Skip to main content
Top
Published in: BMC Infectious Diseases 1/2013

Open Access 01-12-2013 | Research article

Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy

Authors: Mark A Miller, Thomas Louie, Kathleen Mullane, Karl Weiss, Arnold Lentnek, Yoav Golan, Yin Kean, Pam Sears

Published in: BMC Infectious Diseases | Issue 1/2013

Login to get access

Abstract

Background

Clostridium difficile infection (CDI) continues to be a frequent and potentially severe infection. There is currently no validated clinical tool for use at the time of CDI diagnosis to categorize patients in order to predict response to therapy.

Methods

Six clinical and laboratory variables, measured at the time of CDI diagnosis, were combined in order to assess their correlation with treatment response in a large CDI clinical trial database (derivation cohort). The final categorization scheme was chosen in order to maximize the number of categories (discrimination) while maintaining a high correlation with clinical cure assessed two days after the end of therapy. Validation of the derived scoring scheme was done on a second large CDI clinical trial database (validation cohort). A third comparison was done on the two pooled databases (pooled cohort).

Results

In the derivation cohort, the best discrimination and correlation with cure was seen with a five-component ATLAS score (age, treatment with systemic antibiotics, leukocyte count, albumin and serum creatinine as a measure of renal function), which divided CDI patients into 11 groups (scores of 0 to 10 inclusive) and was highly correlated with treatment outcome (R2=0.95; P<0.001). This scheme showed excellent prediction of cure in the validation cohort (overall Kappa=95.2%; P<0.0001), as well as in the pooled cohort, regardless of treatment (fidaxomicin or vancomycin).

