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Allegretti JR, Kelly CR, Louie T, Fischer M, Hota S, Misra B, Van Hise NW, Yen E, Bullock JS, Silverman M, Davis I, McGill SK, Pardi DS, Orenstein R, Grinspan A, El-Nachef N, Feuerstadt P, Borody TJ, Khanna S, Budree S, Kassam Z. Safety and Tolerability of CP101, a Full-Spectrum, Oral Microbiome Therapeutic for the Prevention of Recurrent Clostridioides difficile Infection: A Phase 2 Randomized Controlled Trial. Gastroenterology 2025; 168:357-366.e3. [PMID: 39366468 DOI: 10.1053/j.gastro.2024.09.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 09/09/2024] [Accepted: 09/26/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND & AIMS Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population. METHODS We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 1011 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24. RESULTS A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups. CONCLUSIONS CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133).
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Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Colleen R Kelly
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Thomas Louie
- Department of Medicine and Microbiology, University of Calgary, Calgary, Alberta, Canada
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana
| | - Susy Hota
- Division of Infectious Disease, University Health Network, Toronto, Ontario, Canada
| | | | | | - Eugene Yen
- Division of Gastroenterology, Northwestern Medical Group, Chicago, Illinois
| | | | - Michael Silverman
- St. Joseph's Health Care, Western University, London, Ontario, Canada
| | - Ian Davis
- Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sarah K McGill
- Division of Gastroenterology, University of North Carolina Hospitals, Chapel Hill, North Carolina
| | - Darrell S Pardi
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | - Robert Orenstein
- Division of Infectious Disease, Mayo Clinic, Scottsdale, Arizona
| | - Ari Grinspan
- Division of Gastroenterology, Mount Sinai Hospital, New York, New York
| | - Najwa El-Nachef
- Division of Gastroenterology, University of California San Francisco, San Francisco, California
| | - Paul Feuerstadt
- Division of Gastroenterology, Yale University, New Haven, Connecticut
| | - Thomas J Borody
- Center for Digestive Diseases, Sydney, New South Wales, Australia
| | - Sahil Khanna
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | | | - Zain Kassam
- Innovate Calgary, University of Calgary, Calgary, Alberta, Canada
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Williams MJ, Atienza S, Franzen E, Rathod H, Mejaki B, Graff J, Korman S, Zouine N, Gul Z, Sana S, Medlin S, Buggy BP. Evaluation of Primary Oral Vancomycin Prophylaxis Against Clostridioides difficile Infection During Autologous Stem Cell Transplantation. Open Forum Infect Dis 2024; 11:ofae622. [PMID: 39498172 PMCID: PMC11532790 DOI: 10.1093/ofid/ofae622] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 10/09/2024] [Indexed: 11/07/2024] Open
Abstract
Background Evaluations of oral vancomycin prophylaxis (OVP) against Clostridioides difficile have been reported in stem cell transplant populations with short follow-up periods. The longest known duration of standardized follow-up post-OVP is 90 days within an allogeneic stem cell transplant population. In 2017, we implemented OVP 125 mg twice daily in autologous stem cell transplant (ASCT) recipients beginning the day of admission and continued until the day of discharge. Methods Patients who received an ASCT within our institution between 1 January 2012 and 31 December 2021 were included and separated into 2 groups based on the receipt of OVP. The primary study aim was to measure the incidence of C difficile infection (CDI) during the ASCT admission. A secondary aim was to evaluate for delayed CDI 180 days post-discharge. Other factors evaluated were prior history of CDI, use of systemic antimicrobials, and length of stay. Results Overall, 254 patients were evaluated and 58% received OVP, predominantly as primary prophylaxis (95%). Of the 18 patients who developed in-hospital CDI, 6 were in the OVP group versus 12 in the non-OVP cohort (4% vs 11%, P = .03). In the 180-day follow-up period, OVP use did not increase risk of developing CDI after discontinuation while in-hospital length of stay was identified as a significant factor. Conclusions The use of OVP significantly reduced the incidence of CDI during the in-hospital ASCT course without increasing CDI post-OVP use. These encouraging results should promote further research into the use of OVP in ASCT.
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Affiliation(s)
- Michael J Williams
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Sol Atienza
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Erin Franzen
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Heena Rathod
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Brittany Mejaki
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Justin Graff
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
- Department of Pharmacy, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Sandra Korman
- Quality Management, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Noah Zouine
- Quality Management, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Zartash Gul
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Sherjeel Sana
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Stephen Medlin
- Malignant Hematology and Stem Cell Transplant, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
| | - Brian P Buggy
- Infectious Diseases Section, Aurora St Luke's Medical Center, Milwaukee, Wisconsin, USA
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Li GB, Wang CT, Zhang X, Qiu XY, Chen WJ, Lu JY, Xu L, Wu B, Xiao Y, Lin GL. Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis. World J Gastrointest Surg 2024; 16:1259-1270. [PMID: 38817289 PMCID: PMC11135307 DOI: 10.4240/wjgs.v16.i5.1259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 04/04/2024] [Accepted: 04/19/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM To analyze the clinical features and risk factors of IFD. METHODS Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.
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Affiliation(s)
- Gan-Bin Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Chen-Tong Wang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Xiao Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Xiao-Yuan Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Wei-Jie Chen
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Jun-Yang Lu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Lai Xu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Bin Wu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Yi Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
| | - Guo-Le Lin
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
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San-Juan R, Origuen J, Campion K, Fernández-Ruiz M, Diaz-Pollan B, Callejas-Diaz A, Candela G, Orellana MA, Lora D, Llorente Muñoz I, Garcia MT, Martinez-Uña M, Ferrari JM, Aguado JM. Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial. BMJ Open 2023; 13:e072121. [PMID: 37709311 PMCID: PMC11148698 DOI: 10.1136/bmjopen-2023-072121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/16/2023] Open
Abstract
INTRODUCTION Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER NCT05320068.
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Affiliation(s)
- Rafael San-Juan
- Department of Infectious Diseases, Hospital Universitario "12 de Octubre", Madrid, Spain
- CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigacion Biomedica del Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Julia Origuen
- Department of Infectious Diseases, Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Karen Campion
- Department of Infectious Diseases, Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Mario Fernández-Ruiz
- Department of Infectious Diseases, Hospital Universitario "12 de Octubre", Madrid, Spain
- CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigacion Biomedica del Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Alejandro Callejas-Diaz
- Department of Internal Medicine, Puerta de Hierro University Hospital of Majadahonda, Majadahonda, Spain
| | - Giancarlo Candela
- Department of Internal Medicine, Severo Ochoa University Hospital, Leganes, Spain
| | | | - David Lora
- Clinical Research Unit (I+12), Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Irene Llorente Muñoz
- SCREN, Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Maria Teresa Garcia
- SCREN, Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Maite Martinez-Uña
- Department of Pharmacy, Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Jose Miguel Ferrari
- Department of Pharmacy, Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Jose M Aguado
- Department of Infectious Diseases, Hospital Universitario "12 de Octubre", Madrid, Spain
- CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigacion Biomedica del Hospital Universitario 12 de Octubre, Madrid, Spain
