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L'Huillier JC, Guo WA. The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know. J Trauma Acute Care Surg 2025; 98:357-367. [PMID: 39509684 DOI: 10.1097/ta.0000000000004474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
ABSTRACT The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.
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Affiliation(s)
- Joseph C L'Huillier
- From the Department of Surgery (J.C.L., W.A.G.), Jacobs School of Medicine and Biomedical Sciences, and Division of Health Services Policy and Practice, Department of Epidemiology and Environmental Health (J.C.L.), School of Public Health and Health Professions, University at Buffalo; and Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery (J.C.L., W.A.G.), Erie County Medical Center, Buffalo, New York
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Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffrè M, Pipitone G, Luzzati R. Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options. Clin Microbiol Rev 2024; 37:e0013523. [PMID: 38421181 PMCID: PMC11324037 DOI: 10.1128/cmr.00135-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024] Open
Abstract
SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.
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Affiliation(s)
- Stefano Di Bella
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
| | - Gianfranco Sanson
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
| | - Jacopo Monticelli
- Infectious Diseases
Unit, Trieste University Hospital
(ASUGI), Trieste,
Italy
| | - Verena Zerbato
- Infectious Diseases
Unit, Trieste University Hospital
(ASUGI), Trieste,
Italy
| | - Luigi Principe
- Microbiology and
Virology Unit, Great Metropolitan Hospital
“Bianchi-Melacrino-Morelli”,
Reggio Calabria, Italy
| | - Mauro Giuffrè
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
- Department of Internal
Medicine (Digestive Diseases), Yale School of Medicine, Yale
University, New Haven,
Connecticut, USA
| | - Giuseppe Pipitone
- Infectious Diseases
Unit, ARNAS Civico-Di Cristina
Hospital, Palermo,
Italy
| | - Roberto Luzzati
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
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3
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Fachi JL, Vinolo MAR, Colonna M. Reviewing the Clostridioides difficile Mouse Model: Insights into Infection Mechanisms. Microorganisms 2024; 12:273. [PMID: 38399676 PMCID: PMC10891951 DOI: 10.3390/microorganisms12020273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/16/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024] Open
Abstract
Clostridioides difficile is an anaerobic, spore-forming bacterium associated with intestinal infection, manifesting a broad spectrum of gastrointestinal symptoms, ranging from mild diarrhea to severe colitis. A primary risk factor for the development of C. difficile infection (CDI) is antibiotic exposure. Elderly and immunocompromised individuals are particularly vulnerable to CDI. A pivotal aspect for comprehending the complexities of this infection relies on the utilization of experimental models that mimic human CDI transmission, pathogenesis, and progression. These models offer invaluable insights into host-pathogen interactions and disease dynamics, and serve as essential tools for testing potential therapeutic approaches. In this review, we examine the animal model for CDI and delineate the stages of infection, with a specific focus on mice. Our objective is to offer an updated description of experimental models employed in the study of CDI, emphasizing both their strengths and limitations.
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Affiliation(s)
- José L. Fachi
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Marco A. R. Vinolo
- Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil;
| | - Marco Colonna
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
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Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis 2023; 77:S463-S470. [PMID: 38051967 DOI: 10.1093/cid/ciad644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.
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Affiliation(s)
- Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Markovska R, Dimitrov G, Gergova R, Boyanova L. Clostridioides difficile, a New “Superbug”. Microorganisms 2023; 11:microorganisms11040845. [PMID: 37110267 PMCID: PMC10140992 DOI: 10.3390/microorganisms11040845] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/19/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium. The clinical features of C. difficile infections (CDIs) can vary, ranging from the asymptomatic carriage and mild self-limiting diarrhoea to severe and sometimes fatal pseudomembranous colitis. C. difficile infections (CDIs) are associated with disruption of the gut microbiota caused by antimicrobial agents. The infections are predominantly hospital-acquired, but in the last decades, the CDI patterns have changed. Their prevalence increased, and the proportion of community-acquired CDIs has also increased. This can be associated with the appearance of hypervirulent epidemic isolates of ribotype 027. The COVID-19 pandemic and the associated antibiotic overuse could additionally change the patterns of infections. Treatment of CDIs is a challenge, with only three appropriate antibiotics for use. The wide distribution of C. difficile spores in hospital environments, chronic persistence in some individuals, especially children, and the recent detection of C. difficile in domestic pets can furthermore worsen the situation. “Superbugs” are microorganisms that are both highly virulent and resistant to antibiotics. The aim of this review article is to characterise C. difficile as a new member of the “superbug” family. Due to its worldwide spread, the lack of many treatment options and the high rates of both recurrence and mortality, C. difficile has emerged as a major concern for the healthcare system.
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Development of the Anaerobic Microbiome in the Infant Gut. Pediatr Infect Dis J 2023:00006454-990000000-00384. [PMID: 36917032 DOI: 10.1097/inf.0000000000003905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Ninety-five percent of gut microbiota are anaerobes and vary according to age and diet. Complex carbohydrates in human milk enhance the growth of Bifidobacterium and Bacteroides in the first year. Complex carbohydrates in solid foods enhance the growth of Bacteroides and Clostridium in the second year. Short-chain fatty acids produced by Akkermansia and Faecalibacterium may reduce obesity, diabetes and IBD.
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7
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Raeisi H, Azimirad M, Nabavi-Rad A, Asadzadeh Aghdaei H, Yadegar A, Zali MR. Application of recombinant antibodies for treatment of Clostridioides difficile infection: Current status and future perspective. Front Immunol 2022; 13:972930. [PMID: 36081500 PMCID: PMC9445313 DOI: 10.3389/fimmu.2022.972930] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/03/2022] [Indexed: 11/13/2022] Open
Abstract
Clostridioides difficile (C. difficile), known as the major cause of antibiotic-associated diarrhea, is regarded as one of the most common healthcare-associated bacterial infections worldwide. Due to the emergence of hypervirulent strains, development of new therapeutic methods for C. difficile infection (CDI) has become crucially important. In this context, antibodies have been introduced as valuable tools in the research and clinical environments, as far as the effectiveness of antibody therapy for CDI was reported in several clinical investigations. Hence, production of high-performance antibodies for treatment of CDI would be precious. Traditional approaches of antibody generation are based on hybridoma technology. Today, application of in vitro technologies for generating recombinant antibodies, like phage display, is considered as an appropriate alternative to hybridoma technology. These techniques can circumvent the limitations of the immune system and they can be exploited for production of antibodies against different types of biomolecules in particular active toxins. Additionally, DNA encoding antibodies is directly accessible in in vitro technologies, which enables the application of antibody engineering in order to increase their sensitivity and specificity. Here, we review the application of antibodies for CDI treatment with an emphasis on recombinant fragment antibodies. Also, this review highlights the current and future prospects of the aforementioned approaches for antibody-mediated therapy of CDI.