Conclusions

A combination of five simple and commonly available clinical and laboratory variables measured at the time of CDI diagnosis, combined into a scoring system (ATLAS), are able to accurately predict treatment response to CDI therapy. The ATLAS scoring system may be useful in stratifying CDI patients so that appropriate therapies can be chosen to maximize cure rates, as well as for categorization of patients in CDI therapeutic studies in order allow comparisons of patient groups.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jarvis WR, Schlosser J, Jarvis AA, Chinn RY: National point prevalence of clostridium difficile in US health care facility inpatients, 2008. Am J Infect Control. 2009, 37: 263-270. 10.1016/j.ajic.2009.01.001.CrossRefPubMed Jarvis WR, Schlosser J, Jarvis AA, Chinn RY: National point prevalence of clostridium difficile in US health care facility inpatients, 2008. Am J Infect Control. 2009, 37: 263-270. 10.1016/j.ajic.2009.01.001.CrossRefPubMed
2.
go back to reference Loo VG, Poirier L, Miller MA: A predominantly clonal multi-insitutional outbreak of clostridium difficile-associated diarrhea with high morbidity and mortality. New Engl J Med. 2005, 353: 2442-2449. 10.1056/NEJMoa051639.CrossRefPubMed Loo VG, Poirier L, Miller MA: A predominantly clonal multi-insitutional outbreak of clostridium difficile-associated diarrhea with high morbidity and mortality. New Engl J Med. 2005, 353: 2442-2449. 10.1056/NEJMoa051639.CrossRefPubMed
3.
go back to reference Goorhuis A, Bakker D, Corver J: Emergence of clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis. 2008, 47: 1162-1170. 10.1086/592257.CrossRefPubMed Goorhuis A, Bakker D, Corver J: Emergence of clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis. 2008, 47: 1162-1170. 10.1086/592257.CrossRefPubMed
4.
go back to reference Louie TG, Miller MA, Mullane KM: Fidaxomicin versus vancomycin for clostridium difficile infection. New Engl J Med. 2011, 364: 422-431. 10.1056/NEJMoa0910812.CrossRefPubMed Louie TG, Miller MA, Mullane KM: Fidaxomicin versus vancomycin for clostridium difficile infection. New Engl J Med. 2011, 364: 422-431. 10.1056/NEJMoa0910812.CrossRefPubMed
5.
go back to reference Sougioultzis S, Kyne L, Drudy D, Keates S, Maroo S, Pothoulakis C, Giannasca PJ, Lee CK, Warny M, Monath TP, Kelly CP, Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea: Clostridium difficile toxoid vaccine in recurrent C. Difficile-associated diarrhea. Gastroenterology. 2005, 128: 764-770. 10.1053/j.gastro.2004.11.004.CrossRefPubMed Sougioultzis S, Kyne L, Drudy D, Keates S, Maroo S, Pothoulakis C, Giannasca PJ, Lee CK, Warny M, Monath TP, Kelly CP, Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea: Clostridium difficile toxoid vaccine in recurrent C. Difficile-associated diarrhea. Gastroenterology. 2005, 128: 764-770. 10.1053/j.gastro.2004.11.004.CrossRefPubMed
6.
go back to reference Lowy I, Molrine DC, Leav BA: Treatment with monoclonal antibodies against clostridium difficile toxins. N Engl J Med. 2010, 362: 197-205. 10.1056/NEJMoa0907635.CrossRefPubMed Lowy I, Molrine DC, Leav BA: Treatment with monoclonal antibodies against clostridium difficile toxins. N Engl J Med. 2010, 362: 197-205. 10.1056/NEJMoa0907635.CrossRefPubMed
7.
go back to reference Rubin MS, Bodenstein LE, Kent KC: Severe clostridium difficile colitis. Dis Colon Rectum. 1995, 38: 350-354. 10.1007/BF02054220.CrossRefPubMed Rubin MS, Bodenstein LE, Kent KC: Severe clostridium difficile colitis. Dis Colon Rectum. 1995, 38: 350-354. 10.1007/BF02054220.CrossRefPubMed
8.
go back to reference Belmares J, Gerding DN, Parada JP, Miskevics S, Weaver F, Johnson S: Outcome of metronidazole therapy for clostridium difficile disease and correlation with a scoring system. J Infect. 2007, 55: 495-501. 10.1016/j.jinf.2007.09.015.CrossRefPubMed Belmares J, Gerding DN, Parada JP, Miskevics S, Weaver F, Johnson S: Outcome of metronidazole therapy for clostridium difficile disease and correlation with a scoring system. J Infect. 2007, 55: 495-501. 10.1016/j.jinf.2007.09.015.CrossRefPubMed
9.
go back to reference McEllistrem MC, Carman RJ, Gerding DN, Genheimer CW, Zheng L: A hospital outbreak of clostridium difficile disease associated with isolates carrying binary toxin genes. Clin Infect Dis. 2005, 40: 265-272. 10.1086/427113.CrossRefPubMed McEllistrem MC, Carman RJ, Gerding DN, Genheimer CW, Zheng L: A hospital outbreak of clostridium difficile disease associated with isolates carrying binary toxin genes. Clin Infect Dis. 2005, 40: 265-272. 10.1086/427113.CrossRefPubMed
10.
go back to reference Zar FA, Bakkanagari SR, Moorthi KM, Davis MB: A comparison of vancomycin and metronidazole for the treatment of clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007, 45: 302-307. 10.1086/519265.CrossRefPubMed Zar FA, Bakkanagari SR, Moorthi KM, Davis MB: A comparison of vancomycin and metronidazole for the treatment of clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007, 45: 302-307. 10.1086/519265.CrossRefPubMed
11.
go back to reference Henrich TJ, Krakower D, Bitton A, Yokoe DS: Clinical risk factors for severe clostridium difficile-associated disease. Emerg Infect Dis. 2009, 15: 415-422. 10.3201/eid1503.080312.CrossRefPubMedPubMedCentral Henrich TJ, Krakower D, Bitton A, Yokoe DS: Clinical risk factors for severe clostridium difficile-associated disease. Emerg Infect Dis. 2009, 15: 415-422. 10.3201/eid1503.080312.CrossRefPubMedPubMedCentral