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Ivashkin VT, Lyashenko OS, Drapkina OM, Alexeeva OP, Alekseenko SA, Andreev DN, Baranovsky AY, Goloshchapov OV, Zheleznova NV, Zolnikova OY, Kliaritskaia IL, Korochanskaya NV, Lapina TL, Maev IV, Maslennikov RV, Myazin RG, Pavlov PV, Perekalina MV, Pisarenko NA, Povtoreyko AV, Poluektova EA, Sekretareva LA, Tkachev AV, Troshkina YM, Trukhmanov AS, Ulyanin AI, Filatova SG, Tsukanov VV, Shifrin OS. Clinical Practice Guidelines of the Scientific Society for the Clinical Study of Human Microbiome, of the Russian Gastroenterological Association and the Russian Society for the Prevention of Noncommunicable Diseases on the Diagnosis and Treatment of <i>Clostridioides difficile</i> (<i>C. difficile</i>)-associated Disease in Adults. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:85-119. [DOI: 10.22416/1382-4376-2023-33-3-85-119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim: the clinical practice guidelines intended for gastroenterologists, internal medicine specialists, infectious disease specialists, general practitioners (family doctors), coloproctologists, surgeons and endoscopists present modern methods of diagnosis, prevention and treatment of C. difficile-associated disease.Key points. C. difficile-associated disease is a disease that develops when the diversity of the intestinal microbiota decreases and C. difficile excessively colonizes the colon, the toxins of which damage the intestinal muco-epithelial barrier, followed by the development of inflammation in the colon wall, with diarrhea being a characteristic clinical manifestation. The clinical presentation of the disease can vary from asymptomatic carriage, mild to moderate diarrhea that resolves on its own, to profuse watery diarrhea and pseudomembranous colitis with development of life-threatening complications. The diagnosis of C. difficile-associated disease is based on an assessment of the clinical presentation, medical history, an objective examination of the patient and laboratory stool tests. The disease severity is determined by clinical symptoms and laboratory findings. Additional diagnostic methods that are used according to indications and contribute to the assessment of severity include endoscopy of the colon and abdominal cavity imaging methods. Treatment should be initiated in cases of characteristic clinical presentation of C. difficile-associated disease and positive laboratory stool testing. The choice of drug and treatment regimen depends on the severity of the episode, the presence of complications, and whether the episode is initial, recurrent, or reinfection.Conclusion. Determination of target groups of patients for the diagnosis of clostridial infection is important in preventing overdiagnosis and subsequent unnecessary treatment. Timely diagnosis and treatment of C. difficile-associated disease help avoiding the development of life-threatening complications and improve the prognosis and quality of life of patients.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - O. S. Lyashenko
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
| | | | | | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | - T. L. Lapina
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | - P. V. Pavlov
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | | | - E. A. Poluektova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | | | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - A. I. Ulyanin
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | - V. V. Tsukanov
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State University (Sechenov University)
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Ivashkin VT, Maev IV, Andreev DN, Goloshchapov OV, Derinov AA, Zolnikova OY, Ivashkin KV, Kiseleva OY, Kiryukhin AP, Lyashenko OS, Poluektova EA, Tertychnyy AS, Trukhmanov AS, Ulyanin AI, Sheptulin AA, Shifrin OS. Modern Approaches to the Diagnosis and treatment of <i>Clostridioides difficile (C. difficile)</i>-associated Disease in Adults (literature Review and Expert Council Resolution). RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:19-33. [DOI: 10.22416/1382-4376-2023-33-2-19-33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aim: to review the modern approaches to the diagnosis and treatment ofC. difficile-associated disease in adults and present the resolution of the Expert Council held on March 25, 2023 in Moscow.General provisions.C. difficileis the most important nosocomial pathogen which spores are also commonly found in the environment. Microbiota impairment, primarily due to the use of antibacterial drugs, is a key stage in the development ofC. difficile-associated disease. A search for an infection should be carried out only in patients with diarrhea, and it is advisable to use at least 2 laboratory methods. The drug of choice for first-line treatment is vancomycin. If drug treatment is ineffective or the patient has recurrent clostridial infection, fecal microbiota transplantation should be considered. The probiotic strainSaccharomyces boulardii CNCM I-745has a direct inhibitory effect onC. difficiletoxin A, promotes normalization of the intestinal microbiota composition, and decreases the inflammatory reaction in colonic mucosa colonized with a toxigenic strain ofC. difficile.Conclusions. Addition of the probiotic strainSaccharomyces boulardii CNCM I-745to antibacterial therapy promotes both primary and secondary prevention ofC. difficile-associated disease.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | - A. A. Derinov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. V. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. Yu. Kiseleva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. P. Kiryukhin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. S. Lyashenko
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Tertychnyy
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. I. Ulyanin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. A. Sheptulin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Chang LL, Allegretti J, Skinner AM, Dubberke ER. Oral Vancomycin as Secondary Prophylaxis for Prevention of Recurrent Clostridioides difficile Infection. N Engl J Med 2023; 388:654-656. [PMID: 36791167 DOI: 10.1056/nejmclde2204692] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
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Darkow A, Johnson S, Walker H, Priest DH. When Should Oral Vancomycin Prophylaxis be Used to Prevent C. difficile Infection? Curr Infect Dis Rep 2023. [DOI: 10.1007/s11908-023-00796-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Katzman M, Cohrs AC, Hnatuck PE, Greene WH, Reed SM, Ward MA, Glasser FD, Loser MF, Hale CM. Impact of a Multipronged Approach to Reduce the Incidence of Clostridioides difficile Infections in Hospitalized Patients. Am J Infect Control 2022; 51:668-674. [PMID: 36075295 DOI: 10.1016/j.ajic.2022.08.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Effective approaches to reduce Clostridioides difficile infections (CDI) in hospitalized patients are needed. We report data from 3 years preceding and 3 years following interventions that proved successful, with detailed analysis of all cases the first year after implementation. METHODS Interventions included a nursing protocol to identify cases present on admission by asking if the patient had 1 or more liquid stools in the last 24 hours, and a 2-step testing algorithm with samples positive by polymerase chain reaction (PCR) for the C. difficile toxin gene reflexing to an enzyme immunoassay (EIA) for the toxin antigen. RESULTS Healthcare-associated infections due to CDI fell from ∼160 in each of the preceding 3 years to <65 in each of the subsequent 3 years (P<0.001), while the ratio of observed-to-expected hospital-onset cases diminished to ∼0.50 (P<0.02). In the first year, 395 samples were PCR(+), but only 118 (29.9%) of these were EIA(+). 55 (46.6%) of the PCR(+)/EIA(+) samples were from hospital day 1 or 2 and classified as present on admission. The mean time from stool collection to report of PCR results was ∼7.5 hours, and the EIA took on average only 68 additional minutes to be reported. CONCLUSIONS The number of incident CDI cases can be dramatically decreased by implementing an admission screening question and a 2-step testing algorithm.
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Affiliation(s)
- Michael Katzman
- Department of Medicine and Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PA.
| | - Austin C Cohrs
- Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA
| | - Patricia E Hnatuck
- Department of Quality and Infection Prevention, Milton S. Hershey Medical Center, Hershey, PA
| | - Wallace H Greene
- Department of Clinical Pathology, Milton S. Hershey Medical Center, Hershey, PA
| | - Stephanie M Reed
- Department of Nursing, Milton S. Hershey Medical Center, Hershey, PA
| | | | | | | | - Cory M Hale
- Department of Pharmacy, Milton S. Hershey Medical Center, Hershey, PA
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Johnson S, Gerding DN, Li X, Reda DJ, Donskey CJ, Gupta K, Goetz MB, Climo MW, Gordin FM, Ringer R, Johnson N, Johnson M, Calais LA, Goldberg AM, Ge L, Haegerich T. Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence. Contemp Clin Trials 2022; 116:106756. [DOI: 10.1016/j.cct.2022.106756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 11/26/2022]
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Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis. Antibiotics (Basel) 2022; 11:antibiotics11020183. [PMID: 35203786 PMCID: PMC8868369 DOI: 10.3390/antibiotics11020183] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/26/2022] [Accepted: 01/28/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality as well as high propensity of recurrence. Systemic antibiotic therapy (SAT) represents the top inciting factor of CDI, both primary and recurrent (rCDI). Among the many strategies aimed to prevent CDI in high-risk subjects undergoing SAT, oral vancomycin prophylaxis (OVP) appears promising under a cost-effectiveness perspective. Methods: A systematic review with meta-analysis and trial sequential analysis (TSA) of studies assessing the efficacy and the safety of OVP to prevent primary CDI and rCDI in persons undergoing SAT was carried out. PubMed and EMBASE were searched until 30 September 2021. The protocol was pre-registered on PROSPERO (CRD42019145543). Results: Eleven studies met the inclusion criteria, only one being a randomized controlled trial (RCT). Overall, 929 subjects received OVP and 2011 represented the comparator group (no active prophylaxis). OVP exerted a strong protective effect for CDI occurrence: odds ratio 0.14, 95% confidence interval 0.04–0.38. Moderate heterogeneity was observed: I2 54%. This effect was confirmed throughout several subgroup analyses, including prevention of primary CDI versus rCDI. TSA results pointed at the conclusive nature of the evidence. Results were robust to a variety of sensitivity and quantitative bias analyses, although the underlying evidence was deemed as low quality. No differences between the two groups were highlighted regarding the onset of vancomycin-resistant Enterococcus infections. Conclusions: OVP appears to be an efficacious option for prevention of CDI in high-risk subjects undergoing SAT. Nevertheless, additional data from RCTs are needed to establish OVP as good clinical practice and define optimal dosage and duration.