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Affiliation(s)
- Hamideh Raeisi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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8
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Liu MY, Challa M, McCoul ED, Chen PG. Economic Viability of Penicillin Allergy Testing to Avoid Improper Clindamycin Surgical Prophylaxis. Laryngoscope 2022; 133:1086-1091. [PMID: 35904127 DOI: 10.1002/lary.30329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 07/07/2022] [Accepted: 07/21/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Patients mislabeled with a penicillin allergy are often unnecessarily given prophylactic clindamycin. Thus, otolaryngologists may cause harm due to clindamycin's associated risk of Clostridioides difficile infections (CDI) and surgical site infections (SSI). The objective of this study was to determine the economic feasibility of penicillin allergy testing in preventing unnecessary clindamycin use among patients with an unconfirmed penicillin allergy prior to otolaryngologic surgery. METHODS A break-even analysis was performed using the average cost of penicillin allergy testing and a CDI/SSI to calculate the absolute risk reduction (ARR) in baseline CDI/SSI rate due to clindamycin required for penicillin testing to be economically sustainable. The binomial distribution was used to calculate the probability that current penicillin testing can achieve this study's ARR. RESULTS Preoperative penicillin testing was found to be economically sustainable if it could decrease the baseline CDI rate by an ARR of 1.06% or decrease the baseline SSI rate by an ARR of 1.34%. The probability of penicillin testing achieving these ARRs depended on the baseline CDI and SSI rates. When the CDI rate was at least 5% or the SSI rate was at least 7%, penicillin allergy testing was guaranteed to achieve economic sustainability. CONCLUSION In patients mislabeled with a penicillin allergy, preoperative penicillin allergy testing may be an economically sustainable option to prevent the unnecessary use of prophylactic clindamycin during otolaryngologic surgery. Current practice guidelines should be modified to recommend penicillin allergy testing in patients with an unconfirmed allergy prior to surgery. LEVEL OF EVIDENCE N/A Laryngoscope, 2022.
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Affiliation(s)
- Matthew Y Liu
- Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.,Department of Otolaryngology - Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Megana Challa
- Department of Otolaryngology - Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Edward D McCoul
- Department of Otorhinolaryngology, Ochsner Health System, New Orleans, Louisiana, USA.,Department of Otolaryngology - Head and Neck Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
| | - Philip G Chen
- Department of Otolaryngology - Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Dijkerman M, Breederveld-Walters M, Pijpe A, Breederveld R. Management and outcome of burn injuries during pregnancy: A systematic review and presentation of a comprehensive guideline. Burns 2022; 48:1544-1560. [DOI: 10.1016/j.burns.2022.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 03/10/2022] [Accepted: 03/28/2022] [Indexed: 11/02/2022]
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Lang V, Gunka K, Ortlepp JR, Zimmermann O, Groß U. Risk Factors of Patients With Diarrhea for Having Clostridioides (Clostridium) difficile Infection. Front Microbiol 2022; 13:840846. [PMID: 35359708 PMCID: PMC8963458 DOI: 10.3389/fmicb.2022.840846] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Nosocomial infections with Clostridioides (Clostridium) difficile have become an emergent health threat. We sought to define risk factors for a C. difficile infection (CDI) beyond the widely known ones, such as antibiotic use and prior hospital stay. We therefore focused on a group of patients with diarrhea in order to identify risk factors for C. difficile infection among this symptomatic cohort. A total of 121 hospitalized patients from Seesen/Germany with diarrhea were included who submitted a stool sample and were interviewed about their socio-demographic background, lifestyle and state of health using a standardized questionnaire. Antibiotic potential of diuretics was examined by agar diffusion test. C. difficile was identified in 29 patients resulting in a prevalence of 24.0%. The infection was hospital-acquired in most cases (p < 0.001, 82.1%; n = 23/28, versus 29/91, 31.9%). The generally accepted risk factor previous antibiotic use was confirmed in this study (p = 0.002, n = 23/28 CDI patients, 82.1%, versus n = 44/91 non-CDI patients, 48.4%). The following additional risk factors were identified: regular consumption of proton pump inhibitors; PPI (p = 0.011, n = 24/29, 82.8% vs. n = 52/92, 56.5%), CDI patients ate less vegetables (p = 0.001, n = 12/29, 41.4% vs. 69/92, 75.0%). The intake of the diuretic agent torasemid in patients with CDI (p = 0.005, n = 18/29, 62.1%) was higher than in patients without (n = 30/92, 32.6%). More patients with CDI had to undergo a surgery in the previous year (p = 0.022, n = 13/29, 44.8% vs. n = 21/92, 22.8%) and held more birds (p = 0.056, n = 4/29, 13.8%) than individuals of the negative group (n = 3/92, 3.3%). In conclusion, although no antibiotic potential was detected in diuretics, especially torasemid seems to have significant influence for the occurrence of a CDI as well as a nutrition poor in vegetables. A diet rich in vegetables represented a fourfold lower risk for a CDI (OR 0.240, CI (0.0720 - 0.796]).
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Affiliation(s)
- Vanessa Lang
- Institute of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany
| | - Katrin Gunka
- Institute of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany
| | | | - Ortrud Zimmermann
- Institute of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany
| | - Uwe Groß
- Institute of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany
- *Correspondence: Uwe Groß,
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DeVine MN, MacBrayne CE, Child J, Blackmer AB. Pharmacological Management of Pediatric Clostridioides difficile Infection: Clarifying the Controversies. J Pediatr Health Care 2022; 36:181-192. [PMID: 34412953 DOI: 10.1016/j.pedhc.2021.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 06/19/2021] [Accepted: 06/25/2021] [Indexed: 10/20/2022]
Abstract
Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.
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12
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Hotinger JA, Morris ST, May AE. The Case against Antibiotics and for Anti-Virulence Therapeutics. Microorganisms 2021; 9:2049. [PMID: 34683370 PMCID: PMC8537500 DOI: 10.3390/microorganisms9102049] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 12/14/2022] Open
Abstract
Although antibiotics have been indispensable in the advancement of modern medicine, there are downsides to their use. Growing resistance to broad-spectrum antibiotics is leading to an epidemic of infections untreatable by first-line therapies. Resistance is exacerbated by antibiotics used as growth factors in livestock, over-prescribing by doctors, and poor treatment adherence by patients. This generates populations of resistant bacteria that can then spread resistance genes horizontally to other bacterial species, including commensals. Furthermore, even when antibiotics are used appropriately, they harm commensal bacteria leading to increased secondary infection risk. Effective antibiotic treatment can induce bacterial survival tactics, such as toxin release and increasing resistance gene transfer. These problems highlight the need for new approaches to treating bacterial infection. Current solutions include combination therapies, narrow-spectrum therapeutics, and antibiotic stewardship programs. These mediate the issues but do not address their root cause. One emerging solution to these problems is anti-virulence treatment: preventing bacterial pathogenesis instead of using bactericidal agents. In this review, we discuss select examples of potential anti-virulence targets and strategies that could be developed into bacterial infection treatments: the bacterial type III secretion system, quorum sensing, and liposomes.
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Affiliation(s)
| | | | - Aaron E. May
- Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA; (J.A.H.); (S.T.M.)
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13
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Musher DM, Arasaratnam RJ. Contributions of animal studies to the understanding of infectious diseases. Clin Infect Dis 2021; 74:1872-1878. [PMID: 34555163 DOI: 10.1093/cid/ciab844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Indexed: 11/14/2022] Open
Abstract
Experiments in animals have played an integral role in furthering basic understanding of the pathophysiology, host immune response, diagnosis, and treatment of infectious diseases. However, competing demands of modern-day clinical training and increasingly stringent requirements to perform animal research have reduced the exposure of infectious disease physicians to animal studies. For practitioners of infectious diseases and, especially, for contemporary trainees in infectious diseases, it is important to appreciate this historical body of work and its impact on current clinical practice. In this article, we provide an overview of some major contributions of animal studies to the field of infectious diseases. Areas covered include transmission of infection, elucidation of innate and adaptive host immune responses, testing of antimicrobials, pathogenesis and treatment of endocarditis, osteomyelitis, intraabdominal and urinary tract infection, treatment of infection associated with a foreign body or in the presence of neutropenia, and toxin-mediated disease.
