Molecular diagnostics for bacterial infections in bronchoalveolar lavage – a case-control, pilot study

Kathleen Jahn; Marko Kuisma; Minna Mäki; Peter Grendelmeier; Hans  H. Hirsch; Michael Tamm; Eleni Papakonstantinou; Daiana Stolz

doi:10.4414/smw.2015.14193

Original article

Vol. 145 No. 3940 (2015)

Molecular diagnostics for bacterial infections in bronchoalveolar lavage – a case-control, pilot study

Kathleen Jahn
Marko Kuisma
Minna Mäki
Peter Grendelmeier
Hans H. Hirsch
Michael Tamm
Eleni Papakonstantinou
Daiana Stolz

DOI: https://doi.org/10.4414/smw.2015.14193
Cite this as:: Swiss Med Wkly. 2015;145:w14193
Published: 20.09.2015

Summary

QUESTIONS UNDER STUDY: The differentiation between infectious and noninfectious pulmonary complications is challenging. Rapid, accurate microbiological results may allow appropriate antibiotic therapy, withholding or adapting antibiotics, and thus reducing costs and risks of empirical antibiotic therapy. The objective of this proof-of-concept pilot study was to investigate the diagnostic yield of a new polymerase chain-reaction (PCR) and microarray-based rapid molecular diagnostic assay and compare the results to conventional microbiology cultures and clinical judgment.

METHODS: Bronchoalveolar lavage specimens were obtained from 35 patients undergoing bronchoscopy for diagnostic reasons. Cases (n = 22) consisted of patients with suspicion of pulmonary bacterial infection. Controls (n = 13) were identified among patients undergoing bronchoscopy for indications other than suspicion of infection.

RESULTS: Demographics were similar in cases and controls. The majority (73%) of patients with pulmonary infection were on empirical antibiotic therapy. Among the 22 cases, bacteria were identified by means of PCR in 77% (n = 17) as compared with 41% (n = 9) by culture (p = 0.030). In contrast, controls yielded a PCR positive result in 45% (n = 7), as compared with no positive cultures (p = 0.005). Compared with culture results, PCR had a sensitivity of 87.5% (95% confidence interval [CI] 47.4–97.9) and specificity of 28.6% (95% CI 8.6–58.1) to diagnose bacterial infection. Compared with clinical judgment, corresponding figures were 77.3% (95% CI 54.5–91.1) and 46.2% (95% CI 19.3–74.8), respectively.

CONCLUSION: The PCR- and microarray-based rapid molecular diagnostic assay offers an alternative to conventional cultures for detection of potentially pathogenic bacteria in bronchoalveolar lavage of patients with pneumonia. However, the clinical relevance is unclear as it may also detect colonisers in patients without a corresponding infection.