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12
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van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Norén T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 2021; 27 Suppl 2:S1-S21. [PMID: 34678515 DOI: 10.1016/j.cmi.2021.09.038] [Citation(s) in RCA: 318] [Impact Index Per Article: 79.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/23/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022]
Abstract
SCOPE In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Erik H Vogelzang
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Adriana Hristea
- University of Medicine and Pharmacy Carol Davila, National Institute for Infectious Diseases Prof Dr Matei Bals, Romania
| | - Benoit Guery
- Infectious Diseases Specialist, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University in Prague and Motol University Hospital, Czech Republic
| | - Torbjorn Norén
- Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides difficile, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
| | | | - John E Coia
- Department of Clinical Microbiology, Hospital South West Jutland and Department of Regional Health Research IRS, University of Southern Denmark, Esbjerg, Denmark
| | - Abraham Goorhuis
- Department of Infectious Diseases, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands
| | - Tessel M van Rossen
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Rogier E Ooijevaar
- Department of Gastroenterology, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Karen Burns
- Departments of Clinical Microbiology, Beaumont Hospital & Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Sarah Tschudin-Sutter
- Department of Infectious Diseases and Infection Control, University Hospital Basel, University Basel, Universitatsspital, Basel, Switzerland
| | - Mark H Wilcox
- Department of Microbiology, Old Medical, School Leeds General Infirmary, Leeds Teaching Hospitals & University of Leeds, Leeds, United Kingdom
| | - Maria J G T Vehreschild
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Fidelma Fitzpatrick
- Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ed J Kuijper
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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13
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Bogdanová K, Doubravská L, Vágnerová I, Hricová K, Pudová V, Röderová M, Papajk J, Uvízl R, Langová K, Kolář M. Clostridioides difficile and Vancomycin-Resistant Enterococci in COVID-19 Patients with Severe Pneumonia. Life (Basel) 2021; 11:life11111127. [PMID: 34833003 PMCID: PMC8653967 DOI: 10.3390/life11111127] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 10/14/2021] [Accepted: 10/20/2021] [Indexed: 01/08/2023] Open
Abstract
Broad-spectrum antibiotics administered to patients with severe COVID-19 pneumonia pose a risk of infection caused by Clostridioides difficile. This risk is reduced mainly by strict hygiene measures and early de-escalation of antibiotic therapy. Recently, oral vancomycin prophylaxis (OVP) has also been discussed. This retrospective study aimed to assess the prevalence of C. difficile in critical COVID-19 patients staying in an intensive care unit of a tertiary hospital department of anesthesiology, resuscitation, and intensive care from November 2020 to May 2021 and the rates of vancomycin-resistant enterococci (VRE) after the introduction of OVP and to compare the data with those from controls in the pre-pandemic period (November 2018 to May 2019). During the COVID-19 pandemic, there was a significant increase in toxigenic C. difficile rates to 12.4% of patients, as compared with 1.6% in controls. The peak rates were noted in February 2021 (25% of patients), immediately followed by initiation of OVP, changes to hygiene precautions, and more rapid de-escalation of antibiotic therapy. Subsequently, toxigenic C. difficile detection rates started to fall. There was a nonsignificant increase in VRE detected in non-gastrointestinal tract samples to 8.9% in the COVID-19 group, as compared to 5.3% in the control group. Molecular analysis confirmed mainly clonal spread of VRE.
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Affiliation(s)
- Kateřina Bogdanová
- Department of Microbiology, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (K.B.); (I.V.); (M.K.)
| | - Lenka Doubravská
- Department of Anesthesiology, Resuscitation and Intensive Care, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (J.P.); (R.U.)
- Correspondence: ; Tel.: +420-588-445-979
| | - Iva Vágnerová
- Department of Microbiology, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (K.B.); (I.V.); (M.K.)
| | - Kristýna Hricová
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 779 00 Olomouc, Czech Republic; (K.H.); (V.P.); (M.R.)
| | - Vendula Pudová
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 779 00 Olomouc, Czech Republic; (K.H.); (V.P.); (M.R.)
| | - Magdaléna Röderová
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 779 00 Olomouc, Czech Republic; (K.H.); (V.P.); (M.R.)
| | - Jan Papajk
- Department of Anesthesiology, Resuscitation and Intensive Care, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (J.P.); (R.U.)
| | - Radovan Uvízl
- Department of Anesthesiology, Resuscitation and Intensive Care, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (J.P.); (R.U.)
| | - Kateřina Langová
- Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 779 00 Olomouc, Czech Republic;
| | - Milan Kolář
- Department of Microbiology, University Hospital Olomouc, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic; (K.B.); (I.V.); (M.K.)
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14
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Baunwall SMD, Dahlerup JF, Engberg JH, Erikstrup C, Helms M, Juel MA, Kjeldsen J, Nielsen HL, Nilsson AC, Rode AA, Vinter-Jensen L, Hvas CL. Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT). Scand J Gastroenterol 2021; 56:1056-1077. [PMID: 34261379 DOI: 10.1080/00365521.2021.1922749] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.
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Affiliation(s)
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Helms
- Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
| | | | - Jens Kjeldsen
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Anne Abildtrup Rode
- Department of Internal Medicine, Zealand University Hospital, Roskilde, Denmark
| | - Lars Vinter-Jensen
- Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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15
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Bao H, Lighter J, Dubrovskaya Y, Merchan C, Siegfried J, Papadopoulos J, Jen SP. Oral Vancomycin as Secondary Prophylaxis for Clostridioides difficile Infection. Pediatrics 2021; 148:peds.2020-031807. [PMID: 34330867 DOI: 10.1542/peds.2020-031807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/05/2021] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES Secondary oral vancomycin prophylaxis (OVP) has been used in adults with a history of Clostridioides difficile infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice has not been studied in pediatric patients. The objective of this study was to assess the utility of secondary OVP in pediatric patients with previous CDI who received subsequent antibiotic exposure. METHODS A multicampus, retrospective cohort evaluation was conducted among patients aged ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter from 2013-2019. Patients who received concomitant OVP with antibiotics were compared with unexposed patients. The primary outcome was CDI recurrence within 8 weeks after antibiotic exposure. Infection with vancomycin-resistant enterococci and risk factors for CDI recurrence were assessed. RESULTS A total of 148 patients were screened, of which 30 and 44 patients received OVP and no OVP, respectively. Patients who received OVP had greater antibiotic use and hospital lengths of stay. The incidence of CDI recurrence within 8 weeks of antibiotic exposure was significantly lower in patients who received OVP (3% vs 25%; P = .02) despite this group having notably more risk factors for recurrence. There were no vancomycin-resistant enterococci infections in any patients within either group. After adjustment in a multivariable analysis, secondary OVP was associated with less risk of recurrence (odds ratio, 0.10; 95% confidence interval, 0.01-0.86; P = .04). CONCLUSIONS Secondary OVP while receiving systemic antibiotics reduces the risk of recurrent CDI in pediatric patients with a history of CDI.
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Affiliation(s)
- Hongkai Bao
- Department of Pharmacy, Montefiore Medical Center, The Bronx, New York
| | | | - Yanina Dubrovskaya
- Medicine, New York University School of Medicine, New York, New York.,Department of Pharmacy, NYU Langone Health, New York, New York
| | | | | | - John Papadopoulos
- Medicine, New York University School of Medicine, New York, New York.,Department of Pharmacy, NYU Langone Health, New York, New York
| | - Shin-Pung Jen
- Department of Pharmacy, Newark Beth Israel Medical Center, Newark, New Jersey
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16
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Šamadan L, Jeličić M, Vince A, Papić N. Nonalcoholic Fatty Liver Disease-A Novel Risk Factor for Recurrent Clostridioides difficile Infection. Antibiotics (Basel) 2021; 10:antibiotics10070780. [PMID: 34198964 PMCID: PMC8300633 DOI: 10.3390/antibiotics10070780] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 12/17/2022] Open
Abstract
Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients ≥ 60 years hospitalized with CDI. The cohort was divided into two groups: those who were and were not readmitted with CDI within 3 months of discharge. Of the 329 patients included, 107 patients (32.5%) experienced rCDI. Patients with rCDI were older, had higher Charlson Age-Comorbidity Index (CACI) and were more frequently hospitalized within 3 months. Except for chronic kidney disease and NAFLD, which were more frequent in the rCDI group, there were no differences in other comorbidities, antibiotic classes used and duration of antimicrobial therapy. Multivariable Cox regression analysis showed that age >75 years, NAFLD, CACI >6, chronic kidney disease, statins and immobility were associated with rCDI. In conclusion, our study identified NAFLD as a possible new host-related risk factor associated with rCDI.
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Affiliation(s)
- Lara Šamadan
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
| | - Mia Jeličić
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Adriana Vince
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Neven Papić
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
- Correspondence:
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17
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Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124-1147. [PMID: 34003176 DOI: 10.14309/ajg.0000000000001278] [Citation(s) in RCA: 296] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 03/25/2021] [Indexed: 02/06/2023]
Abstract
Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.
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Affiliation(s)
- Colleen R Kelly
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kerry LaPlante
- Department of Pharmacy Practice, University of Rhode Island College of Pharmacy, Kingston, Rhode Island, USA
| | - David B Stewart
- Department of Surgery, University of Arizona Health Sciences, Tucson, Arizona, USA
| | - Berkeley N Limketkai
- Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA
| | - Neil H Stollman
- Division of Gastroenterology, Alta Bates Summit Medical Center, East Bay Center for Digestive Health, Oakland, California, USA
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18
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Johnson SW, Brown SV, Priest DH. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clin Infect Dis 2021; 71:1133-1139. [PMID: 31560051 DOI: 10.1093/cid/ciz966] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 09/26/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Limited retrospective data suggest prophylactic oral vancomycin may prevent Clostridioides difficile infection (CDI). We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility-onset CDI (HCFO-CDI) in targeted patients. METHODS We conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina, between October 2018 and April 2019. Included patients were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days postcompletion of systemic antibiotics [OVP]) or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), incidence of vancomycin-resistant Enterococci (VRE) colonization after receiving OVP, adverse effects, and cost of OVP. RESULTS A total of 100 patients were evaluated, 50 patients in each arm. Baseline and hospitalization characteristics were similar, except antibiotic exposure. No events of HCFO-CDI were noted in the OVP group compared with 6 (12%) in the no-prophylaxis group (P = .03). CO-HCFA-CDI was identified in 2 patients who were previously diagnosed with HCFO-CDI. No patients developed new VRE colonization, with only 1 patient reporting mild gastrointestinal side effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $1302, $26.04 per patient. CONCLUSION OVP appears to protect against HCFO-CDI during in-patient stay in targeted patients during systemic antibiotic exposure. Further prospective investigation is warranted.
