Clostridium difficile in Oncology Patients—Review of Diagnosis and Management in the Indian Setting
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(04): 286-292
DOI: DOI: 10.1055/s-0042-1760316
Abstract
Clostridoides (formerly Clostridium) difficile (C. difficile) is a toxin-producing, gram-positive anaerobic bacillus, commonly implicated in antibiotic-associated diarrhea and pseudomembranous colitis. The true burden of C. difficile infection is unclear in India, as it is likely underdiagnosed and underreported. Its incidence is much higher in oncology patients where it can contribute significantly to morbidity and mortality. There are several challenges in the Indian setting, including lack of uniform availability of testing infrastructure, as well as therapy. Oncology patients further present with a unique set of challenges. This article will review the approach to diagnosis and management of C. difficile-associated diarrhea in India, with a focus on oncology patients.
Keywords
Clostridium difficile - gram-positive anaerobic bacillus
Publication History
Artikel online veröffentlicht:
01. March 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Abstract
Clostridoides (formerly Clostridium) difficile (C. difficile) is a toxin-producing, gram-positive anaerobic bacillus, commonly implicated in antibiotic-associated diarrhea and pseudomembranous colitis. The true burden of C. difficile infection is unclear in India, as it is likely underdiagnosed and underreported. Its incidence is much higher in oncology patients where it can contribute significantly to morbidity and mortality. There are several challenges in the Indian setting, including lack of uniform availability of testing infrastructure, as well as therapy. Oncology patients further present with a unique set of challenges. This article will review the approach to diagnosis and management of C. difficile-associated diarrhea in India, with a focus on oncology patients.
Keywords
Clostridium difficile - gram-positive anaerobic bacillus
Introduction
Clostridium difficile is a toxin-producing gram-positive anaerobic bacillus, commonly implicated in antibiotic-associated diarrhea (CDAD) and pseudomembranous colitis. CDAD remains a formidable problem in healthcare facilities across the globe. In 2011, close to half a million cases of C. difficile infection (CDI) were reported in the United States, with the majority of cases occurring in the elderly patients (over 65 years of age).[1] There is also a financial price to pay for these infections. A meta-analysis of 42 studies published in 2016 showed that CDI placed a significant financial burden on the US healthcare system.[2] In this study, the average and incremental length of stay for CDI in-patient treatment were 11.1 (90% confidence interval [CI]: 8.7–13.6) and 9.7 (90% CI: 9.6–9.8) days respectively. Total annual CDI-attributable cost in the United States was calculated to be US$ 6.3 (range: $1.9–$7.0) billion).[2]
CDI is a common problem in oncology patients. A retrospective review found that 17.3% of the 225 patients with solid tumors admitted to a hospital with diarrhea had CDAD.[3]
A multicenter survey of oncology units showed that the pooled rate of hospital-acquired CDAD in patients with cancer was more than twice the rate reported for all patients in the United States.[4]
The incidence of CDAD has been estimated to be between 7.1 and 30% in various Indian studies.[5] [6] [7] A study published in 2017 from India showed that out of the 791 patients with nosocomial diarrhea included, 6% had CDAD. Among these patients, malignancy was found to be the most common underlying condition.[8] A 2021 study from a tertiary care center in south India showed the prevalence of CDAD in cancer patients to be 18.67%.[9]
Due to the lack of large-scale data and multicentric studies, the true burden of this problem is unknown in India. Lack of uniform availability of testing infrastructure as well as access to therapy is among the challenges faced in Indian settings. Drugs such as fidaxomicin are not available, and modalities such as fecal microbiota transplantation (FMT) are not well established in most Indian hospitals. Oncology patients further present with their unique set of challenges. They have multiple risk factors for the development of CDAD; chemotherapy itself can lead to dysbiosis of the gut flora. Antibiotic exposure in these patients is generally frequent and can be for longer durations. These patients also have multiple hospital encounters leading to increase in incidences of nosocomial infections.
There are no national guidelines and there is lack of clarity regarding testing protocols for CDAD in India. Also, FMT is performed in very few centers in the country and there are no established protocols regarding donor screening and administration. This article reviews the approach to diagnosis and management of CDAD in India and sheds light on how we can overcome some diagnostic and therapeutic challenges, with a focus on oncology patients. It also suggests a protocol for performing FMT, and suggests various steps that can be taken by hospitals across the country to curb the problem of CDI.