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Affiliation(s)
- Daniel M Musher
- Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
| | - Reuben J Arasaratnam
- Veterans Affairs North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX, USA
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14
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Rodriguez C, Mith H, Taminiau B, Bouchafa L, Van Broeck J, Soumillion K, Ngyuvula E, García-Fuentes E, Korsak N, Delmée M, Daube G. First isolation of Clostridioides difficile from smoked and dried freshwater fish in Cambodia. Food Control 2021. [DOI: 10.1016/j.foodcont.2021.107895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Faden H. Review and Commentary on the Importance of Bile Acids in the Life Cycle of Clostridioides difficile in Children and Adults. J Pediatric Infect Dis Soc 2021; 10:659-664. [PMID: 33626138 DOI: 10.1093/jpids/piaa150] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 11/18/2020] [Indexed: 12/16/2022]
Abstract
Clostridioides difficile, a spore-forming anaerobe, resides in the intestine. The life cycle of C. difficile illustrates an interdependent relationship between bile acids, commensal microbiota, and C. difficile. Primary bile acids are critical for the germination of C. difficile spores in the small intestine, while secondary bile acids serve as a counterbalance to inhibit the growth of the organism in the colon. Many commensal bacteria especially Clostridium spp. are responsible for transforming primary bile acids into secondary bile acids. Antibiotics eliminate bacteria that convert primary bile acids into secondary bile acids and, thus, allow C. difficile to flourish and cause diarrhea. In children younger than 2 years of age, who normally only produce primary bile acids, colonization with toxin-producing C. difficile is exceedingly common. The reason for the absence of C. difficile diarrhea in the children remains unexplained.
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Affiliation(s)
- Howard Faden
- Department of Pediatrics, Division of Infectious Diseases, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York, USA
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16
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Páramo-Zunzunegui J, Ortega-Fernández I, Calvo-Espino P, Diego-Hernández C, Ariza-Ibarra I, Otazu-Canals L, Danés-Grases JE, Menchero-Sánchez A. Severe Clostridium difficile colitis as potential late complication associated with COVID-19. Ann R Coll Surg Engl 2020; 102:e176-e179. [PMID: 32803988 PMCID: PMC7450442 DOI: 10.1308/rcsann.2020.0166] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Spain has been one of the most affected countries by the COVID-19 outbreak. After the high impact of the pandemic, a wide clinical spectrum of late complications associated with COVID-19 are being observed. We report a case of a severe Clostridium difficile colitis in a post-treatment and recovered COVID-19 patient. A 64-year-woman with a one-month hospital admission for severe bilateral pneumonia associated with COVID-19 and 10 days after discharge presented with diarrhoea and abdominal pain. Severe C. difficile-associated colitis is diagnosed according to clinical features and CT findings. An urgent pancolectomy was performed due to her bad response to conservative treatment. Later evolution slowly improved to recovery. C. difficile-associated colitis is one of the most common hospital-acquired infections. Significant patient-related risk factors for C. difficile infection are antibiotic exposure, older age, and hospitalisation. Initial therapeutic recommendations in our country included administration broad-spectrum antibiotics to all patients with bilateral pneumonia associated with SARS-CoV-2. These antibiotics are strongly associated with C. difficile infection. Our patient developed a serious complication of C. difficile due to the use of broad-spectrum antibiotics. The appearance of late digestive symptoms in patients diagnosed and treated for COVID-19 should alert clinicians to the possibility of C. difficile infection. The updated criteria for severe colitis and severe C. difficile infection should be considered to ensure an early effective treatment for the complication.
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Affiliation(s)
- J Páramo-Zunzunegui
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
- CORRESPONDENCE TO Javier Páramo Zunzunegui, E:
| | - I Ortega-Fernández
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
| | - P Calvo-Espino
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
| | - C Diego-Hernández
- Department of Histopathology, University Hospital of Móstoles, Madrid, Spain
| | - I Ariza-Ibarra
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
| | - L Otazu-Canals
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
| | - JE Danés-Grases
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
| | - A Menchero-Sánchez
- Department of General and Digestive Surgery, University Hospital of Móstoles, Madrid, Spain
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Nwachuku E, Shan Y, Senthil-Kumar P, Braun T, Shadis R, Kirton O, Vu TQ. Toxic Clostridioides (formerly Clostridium) difficile colitis: No longer a diarrhea associated infection. Am J Surg 2020; 221:240-242. [PMID: 32680621 DOI: 10.1016/j.amjsurg.2020.06.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 04/30/2020] [Accepted: 06/19/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is traditionally taught to be an antibiotic associated diarrheal infection. This diagnosis is based on the presence of clinical symptoms (usually defined as more than 3 watery, loose or unformed stool within 24 h) coupled with a diagnostic test. There is now a new presentation of CDI, including progression to toxic megacolon, in patients without diarrhea. METHODS We report a case series of 9 surgical patients from a single institution who developed CDI without preceding diarrhea. RESULT All 9 patients had CDI with positive laboratory testing for C. difficile toxin. They, however, presented with a lack of or minimal bowel movements. Six patients had rapid development of abdominal distention, 1 patient had a single episode of watery stool in 3 days, while the other 2 patients presented with constipation. Seven patients received stool softeners, suppositories and/or enemas for presumed constipation. Four patients had a mild course of infection and were successfully treated medically. The other 5 patients developed toxic megacolon, and eventually required total abdominal colectomy. Out of the 5 patients that required total colectomy, 2 expired. CONCLUSION CDI must be suspected in patients who rapidly develop abdominal distention, vague abdominal complaints or change in bowel function even in the absence of diarrhea, especially if coupled with multi-system organ failure.
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Affiliation(s)
| | - Yizhi Shan
- Department of Surgery, Abington Hospital, Jefferson Health, USA
| | | | - Todd Braun
- Department of Infectious Disease, Abington Hospital, Jefferson Health, USA
| | - Ryan Shadis
- Department of Surgery, Abington Hospital, Jefferson Health, USA
| | - Orlando Kirton
- Department of Surgery, Abington Hospital, Jefferson Health, USA
| | - Thai Q Vu
- Department of Surgery, Abington Hospital, Jefferson Health, USA
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18
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Kukla M, Adrych K, Dobrowolska A, Mach T, Reguła J, Rydzewska G. Guidelines for Clostridium difficile infection in adults. PRZEGLAD GASTROENTEROLOGICZNY 2020; 15:1-21. [PMID: 32215122 PMCID: PMC7089862 DOI: 10.5114/pg.2020.93629] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 02/17/2020] [Indexed: 12/16/2022]
Abstract
Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem, especially in well developed countries. There has been evident increase in incidence and severity of CDI. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection. Antibiotics are the fundamental treatment of CDI. In patients who had recurrent CDI fecal microbiota transplantation seems to be promising and efficient strategy. These guidelines systematize existing data and include recent changes implemented in the management of CDI.