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Affiliation(s)
- Steven W Johnson
- Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Science, Buies Creek, North Carolina, USA.,Department of Pharmacy, Novant Health Forsyth Medical Center, Winston-Salem, North Carolina, USA
| | - Shannon V Brown
- Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Science, Buies Creek, North Carolina, USA
| | - David H Priest
- Novant Health Institute for Safety and Quality, Winston-Salem, North Carolina, USA.,Novant Health Infectious Disease Specialists, Winston-Salem, North Carolina, USA
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19
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Keats KR, Stitt TM, Chastain DB, Jivan BP, Matznick E, Waller JL, Clemmons AB. Evaluating Clostridioides difficile infection (CDI) treatment duration in hematology/oncology patients receiving concurrent non-CDI antibiotics. J Oncol Pharm Pract 2021; 28:542-550. [PMID: 33663290 DOI: 10.1177/1078155221998735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
PURPOSE To determine the impact of Clostridioides difficile infection (CDI) treatment duration on CDI recurrence in hematology/oncology patients receiving concurrent non-CDI antibiotics. PATIENTS AND METHODS This multi-site, retrospective study examined hematology/oncology patients age ≥18 years hospitalized with active CDI who received ≥1 dose of concurrent non-CDI antibiotics between September 2013 and June 2019. All patients were classified by two definitions for statistical analysis: standard (10-14 days) versus prolonged (>14 days) duration of CDI treatment and non-extended (≤24 hours after stopping non-CDI antibiotics) versus extended (>24 hours after stopping non-CDI antibiotics) CDI treatment. Primary outcome was CDI recurrence within 180 days of completing CDI treatment. Secondary outcomes included hospital length of stay (LOS) as well as mortality and incidence of vancomycin-resistant enterococcus (VRE) infections at 180 days. RESULTS Of the 198 patients included, 112 were classified as prolonged versus 86 standard duration and 138 were classified as extended versus 60 non-extended duration. After accounting for demographic differences, no difference existed in the primary outcome of CDI recurrence in either prolonged versus standard or extended versus non-extended analysis (all p > 0.05). Patients who received prolonged versus standard CDI treatment had longer LOS (p < 0.0001) while no difference existed in extended versus non-extended (p > 0.05). No difference in mortality existed in prolonged versus standard (p > 0.05) while those who received extended versus non-extended CDI treatment had significantly lower mortality (p = 0.0008). CONCLUSIONS Neither prolonging CDI treatment beyond standard duration nor extending duration beyond end of non-CDI antibiotics was associated with decreased CDI recurrence rate.
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Affiliation(s)
- Kelli R Keats
- Department of Pharmacy Services, AU Medical Center, Augusta, GA, USA.,College of Pharmacy, University of Georgia, Augusta, GA, USA
| | - Tia M Stitt
- College of Pharmacy, University of Georgia, Albany, GA, USA
| | | | - Bhaumik P Jivan
- College of Pharmacy, University of Georgia, Augusta, GA, USA
| | - Elizabeth Matznick
- Department of Population Health Sciences, Augusta University, Augusta, GA, USA
| | - Jennifer L Waller
- Department of Population Health Sciences, Augusta University, Augusta, GA, USA
| | - Amber B Clemmons
- Department of Pharmacy Services, AU Medical Center, Augusta, GA, USA.,College of Pharmacy, University of Georgia, Augusta, GA, USA
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20
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Tariq R, Laguio-Vila M, Tahir MW, Orenstein R, Pardi DS, Khanna S. Efficacy of oral vancomycin prophylaxis for prevention of Clostridioides difficile infection: a systematic review and meta-analysis. Therap Adv Gastroenterol 2021; 14:1756284821994046. [PMID: 33747124 PMCID: PMC7905721 DOI: 10.1177/1756284821994046] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/21/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. METHODS A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. RESULTS Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03-1.03; p = 0.06). There was significant heterogeneity with I 2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20-0.59; p < 0.00001). Significant heterogeneity was seen with I 2 = 59%. DISCUSSION Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI.
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Affiliation(s)
- Raseen Tariq
- Divison of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
- Department of Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | | | | | | | - Darrell S. Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Kampouri E, Croxatto A, Prod’hom G, Guery B. Clostridioides difficile Infection, Still a Long Way to Go. J Clin Med 2021; 10:jcm10030389. [PMID: 33498428 PMCID: PMC7864166 DOI: 10.3390/jcm10030389] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/11/2022] Open
Abstract
Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.
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Affiliation(s)
- Eleftheria Kampouri
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
| | - Antony Croxatto
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Guy Prod’hom
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Benoit Guery
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
- Correspondence: ; Tel.: +41-21-314-1643
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22
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Uncovering the Harms of Treating Clostridioides difficile Colonization. mSphere 2021; 6:6/1/e01296-20. [PMID: 33441413 PMCID: PMC7845611 DOI: 10.1128/msphere.01296-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Patients with toxin-negative Clostridioides difficile-positive diarrhea are often treated with oral vancomycin with the assumption that treatment is more beneficial than harmful. However, this hypothesis has never been formally tested, and recent studies suggest that most such patients recover quickly without treatment and can be colonized rather than infected. Patients with toxin-negative Clostridioides difficile-positive diarrhea are often treated with oral vancomycin with the assumption that treatment is more beneficial than harmful. However, this hypothesis has never been formally tested, and recent studies suggest that most such patients recover quickly without treatment and can be colonized rather than infected. Fishbein et al. conducted a prospective, placebo-controlled randomized trial to systematically evaluate the effects, risks, and benefits of oral vancomycin in these patients (S. R. S. Fishbein, T. Hink, K. A. Reske, C. Cass, et al., mSphere 6:e00936-20, 2020, https://doi.org/10.1128/mSphere.00936-20). Although small, the results are intriguing and suggest the adverse antibiotic-induced effects of vancomycin outweigh the clinical benefit when colonization is more likely than disease.
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23
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Adelman MW, Woodworth MH, Shaffer VO, Martin GS, Kraft CS. Critical Care Management of the Patient with Clostridioides difficile. Crit Care Med 2021; 49:127-139. [PMID: 33156122 PMCID: PMC7967892 DOI: 10.1097/ccm.0000000000004739] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients. DATA SOURCES We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles. STUDY SELECTION We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence. DATA EXTRACTION We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review. DATA SYNTHESIS C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk. CONCLUSIONS Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.
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Affiliation(s)
- Max W. Adelman
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Michael H. Woodworth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Virginia O. Shaffer
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Greg S. Martin
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Emory Critical Care Center, Atlanta, GA, USA
| | - Colleen S. Kraft
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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24
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Carlson TJ, Gonzales-Luna AJ. Utilizing antibiotics to prevent Clostridioides difficile infection: does exposure to a risk factor decrease risk? A systematic review. J Antimicrob Chemother 2020; 75:2735-2742. [PMID: 32696044 DOI: 10.1093/jac/dkaa251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/04/2020] [Accepted: 05/11/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Antibiotic use is a major risk factor for Clostridioides difficile infection (CDI). However, antibiotics recommended for CDI treatment are being utilized in clinical practice as prophylactic agents. OBJECTIVES To comprehensively summarize and critically evaluate the published literature investigating the effectiveness of antibiotic CDI prophylaxis. METHODS A systematic search for relevant literature was conducted in PubMed and ClinicalTrials.gov. Two investigators independently screened each article for inclusion, and the references of the included articles were studied to identify additional relevant articles. Data extraction and an assessment of risk of bias was completed for all included studies. Unadjusted risk ratios and 95% CI were calculated for each study, with CDI being the outcome variable and prophylaxis (prophylaxis versus control) representing the exposure. RESULTS In total, 13 articles were identified in PubMed and 9 ongoing or unpublished trials were identified in ClinicalTrials.gov. The effect of antibiotic prophylaxis on CDI rates varied between studies; however, most favoured the use of antibiotic prophylaxis. CONCLUSIONS The authors of this review conclude that the current literature carries a high risk of bias and the results should be interpreted with caution.
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Affiliation(s)
- Travis J Carlson
- Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, One University Parkway, High Point, NC 27268, USA
| | - Anne J Gonzales-Luna
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA
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25
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Austin K, Sweet M, Likar E, LaSala PR, Murray A, Wen S, Ross KG, Kanate AS, Veltri L, Matuga R, Cumpston A. Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients. Transpl Infect Dis 2020; 22:e13438. [PMID: 32767807 DOI: 10.1111/tid.13438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 07/29/2020] [Accepted: 07/30/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridium difficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population. METHODS The primary objectives of this study were to identify the rate of C difficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient. RESULTS Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of C difficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles. CONCLUSIONS Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.
