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Diagnostic testing methods for Clostridium difficile infection: A statewide survey of Ohio acute care hospitals
ARTICLE IN PRESS American Journal of Infection Control ■■ (2016) ■■-■■
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief Report
Diagnostic testing methods for Clostridium difficile infection: A statewide survey of Ohio acute care hospitals Ken Koon Wong MD a, Byungwoo Choi MD a, Thomas G. Fraser MD a, Curtis J. Donskey MD b,c, Abhishek Deshpande MD, PhD a,d,* a
Department of Infectious Diseases, Cleveland Clinic, Medicine Institute, Cleveland, OH Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH c Geriatric Research, Education, and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH d Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH b
Key Words: Clostridium difficile Diagnostic tests NAAT Molecular testing
We surveyed Ohio acute care hospitals on laboratory testing used for diagnosis of Clostridium difficile infection (CDI). Of 146 hospitals surveyed, 109 (84%) used nucleic acid amplification tests (NAATs) as standalone diagnostic assays. Only 53 (42.4%) hospitals using NAATs had a mechanism in place to prevent repeat CDI testing. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Multiple testing methods are available to diagnose Clostridium difficile infection (CDI).1 In the past, the toxin A&B enzyme immunoassay (EIA) was commonly used as a stand-alone test because it has a short turnaround time and is inexpensive. However, the 2010 Society for Healthcare Epidemiology of America and Infectious Disease Society of America clinical practice guidelines for CDI in adults recommended that the EIA for toxin not be used as a standalone test because of suboptimal sensitivity.1 In response, many laboratories in the United States switched to use of sensitive nucleic acid amplification tests (NAATs) for diagnosis of CDI. However, there is now increasing concern that use of NAATs as stand-alone tests may often result in diagnosis of asymptomatic carriers of toxigenic C difficile as CDI cases. In England, CDI testing often involves use of a 2-step algorithm in which EIA for glutamate dehydrogenase (GDH) is used as an initial screen with GDH-positive stool specimens undergoing EIA testing for toxin; a positive toxin assay indicates CDI, whereas a negative toxin assay suggests an asymptomatic carrier who may contribute to transmission as a fecal excretor.2 Fecal excretors are isolated, but not routinely treated or reported as CDI cases. Given the uncertainty regarding optimal CDI test strategies, there is the potential for significant variation in di-
* Address correspondence to Abhishek Deshpande, MD, PhD, Medicine Institute Center for Value Based Care Research, 9500 Euclid Ave, Desk G10, Cleveland Clinic, Cleveland, OH 44195. E-mail address: [email protected] (A. Deshpande). Conflicts of interest: C.J.D. has received research support from Cepheid. A.D. has received research support from 3M. All other authors report no conflicts of interest relevant to this article.
agnostic methods used by different hospitals. The objective of this study was to investigate the variation in CDI diagnostic testing methods by conducting a survey of acute care hospitals in the State of Ohio. METHODS The research protocol was approved by the Cleveland Clinic Institutional Review Board. Acute care hospitals in Ohio were identified from the Medicare.gov Hospital Compare Web site (https://www .medicare.gov/hospitalcompare). A total of 169 acute care academic and community hospitals from 88 counties in Ohio were identified in January 2015. Two authors (K.K.W. and B.C.) called each of the hospitals and administered a standardized questionnaire to key laboratory personnel through telephone interviews. Participation in the survey was voluntary. The questionnaire was reviewed with the microbiology supervisor regarding type of diagnostic test in use in 2013 and in 2014, the model and make of the diagnostic testing kit or machine, the availability of a written standard operating procedure, and if they use a 2-step testing protocol for diagnosing CDI. We also reviewed if the laboratories had a hard stop or recommended against repeat testing of CDI stool samples. Analysis consisted of descriptive statistics. RESULTS Of 169 hospitals surveyed, 146 (86.4%) facilities from 73 counties participated, including 22 tertiary care and 124 community hospitals. The 146 study hospitals represented 80 different health
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.09.007
ARTICLE IN PRESS 2
K.K. Wong et al. / American Journal of Infection Control ■■ (2016) ■■-■■
