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Performance of Clostridioides difficile infection severity scores and risk factors related to 30-day all-cause mortality in patients with cancer

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Abstract

Purpose

There are currently no standard definitions for assessing the severity of Clostridioides difficile infection (CDI) in cancer patients. We evaluated the performance of scoring systems for severity and analyzed risk factors for mortality in a cancer cohort.

Methods

We conducted an observational study in patients with cancer and CDI. We calculated the incidence of hospital-onset (HO-CDI) and community-onset health-care facility associated (CO-HCFA-CDI) episodes. We classified severity using five prognostic scales and calculated sensitivity, specificity, positive (PPV), and negative predictive values (NPV) for mortality and intensive care unit (ICU) admission. In addition, multivariate regression was performed to assess variables associated with mortality.

Results

The HO-CDI and CO-HCFA-CDI incidence rates were 3.7 cases/10,000 patient-days and 1.9 cases/1,000 admissions, respectively. ESCMID criteria showed the higher sensitivity (97%, 95% CI; 85–100%) and NPV (98%, 95% CI; 85–100%), while ATLAS (≥ 6 points) had the highest specificity (95%, 95% CI; 90–98%) for 30-day all-cause mortality; similar performance was observed for ICU admission. Characteristics associated with fatal outcome were neutropenia (≤ 100 cells/ml) (aOR; 3.03, 95% CI; 1.05–8.74, p = 0.040), male gender (aOR; 2.90, 95% CI; 1.08–7.80, p = 0.034), high serum creatinine (aOR; 1.71, 95% CI; 1.09–2.70, p = 0.020), and albumin (aOR; 0.17, 95% CI; 0.07–0.42, p < 0.001).

Conclusions

Some of the current scales may not be appropriate to discriminate severity in patients with cancer. The variables in this study associated with unfavorable outcomes could be evaluated in prospective studies to develop prognostic scores that identify susceptible patients, especially in immunocompromised populations.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

NA.

References

  1. McGlone SM, Bailey RR, Zimmer SM et al (2012) The economic burden of Clostridium difficile. Clin Microbiol Infect 18:282–289. https://doi.org/10.1111/j.1469-0691.2011.03571.x

    Article  CAS  PubMed  Google Scholar 

  2. Guh AY, Mu Y, Winston LG et al (2020) Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med 382:1320–1330. https://doi.org/10.1056/NEJMoa1910215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dutta D, Jafri F, Stuhr D et al (2021) A contemporary review of Clostridioides difficile infections in patients with haematologic diseases. J Intern Med 289:293–308. https://doi.org/10.1111/joim.13173

    Article  CAS  PubMed  Google Scholar 

  4. Neemann K, Freifeld A (2017) Clostridium difficile –associated diarrhea in the oncology patient. J Oncol Pract 13:25–30. https://doi.org/10.1200/JOP.2016.018614

    Article  PubMed  Google Scholar 

  5. Hebbard AIT, Slavin MA, Reed C et al (2016) The epidemiology of Clostridium difficile infection in patients with cancer. Expert Rev Anti Infect Ther 14:1077–1085. https://doi.org/10.1080/14787210.2016.1234376

    Article  CAS  PubMed  Google Scholar 

  6. Larrainzar-Coghen T, Rodríguez-Pardo D, Barba P et al (2018) Prognosis of Clostridium difficile infection in adult oncohaematological patients: experience from a large prospective observational study. Eur J Clin Microbiol Infect Dis 37:2075–2082. https://doi.org/10.1007/s10096-018-3341-4

    Article  PubMed  Google Scholar 

  7. Lee-Tsai YL, Luna-Santiago R, Demichelis-Gómez R et al (2019) Determining the risk factors associated with the development of Clostridium difficile infection in patients with hematological diseases. Blood Res 54:120–124. https://doi.org/10.5045/br.2019.54.2.120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Delgado A, Reveles IA, Cabello FT, Reveles KR (2017) Poorer outcomes among cancer patients diagnosed with Clostridium difficile infections in United States community hospitals. BMC Infect Dis 17:448. https://doi.org/10.1186/s12879-017-2553-z

