Advertisement

Pathogenic significance of hemorrhagic pneumonia in hematologic malignancy patients with Stenotrophomonas maltophilia bacteremia: clinical and microbiological analysis

  • Si-Ho Kim
  • Min Kyeong Cha
  • Cheol-In KangEmail author
  • Jae-Hoon Ko
  • Kyungmin Huh
  • Sun Young Cho
  • Doo Ryeon Chung
  • Kyong Ran Peck
Original Article
  • 77 Downloads

Abstract

Hemorrhagic pneumonia (HP) is known as the clinical manifestation of Stenotrophomonas maltophilia infection, while catheter-related blood stream infection (CRBSI) is the common clinical presentation of S. maltophilia bacteremia (SMB). The purpose of this study is to evaluate the risk factors for mortality in hematologic malignancy patients with SMB and to analyze clinical and microbiological characteristics of HP associated with SMB and CRBSI. SMB cases of patients with a hematologic malignancy were collected from 2006 through 2016. The overall 30-day mortality rate and mortality risk factors were assessed. The expression of major virulence-associated genes from S. maltophilia isolates, which included genes encoding type-1 fimbriae (smf-1), proteases (StmPr1 and StmPr2), and esterase (Smlt3773), from the blood of patients with HP and CRBSI was investigated. The phenotypic and genotypic traits were also compared. A total of 118 cases of SMB were included. The overall 30-day mortality rate was 61.0%. A multivariable analysis showed that HP was the most important risk factor for mortality (adjusted OR = 106.41; 95% CI = 5.18–2184.55). Although no statistical significance was observed in microbiological analysis, isolates from HP have a trend toward a higher protease activity (93.8% vs. 73.3%, P = 0.172). Clinical analysis showed that thrombocytopenia (P = 0.037) and prolonged neutropenia (P = 0.043) were significant factors associated with HP. Our data, which includes hematologic malignancy patients with SMB, suggest that HP is the significant risk factor for mortality and that the unique characteristics of patients and microbes contribute to the pathogenesis.

Keywords

Stenotrophomonas maltophilia Bacteremia Hemorrhagic pneumonia Hematologic malignancy Protease 

Notes

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07041096).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The study was approved by the local ethical research committee (IRB number: 2017-08-016-002).