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Affiliation(s)
- Kristin Austin
- Department of Pharmacy, West Virginia University Medicine, Morgantown, WV, USA
| | - Michael Sweet
- Center for Quality Outcomes, West Virginia University Medicine, Morgantown, WV, USA
| | - Eric Likar
- Department of Pharmacy, West Virginia University Medicine, Morgantown, WV, USA
| | - P Rocco LaSala
- Department of Pathology, West Virginia University Medicine, Morgantown, WV, USA
| | - Amanda Murray
- Department of Microbiology, West Virginia University Medicine, Morgantown, WV, USA
| | - Sijin Wen
- Department of Biostatistics, West Virginia University, Morgantown, WV, USA
| | - Kelly G Ross
- Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
| | - Abraham S Kanate
- Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
| | - Lauren Veltri
- Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
| | - Rebekah Matuga
- Department of Pharmacy, West Virginia University Medicine, Morgantown, WV, USA
| | - Aaron Cumpston
- Department of Pharmacy, West Virginia University Medicine, Morgantown, WV, USA.,Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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26
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Mateu L, Fernández-Rivas G, Sopena N. Diagnosis and treatment of Clostridioides difficile infection. Med Clin (Barc) 2020; 155:30-35. [PMID: 32430207 DOI: 10.1016/j.medcli.2020.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 02/21/2020] [Accepted: 02/24/2020] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile is the main cause of healthcare-associated diarrhoea in adults. The incidence of C.difficile infection (CDI) has increased in recent years. The risk of recurrence of CDI is 15%-25% in a first episode and this risk is increased in subsequent episodes. Toxigenic culture and cytotoxicity tests are the reference techniques for the microbiological diagnosis of CDI. These are laborious and slow techniques and therefore they have been replaced in clinical practice by the application of a multi-step algorithm that includes the detection of glutamate dehydrogenase (GDH), toxins and molecular techniques. The treatment of choice for CDI is Vancomycin. In recent years, new drugs and new treatment strategies have appeared that are especially useful in the treatment of relapses of CDI.
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Affiliation(s)
- Lourdes Mateu
- Servicio de Enfermedades Infecciosas, Hospital Universitari Germans Trias i Pujol. Departamento de Medicina, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol. CIBER de Enfermedades Respiratorias, Badalona, Barcelona, España.
| | - Gema Fernández-Rivas
- Servicio de Microbiología, Laboratorio Clínico de la Metropolitana Norte, Hospital Universitari Germans Trias i Pujol. Departamento de Genética y Microbiología, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol, Badalona, Barcelona, España
| | - Nieves Sopena
- Servicio de Enfermedades Infecciosas, Hospital Universitari Germans Trias i Pujol. Departamento de Medicina, Universitat Autònoma de Barcelona. Institut de Recerca Germans Trias i Pujol. CIBER de Enfermedades Respiratorias, Badalona, Barcelona, España
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27
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Oral vancomycin prophylaxis for the prevention of Clostridium difficile infection: A systematic review and meta-analysis. Infect Control Hosp Epidemiol 2020; 41:1302-1309. [PMID: 32594929 DOI: 10.1017/ice.2020.277] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Recently, oral vancomycin prophylaxis (OVP) has been suggested for the prevention of Clostridium difficile infection (CDI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of this approach. DESIGN Systematic review and meta-analysis. METHODS We conducted a computerized search of MEDLINE, EMBASE, and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for eligibility. Relevant data were extracted and analyzed. Publication bias was assessed using the Egger test. RESULTS Ultimately, 8 retrospective studies and 1 prospective study examining 2174 patients, published between 2016 and 2019 were included in the review. OVP was associated with decreased CDI (odds ratio, 0.263; 95% confidence interval, 0.13-0.52) with considerable heterogeneity (I2 = 61%). Meta-regression showed that total daily dose of OVP correlated with CDI, explaining 100% of heterogeneity between studies. Furthermore, 3 studies evaluated the risk of vancomycin-resistant enterococci (VRE) infection after OVP and found no significant increase. CONCLUSION Our results suggest that OVP might decrease CDI rates in at-risk populations, although this conclusion should be interpreted with caution. Higher daily doses of OVP might increase CDI. Although the use of OVP in high-risk patients may reduce CDI, this suggestion has yet to be validated by prospective blinded randomized controlled trials.
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28
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Oral vancomycin prophylaxis against recurrent Clostridioides difficile infection: Efficacy and side effects in two hospitals. Infect Control Hosp Epidemiol 2020; 41:908-913. [PMID: 32539877 DOI: 10.1017/ice.2020.176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The data regarding the effectiveness of chemical prophylaxis against recurrent C. difficile infection (CDI) remain conflicting. DESIGN Retrospective cohort study on the effectiveness of oral vancomycin for prevention of recurrent CDI. SETTING Two academic centers in New York. METHODS Two participating hospitals implemented an automated alert recommending oral vancomycin 125 mg twice daily in patients with CDI history scheduled to receive systemic antimicrobials. Measured outcomes included breakthrough and recurrent CDI rates, defined as CDI during and 1 month after initiation of prophylaxis, respectively. A self-controlled, before-and-after study design was employed to examine the effect of vancomycin prophylaxis on the prevalence of vancomycin-resistant Enterococcus spp (VRE) colonization and infection. RESULTS We included 264 patients in the analysis. Breakthrough CDI was identified in 17 patients (6.4%; 95% confidence interval [CI], 3.8%-10.1%) and recurrent in 22 patients (8.3%; 95% CI, 5.3%-12.3%). Among the 102 patients with a history of CDI within the 3 months preceding prophylaxis, 4 patients (3.9%; 95% CIs, 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.8%; 95% CIs, 4.1%-16.1%). In the 3-month period following vancomycin prophylaxis, we detected a statistically significant increase in both the absolute number of VRE (χ2, 0.003) and the ratio of VRE to VSE isolates (χ2, 0.003) compared to the combined period of 1.5 months preceding and the 3-4.5 months following prophylaxis. This effect persisted 6 months following prophylaxis. CONCLUSIONS Prophylactic vancomycin is an effective strategy to prevent CDI recurrence, but it increases the risk of VRE colonization. Thus, a careful selection of patients with high benefit-to-risk ratio is needed for the implementation of this preventive policy.
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29
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Connor KA, Conn KM. Analysis of the impact of secondary prophylaxis on Clostridioides difficile recurrence in critically ill adults. SAGE Open Med 2020; 8:2050312120930898. [PMID: 32587690 PMCID: PMC7294487 DOI: 10.1177/2050312120930898] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/11/2020] [Indexed: 12/02/2022] Open
Abstract
Introduction: Clostridioides (formerly Clostridium) difficile infection recurrence in patients re-exposed to antibiotics for treatment of a non-Clostridioides difficile infection is high at approximately 33%. Low-dose per os vancomycin (e.g. 125 mg q12 h) or metronidazole (e.g. 500 mg intravenous/per osq8 h) may help prevent recurrences, but study of secondary prophylaxis in critically ill patients is needed. Objectives: To determine whether critically ill adults receiving low-dose per os vancomycin for secondary Clostridioides difficile infection prophylaxis have fewer recurrences of Clostridioides difficile infection in 90 days compared with patients receiving metronidazole for secondary Clostridioides difficile infection prophylaxis or control (no secondary prophylaxis). Methods: This was a retrospective, two-center, observational study in a large academic medical center and affiliated community hospital. Included patients had a history of Clostridioides difficile infection within 1 year of receiving antibiotics for clinical care. We compared patients receiving secondary prophylaxis with vancomycin or metronidazole and control patients; in addition, an unplanned fourth group (vancomycin/metronidazole combination) was identified and analyzed. The primary outcome was Clostridioides difficile infection recurrence within 90 days of a course of broad-spectrum antibiotic therapy. Fisher’s exact, analysis of variance, and Kruskal–Wallis tests were used to compare Clostridioides difficile infection recurrence with prophylaxis group and additional contributing factors. Results: Eighty-two patients were included: 38 control (46.3%), 20 metronidazole (24.4%), 17 vancomycin (20.7%), and 7 combination (8.5%). Ten of 82 patients (12.2%) had at least one Clostridioides difficile infection recurrence; 8/38 patients in the control group (21.1%), 1/7 patients in the combination group (14.3%), 1/17 patients in the per os vancomycin group (5.9%), and 0/20 in the metronidazole group (0%; p = 0.073). As a post hoc secondary analysis, the three prophylaxis groups were coalesced into one group and compared with control (4.5% vs 21%; p = 0.039). Additional factors (e.g. age, obesity, immunosuppression, acid suppression) were not significantly associated with Clostridioides difficile infection recurrence or with prophylaxis group. Conclusion: There was no difference in Clostridioides difficile infection recurrence between prophylaxis groups, however, given the low recurrence rate, prospective evaluation with a larger sample of critically ill patients is necessary.
