unit, Hospital Universitari Sagrat Cor, Barcelona, Spain
,
Antoni Torres
1   August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona; Biomedical Research Networking Centres in Respiratory Diseases (CIBERES), Barcelona, Spain
3   Department of Pneumology, Hospital Clinic of Barcelona, Barcelona, Spain
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Ventilator-associated pneumonia (VAP) is a severe complication of mechanical ventilation, with mortality reduced most effectively by adequate early antibiotic treatment. The clinical and microbiologic response can be assessed easily from 72 hours after starting antibiotic treatment. Evidence of nonresponse is based on several factors: (1) lack of clinical improvement, (2) radiographic progression, (3) an impaired Sequential Organ Failure Assessment (SOFA) score, (4) no improvement by days 3 to 5 on the Clinical Pulmonary Infection Score (CPIS), (5) no decreased in biomarkers on day 3, and (6) isolation of a new pathogen on day 3. Among the clinical markers of treatment failure, physicians should consider no improvement in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), persistence of fever or hypothermia, persistence of purulent respiratory secretions, and new-onset septic shock or multiple-organ dysfunction syndrome. Microbiological isolation of a new pathogen on day 3 is also associated with higher mortality, but persistence of the original pathogen does not seem to be associated with a worse prognosis. The real impact of changes to treatment after diagnosing nonresponsive VAP is unknown. Physicians must evaluate whether treatments are adequate in terms of sensitivity, dose, and route. Pharmacokinetically and pharmacodynamically optimized doses are recommended in these patients. Clinical stabilization of comorbidities or underlying conditions may be of benefit.

Keywords

ventilator-associated pneumonia - nonresponding pneumonia - mortality - microbiologic assessment - clinical response