References

  1. 1.
    Looney WJ, Narita M, Muhlemann K (2009) Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis 9(5):312–323CrossRefGoogle Scholar
  2. 2.
    Safdar A, Rolston KV (2007) Stenotrophomonas maltophilia: changing spectrum of a serious bacterial pathogen in patients with cancer. Clin Infect Dis 45(12):1602–1609CrossRefGoogle Scholar
  3. 3.
    Rutter WC, Burgess DR, Burgess DS (2017) Increasing incidence of multidrug resistance among cystic fibrosis respiratory bacterial isolates. Microb Drug Resist 23(1):51–55CrossRefGoogle Scholar
  4. 4.
    Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A, Sebaihia M, Saunders D, Arrowsmith C, Carver T, Peters N, Adlem E, Kerhornou A, Lord A, Murphy L, Seeger K, Squares R, Rutter S, Quail MA, Rajandream MA, Harris D, Churcher C, Bentley SD, Parkhill J, Thomson NR, Avison MB (2008) The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol 9(4):R74CrossRefGoogle Scholar
  5. 5.
    Micozzi A, Venditti M, Monaco M, Friedrich A, Taglietti F, Santilli S, Martino P (2000) Bacteremia due to Stenotrophomonas maltophilia in patients with hematologic malignancies. Clin Infect Dis 31(3):705–711CrossRefGoogle Scholar
  6. 6.
    Metan G, Uzun O (2005) Impact of initial antimicrobial therapy in patients with bloodstream infections caused by Stenotrophomonas maltophilia. Antimicrob Agents Chemother 49(9):3980–3981CrossRefGoogle Scholar
  7. 7.
    Toleman MA, Bennett PM, Bennett DM, Jones RN, Walsh TR (2007) Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis 13(4):559–565CrossRefGoogle Scholar
  8. 8.
    Cho SY, Kang CI, Kim J, Ha YE, Chung DR, Lee NY, Peck KR, Song JH (2014) Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia bacteremia? Antimicrob Agents Chemother 58(1):581–583CrossRefGoogle Scholar
  9. 9.
    Cho SY, Lee DG, Choi SM, Park C, Chun HS, Park YJ, Choi JK, Lee HJ, Park SH, Choi JH, Yoo JH (2015) Stenotrophomonas maltophilia bloodstream infection in patients with hematologic malignancies: a retrospective study and in vitro activities of antimicrobial combinations. BMC Infect Dis 15:69CrossRefGoogle Scholar
  10. 10.
    Elsner HA, Duhrsen U, Hollwitz B, Kaulfers PM, Hossfeld DK (1997) Fatal pulmonary hemorrhage in patients with acute leukemia and fulminant pneumonia caused by Stenotrophomonas maltophilia. Ann Hematol 74(4):155–161CrossRefGoogle Scholar
  11. 11.
    Abbas AA, Fryer CJ, Felimban SK, Yousef AA, Fayea NY, Osoba O (2003) Stenotrophomonas maltophilia infection related mortality during induction in childhood acute lymphoblastic leukemia. Med Pediatr Oncol 41(1):93–94CrossRefGoogle Scholar
  12. 12.
    Rousseau A, Morcos M, Amrouche L, Fois E, Casetta A, Rio B, Le Tourneaua A, Molina T, Rabbat A, Marie JP, Audouin J (2004) Lethal pulmonary hemorrhage caused by a fulminant Stenotrophomonas maltophilia respiratory infection in an acute myeloid leukemia patient. Leuk Lymphoma 45(6):1293–1296CrossRefGoogle Scholar
  13. 13.
    Ortin X, Jaen-Martinez J, Rodriguez-Luaces M, Alvaro T, Font L (2007) Fatal pulmonary hemorrhage in a patient with myelodysplastic syndrome and fulminant pneumonia caused by Stenotrophomonas maltophilia. Infection 35(3):201–202CrossRefGoogle Scholar
  14. 14.
    Takahashi N, Yoshioka T, Kameoka Y, Tagawa H, Fujishima N, Saitoh H, Hirokawa M, Enomoto K, Sawada K (2011) Fatal hemorrhagic pneumonia caused by Stenotrophomanas maltophilia in a patient with non-Hodgkin lymphoma. J Infect Chemother 17(6):858–862CrossRefGoogle Scholar
  15. 15.
    Araoka H, Fujii T, Izutsu K, Kimura M, Nishida A, Ishiwata K, Nakano N, Tsuji M, Yamamoto H, Asano-Mori Y, Uchida N, Wake A, Taniguchi S, Yoneyama A (2012) Rapidly progressive fatal hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in hematologic malignancy. Transpl Infect Dis 14(4):355–363CrossRefGoogle Scholar
  16. 16.
    Tada K, Kurosawa S, Hiramoto N, Okinaka K, Ueno N, Asakura Y, Kim SW, Yamashita T, Mori SI, Heike Y, Maeshima AM, Tanosaki R, Tobinai K, Fukuda T (2013) Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high mortality due to pulmonary hemorrhage. Bone Marrow Transplant 48(1):74–79CrossRefGoogle Scholar
  17. 17.
    Mori M, Tsunemine H, Imada K, Ito K, Kodaka T, Takahashi T (2014) Life-threatening hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in the treatment of hematologic diseases. Ann Hematol 93(6):901–911CrossRefGoogle Scholar
  18. 18.
    Guzoglu N, Demirkol FN, Aliefendioglu D (2015) Haemorrhagic pneumonia caused by Stenotrophomonas maltophilia in two newborns. J Infect Dev Ctries 9(5):533–535CrossRefGoogle Scholar
  19. 19.
    Gutierrez C, Pravinkumar E, Balachandran D, Schneider V (2016) Fatal hemorrhagic pneumonia: don’t forget Stenotrophomonas maltophilia. Respir Med Case Rep 19:12–14Google Scholar