care systems in Ohio. Most hospitals within the same health care system used the same CDI testing method. In 2013, 129 of the 146 hospitals surveyed (88.4%) were using a stand-alone test for the diagnosis of CDI, including 91 (70.5%) using an NAAT, 37 (28.7%) using a toxin A&B EIA, and 1 (0.8%) using a cell culture cytotoxicity neutralization assay (CCNA). In 2014, the proportion of hospitals using stand-alone NAATs increased: 109 (84.5%) of the hospitals used an NAAT, 19 (14.7%) used a toxin A&B EIA, and 1 used CCNA. The 1 hospital using CCNA planned to switch to a stand-alone NAAT in 2015. Seventeen of the hospitals (11.6%) reported using a 2- or 3-step testing algorithm (GDH combined with NAAT: n = 7, GDH/toxin A&B EIA: n = 1; GDH/toxin A&B EIA combined with NAAT: n = 9). Four hospitals using the 2-step method planned to switch to a stand-alone NAAT in 2015. The manufacturers of NAAT included Meridian (Meridian Bioscience, Cincinnati, OH) (n = 31, 48.4%), Cepheid (Cepheid, Sunnyvale, CA) (n = 23, 35.9%), Quidel (Cepheid, Sunnyvale, CA) (n = 7, 10.9%) and BD (BD Biosciences, San Jose, CA) (n = 1, 1.6%); 2 (3.1%) hospitals chose not to disclose the name of the company. All of the microbiology laboratories reported having a written standard operating procedure for CDI testing. Of the 125 hospitals (including 2- or 3-step testing) using an NAAT, 53 (42.4%) hospitals had a mechanism in place to prevent repeat testing. The hospitals either implemented an automatic electronic stop order or explicitly recommended against repeat testing of CDI; however, such orders could be overwritten by the ordering physician. DISCUSSION Despite the recommendation from the 2010 CDI practice guidelines that EIA for toxin not be used as a stand-alone test for CDI, we found that 28.7% of Ohio acute care hospitals surveyed used this laboratory testing method in 2013. However, there was evidence of a rapid shift away from this testing approach because only 14.7% of the hospitals reported using EIA for toxin as a stand-alone test in 2014. Most hospitals were switching from EIA for toxin to use of NAATs as a stand-alone test method. Of the hospitals surveyed, 70.5% used NAATs as a stand-alone test in 2013 versus 84.5% in 2014. NAATs are being used increasingly as stand-alone tests in the United States because of their high sensitivity and specificity and a quick turnaround time. However, there has been increasing concern that use of NAATs as a stand-alone test can lead to false-positive tests, resulting in overdiagnosis and overtreatment of CDI.3 In the absence of clear signs and symptoms of infection, a positive NAAT is more likely an indicator of C difficile colonization, and treating these patients will expose them to unnecessary antibiotics. Also, the mandatory reporting for CDI using the LabID event allows laboratory testing data to be used without clinical evaluation; therefore, it is critical that molecular diagnostic testing be done only for symptomatic patients. Based on the concerns regarding use of NAATs as a stand-alone test, current European guidelines for diagnosis of CDI recommend 2- or 3-step algorithms that include toxin testing.4 However, in Ohio we found that only 11.6% of hospitals surveyed were using a 2- or 3-step algorithm for diagnosis of CDI, and only 10 (58.8%) included a toxin assay in the algorithm. Recent studies have suggested that patients with positive NAATs but negative stool toxin assays may be unlikely to have adverse outcomes. Based on these studies, Polage et al3 have recommended that 2-step algorithms that include toxin assays should be used rather than stand-alone NAAT testing. Future surveys will be of interest to determine if laboratories begin to move away from stand-alone NAAT testing. Although most clinical laboratories reject formed stool samples, additional steps are needed to discourage unnecessary testing. For many years, the lack of confidence in toxin EIA test results led to the submission of multiple stool samples.5 The Society for Health-
care Epidemiology of America and Infectious Disease Society of America guidelines and the Centers for Disease Control and Prevention clearly recommend against repeat testing or testing for cure.1 Repeat testing adds another layer of unnecessary cost and may also complicate patient care. It is therefore imperative that clinical laboratories should consider implementing an automatic electronic hard stop for repeat testing within the same week or explicitly recommend against repeat testing during order placement. Our findings are consistent with previous studies in demonstrating wide variation in CDI testing methods among hospitals and frequent nonadherence to practice guidelines. In recent surveys of European hospitals, only 40%-64% of hospitals were using recommended laboratory test algorithms to diagnose CDI.6,7 In England, a 2011 survey of diagnostic microbiology laboratories revealed considerable variation in CDI testing practices, and only 24% of the laboratories had changed their testing procedures in response to a guideline published in 2009.8 In Italy, more than half of laboratories surveyed in 2012 were using EIA for toxin as a stand-alone test, and only 34% were using the recommended methods to diagnose CDI.9 In a 2016 pan-European survey of 126 laboratories from 33 countries, use of CDI diagnostics deemed optimal increased from 19% to 46% between 2011 and 2014.10 Similarly, in a 2011 survey of 893 facilities in the United States, close to half the facilities were using EIA for toxin as a standalone test and 46% were using NAAT.11 In conclusion, we found that multiple strategies are being used for diagnosis of CDI in Ohio health care facilities, including standalone EIA for toxin tests that are not recommended in current guidelines. Because our survey was limited to acute care hospitals in Ohio, additional national studies are needed. Finally, there is a need for randomized trials to determine which diagnostic test methods are optimal for diagnosis of CDI. References 1. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. 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). Infect Control Hosp Epidemiol 2010;31:43155. 2. Planche T, Wilcox MH. Diagnostic pitfalls in Clostridium difficile infection. Infect Dis Clin North Am 2015;29:63-82. 3. Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015;175:1792-801. 4. Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 2016;22(Suppl):S63-81. 5. Deshpande A, Pasupuleti V, Patel P, Ajani G, Hall G, Hu B, et al. Repeat stool testing to diagnose Clostridium difficile infection using enzyme immunoassay does not increase diagnostic yield. Clin Gastroenterol Hepatol 2011;9:665-9, e661. 6. Davies KA, Longshaw CM, Davis GL, et al. Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis 2014;14:1208-19. 7. Davies KA, Ashwin H, Longshaw CM, Burns DA, Davis GL, Wilcox MH, et al. Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013. Euro Surveill 2016;21. 8. Chand MA, Fleming MJ, Wellsteed S, Kelsey MC. Impact of changes in Clostridium difficile diagnostic testing on detection of C. difficile infection and all England mandatory surveillance data. J Hosp Infect 2011;79:8-12. 9. Spigaglia P, Barbanti F, Morandi M, Moro ML, Mastrantonio P. Diagnostic testing for Clostridium difficile in Italian microbiological laboratories. Anaerobe 2016;37:29-33. 10. van Dorp SM, Notermans DW, Alblas J, Gastmeier P, Mentula S, Nagy E, et al. Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014. Euro Surveill 2016;21. 11. Dudeck M, Weiner L, Malpiedi P, Edwards J, Peterson K, Sievert D. Risk adjustment for healthcare facility-onset C. difficile and MRSA bacteremia laboratory-identified event reporting in NHSN. 2013. Available from: https://www.medicare.gov/ hospitalcompare/. Accessed September 15, 2016.
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief Report
Diagnostic testing methods for Clostridium difficile infection: A statewide survey of Ohio acute care hospitals Ken Koon Wong MD a, Byungwoo Choi MD a, Thomas G. Fraser MD a, Curtis J. Donskey MD b,c, Abhishek Deshpande MD, PhD a,d,* a
Department of Infectious Diseases, Cleveland Clinic, Medicine Institute, Cleveland, OH Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH c Geriatric Research, Education, and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH d Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH b
Key Words: Clostridium difficile Diagnostic tests NAAT Molecular testing
We surveyed Ohio acute care hospitals on laboratory testing used for diagnosis of Clostridium difficile infection (CDI). Of 146 hospitals surveyed, 109 (84%) used nucleic acid amplification tests (NAATs) as standalone diagnostic assays. Only 53 (42.4%) hospitals using NAATs had a mechanism in place to prevent repeat CDI testing. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Multiple testing methods are available to diagnose Clostridium difficile infection (CDI).1 In the past, the toxin A&B enzyme immunoassay (EIA) was commonly used as a stand-alone test because it has a short turnaround time and is inexpensive. However, the 2010 Society for Healthcare Epidemiology of America and Infectious Disease Society of America clinical practice guidelines for CDI in adults recommended that the EIA for toxin not be used as a standalone test because of suboptimal sensitivity.1 In response, many laboratories in the United States switched to use of sensitive nucleic acid amplification tests (NAATs) for diagnosis of CDI. However, there is now increasing concern that use of NAATs as stand-alone tests may often result in diagnosis of asymptomatic carriers of toxigenic C difficile as CDI cases. In England, CDI testing often involves use of a 2-step algorithm in which EIA for glutamate dehydrogenase (GDH) is used as an initial screen with GDH-positive stool specimens undergoing EIA testing for toxin; a positive toxin assay indicates CDI, whereas a negative toxin assay suggests an asymptomatic carrier who may contribute to transmission as a fecal excretor.2 Fecal excretors are isolated, but not routinely treated or reported as CDI cases. Given the uncertainty regarding optimal CDI test strategies, there is the potential for significant variation in di-
* Address correspondence to Abhishek Deshpande, MD, PhD, Medicine Institute Center for Value Based Care Research, 9500 Euclid Ave, Desk G10, Cleveland Clinic, Cleveland, OH 44195. E-mail address: [email protected] (A. Deshpande). Conflicts of interest: C.J.D. has received research support from Cepheid. A.D. has received research support from 3M. All other authors report no conflicts of interest relevant to this article.