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Affiliation(s)
- Kathryn A Connor
- Department of Pharmacy Practice and Administration, Wegmans School of Pharmacy, St. John Fisher College, Rochester, NY, USA
| | - Kelly M Conn
- Department of Pharmacy Practice and Administration, Wegmans School of Pharmacy, St. John Fisher College, Rochester, NY, USA
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30
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Cho JM, Pardi DS, Khanna S. Update on Treatment of Clostridioides difficile Infection. Mayo Clin Proc 2020; 95:758-769. [PMID: 32247350 DOI: 10.1016/j.mayocp.2019.08.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 07/30/2019] [Accepted: 08/12/2019] [Indexed: 02/06/2023]
Abstract
Clostridioides difficile infection (CDI) is the leading cause of health care-associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.
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Affiliation(s)
- Janice M Cho
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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31
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Webb BJ, Brunner A, Lewis J, Ford CD, Lopansri BK. Repurposing an Old Drug for a New Epidemic: Ursodeoxycholic Acid to Prevent Recurrent Clostridioides difficile Infection. Clin Infect Dis 2020; 68:498-500. [PMID: 30020421 DOI: 10.1093/cid/ciy568] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 07/09/2018] [Indexed: 01/11/2023] Open
Abstract
Recurrent Clostridioides difficile infection (rCDI) may be mediated in part by secondary bile acids. Here we report salvage therapy with ursodeoxycholic acid (UDCA) to prevent rCDI in 16 high-risk patients. Patients on UDCA had a low observed recurrence rate (12.5%). Controlled trials are needed to confirm these observations.
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Affiliation(s)
- Brandon J Webb
- Intermountain Healthcare, Division of Epidemiology and Infectious Diseases, Salt Lake City, Utah.,Stanford University, Division of Infectious Diseases and Geographic Medicine, Palo Alto, California
| | - Ali Brunner
- Intermountain Acute Leukemia/Blood and Marrow Transplant Program, LDS Hospital
| | - Julia Lewis
- University of Utah, Division of Infectious Diseases, Salt Lake City
| | - Clyde D Ford
- Intermountain Acute Leukemia/Blood and Marrow Transplant Program, LDS Hospital
| | - Bert K Lopansri
- Intermountain Healthcare, Division of Epidemiology and Infectious Diseases, Salt Lake City, Utah.,University of Utah, Division of Infectious Diseases, Salt Lake City
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32
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Rajasingham R, Enns EA, Khoruts A, Vaughn BP. Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines. Clin Infect Dis 2020; 70:754-762. [PMID: 31001619 PMCID: PMC7319265 DOI: 10.1093/cid/ciz318] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 04/12/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective. METHODS We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy. CONCLUSIONS Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.
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Affiliation(s)
- Radha Rajasingham
- Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota
| | - Eva A Enns
- Division of Health Policy and Management, University of Minnesota School of Public Health
| | - Alexander Khoruts
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis
| | - Byron P Vaughn
- Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis
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33
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Kumar V, Fischer M. Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Expert Opin Biol Ther 2020; 20:73-81. [PMID: 31690143 DOI: 10.1080/14712598.2020.1689952] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.
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Affiliation(s)
- Vinod Kumar
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Monika Fischer
- Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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Martin JSH, Eyre DW, Fawley WN, Griffiths D, Davies K, Mawer DPC, Peto TEA, Crook DW, Walker AS, Wilcox MH. Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes. Clin Infect Dis 2019; 67:1379-1387. [PMID: 29659753 PMCID: PMC6186849 DOI: 10.1093/cid/ciy302] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 05/23/2018] [Indexed: 01/05/2023] Open
Abstract
Background No study has used whole-genome sequencing (WGS) to investigate risk factors for Clostridium difficile (CD) transmission between cases, or assessed the impact of recent acquisition on patient outcome. Methods This 20 month retrospective cohort study included consecutive cytotoxin-positive diarrheal samples, which underwent culture, ribotyping, and WGS (Illumina). Sequenced isolates were compared using single nucleotide variants (SNVs). Independent predictors of acquisition from another case, onward transmission, 120-day recurrence, and 30-day mortality were identified using logistic regression with backwards elimination. Results Of 660 CD cases, 640 (97%) were sequenced, of which 567 (89%) shared a ribotype with a prior case, but only 227 (35%) were ≤2 SNVs from a prior case, supporting recent acquisition. Plausible (<2 SNVs) recent ward-based acquisition from a symptomatic case was more frequent in certain ribotypes; 64% (67/105) for ribotype-027 cases, compared with 11% (6/57) for ribotype-078. Independent risk factors (adjusted P < .05) for CD acquisition included older age, longer inpatient duration, and ribotype; these factors, and male sex, increased onward transmission. Patients with a plausible donor had a greater risk of recurrence (adjusted P = .001) and trended towards greater 30-day mortality (adjusted P = .06). Ribotype had no additional mortality or recurrence impact after adjusting for acquisition (P > .1). Conclusions Greater transmission of certain lineages suggests CD may have different reservoirs and modes of transmission. Acquiring CD from a recent case is associated with poorer clinical outcomes. Clinical characteristics associated with increased healthcare-associated CD transmission could be used to target preventative interventions.
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Affiliation(s)
| | - David W Eyre
- Nuffield Department of Medicine, United Kingdom.,NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom
| | - Warren N Fawley
- Public Health England-Leeds Regional Laboratory, United Kingdom
| | - David Griffiths
- Nuffield Department of Medicine, United Kingdom.,NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom
| | - Kerrie Davies
- Leeds Teaching Hospitals & University of Leeds, United Kingdom
| | | | - Timothy E A Peto
- Nuffield Department of Medicine, United Kingdom.,NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom
| | - Derrick W Crook
- Nuffield Department of Medicine, United Kingdom.,NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.,Public Health England, Colindale, United Kingdom
| | - A Sarah Walker
- Nuffield Department of Medicine, United Kingdom.,NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom
| | - Mark H Wilcox
- Leeds Teaching Hospitals & University of Leeds, United Kingdom
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Mendo-Lopez R, Villafuerte-Gálvez J, White N, Mahoney MV, Kelly CP, Alonso CD. Recent developments in the management of recurrent Clostridioides difficile infection. Anaerobe 2019; 62:102108. [PMID: 31606481 DOI: 10.1016/j.anaerobe.2019.102108] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 09/23/2019] [Accepted: 10/08/2019] [Indexed: 12/19/2022]
Abstract
Clostridioides (formerly Clostridium) difficile is responsible for a substantial burden of nosocomial infection. Recurrent C. difficile infection (rCDI) remains a concern due to its high morbidity, mortality, and cost. Despite the updated 2017 IDSA C. difficile treatment guidelines, there remains a lack of well-studied preventive control measures and treatment modalities for rCDI. There are ongoing efforts to develop novel therapies, such as new antibiotics with a lesser impact on gut microbiota and more targeted therapies, such as bacteriotherapy. This mini review highlights key rCDI management updates, preventive measures and ongoing research on novel treatment strategies including bacteriotherapy.
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Affiliation(s)
- Rafael Mendo-Lopez
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Javier Villafuerte-Gálvez
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Nicole White
- Department of Medicine, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Monica V Mahoney
- Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Ciaran P Kelly
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Carolyn D Alonso
- Department of Medicine, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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Does oral vancomycin prophylaxis during systemic antibiotic exposure prevent Clostridioides difficile infection relapses? Still in search of an answer. Infect Control Hosp Epidemiol 2019; 40:1084-1086. [DOI: 10.1017/ice.2019.192] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Mullane KM, Dubberke ER. Management of Clostridioides (formerly Clostridium) difficile infection (CDI) in solid organ transplant recipients: Guidelines from the American Society of Transplantation Community of Practice. Clin Transplant 2019; 33:e13564. [PMID: 31002420 DOI: 10.1111/ctr.13564] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 04/09/2019] [Indexed: 02/06/2023]
Abstract
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice address the prevention and management of Clostridium difficile infection in solid organ transplant (SOT) recipients. Clostridioides (formerly Clostridium) difficile infection (CDI) is among the most common hospital acquired infections. In SOT recipients, the incidence of CDI varies by type and number or organs transplanted. While a meta-analysis of published literature found the prevalence of postoperative CDI in the general surgical population to be approximately 0.51%, the prevalence of CDI that is seen in the solid organ transplant population ranges from a low of 3.2% in the pancreatic transplant population to 12.7% in those receiving multiple organ transplants. There are no randomized, controlled trials evaluating the management of CDI in the SOT population. Herein is a review and summary of the currently available literature that has been synthesized into updated treatment guidelines for the management of CDI in the SOT population.
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Affiliation(s)
- Kathleen M Mullane
- Department of Medicine, Section of Infectious Diseases & Global Health, University of Chicago, Chicago, Illinois
| | - Erik R Dubberke
- Department of Medicine, Division of Infectious Diseases, School of Medicine, Washington University, St. Louis, Missouri
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Affiliation(s)
- Ana M Alvarez
- Pediatric Infectious Diseases and Immunology, University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES), 910 North Jefferson Street, Jacksonville, FL 32209, USA; Wolfson Children's Hospital, 800 Prudential Drive, Jacksonville, FL 32207, USA
| | - Mobeen H Rathore
- Pediatric Infectious Diseases and Immunology, University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES), 910 North Jefferson Street, Jacksonville, FL 32209, USA; Wolfson Children's Hospital, 800 Prudential Drive, Jacksonville, FL 32207, USA.