Diagnosis of CDAD in the Oncology Population in India
Population Criteria for Testing
Diarrhea in the oncology patients can have a wide range of differential diagnoses. These can include:
Chemotherapeutic agents
Immunotherapeutic agents
Surgery
Radiation therapy
Underlying malignancy
Infectious causes, including C. difficile
Clinical Practice Guidelines for CDI issued by the Infectious Disease Society of America (IDSA) in 2017 recommend testing when the patient has had three or more unformed stools in the preceding 24 hours.[10] Other causes of diarrhea in this population need to be considered carefully before ordering a stool C. difficile assay.
Principles of Laboratory Testing
Pathogenicity of C. difficile to cause CDAD is associated with production of two toxins, that is, toxin A (enterotoxin) and toxin B (cytotoxin). Not all strains of C. difficile possess the gene locus containing tcdA and tcdB genes to express these toxins. Hence, the diagnosis of CDI is based on the detection of these toxins and not just the detection of bacteria.
Clinical utility of any modality of laboratory testing to “rule in” (positive predictive value—PPV) or “rule out” (negative predictive value) diagnosis of CDI depends on its specificity and sensitivity, respectively. It is also decided by the prevalence of the disease in a particular population, and hence, denotes the pretest probability of the disease. Since diarrhea in oncology patients can have numerous infectious and noninfectious differential diagnoses, exclusion of these before ordering a C. difficile test enhances the PPV of the test.
C. difficile colonizes the large bowel of the gastrointestinal (GI) tract. It can be a part of the normal gut flora of children less than 2 years of age, in whom colonization rates can exceed 40%.[11] Colonization rates as high as 30%[12] are also seen in adults with prolonged hospitalization, such as the patients hospitalized in the oncology units. This is another reason why exclusion of other etiologies is essential for the accurate clinical interpretation of positive results.
Modalities of Laboratory Testing
Variety of testing modalities are available for the diagnosis of CDI, as summarized in [Table 1].
Testing modality |
Basic principle |
Sensitivity (SS)/specificity (SP) |
Advantages |
Limitations |
---|---|---|---|---|
Toxigenic culture (TC) |
Inoculation of stool on a selective/chromogenic medium |
SS: 22–100% SP: 90% (6) |
High sensitivity. Performance of drug susceptibility testing |
Cumbersome to perform Need of technical expertise Prolonged turnaround time—around 1 week Low positive predictive value (PPV) due to growth of non-toxigenic strains |
Cell culture cytotoxicity neutralization assay (CCNA) |
Observation of cytopathic effect (CPE), cell rounding and neutralization of CPE with antitoxin |
SS: 75–85% SP: 93–100% (7) |
Reference gold standard for laboratory confirmation of C. difficile infection (CDI) Very high specificity |
High level of expertise needed |
Glutamate dehydrogenase (GDH) antigen |
Detection of GDH enzyme secreted by C. difficile using: Rapid lateral flow immuno-chromatography Enzyme linked immunosorbent assay (ELISA) Enzyme linked fluorescence immunoassay (ELFA) |
SS: 71–95% SP: 87–90% (8) |
Easy to perform Rapid results Inexpensive Excellent sensitivity, can be used as a screening test |
Positive results in both toxigenic as well as nontoxigenic strains, hence low PPV |
Toxin A and B immunoassays (TIA) |
Detection of toxin A and B in the specimen using: rapid lateral flow immuno-chromatography ELISA ELFA |
SS: 60–86% SP: 91–98% (9) |
Easy to perform Rapid results Inexpensive |
Inconsistent sensitivity due to variations in strains and kits Cannot be used as the sole test for the diagnosis of CDI due to false negative results. |
Nucleic acid amplification test (NAAT) |
Exponential amplification and detection of tcdA and tcdB genes using real-time polymerase chain reaction (PCR) Cartridge based PCR assays LAMP (ligase mediated amplification) Multiplex PCR syndromic gastrointestinal panels |
SS: 82–100% SP: 90–100% (10) |
High sensitivity, specificity Rapid turnaround time Excellent negative predictive value (NPV) |
