Download PDF
Semin Respir Crit Care Med 2022; 43(02): 219-228
DOI: 10.1055/s-0041-1739359
Review Article

Classical and Molecular Techniques to Diagnose HAP/VAP

Cherie Renaud
1   Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
,
Marin H. Kollef
1   Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), are the most common nosocomial infections occurring in critically ill patients requiring intensive care. However, challenges exist in making a timely and accurate diagnosis of HAP and VAP. Under diagnosis of HAP and VAP can result in greater mortality risk, especially if accompanied by delays in the administration of appropriate antimicrobial treatment. Over diagnosis of HAP and VAP results in the unnecessary administration of broad spectrum antibiotics that can lead to further escalation of antibiotic resistance. Optimal diagnosis and management of HAP and VAP require a systematic approach that combines clinical and radiographic assessments along with proper microbiologic techniques. The use of more invasive sampling methods (bronchoalveolar lavage and protected specimen brush) may enhance specimen collection resulting in more specific diagnoses to limit unnecessary antibiotic exposure. Molecular techniques, currently in use and investigational technique, may improve the diagnosis of HAP and VAP by allowing more rapid identification of offending pathogens, if present, thus increasing both appropriate antibiotic treatment and avoiding unnecessary drug exposure.

Keywords

nosocomial - pneumonia - diagnosis - microbiology - bacteria - viruses


Publication History

Article published online:
18 January 2022

© 2022. Thieme. All rights reserved.

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

 