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Affiliation(s)
- Michał Kukla
- Department of Internal Medicine and Geriatrics, Jagiellonian University Medical College, Krakow, Poland
- Department of Endoscopy, University Hospital, Krakow, Poland
| | - Krystian Adrych
- Department of Gastroenterology and Hepatology, Medical University of Gdansk, Gdansk, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Tomasz Mach
- Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, Krakow, Poland
| | - Jarosław Reguła
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Postgraduate Education Centre, Warsaw, Poland
- Department of Gastrointestinal Oncology, “Maria Sklodowska-Curie” Clinical Oncology Institute, Warsaw, Poland
| | - Grażyna Rydzewska
- Central Clinical Hospital of Ministry of Inferior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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19
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Diarrhoeal events can trigger long-term Clostridium difficile colonization with recurrent blooms. Nat Microbiol 2020; 5:642-650. [PMID: 32042128 DOI: 10.1038/s41564-020-0668-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 01/07/2020] [Indexed: 11/08/2022]
Abstract
Although Clostridium difficile is widely considered an antibiotic- and hospital-associated pathogen, recent evidence indicates that this is an insufficient depiction of the risks and reservoirs. A common thread that links all major risk factors of infection is their association with gastrointestinal disturbances, but this relationship to C. difficile colonization has never been tested directly. Here, we show that disturbances caused by diarrhoeal events trigger susceptibility to C. difficile colonization. Using survey data of the human gut microbiome, we detected C. difficile colonization and blooms in people recovering from food poisoning and Vibrio cholerae infections. Carriers remained colonized for year-long time scales and experienced highly variable patterns of C. difficile abundance, where increased shedding over short periods of 1-2 d interrupted week-long periods in which C. difficile was undetectable. Given that short shedding events were often linked to gastrointestinal disturbances, our results help explain why C. difficile is frequently detected as a co-infecting pathogen in patients with diarrhoea. To directly test the impact of diarrhoea on susceptibility to colonization, we developed a mouse model of variable disturbance intensity, which allowed us to monitor colonization in the absence of disease. As mice exposed to avirulent C. difficile spores ingested increasing quantities of laxatives, more individuals experienced C. difficile blooms. Our results indicate that the likelihood of colonization is highest in the days immediately following acute disturbances, suggesting that this could be an important window during which transmission could be interrupted and the incidence of infection lowered.
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20
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Khanna S, Gerding DN. Current and future trends in clostridioides (clostridium) difficile infection management. Anaerobe 2019; 58:95-102. [PMID: 31054313 DOI: 10.1016/j.anaerobe.2019.04.010] [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: 03/02/2019] [Revised: 04/28/2019] [Accepted: 04/29/2019] [Indexed: 01/01/2023]
Abstract
Current and future management of Clostridioides difficile infection (CDI) including antibiotic treatment is increasingly focused on preventive strategies, either prevention of recurrent CDI (rCDI) or primary prevention of CDI. In addition to newer narrow spectrum antibiotics and pulse dosing of antibiotic treatment, multiple widely differing approaches to prevention of CDI and rCDI are under clinical development or recently approved for clinical use. They include immunologics, both passive monoclonal antibodies and active vaccines targeted at C. difficile toxins, approaches to reduce antibiotic dysbiosis in the gut, microbiome restoration using fecal microbiome transplants (FMT) or biotherapeutic bacterial derivatives, and substitution of non-toxigenic C. difficile (NTCD) for toxigenic C. difficile. Newer antibiotics, monoclonal antibodies, and FMT are targeted at reducing rCDI whereas vaccines and reduction of antibiotic dysbiosis in the gut are targeted at prevention of primary CDI. Biotherapeutics may be used for prevention of either primary CDI or rCDI. Approaches such as monoclonal antibodies, FMT, and biotherapeutics provide rapid but transient preventive benefits, whereas vaccines require weeks to months to be effective, but will presumably provide long term prevention. More rapid but transient prevention strategies such as FMT and biotherapeutics could be used in combination with vaccines to provide both rapid and durable CDI prevention.
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21
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Pathogen Colonization Resistance in the Gut and Its Manipulation for Improved Health. THE AMERICAN JOURNAL OF PATHOLOGY 2019; 189:1300-1310. [PMID: 31100210 DOI: 10.1016/j.ajpath.2019.03.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/15/2019] [Accepted: 03/05/2019] [Indexed: 02/07/2023]
Abstract
Mammals have coevolved with a large community of symbiotic, commensal, and some potentially pathogenic microbes. The trillions of bacteria and hundreds of species in our guts form a relatively stable community that resists invasion by outsiders, including pathogens. This powerful protective force is referred to as colonization resistance. We discuss the variety of proposed or demonstrated mechanisms that can mediate colonization resistance and some potential ways to manipulate them for improved human health. Instances in which certain bacterial pathogens can overcome colonization resistance are also discussed.
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22
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Cheng S, Zhu L, Faden HS. Interactions of bile acids and the gut microbiota: learning from the differences in Clostridium difficile infection between children and adults. Physiol Genomics 2019; 51:218-223. [PMID: 31074701 DOI: 10.1152/physiolgenomics.00034.2019] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Bile acids and microbiota differ significantly in the gut of children and adults. In the first 3 yr of life, intestinal bile consists mostly of two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA); however, in adults, primary bile acids are transformed into the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid. This difference has a major impact on the gut microbiome, especially on anaerobic spore-forming bacteria. CA augments germination of spores in the terminal ileum. On the other hand, DCA curtails the number of germinated anaerobes entering the cecum from the terminal ileum. The control mechanism that exists in the adult cecum is absent in the young child and results in unrestrained proliferation of anaerobes, such as Clostridium difficile, in the cecum. A similar situation may develop during antibiotic therapy when an antibiotic eradicates the anaerobic population capable of converting primary bile acids into secondary bile acids.
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Affiliation(s)
- Sijing Cheng
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , China
| | - Lixin Zhu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou , China.,Department of Biochemistry; Genome, Environment and Microbiome Community of Excellence, the State University of New York at Buffalo , Buffalo, New York
| | - Howard S Faden
- University at Buffalo, Jacobs School of Medicine and Biological Sciences, Department of Pediatrics, Division of Infectious Diseases , Buffalo, New York
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Abstract
Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.