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Morrisette T, Van Matre AG, Miller MA, Mueller SW, Bajrovic V, Abidi MZ, Benamu E, Kaiser JN, Barber GR, Chase S, Tobin J, Fish DN, Gutman JA. Oral Vancomycin Prophylaxis as Secondary Prevention Against Clostridioides difficile Infection in the Hematopoietic Stem Cell Transplantation and Hematologic Malignancy Population. Biol Blood Marrow Transplant 2019; 25:2091-2097. [PMID: 31255741 DOI: 10.1016/j.bbmt.2019.06.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/27/2019] [Accepted: 06/24/2019] [Indexed: 01/02/2023]
Abstract
Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI.
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Affiliation(s)
- Taylor Morrisette
- Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado; Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado
| | - Amanda G Van Matre
- Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
| | - Matthew A Miller
- Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado
| | - Scott W Mueller
- Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
| | - Valida Bajrovic
- Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado
| | - Maheen Z Abidi
- Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado
| | - Esther Benamu
- Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado
| | - Jeffrey N Kaiser
- Department of Pharmacy-Blood Cancer and Bone Marrow Transplant, University of Colorado Hospital, Aurora, Colorado
| | - Gerard R Barber
- Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado
| | - Stephanie Chase
- Department of Pharmacy-Blood Cancer and Bone Marrow Transplant, University of Colorado Hospital, Aurora, Colorado
| | - Jennifer Tobin
- Department of Pharmacy-Blood Cancer and Bone Marrow Transplant, University of Colorado Hospital, Aurora, Colorado
| | - Douglas N Fish
- Department of Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
| | - Jonathan A Gutman
- Department of Blood Cancer and Bone Marrow Transplant, University of Colorado School of Medicine, Aurora, Colorado.
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Singh T, Bedi P, Bumrah K, Singh J, Rai M, Seelam S. Updates in Treatment of Recurrent Clostridium difficile Infection. J Clin Med Res 2019; 11:465-471. [PMID: 31236163 PMCID: PMC6575119 DOI: 10.14740/jocmr3854] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/31/2019] [Indexed: 12/18/2022] Open
Abstract
Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.
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Affiliation(s)
- Tanveer Singh
- Department of Hospital Medicine, Rochester General Hospital, Rochester, NY 14621, USA
| | - Prabhjot Bedi
- Department of Medicine, UPMC East, Monroeville, PA 15146, USA
| | | | - Jeevandeep Singh
- Department of Medicine, Montefiore Medical Center-Wakefield, Bronx, NY 10466, USA
| | - Manoj Rai
- Department of Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Susmitha Seelam
- Department of Medicine, UPMC East, Monroeville, PA 15146, USA
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Ganetsky A, Han JH, Hughes ME, Babushok DV, Frey NV, Gill SI, Hexner EO, Loren AW, Luger SM, Mangan JK, Martin ME, Smith J, Freyer CW, Gilmar C, Schuster M, Stadtmauer EA, Porter DL. Oral Vancomycin Prophylaxis Is Highly Effective in Preventing Clostridium difficile Infection in Allogeneic Hematopoietic Cell Transplant Recipients. Clin Infect Dis 2019; 68:2003-2009. [PMID: 30256954 PMCID: PMC6541731 DOI: 10.1093/cid/ciy822] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 09/20/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a leading cause of infectious complications in allogeneic hematopoietic cell transplant recipients (alloHCT). We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. METHODS We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin, as compared to no prophylaxis, in 145 consecutive adult alloHCT recipients at the University of Pennsylvania between April 2015 and November 2016. Patients received oral vancomycin 125 mg twice daily, starting on admission and continuing until discharge. The primary outcome of interest was the association between oral vancomycin prophylaxis and CDI diagnosis. Secondary outcomes included graft-versus-host disease (GVHD) and relapse. RESULTS There were no cases of CDI in patients that received prophylaxis (0/90, 0%), whereas 11/55 (20%) patients who did not receive prophylaxis developed CDI (P < .001). Oral vancomycin prophylaxis was not associated with a higher risk of acute, grades 2-4 GVHD (subhazard ratio [sHR] 1.59; 95% confidence interval [CI] 0.88-2.89; P = .12), acute, grades 3-4 GVHD (sHR 0.65; 95% CI 0.25-1.66; P = .36), or acute, grades 2-4 gastrointestinal GVHD (sHR 1.95; 95% CI 0.93-4.07; P = .08) at day 180 post-transplant. No associations between oral vancomycin and relapse or survival were observed. CONCLUSIONS Prophylaxis with oral vancomycin is highly effective in preventing CDI in alloHCT recipients without increasing the risk of graft-versus-host disease or disease relapse. Further evaluation via a prospective study is warranted.
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Affiliation(s)
- Alex Ganetsky
- Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia
| | - Jennifer H Han
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
- Department of Healthcare Epidemiology, Infection Prevention and Control, Hospital of the University of Pennsylvania, Philadelphia
| | - Mitchell E Hughes
- Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia
| | - Daria V Babushok
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Noelle V Frey
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Saar I Gill
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Elizabeth O Hexner
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Alison W Loren
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Selina M Luger
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - James K Mangan
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Mary Ellen Martin
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Jacqueline Smith
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Craig W Freyer
- Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia
| | - Cheryl Gilmar
- Department of Healthcare Epidemiology, Infection Prevention and Control, Hospital of the University of Pennsylvania, Philadelphia
| | - Mindy Schuster
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Edward A Stadtmauer
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - David L Porter
- Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
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Song JH, Kim YS. Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut Liver 2019; 13:16-24. [PMID: 30400734 PMCID: PMC6346998 DOI: 10.5009/gnl18071] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/12/2018] [Accepted: 03/22/2018] [Indexed: 12/15/2022] Open
Abstract
The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.
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Affiliation(s)
- Jung Hoon Song
- Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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Saha S, Khanna S. Management of Clostridioides difficile colitis: insights for the gastroenterologist. Therap Adv Gastroenterol 2019; 12:1756284819847651. [PMID: 31105766 PMCID: PMC6505238 DOI: 10.1177/1756284819847651] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 04/10/2019] [Indexed: 02/04/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.
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Affiliation(s)
- Srishti Saha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
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Oral vancomycin prophylaxis during systemic antibiotic exposure to preventClostridiodes difficileinfection relapses. Infect Control Hosp Epidemiol 2019; 40:662-667. [DOI: 10.1017/ice.2019.88] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AbstractObjective:To determine whether oral vancomycin prophylaxis accompanying systemic antibiotics reduces the risk of relapse in patients with history ofClostridioides difficileinfection (CDI).Design:Retrospective cohort study.Patients:Adult inpatients with a history of CDI who received systemic antibiotics in either of 2 hospitals between January 2009 and June 2015.Methods:We compared relapse rates in patients who started oral vancomycin concurrently with systemic antibiotics (exposed group) versus those who did not. We assessed for CDI relapse by toxin or nucleic acid testing at 90 days. We used inverse probability weighting and machine learning to adjust for confounders, to estimate propensity for treatment, and to calculate odds ratios for CDI relapse. We performed secondary analyses limited to toxin-positive relapses, patients with 1 versus >1 prior CDI episodes, and patients who received oral vancomycin on each antibiotic day.Results:CDI relapse occurred within 90 days in 19 of 193 exposed patients (9.8%) versus 53 of 567 unexposed patients (9.4%; unadjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.60–1.81; adjusted OR, 0.63; 95% CI, 0.35–1.14). CDI relapses at 90 days were less frequent in exposed patients with only 1 prior episode of CDI (OR, 0.42; 95% CI, 0.19–0.93) but not in those with >1 prior episode (OR, 1.19; 95% CI, 0.42–3.33). Our findings were consistent with a lack of benefit of oral vancomycin when restricting results to toxin-positive relapses and to patients who received vancomycin each antibiotic day.Conclusions:Prophylactic oral vancomycin was not consistently associated with reduced risk of CDI relapse among hospitalized patients receiving systemic antibiotics. However, patients with only 1 prior CDI episode may benefit.