  • References

  • 1 Bergin SP, Coles A, Calvert SB. et al. PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU. Chest 2020; 158 (06) 2370-2380
    CrossrefPubMedSearch in Google Scholar
  • 2 Vincent JL, Sakr Y, Singer M. et al; EPIC III Investigators. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020; 323 (15) 1478-1487
    CrossrefPubMedSearch in Google Scholar
  • 3 Magill SS, O'Leary E, Janelle SJ. et al. Emerging Infections Program Hospital Prevalence Survey Team. Changes in prevalence of health care-associated infections in U.S. hospitals. N Engl J Med 2018; 379 (18) 1732-1744
    CrossrefPubMedSearch in Google Scholar
  • 4 Magill SS, Edwards JR, Bamberg W. et al. Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370 (13) 1198-1208
    CrossrefPubMedSearch in Google Scholar
  • 5 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
    CrossrefPubMedSearch in Google Scholar
  • 6 Torres A, Niederman MS, Chastre J. et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 2017; 50 (03) 1700582
    CrossrefPubMedSearch in Google Scholar
  • 7 Grossman RF, Fein A. Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia. Executive summary. Chest 2000; 117 (4, suppl 2) 177S-181S
    CrossrefPubMedSearch in Google Scholar
  • 8 Morrow LE, Kollef MH, Casale TB. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial. Am J Respir Crit Care Med 2010; 182 (08) 1058-1064
    CrossrefPubMedSearch in Google Scholar
  • 9 Calandra T, Cohen J. International Sepsis Forum Definition of Infection in the ICU Consensus Conference. The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 2005; 33 (07) 1538-1548
    CrossrefPubMedSearch in Google Scholar
  • 10 Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36 (05) 309-332
    CrossrefPubMedSearch in Google Scholar
  • 11 Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143 (5 Pt 1): 1121-1129
    CrossrefPubMedSearch in Google Scholar
  • 12 Zimlichman E, Henderson D, Tamir O. et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med 2013; 173 (22) 2039-2046
    CrossrefPubMedSearch in Google Scholar
  • 13 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 (10) CD006482
    PubMedSearch in Google Scholar
  • 14 Klompas M. Does this patient have ventilator-associated pneumonia?. JAMA 2007; 297 (14) 1583-1593
    CrossrefPubMedSearch in Google Scholar
  • 15 Kalanuria AA, Ziai W, Mirski M. Ventilator-associated pneumonia in the ICU. Crit Care 2014; 18 (02) 208
    CrossrefPubMedSearch in Google Scholar
  • 16 Kirtland SH, Corley DE, Winterbauer RH. et al. The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest 1997; 112 (02) 445-457
    CrossrefPubMedSearch in Google Scholar
  • 17 Shan J, Chen HL, Zhu JH. Diagnostic accuracy of clinical pulmonary infection score for ventilator-associated pneumonia: a meta-analysis. Respir Care 2011; 56 (08) 1087-1094
    CrossrefPubMedSearch in Google Scholar
  • 18 Fàbregas N, Ewig S, Torres A. et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54 (10) 867-873
    CrossrefPubMedSearch in Google Scholar
  • 19 Wunderink RG, Woldenberg LS, Zeiss J, Day CM, Ciemins J, Lacher DA. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. Chest 1992; 101 (02) 458-463
    CrossrefPubMedSearch in Google Scholar
  • 20 Fernando SM, Tran A, Cheng W. et al. Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med 2020; 46 (06) 1170-1179
    CrossrefPubMedSearch in Google Scholar
  • 21 Tejerina E, Esteban A, Fernández-Segoviano P. et al. Accuracy of clinical definitions of ventilator-associated pneumonia: comparison with autopsy findings. J Crit Care 2010; 25 (01) 62-68
    CrossrefPubMedSearch in Google Scholar
  • 22 Staub LJ, Biscaro RRM, Maurici R. Accuracy and applications of lung ultrasound to diagnose ventilator-associated pneumonia: a systematic review. J Intensive Care Med 2018; 33 (08) 447-455
    CrossrefPubMedSearch in Google Scholar
  • 23 Bouhemad B, Dransart-Rayé O, Mojoli F, Mongodi S. Lung ultrasound for diagnosis and monitoring of ventilator-associated pneumonia. Ann Transl Med 2018; 6 (21) 418
    CrossrefPubMedSearch in Google Scholar
  • 24 Staub LJ, Biscaro RRM, Maurici R. Emergence of alveolar consolidations in serial lung ultrasound and diagnosis of ventilator-associated pneumonia. J Intensive Care Med 2021; 36 (03) 304-312
    CrossrefPubMedSearch in Google Scholar
  • 25 Luyt CE, Combes A, Reynaud C. et al. Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008; 34 (08) 1434-1440
    CrossrefPubMedSearch in Google Scholar
  • 26 Ramirez P, Garcia MA, Ferrer M. et al. Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia. Eur Respir J 2008; 31 (02) 356-362