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24
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Sartelli M, Di Bella S, McFarland LV, Khanna S, Furuya-Kanamori L, Abuzeid N, Abu-Zidan FM, Ansaloni L, Augustin G, Bala M, Ben-Ishay O, Biffl WL, Brecher SM, Camacho-Ortiz A, Caínzos MA, Chan S, Cherry-Bukowiec JR, Clanton J, Coccolini F, Cocuz ME, Coimbra R, Cortese F, Cui Y, Czepiel J, Demetrashvili Z, Di Carlo I, Di Saverio S, Dumitru IM, Eckmann C, Eiland EH, Forrester JD, Fraga GP, Frossard JL, Fry DE, Galeiras R, Ghnnam W, Gomes CA, Griffiths EA, Guirao X, Ahmed MH, Herzog T, Kim JI, Iqbal T, Isik A, Itani KMF, Labricciosa FM, Lee YY, Juang P, Karamarkovic A, Kim PK, Kluger Y, Leppaniemi A, Lohsiriwat V, Machain GM, Marwah S, Mazuski JE, Metan G, Moore EE, Moore FA, Ordoñez CA, Pagani L, Petrosillo N, Portela F, Rasa K, Rems M, Sakakushev BE, Segovia-Lohse H, Sganga G, Shelat VG, Spigaglia P, Tattevin P, Tranà C, Urbánek L, Ulrych J, Viale P, Baiocchi GL, Catena F. 2019 update of the WSES guidelines for management of Clostridioides ( Clostridium) difficile infection in surgical patients. World J Emerg Surg 2019; 14:8. [PMID: 30858872 PMCID: PMC6394026 DOI: 10.1186/s13017-019-0228-3] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 02/17/2019] [Indexed: 02/08/2023] Open
Abstract
In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
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Affiliation(s)
- Massimo Sartelli
- Department of Surgery, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Stefano Di Bella
- Infectious Diseases Department, Trieste University Hospital, Trieste, Italy
| | - Lynne V. McFarland
- Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN USA
| | - Luis Furuya-Kanamori
- Research School of Population Health, Australian National University, Acton, ACT Australia
| | - Nadir Abuzeid
- Department of Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Khartoum, Sudan
| | - Fikri M. Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Luca Ansaloni
- Department of General Surgery, Bufalini Hospital, Cesena, Italy
| | - Goran Augustin
- Department of Surgery, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Miklosh Bala
- Trauma and Acute Care Surgery Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Offir Ben-Ishay
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Walter L. Biffl
- Trauma and Acute Care Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA USA
| | - Stephen M. Brecher
- Pathology and Laboratory Medicine, VA Boston Healthcare System, West Roxbury MA and BU School of Medicine, Boston, MA USA
| | - Adrián Camacho-Ortiz
- Department of Internal Medicine, University Hospital, Dr. José E. González, Monterrey, Mexico
| | - Miguel A. Caínzos
- Department of Surgery, University of Santiago de Compostela, A Coruña, Spain
| | - Shirley Chan
- Department of General Surgery, Medway Maritime Hospital, Gillingham, Kent UK
| | - Jill R. Cherry-Bukowiec
- Department of Surgery, Division of Acute Care Surgery, University of Michigan, Ann Arbor, MI USA
| | - Jesse Clanton
- Department of Surgery, West Virginia University Charleston Division, Charleston, WV USA
| | | | - Maria E. Cocuz
- Faculty of Medicine, Transilvania University, Infectious Diseases Hospital, Brasov, Romania
| | - Raul Coimbra
- Riverside University Health System Medical Center and Loma Linda University School of Medicine, Moreno Valley, CA USA
| | | | - Yunfeng Cui
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
| | - Jacek Czepiel
- Department of Infectious Diseases, Jagiellonian University, Medical College, Kraków, Poland
| | - Zaza Demetrashvili
- Department of Surgery, Tbilisi State Medical University, Kipshidze Central University Hospital, Tbilisi, Georgia
| | - Isidoro Di Carlo
- Department of Surgical Sciences, Cannizzaro Hospital, University of Catania, Catania, Italy
| | - Salomone Di Saverio
- Department of Surgery, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Irina M. Dumitru
- Clinical Infectious Diseases Hospital, Ovidius University, Constanta, Romania
| | - Christian Eckmann
- Department of General, Visceral and Thoracic Surgery, Klinikum Peine, Hospital of Medical University Hannover, Peine, Germany
| | | | | | - Gustavo P. Fraga
- Division of Trauma Surgery, Hospital de Clinicas, School of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Jean L. Frossard
- Service of Gastroenterology and Hepatology, Geneva University Hospital, Genève, Switzerland
| | - Donald E. Fry
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL USA
- University of New Mexico School of Medicine, Albuquerque, NM USA
| | - Rita Galeiras
- Critical Care Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain
| | - Wagih Ghnnam
- Department of Surgery Mansoura, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Carlos A. Gomes
- Surgery Department, Hospital Universitario (HU) Terezinha de Jesus da Faculdade de Ciencias Medicas e da Saude de Juiz de Fora (SUPREMA), Hospital Universitario (HU) Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, Brazil
| | | | - Xavier Guirao
- Unit of Endocrine, Head, and Neck Surgery and Unit of Surgical Infections Support, Department of General Surgery, Parc Taulí, Hospital Universitari, Sabadell, Spain
| | - Mohamed H. Ahmed
- Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, Buckinghamshire UK
| | - Torsten Herzog
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Jae Il Kim
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Tariq Iqbal
- Department of Gastroenterology, Queen Elizabeth Hospital, Birmingham, UK
| | - Arda Isik
- General Surgery Department, Magee Womens Hospital, UPMC, Pittsburgh, USA
| | - Kamal M. F. Itani
- Department of Surgery, VA Boston Health Care System, Boston University and Harvard Medical School, Boston, MA USA
| | | | - Yeong Y. Lee
- School of Medical Sciences, University Sains Malaysia, Kota Bharu, Kelantan Malaysia
| | - Paul Juang
- Department of Pharmacy Practice, St Louis College of Pharmacy, St Louis, MO USA
| | - Aleksandar Karamarkovic
- Faculty of Mediine University of Belgrade Clinic for Surgery “Nikola Spasic”, University Clinical Center “Zvezdara” Belgrade, Belgrade, Serbia
| | - Peter K. Kim
- Department of Surgery, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Yoram Kluger
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Ari Leppaniemi
- Abdominal Center, Helsinki University Hospital Meilahti, Helsinki, Finland
| | - Varut Lohsiriwat
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Gustavo M. Machain
- Department of Surgery, Universidad Nacional de Asuncion, Asuncion, Paraguay
| | - Sanjay Marwah
- Department of Surgery, Post-Graduate Institute of Medical Sciences, Rohtak, India
| | - John E. Mazuski
- Department of Surgery, Washington University School of Medicine, Saint Louis, USA
| | - Gokhan Metan
- Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ernest E. Moore
- Department of Surgery, University of Colorado, Denver Health Medical Center, Denver, CO USA
| | | | - Carlos A. Ordoñez
- Department of Surgery, Fundación Valle del Lili, Hospital Universitario del Valle, Universidad del Valle, Cali, Colombia
| | - Leonardo Pagani
- Infectious Diseases Unit, Bolzano Central Hospital, Bolzano, Italy
| | - Nicola Petrosillo
- National Institute for Infectious Diseases - INMI - Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Francisco Portela
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Kemal Rasa
- Department of Surgery, Anadolu Medical Center, Kocaali, Turkey
| | - Miran Rems
- Department of Abdominal and General Surgery, General Hospital Jesenice, Jesenice, Slovenia
| | | | | | - Gabriele Sganga
- Division of Emergency Surgery, Department of Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Vishal G. Shelat
- Department of Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Patrizia Spigaglia
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Pierre Tattevin
- Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France
| | - Cristian Tranà
- Department of Surgery, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Libor Urbánek
- First Department of Surgery, Faculty of Medicine, Masaryk University Brno and University Hospital of St. Ann Brno, Brno, Czech Republic
| | - Jan Ulrych
- First Department of Surgery, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Pierluigi Viale
- Clinic of Infectious Diseases, St Orsola-Malpighi University Hospital, Bologna, Italy
| | - Gian L. Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Fausto Catena
- Emergency Surgery Department, Maggiore Parma Hospital, Parma, Italy
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25
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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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26
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Dieterle MG, Rao K, Young VB. Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections. Ann N Y Acad Sci 2019; 1435:110-138. [PMID: 30238983 PMCID: PMC6312459 DOI: 10.1111/nyas.13958] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 07/16/2018] [Accepted: 08/03/2018] [Indexed: 12/15/2022]
Abstract
Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. The high incidence has driven new research on improved prevention such as the emerging use of probiotics, intestinal microbiome manipulation during antibiotic therapies, vaccinations, and newer antibiotics that reduce the disruption of the intestinal microbiome. While the treatment of acute C. difficile is effective in most patients, it can be further optimized by adjuvant therapies that improve the initial treatment success and decrease the risk of subsequent recurrence. Finally, the high risk of recurrence has led to multiple emerging therapies that target toxin activity, recovery of the intestinal microbial community, and elimination of latent C. difficile in the intestine. In summary, CDIs illustrate the complex interaction among host physiology, microbial community, and pathogen that requires specific therapies to address each of the factors leading to primary infection and recurrence.