References

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Mundy LM, Auwaerter PG, Oldach D. Community-acquired pneumonia: impact of immune status. AM J Respir Crit Care Med. 1995;152:1309–15.
Tissari P, Zumla A, Tarkka E, Mero S, Savolainen L, Vaara M et al. Accurate and rapid identification of bacterial species from positive blood cultures with DNA-based microarray platform: an observational study. Lancet. 2010;375:224–30.
Jain P, Sandur S, Meli Y, Arroliga AC, Stoller JK, Metha AC. Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates. Chest. 2004;125(2):712–22.
Patel NR, Lee PS, Kim JH, Weimhouse GL, Koziel H. The influence of diagnostic bronchoscopy on clinical outcomes comparing adult autologous and allogenic bone marrow transplant patients. Chest. 2005;127(4):1388–96.
Yokoi T, Hirabayashi N, Ito M, Uno Y, Tsuzuki T, Yatabe Y, et al. Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases. Nagoya BMT Group. Virchows Arch. 1997;431(4):275–82.
Sharma S, Nadrous HF, Peters SG, Tefferi A, Litzow MR, Aubry MC, et al. Pulmonary complications in adult blood and bone marrow transplant recipients: autopsy findings. Chest. 2005;128(3):1385–92.
Choi MH, Jung JI, Chung WD, Kim YJ, Lee SE, Han DH, Ahn MI, et al. Acute pulmonary complications in patients with hematologic malignancies. Radiographics. 2014;34(6):1755–68.doi: 10.1148/rg.346130107
Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Müller B, Tamm M. Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection. Swiss Med Wkly. 2006;136(27-28):434–40.
Bodey GP, Rolston KV. Management of fever in neutropenic patients. J Infect Chemother. 2001;7(1):1–9.
Pizzo PA. Fever in immunocompromised patients. N Engl J Med. 1999;341(12):893–900.
Joos L, Chhajed PN, Wallner J, Battegay M, Steiger J, Gratwohl A, et al. Pulmonary infections diagnosed by BAL: A 12 year-experience in 1066 immunocompromised patients. Respir Med. 2007;101(1):93–7.
Dunagan DP, Baker AM, Hurd DD, Haponik EF. Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation. Chest. 1997;111(1):135–41.
White P, Bonacum JT, Miller CB. Utility of fiberoptic bronchoscopy in bone marrow transplant patients. Bone Marrow Transplant. 1997;20(8):681–7.
Bonafede MM, Suaya JA, Wilson KL, Mannino DM, Polsky D. Incidence and Cost of CAP in a Large Working-Age Population. Am J Manag Care. 2012;18(7):380–7.
Mandell LA, Wunderink RG, Anzueto A. Infectious diseases Society of America/ American Thoracic Society consensus guidelines on the managment of community acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27–72.
Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson Jr. RH, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the infectious society of america (IDSA) and the american society for microbiology (ASM). Clin Inf Dis. 2013;57(4):485–8.doi:10.1093/cid/cit441
Grendelmeier P, Tamm M, Pflimlin E, Stolz D. Propofol sedation for flexible bronchoscopy: a randomised, noninferiority trial. European Respir J. 2014;43(2):591–601.
Schlatter L, Pflimlin E, Fehrke B, Meyer A, Tamm M, Stolz D. Propofol versus propofol plus hydrocodone for flexible bronchoscopy: a randomised study. Eur Respir J. 2011;38:529–37.
Brownback KR, Simpson SQ. Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients. Ann Thorac Med. 2013;8(3):153–9.
Schulte B, Eickmeyer H, Heininger A, Juretzek S, Karrasch M, Denis O, et al. Detection of Pneumonia Associated Pathogens Using a Prototype Multiplexed Pneumonia Test in Hospitalized Patients with Severe Pneumonia PLoS One. 2014;9(11):e110566.
Patel IS, Seemungal TAR, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002;57:759–64.
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Schaub N, Boldanova T, Noveanu M, Arenja N, Hermann H, Twerenbold R, et al. Incremental value of multiplex real-time PCR for the early diagnosis of sepsis in the emergency department. Swiss Med Wkly. 2014;144:w13911.

How to Cite

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Jahn K, Kuisma M, Mäki M, Grendelmeier P, Hirsch HH, Tamm M, Papakonstantinou E, Stolz D. Molecular diagnostics for bacterial infections in bronchoalveolar lavage – a case-control, pilot study. Swiss Med Wkly [Internet]. 2015 Sep. 20 [cited 2024 Apr. 18];145(3940):w14193. Available from: https://smw.ch/index.php/smw/article/view/2081

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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[1] Waite S, Jeudy J, White CS. Acute lung infections in normal and immunocompromised hosts. Radiol Clin North Am. 2006;44(2):295–315,ix.

[2] Mundy LM, Auwaerter PG, Oldach D. Community-acquired pneumonia: impact of immune status. AM J Respir Crit Care Med. 1995;152:1309–15.

[3] Tissari P, Zumla A, Tarkka E, Mero S, Savolainen L, Vaara M et al. Accurate and rapid identification of bacterial species from positive blood cultures with DNA-based microarray platform: an observational study. Lancet. 2010;375:224–30.