    CrossrefPubMedSearch in Google Scholar
  • 27 Fagon JY. Biological markers and diagnosis of ventilator-associated pneumonia. Crit Care 2011; 15 (02) 130
    CrossrefPubMedSearch in Google Scholar
  • 28 Anand NJ, Zuick S, Klesney-Tait J, Kollef MH. Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in BAL fluid of patients with pulmonary infiltrates in the ICU. Chest 2009; 135 (03) 641-647
    CrossrefPubMedSearch in Google Scholar
  • 29 Salluh JIF, Souza-Dantas VC, Póvoa P. The current status of biomarkers for the diagnosis of nosocomial pneumonias. Curr Opin Crit Care 2017; 23 (05) 391-397
    CrossrefPubMedSearch in Google 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
    CrossrefPubMedSearch in Google Scholar
  • 31 Fagon JY, 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 (08) 621-630
    CrossrefPubMedSearch in Google Scholar
  • 32 Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355 (25) 2619-2630
    CrossrefPubMedSearch in Google Scholar
  • 33 Shorr AF, Sherner JH, Jackson WL, Kollef MH. Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis. Crit Care Med 2005; 33 (01) 46-53
    CrossrefPubMedSearch in Google Scholar
  • 34 Solé Violán J, Fernández JA, Benítez AB, Cardeñosa Cendrero JA, Rodríguez de Castro F. Impact of quantitative invasive diagnostic techniques in the management and outcome of mechanically ventilated patients with suspected pneumonia. Crit Care Med 2000; 28 (08) 2737-2741
    CrossrefPubMedSearch in Google Scholar
  • 35 Guillamet MCV, Burnham JP, Kollef MH. Novel approaches to hasten detection of pathogens and antimicrobial resistance in the intensive care unit. Semin Respir Crit Care Med 2019; 40 (04) 454-464
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Hyams C, Williams OM, Williams P. Urinary antigen testing for pneumococcal pneumonia: is there evidence to make its use uncommon in clinical practice?. ERJ Open Res 2020; 6 (01) 2019
    CrossrefPubMedSearch in Google Scholar
  • 37 Mercante JW, Winchell JM. Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev 2015; 28 (01) 95-133
    CrossrefPubMedSearch in Google Scholar
  • 38 Muyldermans A, Descheemaeker P, Boel A, Desmet S, Van Gasse N, Reynders M. National Expert Committee on Infectious Serology. What is the risk of missing legionellosis relying on urinary antigen testing solely? A retrospective Belgian multicenter study. Eur J Clin Microbiol Infect Dis 2020; 39 (04) 729-734
    CrossrefPubMedSearch in Google Scholar
  • 39 CDC. Coronavirus disease 2019 (COVID-19): interim guidance for antigen testing for SARS-CoV-2. Atlanta, GA: US Department of Health and Human Services, CDC; 2020 . Accessed February 25, 2021 at: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html
    PubMedSearch in Google Scholar
  • 40 Pray IW, Ford L, Cole D. et al. CDC COVID-19 Surge Laboratory Group. Performance of an antigen-based test for asymptomatic and symptomatic SARS-CoV-2 testing at two university campuses—Wisconsin, September-October 2020. MMWR Morb Mortal Wkly Rep 2021; 69 (5152): 1642-1647
    CrossrefPubMedSearch in Google Scholar
  • 41 Wolk DM, Struelens MJ, Pancholi P. et al. Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays. J Clin Microbiol 2009; 47 (03) 823-826
    CrossrefPubMedSearch in Google Scholar
  • 42 Trevino SE, Pence MA, Marschall J, Kollef MH, Babcock HM, Burnham CD. Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship. Eur J Clin Microbiol Infect Dis 2017; 36 (05) 879-885
    CrossrefPubMedSearch in Google Scholar
  • 43 Paonessa JR, Shah RD, Pickens CI. et al. Rapid detection of methicillin-resistant Staphylococcus aureus in BAL: a pilot randomized controlled trial. Chest 2019; 155 (05) 999-1007
    CrossrefPubMedSearch in Google Scholar
  • 44 Poole S, Kidd SP, Saeed K. A review of novel technologies and techniques associated with identification of bloodstream infection etiologies and rapid antimicrobial genotypic and quantitative phenotypic determination. Expert Rev Mol Diagn 2018; 18 (06) 543-555
    CrossrefPubMedSearch in Google Scholar
  • 45 Luyt CE, Hékimian G, Bonnet I. et al. Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study. Crit Care 2020; 24 (01) 378
    CrossrefPubMedSearch in Google Scholar
  • 46 Monard C, Pehlivan J, Auger G. et al; ADAPT study group. Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia. Crit Care 2020; 24 (01) 434
    CrossrefPubMedSearch in Google Scholar
  • 47 Peiffer-Smadja N, Bouadma L, Mathy V. et al. Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia. Crit Care 2020; 24 (01) 366
    CrossrefPubMedSearch in Google Scholar