agnostic methods used by different hospitals. The objective of this study was to investigate the variation in CDI diagnostic testing methods by conducting a survey of acute care hospitals in the State of Ohio. METHODS The research protocol was approved by the Cleveland Clinic Institutional Review Board. Acute care hospitals in Ohio were identified from the Medicare.gov Hospital Compare Web site (https://www .medicare.gov/hospitalcompare). A total of 169 acute care academic and community hospitals from 88 counties in Ohio were identified in January 2015. Two authors (K.K.W. and B.C.) called each of the hospitals and administered a standardized questionnaire to key laboratory personnel through telephone interviews. Participation in the survey was voluntary. The questionnaire was reviewed with the microbiology supervisor regarding type of diagnostic test in use in 2013 and in 2014, the model and make of the diagnostic testing kit or machine, the availability of a written standard operating procedure, and if they use a 2-step testing protocol for diagnosing CDI. We also reviewed if the laboratories had a hard stop or recommended against repeat testing of CDI stool samples. Analysis consisted of descriptive statistics. RESULTS Of 169 hospitals surveyed, 146 (86.4%) facilities from 73 counties participated, including 22 tertiary care and 124 community hospitals. The 146 study hospitals represented 80 different health
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.09.007
ARTICLE IN PRESS 2
K.K. Wong et al. / American Journal of Infection Control ■■ (2016) ■■-■■
care systems in Ohio. Most hospitals within the same health care system used the same CDI testing method. In 2013, 129 of the 146 hospitals surveyed (88.4%) were using a stand-alone test for the diagnosis of CDI, including 91 (70.5%) using an NAAT, 37 (28.7%) using a toxin A&B EIA, and 1 (0.8%) using a cell culture cytotoxicity neutralization assay (CCNA). In 2014, the proportion of hospitals using stand-alone NAATs increased: 109 (84.5%) of the hospitals used an NAAT, 19 (14.7%) used a toxin A&B EIA, and 1 used CCNA. The 1 hospital using CCNA planned to switch to a stand-alone NAAT in 2015. Seventeen of the hospitals (11.6%) reported using a 2- or 3-step testing algorithm (GDH combined with NAAT: n = 7, GDH/toxin A&B EIA: n = 1; GDH/toxin A&B EIA combined with NAAT: n = 9). Four hospitals using the 2-step method planned to switch to a stand-alone NAAT in 2015. The manufacturers of NAAT included Meridian (Meridian Bioscience, Cincinnati, OH) (n = 31, 48.4%), Cepheid (Cepheid, Sunnyvale, CA) (n = 23, 35.9%), Quidel (Cepheid, Sunnyvale, CA) (n = 7, 10.9%) and BD (BD Biosciences, San Jose, CA) (n = 1, 1.6%); 2 (3.1%) hospitals chose not to disclose the name of the company. All of the microbiology laboratories reported having a written standard operating procedure for CDI testing. Of the 125 hospitals (including 2- or 3-step testing) using an NAAT, 53 (42.4%) hospitals had a mechanism in place to prevent repeat testing. The hospitals either implemented an automatic electronic stop order or explicitly recommended against repeat testing of CDI; however, such orders could be overwritten by the ordering physician. DISCUSSION Despite the recommendation from the 2010 CDI practice guidelines that EIA for toxin not be used as a stand-alone test for CDI, we found that 28.7% of Ohio acute care hospitals surveyed used this laboratory testing method in 2013. However, there was evidence of a rapid shift away from this testing approach because only 14.7% of the hospitals reported using EIA for toxin as a stand-alone test in 2014. Most hospitals were switching from EIA for toxin to use of NAATs as a stand-alone test method. Of the hospitals surveyed, 70.5% used NAATs as a stand-alone test in 2013 versus 84.5% in 2014. NAATs are being used increasingly as stand-alone tests in the United States because of their high sensitivity and specificity and a quick turnaround time. However, there has been increasing concern that use of NAATs as a stand-alone test can lead to false-positive tests, resulting in overdiagnosis and overtreatment of CDI.3 In the absence of clear signs and symptoms of infection, a positive NAAT is more likely an indicator of C difficile colonization, and treating these patients will expose them to unnecessary antibiotics. Also, the mandatory reporting for CDI using the LabID event allows laboratory testing data to be used without clinical evaluation; therefore, it is critical that molecular diagnostic testing be done only for symptomatic patients. Based on the concerns regarding use of NAATs as a stand-alone test, current European guidelines for diagnosis of CDI recommend 