Publication History

Article published online:
27 January 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Ferrer M, Torres A. Epidemiology of ICU-acquired pneumonia. Curr Opin Crit Care 2018; 24 (05) 325-331
    CrossrefPubMedGoogle Scholar
  • 2 Álvarez-Lerma F, Palomar-Martínez M, Sánchez-García M. et al. Prevention of ventilator-associated pneumonia: the multimodal approach of the Spanish ICU “Pneumonia Zero” program. Crit Care Med 2018; 46 (02) 181-188
    CrossrefPubMedGoogle Scholar
  • 3 Rouzé A, Martin-Loeches I, Povoa P. et al; coVAPid Study Group. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med 2021; 47 (02) 188-198
    CrossrefPubMedGoogle Scholar
  • 4 Ibn Saied W, Mourvillier B, Cohen Y. et al; OUTCOMEREA Study Group. A comparison of the mortality risk associated with ventilator-acquired bacterial pneumonia and nonventilator ICU-acquired bacterial pneumonia. Crit Care Med 2019; 47 (03) 345-352
    CrossrefPubMedGoogle Scholar
  • 5 Vidaur L, Gualis B, Rodriguez A. et al. Clinical resolution in patients with suspicion of ventilator-associated pneumonia: a cohort study comparing patients with and without acute respiratory distress syndrome. Crit Care Med 2005; 33 (06) 1248-1253
    CrossrefPubMedGoogle Scholar
  • 6 Luna CM, Blanzaco D, Niederman MS. et al. Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 2003; 31 (03) 676-682
    CrossrefPubMedGoogle Scholar
  • 7 Ranzani OT, Prina E, Torres A. Nosocomial pneumonia in the intensive care unit: how should treatment failure be predicted?. Rev Bras Ter Intensiva 2014; 26 (03) 208-211
    CrossrefPubMedGoogle Scholar
  • 8 Dennesen PJW, van der Ven AJ, Kessels AG, Ramsay G, Bonten MJ. Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. Am J Respir Crit Care Med 2001; 163 (06) 1371-1375
    CrossrefPubMedGoogle Scholar
  • 9 Luna CM, Niederman MS. What is the natural history of resolution of nosocomial pneumonia?. Semin Respir Crit Care Med 2002; 23 (05) 471-479
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Kalil AC, Metersky ML, Klompas M. et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63 (05) e61-e111
    CrossrefPubMedGoogle Scholar
  • 11 Esperatti M, Ferrer M, Giunta V. et al. Validation of predictors of adverse outcomes in hospital-acquired pneumonia in the ICU. Crit Care Med 2013; 41 (09) 2151-2161
    CrossrefPubMedGoogle Scholar
  • 12 Ioanas M, Ferrer M, Cavalcanti M. et al. Causes and predictors of nonresponse to treatment of intensive care unit-acquired pneumonia. Crit Care Med 2004; 32 (04) 938-945
    CrossrefPubMedGoogle Scholar
  • 13 Cavalcanti M, Ferrer M, Ferrer R, Morforte R, Garnacho A, Torres A. Risk and prognostic factors of ventilator-associated pneumonia in trauma patients. Crit Care Med 2006; 34 (04) 1067-1072
    CrossrefPubMedGoogle Scholar
  • 14 Planquette B, Timsit J-F, Misset BY. et al; OUTCOMEREA Study Group. Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure. Am J Respir Crit Care Med 2013; 188 (01) 69-76
    CrossrefPubMedGoogle Scholar
  • 15 Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162 (2, Pt 1): 505-511
    CrossrefPubMedGoogle Scholar
  • 16 Dianti M, Luna CM. Do we need biomarkers for the follow-up and shortening of antibiotic treatment duration?. Curr Opin Crit Care 2018; 24 (05) 361-369
    CrossrefPubMedGoogle Scholar
  • 17 Torres A, Barberán J, Ceccato A. et al. Hospital-acquired pneumonia. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) guidelines. 2019 update. Arch Bronconeumol 2020; 56 (Suppl. 01) 11-19
    PubMedGoogle Scholar
  • 18 Luyt C-E, Combes A, Reynaud C. et al. Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008; 34 (08) 1434-1440
    CrossrefPubMedGoogle Scholar
  • 19 Nobre V, Harbarth S, Graf J-D, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008; 177 (05) 498-505
    CrossrefPubMedGoogle Scholar
  • 20 Stolz D, Smyrnios N, Eggimann P. et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34 (06) 1364-1375
    CrossrefPubMedGoogle Scholar
  • 21 de Jong E, van Oers JA, Beishuizen A. et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16 (07) 819-827
    CrossrefPubMedGoogle Scholar
  • 22 Bouadma L, Luyt C-E, Tubach F. et al; PRORATA Trial Group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375 (9713): 463-474
    CrossrefPubMedGoogle Scholar
  • 23 Niederman MS. Antibiotic use in sepsis: how and why less can really mean more (survival). Am J Respir Crit Care Med 2021; 203 (02) 157-158
    CrossrefPubMedGoogle Scholar
  • 24 Kyriazopoulou E, Liaskou-Antoniou L, Adamis G. et al. Procalcitonin to reduce long-term infection-associated adverse events in sepsis. a randomized trial. Am J Respir Crit Care Med 2021; 203 (02) 202-210
    CrossrefPubMedGoogle Scholar
  • 25 Luyt C-E, Guérin V, Combes A. et al. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 2005; 171 (01) 48-53
    CrossrefPubMedGoogle Scholar
  • 26 Coelho L, Rabello L, Salluh J. et al; TAVeM Study Group. C-reactive protein and procalcitonin profile in ventilator-associated lower respiratory infections. J Crit Care 2018; 48: 385-389
    CrossrefPubMedGoogle Scholar
  • 27 Póvoa P, Coelho L, Almeida E. et al. C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study. Eur Respir J 2005; 25 (05) 804-812
    CrossrefPubMedGoogle Scholar
  • 28 Póvoa P, Martin-Loeches I, Ramirez P. et al. Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study. J Crit Care 2017; 41: 91-97
    CrossrefPubMedGoogle Scholar
  • 29 Seligman R, Meisner M, Lisboa TC. et al. Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care 2006; 10 (05) R125
    CrossrefPubMedGoogle Scholar
  • 30 Póvoa P, Martin-Loeches I, Ramirez P. et al. Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study. Ann Intensive Care 2016; 6 (01) 32
    CrossrefPubMedGoogle Scholar
  • 31 Boeck L, Eggimann P, Smyrnios N. et al. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP. Eur Respir J 2011; 37 (03) 595-603
    CrossrefPubMedGoogle Scholar
  • 32 Krüger S, Frechen D, Ewig S. Prognosis of ventilator-associated pneumonia: what lies beneath. Eur Respir J 2011; 37 (03) 486-488
    CrossrefPubMedGoogle Scholar
  • 33 Montravers P, Fagon J-Y, Chastre J. et al. Follow-up protected specimen brushes to assess treatment in nosocomial pneumonia. Am Rev Respir Dis 1993; 147 (01) 38-44
    CrossrefPubMedGoogle Scholar
  • 34 A'Court CHD, Garrard CS, Crook D. et al. Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. Q J Med 1993; 86 (10) 635-648
    CrossrefPubMedGoogle Scholar
  • 35 Prats E, Dorca J, Pujol M. et al. Effects of antibiotics on protected specimen brush sampling in ventilator-associated pneumonia. Eur Respir J 2002; 19 (05) 944-951
    CrossrefPubMedGoogle Scholar
  • 36 Ceccato A, Dominedò C, Ferrer M. et al. Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study. Eur Respir J 2021; 2100620
    PubMedGoogle Scholar
  • 37 Martin-Loeches I, Ceccato A, Carbonara M. et al. Impact of cardiovascular failure in intensive care unit-acquired pneumonia: a single-center, prospective study. Antibiotics (Basel) 2021; 10 (07) 798
    CrossrefPubMedGoogle Scholar
  • 38 Ferrer M, Difrancesco LF, Liapikou A. et al. Polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome. Crit Care 2015; 19: 450
    CrossrefPubMedGoogle Scholar
  • 39 Dominedò C, Ceccato A, Niederman M. et al. Predictive performance of risk factors for multidrug-resistant pathogens in nosocomial pneumonia. Ann Am Thorac Soc 2021; 18 (05) 807-814
    CrossrefPubMedGoogle Scholar
  • 40 Ranzani OT, Motos A, Chiurazzi C. et al. Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect 2020; 26 (11) 1456-1463
    CrossrefPubMedGoogle Scholar
  • 41 Ceccato A, Di Giannatale P, Nogas S, Torres A. Safety considerations of current drug treatment strategies for nosocomial pneumonia. Expert Opin Drug Saf 2021; 20 (02) 181-190
    CrossrefPubMedGoogle Scholar