12.
go back to reference Louie T, Gerson M, Grimard D: Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with clostridium difficile-associated diarrhea (CDAD). program and abstracts of the 47th annual interscience conference on antimicrobial agents and chemotherapy. 2007, Chicago, Illinois: Abstract K-425a, September 17–20 Louie T, Gerson M, Grimard D: Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with clostridium difficile-associated diarrhea (CDAD). program and abstracts of the 47th annual interscience conference on antimicrobial agents and chemotherapy. 2007, Chicago, Illinois: Abstract K-425a, September 17–20
13.
go back to reference Gujja D, Friedenberg FK: Predictors of serious complications due to clostridium difficile infection. Aliment Pharmacol Ther. 2009, 29: 635-642. 10.1111/j.1365-2036.2008.03914.x.CrossRefPubMed Gujja D, Friedenberg FK: Predictors of serious complications due to clostridium difficile infection. Aliment Pharmacol Ther. 2009, 29: 635-642. 10.1111/j.1365-2036.2008.03914.x.CrossRefPubMed
15.
go back to reference Fujitani S, George WL, Murthy AR: Comparison of clinical severity score indices for clostridium difficile infection. Infection Control & Hospital Epidemiology. 2011, 32: 220-228. 10.1086/658336.CrossRef Fujitani S, George WL, Murthy AR: Comparison of clinical severity score indices for clostridium difficile infection. Infection Control & Hospital Epidemiology. 2011, 32: 220-228. 10.1086/658336.CrossRef
16.
go back to reference Toro DH, Amaral-Mojica KM, Rocha-Rodriguez R, Gutierrez-Nunez J: An innovative severity score index for C. Difficile infection: a prospective study. Infect Dis in Clin Practice. 2011, 19: 336-339. 10.1097/IPC.0b013e31821895a8.CrossRef Toro DH, Amaral-Mojica KM, Rocha-Rodriguez R, Gutierrez-Nunez J: An innovative severity score index for C. Difficile infection: a prospective study. Infect Dis in Clin Practice. 2011, 19: 336-339. 10.1097/IPC.0b013e31821895a8.CrossRef
17.
go back to reference Brouwers MC, Rawski E, Spithoff K, Oliver TK: Inventory of cancer guidelines: a tool to advance the guideline enterprise and improve the uptake of evidence. Expert Review of Pharmacoeconomics & Outcomes Research. 2011, 11: 151-161. 10.1586/erp.11.11.CrossRef Brouwers MC, Rawski E, Spithoff K, Oliver TK: Inventory of cancer guidelines: a tool to advance the guideline enterprise and improve the uptake of evidence. Expert Review of Pharmacoeconomics & Outcomes Research. 2011, 11: 151-161. 10.1586/erp.11.11.CrossRef
18.
go back to reference Levy MM, Dellinger RP, Townsend SR: The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010, 36: 222-231. 10.1007/s00134-009-1738-3.CrossRefPubMedPubMedCentral Levy MM, Dellinger RP, Townsend SR: The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010, 36: 222-231. 10.1007/s00134-009-1738-3.CrossRefPubMedPubMedCentral
19.
go back to reference Cohen SH, Gerding DN, Johnson S: Clinical practice guidelines for clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infection Control & Hospital Epidemiology. 2010, 31: 431-455. 10.1086/651706.CrossRef Cohen SH, Gerding DN, Johnson S: Clinical practice guidelines for clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infection Control & Hospital Epidemiology. 2010, 31: 431-455. 10.1086/651706.CrossRef
20.
go back to reference Bauer MP, Kuijper EJ, van Dissel JT: European society of clinical microbiology and infectious diseases (ESCMID): treatment guidance document for clostridium difficile infection (CDI). Clin Microbiol Infect. 2009, 15: 1067-1079. 10.1111/j.1469-0691.2009.03099.x.CrossRefPubMed Bauer MP, Kuijper EJ, van Dissel JT: European society of clinical microbiology and infectious diseases (ESCMID): treatment guidance document for clostridium difficile infection (CDI). Clin Microbiol Infect. 2009, 15: 1067-1079. 10.1111/j.1469-0691.2009.03099.x.CrossRefPubMed
21.
go back to reference Crook DW, Walker AS, Kean Y: Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012, 55 (Supp 2): S93-S103.CrossRefPubMedPubMedCentral Crook DW, Walker AS, Kean Y: Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012, 55 (Supp 2): S93-S103.CrossRefPubMedPubMedCentral
22.
go back to reference Corter JE, Gluck MA: Explaining basic categories: feature predictability and information. Psychol Bull. 1992, 111: 291-303.CrossRef Corter JE, Gluck MA: Explaining basic categories: feature predictability and information. Psychol Bull. 1992, 111: 291-303.CrossRef
23.
go back to reference Miller M, Gravel D, Mulvey M: Health care-associated clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis. 2010, 50: 194-201. 10.1086/649213.CrossRefPubMed Miller M, Gravel D, Mulvey M: Health care-associated clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis. 2010, 50: 194-201. 10.1086/649213.CrossRefPubMed
Metadata
Title
Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy
Authors
Mark A Miller
Thomas Louie
Kathleen Mullane
Karl Weiss
Arnold Lentnek
Yoav Golan
Yin Kean
Pam Sears
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2013
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-13-148

Other articles of this Issue 1/2013

BMC Infectious Diseases 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine