Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease.

Shan-Shan Gong, Yi-Hong Fan, Qing-Qing Han, Bin Lv, Yi Xu
Author Information
  1. Shan-Shan Gong: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
  2. Yi-Hong Fan: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China. yhfansjr@163.com.
  3. Qing-Qing Han: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
  4. Bin Lv: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
  5. Yi Xu: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.

Abstract

BACKGROUND: When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.
AIM: To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.
METHODS: A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios (OR) and 95% confidence intervals (CIs).
RESULTS: Seventy (28.11%) out of 249 IBD patients developed opportunistic infections. infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247 (95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457 (95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab (IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity (OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.
CONCLUSION: Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.

Keywords

References

  1. Gastroenterology. 1976 Mar;70(3):439-44 [PMID: 1248701]
  2. Br Med J. 1955 Oct 29;2(4947):1041-8 [PMID: 13260656]
  3. Eur J Gastroenterol Hepatol. 2004 Aug;16(8):775-8 [PMID: 15256979]
  4. Arthritis Rheum. 2007 May 15;57(4):679-85 [PMID: 17471545]
  5. Arthritis Rheum. 2007 Jun;56(6):1754-64 [PMID: 17530704]
  6. Gastroenterology. 2007 Aug;133(2):412-22 [PMID: 17681162]
  7. Gut. 2008 Feb;57(2):205-10 [PMID: 17905821]
  8. Gastroenterology. 2008 Apr;134(4):929-36 [PMID: 18294633]
  9. Inflamm Bowel Dis. 2008 Oct;14(10):1432-42 [PMID: 18484669]
  10. Am J Gastroenterol. 2008 Jun;103(6):1443-50 [PMID: 18513271]
  11. Dig Dis Sci. 2010 Feb;55(2):415-20 [PMID: 19255850]
  12. Inflamm Bowel Dis. 2009 Sep;15(9):1295-301 [PMID: 19340881]
  13. Gastroenterology. 2010 Feb;138(2):463-8; quiz e10-1 [PMID: 19818785]
  14. J Gastroenterol Hepatol. 2010 Nov;25(11):1732-8 [PMID: 21039834]
  15. Aliment Pharmacol Ther. 2011 Jan;33(1):23-32 [PMID: 21083583]
  16. Aliment Pharmacol Ther. 2011 Feb;33(4):428-41 [PMID: 21198703]
  17. Gastroenterol Hepatol (N Y). 2011 Nov;7(11):750-2 [PMID: 22298971]
  18. J Gastroenterol. 2013 May;48(5):595-600 [PMID: 23053426]
  19. Virol J. 2013 Feb 01;10:43 [PMID: 23374225]
  20. Am J Gastroenterol. 2013 Aug;108(8):1268-76 [PMID: 23649185]
  21. Clin Gastroenterol Hepatol. 2014 Mar;12(3):414-22.e5 [PMID: 23856361]
  22. Inflamm Bowel Dis. 2014 Jan;20(1):196-212 [PMID: 24051931]
  23. J Crohns Colitis. 2013 Dec;7(12):982-1018 [PMID: 24184171]
  24. Gastroenterology. 2014 May;146(6):1489-99 [PMID: 24560869]
  25. J Crohns Colitis. 2014 Jun;8(6):443-68 [PMID: 24613021]
  26. Rheumatology (Oxford). 2014 Oct;53(10):1872-85 [PMID: 24821849]
  27. Environ Sci Technol. 2015 Jun 2;49(11):6772-82 [PMID: 25961663]
  28. N Engl J Med. 2015 Jul 16;373(3):287-8 [PMID: 26176396]
  29. Inflamm Bowel Dis. 2015 Aug;21(8):1957-66 [PMID: 26199993]
  30. Chin Med J (Engl). 2016 Feb 20;129(4):435-41 [PMID: 26879017]
  31. Clin Gastroenterol Hepatol. 2016 Oct;14(10):1385-1397.e10 [PMID: 27189910]
  32. Am J Gastroenterol. 2016 Aug;111(8):1141-6 [PMID: 27215924]
  33. Rheum Dis Clin North Am. 2017 Feb;43(1):27-41 [PMID: 27890172]
  34. Epidemiol Infect. 2017 Jul;145(10):2095-2099 [PMID: 28502260]
  35. Inflamm Bowel Dis. 2017 Jun;23(6):1034-1039 [PMID: 28511200]
  36. Gastroenterology. 2018 Aug;155(2):337-346.e10 [PMID: 29655835]
  37. Expert Rev Gastroenterol Hepatol. 2018 Nov;12(11):1101-1108 [PMID: 30277409]
  38. Adv Clin Chem. 2018;87:161-190 [PMID: 30342711]
  39. J Crohns Colitis. 2019 Jan 18;:null [PMID: 30668662]
  40. Ter Arkh. 2018 Dec 30;90(12):107-111 [PMID: 30701842]
  41. Intest Res. 2019 Apr;17(2):160-170 [PMID: 30704158]
  42. Antimicrob Resist Infect Control. 2019 Jan 29;8:22 [PMID: 30728954]
  43. Gut. 1993 Oct;34(10):1357-63 [PMID: 8244101]

MeSH Term

Adolescent
Adult
Aged
Case-Control Studies
Child
China
Drug Therapy, Combination
Feces
Female
Follow-Up Studies
Humans
Immunosuppressive Agents
Incidence
Inflammatory Bowel Diseases
Infliximab
Leukocyte L1 Antigen Complex
Male
Mesalamine
Middle Aged
Opportunistic Infections
Prospective Studies
Risk Factors
Young Adult

Chemicals

Immunosuppressive Agents
Leukocyte L1 Antigen Complex
Mesalamine
Infliximab

Word Cloud

Created with Highcharts 10.0.0opportunisticinfectionsIBDpatientsriskuseinfectionfactorsdiseaseORbowelsignificantlyincreasedincidencestudyanalysisusedimmunosuppressants95%CI:1IFXinflammatoryrateimmunosuppressiveagentsChinarelatedtwoimmunosuppressantlevelsfecalcalprotectinyieldedcombinationrelativeseverealoneincreaseNestedcase-controlBACKGROUND:occurcommonlydisplaymorbiditymortalityincreasingbiologicalbecominghottopicperspectivedrugsafetyDespitewell-establishedroleprognosisepidemiologicaldatainvestigatingopportunis-ticBesidesChineseremainunclearAIM:predictexploreMETHODS:single-centerprospectiveconductedfollowed12mocalculateinfectedpatientnon-infectedselectedcontrolsconditionallogisticregressionassessassociationsputativerepresentedoddsratios95%confidenceintervalsCIsRESULTS:Seventy2811%249developedrespiratorysyncytialvirusfound2416respectivelyunivariateseverityhighC-reactiveproteinerythrocytesedimentationindividuallyMultivariateindicated3247128-9341whereas6457726-24152Interestinglyinfliximab5-aminosalicylicacidalsoobservedgreatestactivity=9090532-53941remissionstageHoweverCONCLUSION:FactorselevatedmedicationsespeciallymajorInflammatoryOpportunistic

Similar Articles

Cited By