Positive results may be obtained with colonization and needs clinical correlation |
GDH antigen |
Assay for toxin A |
Assay for toxin B |
Recommended approach and comments |
---|---|---|---|
Positive |
Positive |
Positive |
Treat as CDAD |
Positive |
Positive |
Negative |
Treat as CDAD |
Positive |
Negative |
Positive |
Treat as CDAD |
Negative |
Negative |
Negative |
Do not treat as CDAD |
Positive |
Negative |
Negative |
May indicate colonization. If high clinical suspicion, PCR for C. difficile should be done in oncology patients; do not treat if PCR is negative. |
NAAT |
|||
Positive |
Positive |
Positive |
Treat as CDAD |
Negative |
Negative |
Negative |
Do not treat as CDAD |
Positive |
Negative |
Negative |
Probable colonization if pretest probability low, do not treat as CDAD Probable CDAD if pretest high, treat as CDAD |
Positive |
Negative |
Positive |
Treat as CDAD |
Positive |
Positive |
Negative |
Treat as CDAD |
Do not perform repeat testing routinely within 7 days of the same episode of diarrhea, if initial test is negative |
Repeat testing may be considered in patients with worsening of symptoms and a high index of clinical suspicion for CDI |
Do not test for screening asymptomatic carriers |
Episodes of recurrent CDI should be assessed by repeat testing |
No value in testing to establish cure—more than 60% tests remain positive after successful therapy |
Testing should not be routinely performed in the first 2 years of life unless clinical suspicion for CDAD is high |
Factor |
Points assigned |
---|---|
Age > 60 years |
1 |
Body temperature > 38.3 C |
1 |
Albumin < 2.5 g/dl |
1 |
Endoscopic evidence of pseudomembranous colitis |
2 |
Treatment in the ICU |
2 |
At least 50 g of stool specimen is submitted by the donor on the day of FMT using sterile stool collection kit provided by the laboratory. Time of specimen voiding is noted |
Donor stool sample is processed in biosafety cabinet, the technician donning aprons, impervious gown, and cap |
Using sterile wooden spatula, 50 g of stools is emulsified in 250 mL of nonbuffered sterile saline (autoclaved in a screw capped glass bottle and cooled) |
Emulsion is sieved through triple layered sterile gauze to filter out coarse particles (>1–2 mm). Resultant filtrate is collected in a sterile flask and transferred to the endoscopy suite with an airtight seal |
FMT solution needs to be infused within 6 hours of donor voiding. The solution is stored at room temperature until the procedure |
Patients should not be taking any antibiotics or probiotics 48 hours before FMT |
If diarrhea persists 1 week after procedure, C. difficile NAAT testing should be done and repeat FMT may be considered if positive |
References
- Lessa FC, Gould CV, McDonald LC. Current status of Clostridium difficile infection epidemiology. Clin Infect Dis 2012; 55 (Suppl 2, Suppl 2): S65-S70
- Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis 2016; 16 (01) 447
- Rodríguez Garzotto A, Mérida García A, Muñoz Unceta N. et al. Risk factors associated with Clostridium difficile infection in adult oncology patients. Support Care Cancer 2015; 23 (06) 1569-1577
- Chopra T, Chandrasekar P, Salimnia H, Heilbrun LK, Smith D, Alangaden GJ. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation. Clin Transplant 2011; 25 (01) E82-E87
- Dhawan B, Chaudhry R. An update on Clostridium difficile infection. Trop Gastroenterol 1997; 18 (04) 149-152
- Chaudhry R, Joshy L, Kumar L, Dhawan B. Changing pattern of Clostridium difficile associated diarrhoea in a tertiary care hospital: a 5 year retrospective study. Indian J Med Res 2008; 127 (04) 377-382
- Gupta U, Yadav RN. Clostridium difficile in hospital patients. Indian J Med Res 1985; 82: 398-401
- Chaudhry R, Sharma N, Gupta N. et al. Nagging presence o Clostridium difficile
- Kannambath R, Biswas R, Mandal J, Vinod KV, Dubashi B, Parameswaran N. Clostridioides difficile diarrhea: an emerging problem in a South Indian Tertiary Care Hospital. J Lab Physicians 2021; 13 (04) 346-352
- McDonald LC, Gerding DN, Johnson S. et al. 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 2018; 66 (07) e1-e48
- Bolton RP, Tait SK, Dear PR, Losowsky MS. Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child 1984; 59 (05) 466-472
- Loo VG, Bourgault AM, Poirier L. et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011; 365 (18) 1693-1703
- Erb S, Frei R, Strandén AM, Dangel M, Tschudin-Sutter S, Widmer AF. Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients. Clin Microbiol Infect 2015; 21 (11) 998.e9-998.e15
- Johnson S, Lavergne V, Skinner AM. et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 73 (05) e1029-e1044
- Mikamo H, Tateda K, Yanagihara K. et al. Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan. J Infect Chemother 2018; 24 (09) 744-752
- Chiu CY, Sarwal A, Feinstein A, Hennessey K. Effective dosage of oral vancomycin in treatment for initial episode o Clostridioides difficile
- Pogue JM, DePestel DD, Kaul DR, Khaled Y, Frame DG. Systemic absorption of oral vancomycin in a peripheral blood stem cell transplant patient with severe graft-versus-host disease of the gastrointestinal tract. Transpl Infect Dis 2009; 11 (05) 467-470
- McDonald LC, Killgore GE, Thompson A. et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353 (23) 2433-2441
- Adler A, Miller-Roll T, Bradenstein R. et al. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole. Diagn Microbiol Infect Dis 2015; 83 (01) 21-24
- Freeman J, Vernon J, Morris K. et al; Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes' Study Group. Pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes. Clin Microbiol Infect 2015; 21 (03) 248.e9-248.e16
- Banawas SS Clostridium difficile
- Leeds JA, Sachdeva M, Mullin S, Barnes SW, Ruzin A. In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin. J Antimicrob Chemother 2014; 69 (01) 41-44
- Popovic N, Korac M, Nesic Z. et al. Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study. Eur J Clin Microbiol Infect Dis 2018; 37 (04) 745-754
- Garey KW, Ghantoji SS, Shah DN. et al. A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection. J Antimicrob Chemother 2011; 66 (12) 2850-2855
- Mullane KM, Miller MA, Weiss K. et al. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis 2011; 53 (05) 440-447
- Lee CH, Steiner T, Petrof EO. et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent clostridium difficile infection: a randomized clinical trial. JAMA 2016; 315 (02) 142-149
- Saha S, Mara K, Pardi DS, Khanna S. Durability of response to fecal microbiota transplantation after exposure to risk factors for recurrence in patients with Clostridioides difficile infection. Clin Infect Dis 2021; 73 (07) e1706-e1712
- Tauxe WM, Dhere T, Ward A, Racsa LD, Varkey JB, Kraft CS. Fecal microbiota transplant protocol for clostridium difficile infection. Lab Med 2015; 46 (01) e19-e23
- Kelly CR, Fischer M, Allegretti JR. et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021; 116 (06) 1124-1147
- Kuon C, Wannier R, Sterken D, Fang MC, Wolf J, Prasad PA. Are antimotility agents safe for use i Clostridioides difficile
- McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320 (04) 204-210
- Kundrapu S, Sunkesula V, Jury LA, Sitzlar BM, Donskey CJ. Daily disinfection of high-touch surfaces in isolation rooms to reduce contamination of healthcare workers' hands. Infect Control Hosp Epidemiol 2012; 33 (10) 1039-1042
- Aldeyab MA, Kearney MP, Scott MG. et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother 2012; 67 (12) 2988-2996
Address for correspondence
Publikationsverlauf
Artikel online veröffentlicht:
01. März 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
References
- Lessa FC, Gould CV, McDonald LC. Current status of Clostridium difficile infection epidemiology. Clin Infect Dis 2012; 55 (Suppl 2, Suppl 2): S65-S70
- Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis 2016; 16 (01) 447
- Rodríguez Garzotto A, Mérida García A, Muñoz Unceta N. et al. Risk factors associated with Clostridium difficile infection in adult oncology patients. Support Care Cancer 2015; 23 (06) 1569-1577
- Chopra T, Chandrasekar P, Salimnia H, Heilbrun LK, Smith D, Alangaden GJ. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation. Clin Transplant 2011; 25 (01) E82-E87