2- or 3-step algorithms that include toxin testing.4 However, in Ohio we found that only 11.6% of hospitals surveyed were using a 2- or 3-step algorithm for diagnosis of CDI, and only 10 (58.8%) included a toxin assay in the algorithm. Recent studies have suggested that patients with positive NAATs but negative stool toxin assays may be unlikely to have adverse outcomes. Based on these studies, Polage et al3 have recommended that 2-step algorithms that include toxin assays should be used rather than stand-alone NAAT testing. Future surveys will be of interest to determine if laboratories begin to move away from stand-alone NAAT testing. Although most clinical laboratories reject formed stool samples, additional steps are needed to discourage unnecessary testing. For many years, the lack of confidence in toxin EIA test results led to the submission of multiple stool samples.5 The Society for Health-
care Epidemiology of America and Infectious Disease Society of America guidelines and the Centers for Disease Control and Prevention clearly recommend against repeat testing or testing for cure.1 Repeat testing adds another layer of unnecessary cost and may also complicate patient care. It is therefore imperative that clinical laboratories should consider implementing an automatic electronic hard stop for repeat testing within the same week or explicitly recommend against repeat testing during order placement. Our findings are consistent with previous studies in demonstrating wide variation in CDI testing methods among hospitals and frequent nonadherence to practice guidelines. In recent surveys of European hospitals, only 40%-64% of hospitals were using recommended laboratory test algorithms to diagnose CDI.6,7 In England, a 2011 survey of diagnostic microbiology laboratories revealed considerable variation in CDI testing practices, and only 24% of the laboratories had changed their testing procedures in response to a guideline published in 2009.8 In Italy, more than half of laboratories surveyed in 2012 were using EIA for toxin as a stand-alone test, and only 34% were using the recommended methods to diagnose CDI.9 In a 2016 pan-European survey of 126 laboratories from 33 countries, use of CDI diagnostics deemed optimal increased from 19% to 46% between 2011 and 2014.10 Similarly, in a 2011 survey of 893 facilities in the United States, close to half the facilities were using EIA for toxin as a standalone test and 46% were using NAAT.11 In conclusion, we found that multiple strategies are being used for diagnosis of CDI in Ohio health care facilities, including standalone EIA for toxin tests that are not recommended in current guidelines. Because our survey was limited to acute care hospitals in Ohio, additional national studies are needed. Finally, there is a need for randomized trials to determine which diagnostic test methods are optimal for diagnosis of CDI. References 1. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. 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). Infect Control Hosp Epidemiol 2010;31:43155. 2. Planche T, Wilcox MH. Diagnostic pitfalls in Clostridium difficile infection. Infect Dis Clin North Am 2015;29:63-82. 3. Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015;175:1792-801. 4. Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 2016;22(Suppl):S63-81. 5. Deshpande A, Pasupuleti V, Patel P, Ajani G, Hall G, Hu B, et al. Repeat stool testing to diagnose Clostridium difficile infection using enzyme immunoassay does not increase diagnostic yield. Clin Gastroenterol Hepatol 2011;9:665-9, e661. 6. Davies KA, Longshaw CM, Davis GL, et al. Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis 2014;14:1208-19. 7. Davies KA, Ashwin H, Longshaw CM, Burns DA, Davis GL, Wilcox MH, et al. Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013. Euro Surveill 2016;21. 8. Chand MA, Fleming MJ, Wellsteed S, Kelsey MC. Impact of changes in Clostridium difficile diagnostic testing on detection of C. difficile infection and all England mandatory surveillance data. J Hosp Infect 2011;79:8-12. 9. Spigaglia P, Barbanti F, Morandi M, Moro ML, Mastrantonio P. Diagnostic testing for Clostridium difficile in Italian microbiological laboratories. Anaerobe 2016;37:29-33. 10. van Dorp SM, Notermans DW, Alblas J, Gastmeier P, Mentula S, Nagy E, et al. Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014. Euro Surveill 2016;21. 11. Dudeck M, Weiner L, Malpiedi P, Edwards J, Peterson K, Sievert D. Risk adjustment for healthcare facility-onset C. difficile and MRSA bacteremia laboratory-identified event reporting in NHSN. 2013. Available from: https://www.medicare.gov/ hospitalcompare/. Accessed September 15, 2016.