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhang VRY, Woo ASJ, Scaduto C et al (2021) Systematic review on the definition and predictors of severe Clostridiodes difficile infection. J Gastroenterol Hepatol 36:89–104. https://doi.org/10.1111/jgh.15102

    Article  PubMed  Google Scholar 

  10. McDonald LC, Gerding DN, Johnson S et al (2018) Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 66:e1–e48. https://doi.org/10.1093/cid/cix1085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Debast SB, Bauer MP, Kuijper EJ (2014) European society of clinical microbiology and infectious diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20:1–26. https://doi.org/10.1111/1469-0691.12418

    Article  CAS  PubMed  Google Scholar 

  12. Zar FA, Bakkanagari SR, Moorthi KMLST, Davis MB (2007) A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 45:302–307. https://doi.org/10.1086/519265

    Article  CAS  PubMed  Google Scholar 

  13. Kelly CR, Fischer M, Allegretti JR et al (2021) ACG Clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 116:1124–1147. https://doi.org/10.14309/ajg.0000000000001278

    Article  PubMed  Google Scholar 

  14. Miller MA, Louie T, Mullane K et al (2013) Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect Dis 13:148. https://doi.org/10.1186/1471-2334-13-148

    Article  PubMed  PubMed Central  Google Scholar 

  15. Surawicz CM, Brandt LJ, Binion DG et al (2013) Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 108:478–498. https://doi.org/10.1038/ajg.2013.4

    Article  CAS  PubMed  Google Scholar 

  16. MedCalc Software Ltd Diagnostic test evaluation calculator (Version 20.110). https://www.medcalc.org/calc/diagnostic_test.php. Accessed 7 Jun 2022

  17. Hensgens MPM, Goorhuis A, Dekkers OM et al (2013) All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile Infection: a multicenter cohort study. Clin Infect Dis 56:1108–1116. https://doi.org/10.1093/cid/cis1209

    Article  PubMed  Google Scholar 

  18. Abou Chakra CN, Pepin J, Valiquette L (2012) Prediction tools for unfavourable outcomes in Clostridium difficile Infection: a systematic review. PLoS ONE 7:e30258

  19. Kamboj M, Son C, Cantu S et al (2012) Hospital-onset Clostridium difficile infection rates in persons with cancer or hematopoietic stem cell transplant: a C3IC network report. Infect Control Hosp Epidemiol 33:1162–1165. https://doi.org/10.1086/668023

    Article  PubMed  PubMed Central  Google Scholar 

  20. Finn E, Andersson FL, Madin-Warburton M (2021) Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect Dis 21:456. https://doi.org/10.1186/s12879-021-06147-y

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yu H, Flaster N, Casanello AL, Curcio D (2021) Assessing risk factors, mortality, and healthcare utilization associated with Clostridioides difficile infection in four Latin American countries. Braz J Infect Dis 25:101040

  22. Chiang H-Y, Huang H-C, Chung C-W et al (2019) Risk prediction for 30-day mortality among patients with Clostridium difficile infections: a retrospective cohort study. Antimicrob Resist Infect Control 8:175. https://doi.org/10.1186/s13756-019-0642-z

    Article  PubMed  PubMed Central  Google Scholar 

  23. Stevens VW, Shoemaker HE, Jones MM et al (2020) Validation of the SHEA/IDSA severity criteria to predict poor outcomes among inpatients and outpatients with Clostridioides difficile infection. Infect Control Hosp Epidemiol 41:510–516. https://doi.org/10.1017/ice.2020.8

    Article  PubMed  Google Scholar 

  24. Milenković B, Šuljagić V, Perić A, et al (2021) Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study. Eur J Hosp Pharm ejhpharm-2020–002574. https://doi.org/10.1136/ejhpharm-2020-002574

  25. Ochoa-Hein E, Sifuentes-Osornio J, Ponce de León-Garduño A et al (2018) Factors associated with an outbreak of hospital-onset, healthcare facility-associated Clostridium difficile infection (HO-HCFA CDI) in a Mexican tertiary care hospital: a case-control study. PLOS ONE 13:e0198212

  26. Yoon YK, Kim MJ, Sohn JW et al (2014) Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy. Support Care Cancer 22:2039–2048. https://doi.org/10.1007/s00520-014-2174-7