  • 48 Hou D, Ju M, Wang Y. et al. PCR coupled to electrospray ionization mass spectrometry for microbiological diagnosis and surveillance of ventilator-associated pneumonia. Exp Ther Med 2020; 20 (04) 3587-3594
    PubMedSearch in Google Scholar
  • 49 Edwards T, Williams C, Teethaisong Y. et al. A highly multiplexed melt-curve assay for detecting the most prevalent carbapenemase, ESBL, and AmpC genes. Diagn Microbiol Infect Dis 2020; 97 (04) 115076
    CrossrefPubMedSearch in Google Scholar
  • 50 Gastli N, Loubinoux J, Daragon M. et al. Multicentric evaluation of BioFire FilmArray pneumonia panel for rapid bacteriological documentation of pneumonia. Clin Microbiol Infect 2020; 27 (09) 1308-1314
    CrossrefPubMedSearch in Google Scholar
  • 51 Micek ST, Chew B, Hampton N, Kollef MH. A case-control study assessing the impact of nonventilated hospital-acquired pneumonia on patient outcomes. Chest 2016; 150 (05) 1008-1014
    CrossrefPubMedSearch in Google Scholar
  • 52 Shorr AF, Fisher K, Micek ST, Kollef MH. The burden of viruses in pneumonia associated with acute respiratory failure: an underappreciated issue. Chest 2018; 154 (01) 84-90
    CrossrefPubMedSearch in Google Scholar
  • 53 Schwierzeck V, König JC, Kühn J. et al. First reported nosocomial outbreak of severe acute respiratory syndrome Coronavirus 2 in a pediatric dialysis unit. Clin Infect Dis 2021; 72 (02) 265-270
    CrossrefPubMedSearch in Google Scholar
  • 54 Chung HY, Jian MJ, Chang CK. et al. Novel dual multiplex real-time RT-PCR assays for the rapid detection of SARS-CoV-2, influenza A/B, and respiratory syncytial virus using the BD MAX open system. Emerg Microbes Infect 2021; 10 (01) 161-166
    CrossrefPubMedSearch in Google Scholar
  • 55 Webber DM, Wallace MA, Burnham CA, Anderson NW. Evaluation of the BioFire FilmArray pneumonia panel for detection of viral and bacterial pathogens in lower respiratory tract specimens in the setting of a tertiary care academic medical center. J Clin Microbiol 2020; 58 (07) e00343-e20
    CrossrefPubMedSearch in Google Scholar
  • 56 Singhal N, Kumar M, Kanaujia PK, Virdi JS. MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Front Microbiol 2015; 6: 791
    CrossrefPubMedSearch in Google Scholar
  • 57 Cordovana M, Kostrzewa M, Glandorf J, Bienia M, Ambretti S, Pranada AB. A full MALDI-based approach to detect plasmid encoded KPC-producing Klebsiella pneumoniae . Front Microbiol 2018; 9: 2854
    CrossrefPubMedSearch in Google Scholar
  • 58 Oviaño M, Bou G. Matrix-assisted laser desorption ionization time of flight mass spectrometry for the rapid detection of antimicrobial resistance mechanisms and beyond. Clin Microbiol Rev 2018; 32 (01) e00037-e18
    CrossrefPubMedSearch in Google Scholar
  • 59 Westblade LF, Garner OB, MacDonald K. et al. Assessment of reproducibility of matrix-assisted laser desorption ionization-time of flight mass spectrometry for bacterial and yeast identification. J Clin Microbiol 2015; 53 (07) 2349-2352
    CrossrefPubMedSearch in Google Scholar
  • 60 Wu CJ, Chen YP, Wang HC. et al. Identification of fungal pathogens from clinical specimens using multi-locus PCR coupled with electrospray ionization mass spectrometry. Diagn Microbiol Infect Dis 2014; 78 (02) 141-143
    CrossrefPubMedSearch in Google Scholar
  • 61 Peeters B, Herijgers P, Beuselinck K. et al. Comparison of PCR-electrospray ionization mass spectrometry with 16S rRNA PCR and amplicon sequencing for detection of bacteria in excised heart valves. J Clin Microbiol 2016; 54 (11) 2825-2831
    CrossrefPubMedSearch in Google Scholar
  • 62 Koncan R, Parisato M, Sakarikou C. et al. Direct identification of major Gram-negative pathogens in respiratory specimens by respiFISH® HAP Gram (-) Panel, a beacon-based FISH methodology. Eur J Clin Microbiol Infect Dis 2015; 34 (10) 2097-2102
    CrossrefPubMedSearch in Google Scholar
  • 63 Prudent E, Raoult D. Fluorescence in situ hybridization, a complementary molecular tool for the clinical diagnosis of infectious diseases by intracellular and fastidious bacteria. FEMS Microbiol Rev 2019; 43 (01) 88-107
    CrossrefPubMedSearch in Google Scholar
  • 64 Martinez RM, Bauerle ER, Fang FC, Butler-Wu SM. Evaluation of three rapid diagnostic methods for direct identification of microorganisms in positive blood cultures. J Clin Microbiol 2014; 52 (07) 2521-2529
    CrossrefPubMedSearch in Google Scholar
  • 65 Deck MK, Anderson ES, Buckner RJ. et al. Rapid detection of Enterococcus spp. direct from blood culture bottles using Enterococcus QuickFISH method: a multicenter investigation. Diagn Microbiol Infect Dis 2014; 78 (04) 338-342
    CrossrefPubMedSearch in Google Scholar