  20. 20.
    Katayama O, Kitagawa T, Onaka T, Yonezawa A (2017) Rapidly progressive hemorrhagic pneumonia caused by Stenotrophomonas maltophilia occurring early after bone marrow transplantation in a patient with myelodysplastic syndrome. Rinsho Ketsueki 58(4):323–325Google Scholar
  21. 21.
    Windhorst S, Frank E, Georgieva DN, Genov N, Buck F, Borowski P, Weber W (2002) The major extracellular protease of the nosocomial pathogen Stenotrophomonas maltophilia: characterization of the protein and molecular cloning of the gene. J Biol Chem 277(13):11042–11049CrossRefGoogle Scholar
  22. 22.
    Pompilio A, Pomponio S, Crocetta V, Gherardi G, Verginelli F, Fiscarelli E, Dicuonzo G, Savini V, D'Antonio D, Di Bonaventura G (2011) Phenotypic and genotypic characterization of Stenotrophomonas maltophilia isolates from patients with cystic fibrosis: genome diversity, biofilm formation, and virulence. BMC Microbiol 11:159CrossRefGoogle Scholar
  23. 23.
    DuMont AL, Cianciotto NP (2017) Stenotrophomonas maltophilia serine protease StmPr1 induces matrilysis, anoikis, and protease-activated receptor 2 activation in human lung epithelial cells. Infect Immun 85(12).  https://doi.org/10.1128/IAI.00544-17
  24. 24.
    Nicoletti M, Iacobino A, Prosseda G, Fiscarelli E, Zarrilli R, De Carolis E, Petrucca A, Nencioni L, Colonna B, Casalino M (2011) Stenotrophomonas maltophilia strains from cystic fibrosis patients: genomic variability and molecular characterization of some virulence determinants. Int J Med Microbiol 301(1):34–43CrossRefGoogle Scholar
  25. 25.
    Kim SH, Cho SY, Kang CI, Seok H, Huh K, Ha YE, Chung DR, Lee NY, Peck KR, Song JH (2018) Clinical predictors of Stenotrophomonas maltophilia bacteremia in adult patients with hematologic malignancy. Ann Hematol 97(2):343–350CrossRefGoogle Scholar
  26. 26.
    Seifert H (2009) The clinical importance of microbiological findings in the diagnosis and management of bloodstream infections. Clin Infect Dis 48(Suppl 4):S238–S245CrossRefGoogle Scholar
  27. 27.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383CrossRefGoogle Scholar
  28. 28.
    Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. Jama 286(14):1754–1758CrossRefGoogle Scholar
  29. 29.
    Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49(1):1–45CrossRefGoogle Scholar
  30. 30.
    Horan TC, Andrus M, Dudeck MA (2008) 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 36(5):309–332CrossRefGoogle Scholar
  31. 31.
    Hotta G, Matsumura Y, Kato K, Nakano S, Yunoki T, Yamamoto M, Nagao M, Ito Y, Takakura S, Ichiyama S (2014) Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: a comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter species. PLoS One 9(11):e112208CrossRefGoogle Scholar
  32. 32.
    Figueiredo PM, Furumura MT, Santos AM, Sousa AC, Kota DJ, Levy CE, Yano T (2006) Cytotoxic activity of clinical Stenotrophomonas maltophilia. Lett Appl Microbiol 43(4):443–449CrossRefGoogle Scholar
  33. 33.
    Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I, Ruzicka F (2007) Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS 115(8):891–899CrossRefGoogle Scholar
  34. 34.
    Kaiser S, Biehler K, Jonas D (2009) A Stenotrophomonas maltophilia multilocus sequence typing scheme for inferring population structure. J Bacteriol 191(9):2934–2943CrossRefGoogle Scholar
  35. 35.
    Maertens J, Cesaro S, Maschmeyer G, Einsele H, Donnelly JP, Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, Bretagne S, Cordonnier C, the European Conference on Infections in Leukaemia ajvotEGfB, Marrow Transplantation tEOfR, Treatment of Cancer tIHS, the European L (2016) ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 71(9):2397–2404CrossRefGoogle Scholar
  36. 36.
    Aisenberg G, Rolston KV, Dickey BF, Kontoyiannis DP, Raad II, Safdar A (2007) Stenotrophomonas maltophilia pneumonia in cancer patients without traditional risk factors for infection, 1997-2004. Eur J Clin Microbiol Infect Dis 26(1):13–20CrossRefGoogle Scholar
  37. 37.
    Cervia JS, Ortolano GA, Canonica FP (2008) Hospital tap water as a source of Stenotrophomonas maltophilia infection. Clin Infect Dis 46(9):1485–1487CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Si-Ho Kim
    • 1
  • Min Kyeong Cha
    • 1
    • 2
  • Cheol-In Kang
    • 1
    Email author
  • Jae-Hoon Ko
    • 1
  • Kyungmin Huh
    • 1
  • Sun Young Cho
    • 1
  • Doo Ryeon Chung
    • 1
    • 2
  • Kyong Ran Peck
    • 1
  1. 1.Division of Infectious Diseases, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Asia Pacific Foundation for Infectious Diseases (APFID)SeoulRepublic of Korea

Personalised recommendations