    Article  PubMed  Google Scholar 

  27. Vargas E, Apewokin S, Madan R (2017) Role of the leukocyte response in normal and immunocompromised host after Clostridium difficile infection. Anaerobe 45:101–105. https://doi.org/10.1016/j.anaerobe.2017.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Trevethan R (2017) Sensitivity, specificity, and predictive values: foundations, pliabilities, and pitfalls in research and practice. Front Public Health 5:307. https://doi.org/10.3389/fpubh.2017.00307

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wang MS, Evans CT, Rodriguez T et al (2013) Clostridium difficile infection and limitations of markers for severity in patients with hematologic malignancy. Infect Control Hosp Epidemiol 34:127–132. https://doi.org/10.1086/669081

    Article  PubMed  Google Scholar 

  30. Sahu KK, Mishra AK, Jindal V et al (2021) To study the contributing factors and outcomes of Clostridioides difficile infection in patients with solid tumors. Heliyon 7:e08450

  31. Jose S, Madan R (2016) Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections. Anaerobe 41:85–90. https://doi.org/10.1016/j.anaerobe.2016.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang AM, Marini BL, Frame D et al (2014) Risk factors for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis 16:744–750. https://doi.org/10.1111/tid.12267

    Article  CAS  PubMed  Google Scholar 

  33. di Masi A, Leboffe L, Polticelli F et al (2018) Human serum albumin is an essential component of the host defense mechanism against Clostridium difficile intoxication. J Infect Dis 218:1424–1435. https://doi.org/10.1093/infdis/jiy338

    Article  PubMed  Google Scholar 

  34. Dansinger ML, Johnson S, Jansen PC et al (1996) Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study. Clin Infect Dis 22:932–937. https://doi.org/10.1093/clinids/22.6.932

    Article  CAS  PubMed  Google Scholar 

  35. Kim S, McClave SA, Martindale RG et al (2017) Hypoalbuminemia and clinical outcomes: what is the mechanism behind the relationship? Am Surg 83:1220–1227. https://doi.org/10.1177/000313481708301123

    Article  PubMed  Google Scholar 

  36. Carlson TJ, Gonzales-Luna AJ, Nebo K et al (2020) Assessment of kidney injury as a severity criteria for Clostridioides difficile infection. Open Forum Infect Dis 7:ofaa476. https://doi.org/10.1093/ofid/ofaa476

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the Plan de Estudios Combinados en Medicina (PECEM) of the Faculty of Medicine, UNAM and the Consejo Nacional de Ciencia y Tecnología (CONACyT) in Mexico for the scholarship number 969627 provided to DDM.

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Instituto Nacional de Cancerologia, Mexico City, Mexico

    Daniel De-la-Rosa-Martinez, Paola Zinser-Peniche, Alexandra Martin-Onraet, Frida Rivera-Buendía & Diana Vilar-Compte

  2. Plan de Estudios Combinados en Medicina (PECEM), Faculty of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico

    Daniel De-la-Rosa-Martinez

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  1. Daniel De-la-Rosa-Martinez
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Contributions

Conceptualization: DDM, PZP FRB and DVC; Methodology: DDM, PZP FRB and DVC. Formal analysis and investigation; DDM, PZP, FRB, AMO and DVC. Writing-original draft preparation: DDM and DVC; Writing-review and editing: DDM, PZP, FRB, AMO and DVC. Supervision: DVC. Abreviations: DDM; Daniel-De-la-Rosa-Martinez, PZP; Paola Zinser-Peniche, FRB; Frida Rivera-Buendia, AMO; Alexandra Martin-Onraet, DVC; Diana Vilar-Compte.

Corresponding author

Correspondence to Diana Vilar-Compte.

Ethics declarations

Ethics approval

The study was approved by the ethical committee of the Instituto Nacional de Cancerologia, Mexico City (No CEI/1420/19). In addition, part of these patients was included in a previously published case–control study.

Consent to participate

NA, this is a register study.

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NA.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

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De-la-Rosa-Martinez, D., Zinser-Peniche, P., Martin-Onraet, A. et al. Performance of Clostridioides difficile infection severity scores and risk factors related to 30-day all-cause mortality in patients with cancer. Support Care Cancer 31, 187 (2023). https://doi.org/10.1007/s00520-023-07651-4

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