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Tilton CS, Johnson SW. Development of a risk prediction model for hospital-onset Clostridium difficile infection in patients receiving systemic antibiotics. Am J Infect Control 2019; 47:280-284. [PMID: 30318399 DOI: 10.1016/j.ajic.2018.08.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 08/16/2018] [Accepted: 08/17/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is recognized as a significant challenge in health care. Identification of high-risk individuals is essential for the development of CDI prevention strategies. The objective of this study was to develop an easily implementable risk prediction model for hospital-onset CDI in patients receiving systemic antimicrobials. METHODS This retrospective, case-control, multicenter study included adult patients admitted to Novant Health Forsyth Medical Center and Novant Health Presbyterian Medical Center from July 1, 2015, to July 1, 2017, who received systemic antibiotics. Cases were subjects with hospital-onset CDI; controls were subjects without a CDI diagnosis. Cases were matched 1:1 with controls by admitted medical unit type. Variables significantly associated with CDI were incorporated into a multivariate analysis. A logistic regression model was used to formulate a point-based risk prediction model. Positive predictive value, negative predictive value, sensitivity, specificity, and accuracy were determined at various point cutoffs of the model. A receiver operating characteristic-area under the curve was created to assess the discrimination of the model. RESULTS A total of 200 subjects (100 cases and 100 controls) were included. Most patients were Caucasian and female. Risk factors for CDI identified and incorporated into the model included age ≥70 years (adjusted odds ratio, 1.89; 95% confidence interval 1.05-3.43; P = .0326) and recent hospitalization in the past 90 days (adjusted odds ratio, 3.55; 95% confidence interval 1.90-6.83; P < .0001). Sensitivity and specificity were 76% and 49%, respectively, for scores ≥2 and 20% and 93%, respectively, for a score of 6. Diagnostic performance of various score cutoffs for the model indicated that a score ≥2 was associated with the highest accuracy (63%). The receiver operating characteristic-area under the curve was 0.7. DISCUSSION We developed a simple-to-implement hospital-onset CDI risk model that included only independent risks that can be obtained immediately on presentation to the health care facility. Despite this, the model had fair discriminatory power. Similar risk factors were found in previously developed models; however, the utility of these models is limited owing to the difficulty of assessing other included risk factors and the inclusion of risk factors that cannot be evaluated until the patient is discharged from the health care facility. CONCLUSIONS Identification of hospitalized patients who are receiving systemic antibiotics, are ≥70 years old, and were recently admitted to the hospital in the past 90 days may allow for an easily implementable hospital-onset CDI risk prevention strategy.
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Affiliation(s)
- Carrie S Tilton
- Department of Pharmacy, Novant Health Forsyth Medical Center, Winston-Salem, NC
| | - Steven W Johnson
- Department of Pharmacy, Novant Health Forsyth Medical Center, Winston-Salem, NC; Department of Pharmacy Practice, Campbell University College of Pharmacy & Health Sciences, Buies Creek, NC.
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Knight EM, Schiller DS, Fulman MK, Rastogi R. Long-Term Efficacy of Oral Vancomycin Prophylaxis for the Prevention of Clostridium difficile Recurrence. J Pharm Pract 2019; 33:633-639. [PMID: 30744479 DOI: 10.1177/0897190019825994] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Limited evidence suggests that prophylactic oral vancomycin may be beneficial in preventing Clostridium difficile infection (CDI) recurrence, but long-term efficacy is unknown. OBJECTIVE To evaluate the long-term efficacy of oral vancomycin prophylaxis (OVP) in preventing CDI recurrence in subjects who require subsequent antibiotic exposure. METHODS A retrospective cohort study was conducted at a community hospital. A total of 91 subjects with a history of CDI between January 2013 and December 2015 who had a subsequent hospitalization requiring systemic antibiotics within 12 months were evaluated. Thirty-two subjects who received prophylaxis with oral vancomycin were compared to 59 subjects who did not receive prophylaxis. RESULTS CDI recurrence within 12 months was significantly lower in subjects receiving OVP compared to those who did not receive OVP (6.3% vs 28.8%; odds ratio [OR]: 0.16; 95% confidence interval [CI]: 0.04-0.77; P = .011) including patients whose previous CDI was an initial episode (3.7% [1/27] vs 28.3% [15/53]; OR: 10.3; 95% CI: 1.28-82.6; P = .009). CONCLUSION Use of OVP in subjects with a history of CDI up to 12 months prior to subsequent antibiotic exposure appears to reduce the risk of CDI recurrence for up to 12 months.
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Affiliation(s)
- Emmanuel M Knight
- Department of Pharmacy Services, Montefiore Nyack Hospital, Nyack, NY, USA
| | - Daryl S Schiller
- Department of Pharmacy Services, Montefiore Nyack Hospital, Nyack, NY, USA
| | - Magda K Fulman
- Department of Pharmacy Services, Montefiore Nyack Hospital, Nyack, NY, USA
| | - Rupangi Rastogi
- Department of Pharmacy Services, Montefiore Nyack Hospital, Nyack, NY, USA
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Zhang K, Beckett P, Abouanaser S, Stankus V, Lee C, Smieja M. Prolonged oral vancomycin for secondary prophylaxis of relapsing Clostridium difficile infection. BMC Infect Dis 2019; 19:51. [PMID: 30642269 PMCID: PMC6332588 DOI: 10.1186/s12879-019-3676-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 01/02/2019] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) is an important cause of diarrhea and continues to be a major burden within healthcare institutions and in the community. For a small subset of patients with frequently relapsing CDI who do not have access to fecal microbiota transplantation (FMT), or fail FMT, there are no clear treatment recommendations. We review our experience with prolonged oral vancomycin for secondary prophylaxis of relapsing CDI. METHODS We performed a retrospective chart review of cases from the C. difficile consultation service at our institution since 2013. The service had three primary physicians providing consultations and performing over 1000 FMTs over the five-year period. Patients with relapsing CDI who were not candidates for FMT, refused, or relapsed after FMT were treated with vancomycin, followed by long-term oral vancomycin at a dose of 125 mg once daily. RESULTS Twenty patients received at least 8 weeks of once-daily oral vancomycin for prophylaxis of relapsing CDI. Patients had a median age of 80 years, and experienced a median of four episodes of CDI prior to long-term vancomycin. Most were female and 75% had received FMT. Only a single case of C. difficile relapse occurred while on long-term vancomycin during 200 patient-months of follow-up. Amongst those who stopped long-term vancomycin, 31% relapsed within 6 weeks. No adverse events were observed. CONCLUSIONS For elderly patients with frequently relapsing C. difficile, prolonged vancomycin once daily at a dose of 125 mg orally was effective in preventing further relapse. Vancomycin secondary prophylaxis may be considered in patients who have failed FMT, or in cases where FMT is not available.
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Affiliation(s)
- Kevin Zhang
- Bachelor of Health Sciences Program, McMaster University, Hamilton, ON, Canada
| | - Patricia Beckett
- St. Joseph's Healthcare Hamilton, L424-St., 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada
| | - Salaheddin Abouanaser
- St. Joseph's Healthcare Hamilton, L424-St., 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada
| | - Vida Stankus
- St. Joseph's Healthcare Hamilton, L424-St., 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada
| | - Christine Lee
- St. Joseph's Healthcare Hamilton, L424-St., 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.,Royal Jubilee Hospital, Victoria, BC, Canada
| | - Marek Smieja
- St. Joseph's Healthcare Hamilton, L424-St., 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada. .,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. .,Michael G. DeGroote Institute of Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
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Orenstein R, Patron RL. Clostridioides difficile therapeutics: guidelines and beyond. Ther Adv Infect Dis 2019; 6:2049936119868548. [PMID: 31448117 PMCID: PMC6693025 DOI: 10.1177/2049936119868548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 07/17/2019] [Indexed: 12/21/2022] Open
Abstract
Clostridioides difficile infection (CDI) has become an increasingly common infection both within and outside of the hospital setting. The management of this infection has been evolving as we learn more about the role of the human microbiota in protecting us from this gastrointestinal opportunist. For many years the focus of treatment had been on eradication of the vegetative, toxin-producing form of the organism, with little regard for its collateral impact on the host's microbiota or risk of recurrence. With the marked increase in C. difficile disease, and, particularly, recurrent disease in the last decade, new guidelines are more focused on targeting and reducing collateral damage to the colonic microbiota. Immune-based strategies that manipulate the microbiota and provide a humoral response to toxins have now become mainstream. Newer strategies are needed to look beyond simply resolving the primary episode but are focused on delayed outcomes such as cure at 90 days, reduced morbidity and mortality, and patient quality of life. The purpose of this review is to familiarize readers with the most recent evidence-based guidelines for C. difficile management, and to describe the role of newer antimicrobials, immunological-, and microbiota-based therapeutics to prevent recurrence and improve the outcomes of people with CDI.
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Affiliation(s)
- Robert Orenstein
- Division of Infectious Diseases, Mayo Clinic
Arizona, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA
| | - Roberto L. Patron
- Division of Infectious Diseases, Mayo Clinic
Arizona, Phoenix, AZ, USA
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Krajicek E, Fischer M, Allegretti JR, Kelly CR. Nuts and Bolts of Fecal Microbiota Transplantation. Clin Gastroenterol Hepatol 2019; 17:345-352. [PMID: 30268564 DOI: 10.1016/j.cgh.2018.09.029] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 09/14/2018] [Accepted: 09/19/2018] [Indexed: 02/07/2023]
Abstract
Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT.
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Affiliation(s)
- Edward Krajicek
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Colleen R Kelly
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, Rhode Island.
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