- Dhawan B, Chaudhry R. An update on Clostridium difficile infection. Trop Gastroenterol 1997; 18 (04) 149-152
- Chaudhry R, Joshy L, Kumar L, Dhawan B. Changing pattern of Clostridium difficile associated diarrhoea in a tertiary care hospital: a 5 year retrospective study. Indian J Med Res 2008; 127 (04) 377-382
- Gupta U, Yadav RN. Clostridium difficile in hospital patients. Indian J Med Res 1985; 82: 398-401
- Chaudhry R, Sharma N, Gupta N. et al. Nagging presence o Clostridium difficile
- Kannambath R, Biswas R, Mandal J, Vinod KV, Dubashi B, Parameswaran N. Clostridioides difficile diarrhea: an emerging problem in a South Indian Tertiary Care Hospital. J Lab Physicians 2021; 13 (04) 346-352
- McDonald LC, Gerding DN, Johnson S. et al. 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 2018; 66 (07) e1-e48
- Bolton RP, Tait SK, Dear PR, Losowsky MS. Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child 1984; 59 (05) 466-472
- Loo VG, Bourgault AM, Poirier L. et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011; 365 (18) 1693-1703
- Erb S, Frei R, Strandén AM, Dangel M, Tschudin-Sutter S, Widmer AF. Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients. Clin Microbiol Infect 2015; 21 (11) 998.e9-998.e15
- Johnson S, Lavergne V, Skinner AM. et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 73 (05) e1029-e1044
- Mikamo H, Tateda K, Yanagihara K. et al. Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan. J Infect Chemother 2018; 24 (09) 744-752
- Chiu CY, Sarwal A, Feinstein A, Hennessey K. Effective dosage of oral vancomycin in treatment for initial episode o Clostridioides difficile
- Pogue JM, DePestel DD, Kaul DR, Khaled Y, Frame DG. Systemic absorption of oral vancomycin in a peripheral blood stem cell transplant patient with severe graft-versus-host disease of the gastrointestinal tract. Transpl Infect Dis 2009; 11 (05) 467-470
- McDonald LC, Killgore GE, Thompson A. et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353 (23) 2433-2441
- Adler A, Miller-Roll T, Bradenstein R. et al. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole. Diagn Microbiol Infect Dis 2015; 83 (01) 21-24
- Freeman J, Vernon J, Morris K. et al; Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes' Study Group. Pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes. Clin Microbiol Infect 2015; 21 (03) 248.e9-248.e16
- Banawas SS Clostridium difficile
- Leeds JA, Sachdeva M, Mullin S, Barnes SW, Ruzin A. In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin. J Antimicrob Chemother 2014; 69 (01) 41-44
- Popovic N, Korac M, Nesic Z. et al. Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study. Eur J Clin Microbiol Infect Dis 2018; 37 (04) 745-754
- Garey KW, Ghantoji SS, Shah DN. et al. A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection. J Antimicrob Chemother 2011; 66 (12) 2850-2855
- Mullane KM, Miller MA, Weiss K. et al. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis 2011; 53 (05) 440-447
- Lee CH, Steiner T, Petrof EO. et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent clostridium difficile infection: a randomized clinical trial. JAMA 2016; 315 (02) 142-149
- Saha S, Mara K, Pardi DS, Khanna S. Durability of response to fecal microbiota transplantation after exposure to risk factors for recurrence in patients with Clostridioides difficile infection. Clin Infect Dis 2021; 73 (07) e1706-e1712
- Tauxe WM, Dhere T, Ward A, Racsa LD, Varkey JB, Kraft CS. Fecal microbiota transplant protocol for clostridium difficile infection. Lab Med 2015; 46 (01) e19-e23
- Kelly CR, Fischer M, Allegretti JR. et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021; 116 (06) 1124-1147
- Kuon C, Wannier R, Sterken D, Fang MC, Wolf J, Prasad PA. Are antimotility agents safe for use i Clostridioides difficile
- McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320 (04) 204-210
- Kundrapu S, Sunkesula V, Jury LA, Sitzlar BM, Donskey CJ. Daily disinfection of high-touch surfaces in isolation rooms to reduce contamination of healthcare workers' hands. Infect Control Hosp Epidemiol 2012; 33 (10) 1039-1042
- Aldeyab MA, Kearney MP, Scott MG. et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother 2012; 67 (12) 2988-2996