[4] Jain P, Sandur S, Meli Y, Arroliga AC, Stoller JK, Metha AC. Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates. Chest. 2004;125(2):712–22.

[5] Patel NR, Lee PS, Kim JH, Weimhouse GL, Koziel H. The influence of diagnostic bronchoscopy on clinical outcomes comparing adult autologous and allogenic bone marrow transplant patients. Chest. 2005;127(4):1388–96.

[6] Yokoi T, Hirabayashi N, Ito M, Uno Y, Tsuzuki T, Yatabe Y, et al. Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases. Nagoya BMT Group. Virchows Arch. 1997;431(4):275–82.

[7] Sharma S, Nadrous HF, Peters SG, Tefferi A, Litzow MR, Aubry MC, et al. Pulmonary complications in adult blood and bone marrow transplant recipients: autopsy findings. Chest. 2005;128(3):1385–92.

[8] Choi MH, Jung JI, Chung WD, Kim YJ, Lee SE, Han DH, Ahn MI, et al. Acute pulmonary complications in patients with hematologic malignancies. Radiographics. 2014;34(6):1755–68.doi: 10.1148/rg.346130107

[9] Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Müller B, Tamm M. Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection. Swiss Med Wkly. 2006;136(27-28):434–40.

[10] Bodey GP, Rolston KV. Management of fever in neutropenic patients. J Infect Chemother. 2001;7(1):1–9.

[11] Pizzo PA. Fever in immunocompromised patients. N Engl J Med. 1999;341(12):893–900.

[12] Joos L, Chhajed PN, Wallner J, Battegay M, Steiger J, Gratwohl A, et al. Pulmonary infections diagnosed by BAL: A 12 year-experience in 1066 immunocompromised patients. Respir Med. 2007;101(1):93–7.

[13] Dunagan DP, Baker AM, Hurd DD, Haponik EF. Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation. Chest. 1997;111(1):135–41.

[14] White P, Bonacum JT, Miller CB. Utility of fiberoptic bronchoscopy in bone marrow transplant patients. Bone Marrow Transplant. 1997;20(8):681–7.

[15] Bonafede MM, Suaya JA, Wilson KL, Mannino DM, Polsky D. Incidence and Cost of CAP in a Large Working-Age Population. Am J Manag Care. 2012;18(7):380–7.

[16] Mandell LA, Wunderink RG, Anzueto A. Infectious diseases Society of America/ American Thoracic Society consensus guidelines on the managment of community acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27–72.

[17] Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson Jr. RH, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the infectious society of america (IDSA) and the american society for microbiology (ASM). Clin Inf Dis. 2013;57(4):485–8.doi:10.1093/cid/cit441

[18] Grendelmeier P, Tamm M, Pflimlin E, Stolz D. Propofol sedation for flexible bronchoscopy: a randomised, noninferiority trial. European Respir J. 2014;43(2):591–601.

[19] Schlatter L, Pflimlin E, Fehrke B, Meyer A, Tamm M, Stolz D. Propofol versus propofol plus hydrocodone for flexible bronchoscopy: a randomised study. Eur Respir J. 2011;38:529–37.

[20] Brownback KR, Simpson SQ. Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients. Ann Thorac Med. 2013;8(3):153–9.

[21] Schulte B, Eickmeyer H, Heininger A, Juretzek S, Karrasch M, Denis O, et al. Detection of Pneumonia Associated Pathogens Using a Prototype Multiplexed Pneumonia Test in Hospitalized Patients with Severe Pneumonia PLoS One. 2014;9(11):e110566.

[22] Patel IS, Seemungal TAR, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002;57:759–64.

[23] Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858–73.

[24] Schaub N, Boldanova T, Noveanu M, Arenja N, Hermann H, Twerenbold R, et al. Incremental value of multiplex real-time PCR for the early diagnosis of sepsis in the emergency department. Swiss Med Wkly. 2014;144:w13911.