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Affiliation(s)
- Michael G. Dieterle
- University of Michigan Medical School, Medical Scientist Training Program (MSTP), Ann Arbor, Michigan
- University of Michigan Department of Microbiology and Immunology, Ann Arbor, Michigan
| | - Krishna Rao
- University of Michigan Department of Internal Medicine, Infectious Diseases Division, Ann Arbor, Michigan
| | - Vincent B. Young
- University of Michigan Department of Microbiology and Immunology, Ann Arbor, Michigan
- University of Michigan Department of Internal Medicine, Infectious Diseases Division, Ann Arbor, Michigan
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27
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Moreira BDO, Pais LS, Costa LDA. Diarreia causada por Clostridium difficile: recentes avanços. HU REVISTA 2018. [DOI: 10.34019/1982-8047.2017.v43.2653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A infecção causada por Clostridium difficile (C. difficile), um dos agentes causadores de diarréia aguda e recorrente, tem como principal fator de risco o uso de antimicrobianos. Recentemente, houve um aumento da incidência e da mortalidade desta afecção. Clinicamente, a mesma pode manifestar-se desde um quadro de diarreia aquosa leve até a forma grave de colite pseudomembranosa. O objetivo deste artigo é apontar as mudanças epidemiológicas da infecção pelo C. difficile, além de rever fatores de risco, manifestações clínicas, métodos diagnósticos, tratamento e prevenção desta infecção. O aumento na gravidade da infecção causada pelo C. difficile é relacionado a uma nova cepa hipervirulenta, BI/NAPI/Ribotipo 027, que apresenta maior capacidade de produção de toxinas. Essa nova cepa, mais virulenta, ainda não foi detectada no Brasil, porém como já foi identificada em outros países da América, alerta para a preocupante capacidade de disseminação universal. Essa revisão é baseada em artigos publicados nos últimos 10 anos, utilizando como base de dados o PubMed e o Scielo (Scientific Eletronic Library Online), com as palavras-chave: Epidemiologia, diarreia, Clostridium difficile e cepa hipervirulenta.
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28
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Affiliation(s)
- Lisa M Kodadek
- Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Tower 110, Baltimore, MD 21287, USA.
| | - Pamela A Lipsett
- Department of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Tower 110, Baltimore, MD 21287, USA; Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Osler 603, Baltimore, MD 21287, USA
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Schäffler H, Breitrück A. Clostridium difficile - From Colonization to Infection. Front Microbiol 2018; 9:646. [PMID: 29692762 PMCID: PMC5902504 DOI: 10.3389/fmicb.2018.00646] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 03/19/2018] [Indexed: 12/19/2022] Open
Abstract
Clostridium difficile is the most frequent cause of nosocomial antibiotic-associated diarrhea. The incidence of C. difficile infection (CDI) has been rising worldwide with subsequent increases in morbidity, mortality, and health care costs. Asymptomatic colonization with C. difficile is common and a high prevalence has been found in specific cohorts, e.g., hospitalized patients, adults in nursing homes and in infants. However, the risk of infection with C. difficile differs significantly between these cohorts. While CDI is a clear indication for therapy, colonization with C. difficile is not believed to be a direct precursor for CDI and therefore does not require treatment. Antibiotic therapy causes alterations of the intestinal microbial composition, enabling C. difficile colonization and consecutive toxin production leading to disruption of the colonic epithelial cells. Clinical symptoms of CDI range from mild diarrhea to potentially life-threatening conditions like pseudomembranous colitis or toxic megacolon. While antibiotics are still the treatment of choice for CDI, new therapies have emerged in recent years such as antibodies against C. difficile toxin B and fecal microbial transfer (FMT). This specific therapy for CDI underscores the role of the indigenous bacterial composition in the prevention of the disease in healthy individuals and its role in the pathogenesis after alteration by antibiotic treatment. In addition to the pathogenesis of CDI, this review focuses on the colonization of C. difficile in the human gut and factors promoting CDI.
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Affiliation(s)
- Holger Schäffler
- Division of Gastroenterology, Department of Medicine II, University of Rostock, Rostock, Germany
| | - Anne Breitrück
- Extracorporeal Immunomodulation Unit, Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany.,Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany
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McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66:e1-e48. [PMID: 29462280 PMCID: PMC6018983 DOI: 10.1093/cid/cix1085] [Citation(s) in RCA: 1358] [Impact Index Per Article: 194.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
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Affiliation(s)
| | | | - Stuart Johnson
- Edward Hines Jr Veterans Administration Hospital, Hines
- Loyola University Medical Center, Maywood, Illinois
| | | | - Karen C Carroll
- Johns Hopkins University School of Medicine, Baltimore, Maryl
| | | | - Erik R Dubberke
- Washington University School of Medicine, St Louis, Missouri
| | | | - Carolyn V Gould
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Ciaran Kelly
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Vivian Loo
- McGill University Health Centre, McGill University, Montréal, Québec, Canada
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The effect of concomitant use of systemic antibiotics in patients with Clostridium difficile infection receiving metronidazole therapy. Epidemiol Infect 2018; 146:558-564. [PMID: 29493484 DOI: 10.1017/s0950268818000390] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Management of Clostridium difficile infection (CDI) involves discontinuation of the offending antibiotic agent as soon as possible. However, the ongoing infection does not allow discontinuation of the offending antibiotic. We aimed to retrospectively investigate the predictors of treatment failure and impact of the concomitant use of systemic antibiotics in patients receiving metronidazole therapy. This study was conducted among patients hospitalised at a second care academic hospital from January 2013 to December 2014. Eligible patients were identified by reviewing stool toxin enzyme immunoassay results for C. difficile. Diarrhoea was defined as the passage of at least three loose or watery stools within 24 h. Among 314 patients with CDI receiving metronidazole therapy, 62 (19.7%) showed treatment failure and 105 (33.4%) received concomitant antibiotics. Underlying dialysis, fever >38.3 °C, low median serum albumin levels and concomitant use of antibiotics were independent predictors of treatment failure in patients with CDI receiving metronidazole therapy. The concomitant use of antibiotics increased the rates of treatment failure and 30-day mortality in patients receiving metronidazole therapy. These results suggest that metronidazole should be used in mild cases of CDI only after discontinuation of the offending antibiotics.
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Abstract
PURPOSE OF REVIEW The rising burden of Clostridium difficile infection (CDI) requires urgent identification of preventable risk factors. Observational studies suggest an association between proton-pump inhibitor (PPI) use and CDI risk. RECENT FINDINGS Key historical literature on PPI and CDI associations is reviewed as a prelude to evaluating the plausibility of a causative association. Impactful literature from the past 18 months is examined in detail and critically appraised through the lens of the Bradford Hill Criteria for determination of causality. The PPI and CDI association has been studied extensively and is valid. Nonetheless, causality is not proven due to extensive and difficult to control confounding in observational studies of CDI patient populations with complex comorbidities. SUMMARY In the authors' opinion, systematic discontinuation of PPIs in patients at risk for CDI is not warranted based on current evidence. Well controlled prospective human studies are needed. Careful and repeated consideration should be given to all PPI prescriptions to avoid potential adverse effects.
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33
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Present and past perspectives on Clostridium difficile infection. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018. [DOI: 10.1016/j.rgmxen.2017.07.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Abstract
Clostridium difficile is the most frequent cause of nosocomial antibiotic-associated diarrhea. The incidence of C. difficile infection (CDI) has been rising worldwide with subsequent increases in morbidity, mortality, and health care costs. Asymptomatic colonization with C. difficile is common and a high prevalence has been found in specific cohorts, e.g., hospitalized patients, adults in nursing homes and in infants. However, the risk of infection with C. difficile differs significantly between these cohorts. While CDI is a clear indication for therapy, colonization with C. difficile is not believed to be a direct precursor for CDI and therefore does not require treatment. Antibiotic therapy causes alterations of the intestinal microbial composition, enabling C. difficile colonization and consecutive toxin production leading to disruption of the colonic epithelial cells. Clinical symptoms of CDI range from mild diarrhea to potentially life-threatening conditions like pseudomembranous colitis or toxic megacolon. While antibiotics are still the treatment of choice for CDI, new therapies have emerged in recent years such as antibodies against C. difficile toxin B and fecal microbial transfer (FMT). This specific therapy for CDI underscores the role of the indigenous bacterial composition in the prevention of the disease in healthy individuals and its role in the pathogenesis after alteration by antibiotic treatment. In addition to the pathogenesis of CDI, this review focuses on the colonization of C. difficile in the human gut and factors promoting CDI.
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Affiliation(s)
- Holger Schäffler
- Division of Gastroenterology, Department of Medicine II, University of Rostock, Rostock, Germany
| | - Anne Breitrück
- Extracorporeal Immunomodulation Unit, Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
- Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany
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Forrester JD, Cai LZ, Mbanje C, Rinderknecht TN, Wren SM. Clostridium difficile infection in low- and middle-human development index countries: a systematic review. Trop Med Int Health 2017; 22:1223-1232. [PMID: 28796388 DOI: 10.1111/tmi.12937] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To describe the impact and epidemiology of Clostridium difficile infection (CDI) in low- and middle-human development index (LMHDI) countries. METHOD Prospectively registered, systematic literature review of existing literature in the PubMed, Ovid and Web of Science databases describing the epidemiology and management of C. difficile in LMHDI countries. Risk factors were compared between studies when available. RESULTS Of the 218 abstracts identified after applying search criteria, 25 studies were reviewed in detail. The weighted pooled infection rate among symptomatic non-immunosuppressed inpatients was 15.8% (95% CI 12.1-19.5%) and was 10.1% (95% CI 3.0-17.2%) among symptomatic outpatients. Subgroup analysis of immunosuppressed patient populations revealed pooled infection rates similar to non-immunosuppressed patient populations. Risk factor analysis was infrequently performed. CONCLUSIONS While the percentages of patients with CDI in LMHDI countries among the reviewed studies are lower than expected, there remains a paucity of epidemiologic data evaluating burden of C. difficile infection in these settings.
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Affiliation(s)
| | | | - Chenesa Mbanje
- College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | | | - Sherry M Wren
- Stanford University, Stanford, CA, USA
- Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA
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Huang YS, Yang JJ, Lee NY, Chen GJ, Ko WC, Sun HY, Hung CC. Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review. Expert Rev Anti Infect Ther 2017; 15:873-892. [PMID: 28782390 DOI: 10.1080/14787210.2017.1364991] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.
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Affiliation(s)
- Yu-Shan Huang
- a Department of Internal Medicine , National Taiwan University Hospital Hsin-Chu Branch , Hsin-Chu , Taiwan
| | - Jen-Jia Yang
- b Department of Internal Medicine , Po Jen General Hospital , Taipei , Taiwan
| | - Nan-Yao Lee
- c Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.,d Department of Medicine , College of Medicine, National Cheng Kung University , Tainan , Taiwan
| | - Guan-Jhou Chen
- e Department of Internal Medicine , National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei , Taiwan
| | - Wen-Chien Ko
- c Department of Internal Medicine , National Cheng Kung University Hospital , Tainan , Taiwan.,d Department of Medicine , College of Medicine, National Cheng Kung University , Tainan , Taiwan
| | - Hsin-Yun Sun
- e Department of Internal Medicine , National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei , Taiwan
| | - Chien-Ching Hung
- e Department of Internal Medicine , National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei , Taiwan.,f Department of Parasitology , National Taiwan University College of Medicine , Taipei , Taiwan.,g Department of Medical Research , China Medical University Hospital , Taichung , Taiwan.,h China Medical University , Taichung , Taiwan
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Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update. Surgery 2017; 162:325-348. [DOI: 10.1016/j.surg.2017.01.018] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 01/25/2017] [Indexed: 12/16/2022]
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Álvarez-Hernández DA, González-Chávez AM, González-Hermosillo-Cornejo D, Franyuti-Kelly GA, Díaz-Girón-Gidi A, Vázquez-López R. Present and past perspectives on Clostridium difficile infection. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2017; 83:41-50. [PMID: 28684034 DOI: 10.1016/j.rgmx.2017.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 03/14/2017] [Accepted: 03/29/2017] [Indexed: 01/05/2023]
Abstract
Clostridium difficile is a Gram-positive bacillus that has become one of the main hospital-acquired human gastrointestinal infections in recent years. Its incidence is on the rise, involving more virulent strains, affecting new and previously uncontemplated groups of patients, and producing changes in clinical presentation and treatment response that influence disease outcome. Early diagnosis and disease stratification based on the severity of C.difficile infection are essential for therapeutic management and the implementation of containment measures. However, the speed at which new strains with greater pathogenicity are developing is surpassing that of the development of new drugs, making it necessary to validate other therapeutic options. The present article is a review of the epidemiologic, pathophysiologic, diagnostic, and therapeutic aspects of C.difficile infection, from its first isolation to the present date, that aims to contribute to the preparation of general physicians and specialists, so that patients with this infection receive opportune and quality medical attention.
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Affiliation(s)
- D A Álvarez-Hernández
- Coordinación de Servicios Médicos, Cruz Roja Mexicana I.A.P., Delegación Huixquilucan, Huixquilucan, Estado de México, México.
| | - A M González-Chávez
- Departamento de Cirugía General, Hospital Español de México, Ciudad de México, México
| | | | - G A Franyuti-Kelly
- Facultad de Ciencias de la Salud, Universidad Anáhuac México Norte, Naucalpan de Juárez, Estado de México, México
| | - A Díaz-Girón-Gidi
- Departamento de Cirugía General, Fundación Clínica Médica Sur, Ciudad de México, México
| | - R Vázquez-López
- Departamento de Microbiología y Parasitología, Facultad de Ciencias de la Salud, Universidad Anáhuac México Norte, Naucalpan de Juárez, Estado de México, México
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Elliott B, Androga GO, Knight DR, Riley TV. Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2017; 49:1-11. [PMID: 28012982 DOI: 10.1016/j.meegid.2016.12.018] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Revised: 12/19/2016] [Accepted: 12/19/2016] [Indexed: 02/07/2023]
Abstract
Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.
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Affiliation(s)
- Briony Elliott
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
| | - Grace O Androga
- School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia
| | - Daniel R Knight
- School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia
| | - Thomas V Riley
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia; School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia; School of Veterinary and Life Sciences, Murdoch University, Murdoch, Australia; Department of Microbiology, PathWest Laboratory Medicine, Perth, Australia.
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40
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Silverman MA, Konnikova L, Gerber JS. Impact of Antibiotics on Necrotizing Enterocolitis and Antibiotic-Associated Diarrhea. Gastroenterol Clin North Am 2017; 46:61-76. [PMID: 28164853 PMCID: PMC5314436 DOI: 10.1016/j.gtc.2016.09.010] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Antibiotic treatment alters the composition and metabolic function of the intestinal microbiota. These alterations may contribute to the pathogenesis of necrotizing enterocolitis (NEC) and antibiotic-associated diarrhea (AAD). Recent studies are beginning to unravel the contribution of specific groups of microbes and their metabolic pathways to these diseases. Probiotics or other microbiota-targeted therapies may provide effect strategies to prevent and treat NEC and AAD.
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Affiliation(s)
- Michael A. Silverman
- Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104
| | - Liza Konnikova
- Department of Pediatric and Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115 and Department of Pediatrics, Harvard Medical School, Boston, MA 02115
| | - Jeffrey S. Gerber
- Center for Pediatric Clinical Effectiveness, Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104 and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
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41
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Khanna S, Pardi DS. Clinical implications of antibiotic impact on gastrointestinal microbiota and Clostridium difficile infection. Expert Rev Gastroenterol Hepatol 2016; 10:1145-1152. [PMID: 26907220 DOI: 10.1586/17474124.2016.1158097] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The human gastrointestinal (GI) microbiota plays an important role in human health. Anaerobic bacteria prevalent in the normal colon suppress the growth of non-commensal microorganisms, thus maintaining colonic homeostasis. The GI microbiota is influenced by both patient-specific and environmental factors, particularly antibiotics. Antibiotics can alter the native GI microbiota composition, leading to decreased colonization resistance and opportunistic proliferation of non-native organisms. A common and potentially serious antibiotic-induced sequela associated with GI microbiota imbalance is Clostridium difficile infection (CDI), which may become recurrent if dysbiosis persists. This review focuses on the association between antibiotics and CDI, and the antibiotic-induced disruption leading to recurrent CDI. Promoting antibiotic stewardship is pivotal in protecting native microbiota and reducing the incidence of CDI and other GI infections.
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Affiliation(s)
- Sahil Khanna
- a Division of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
| | - Darrell S Pardi
- a Division of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
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Bielakova K, Fernandova E, Matejovska-Kubesova H, Weber P, Prudius D, Bednar J. Can we improve the therapy of Clostridium difficile infection in elderly patients? Wien Klin Wochenschr 2016; 128:592-8. [PMID: 27501856 DOI: 10.1007/s00508-016-1056-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 07/08/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is becoming a serious problem predominantly in geriatric patients, who are a significant risk group. The goal of this study was to evaluate the risk factors for mortality in CDI patients and to construct a binary logistic regression model that describes the probability of mortality in geriatric patients suffering from CDI. METHODS In this retrospective study, we evaluated a group of 235 patients over 65 years of age with confirmed diagnoses of CDI, hospitalized at the Department of Internal Medicine, Geriatrics and General Practice, Brno, from January 2008 to December 2013. The examined group comprised 148 women (63 %) and 87 men (37 %). For the diagnosis of CDI, confirmation of A and B toxins in the patients' stool or an autopsy confirmation was crucial. RESULTS The impact of antibiotic therapy on the increased incidence of CDI was clearly confirmed in our study group when examining patients' histories. Other risk factors included cerebrovascular disease, dementia, the presence of pressure ulcers, and immobility. Our new model consisted of a combination of the following parameters: the number of antibiotics used (from patients' history), nutritional status (Mini Nutritional Assessment short-form test), presence of pressure ulcers, and occurrence of fever. CONCLUSION Our logistic regression model may predict mortality in geriatric patients suffering from CDI. This could help improve the therapeutic process.
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Affiliation(s)
- Katarina Bielakova
- Department of Internal Medicine, Geriatrics and General Practice, Faculty of Medicine, Masaryk University, Faculty Hospital Brno, Jihlavska 20, 62500, Brno, Czech Republic.
| | - Emmanuela Fernandova
- Department of Internal Medicine, Geriatrics and General Practice, Faculty of Medicine, Masaryk University, Faculty Hospital Brno, Jihlavska 20, 62500, Brno, Czech Republic
| | - Hana Matejovska-Kubesova
- Department of Internal Medicine, Geriatrics and General Practice, Faculty of Medicine, Masaryk University, Faculty Hospital Brno, Jihlavska 20, 62500, Brno, Czech Republic
| | - Pavel Weber
- Department of Internal Medicine, Geriatrics and General Practice, Faculty of Medicine, Masaryk University, Faculty Hospital Brno, Jihlavska 20, 62500, Brno, Czech Republic
| | - Dana Prudius
- Department of Internal Medicine, Geriatrics and General Practice, Faculty of Medicine, Masaryk University, Faculty Hospital Brno, Jihlavska 20, 62500, Brno, Czech Republic
| | - Josef Bednar
- Department of Statistics and Optimization, Faculty of Mechanical Engineering, Brno University of Technology, Brno, Czech Republic
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43
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Bentley DW. Clostridium difficile -Associated Disease in Long-Term Care Facilities. Infect Control Hosp Epidemiol 2016. [DOI: 10.2307/30146855] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Clostridium difficile is a major cause of gastrointestinal infections. In 1978, Bartlett and colleagues identified C difficile and its toxin as the cause of the antibiotic-associated pseudomembranous colitis (PMC). Within a few years, there was the development of a diagnostic assay, a description of a clinical and pathological spectrum of the disease, a definition of risk factors and characterization of the two toxins that account for the pathological event. Additional information regarding the microbiology, pathogenesis, clinical manifestations, diagnosis and treatment has rapidly developed. These features are beyond the scope of this report, and the reader is referred to several recent reviews.
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44
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Shin JH, Chaves-Olarte E, Warren CA. Clostridium difficile Infection. Microbiol Spectr 2016; 4:10.1128/microbiolspec.EI10-0007-2015. [PMID: 27337475 PMCID: PMC8118380 DOI: 10.1128/microbiolspec.ei10-0007-2015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Indexed: 02/07/2023] Open
Abstract
Clostridium difficile is an anaerobic, Gram-positive, spore-forming, toxin-secreting bacillus that has long been recognized to be the most common etiologic pathogen of antibiotic-associated diarrhea. C. difficile infection (CDI) is now the most common cause of health care-associated infections in the United States and accounts for 12% of these infections (Magill SS et al., N Engl J Med370:1198-1208, 2014). Among emerging pathogens of public health importance in the United States, CDI has the highest population-based incidence, estimated at 147 per 100,000 (Lessa FC et al., N Engl J Med372:825-834, 2015). In a report on antimicrobial resistance, C. difficile has been categorized by the Centers for Disease Control and Prevention as one of three "urgent" threats (http://www.cdc.gov/drugresistance/threat-report-2013/). Although C. difficile was first described in the late 1970s, the past decade has seen the emergence of hypertoxigenic strains that have caused increased morbidity and mortality worldwide. Pathogenic strains, host susceptibility, and other regional factors vary and may influence the clinical manifestation and approach to intervention. In this article, we describe the global epidemiology of CDI featuring the different strains in circulation outside of North America and Europe where strain NAP1/027/BI/III had originally gained prominence. The elderly population in health care settings has been disproportionately affected, but emergence of CDI in children and healthy young adults in community settings has, likewise, been reported. New approaches in management, including fecal microbiota transplantation, are discussed.
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Affiliation(s)
- Jae Hyun Shin
- Department of Medicine, Division of Infectious Disease and International Health, University of Virginia, Charlottesville, VA 22908
| | - Esteban Chaves-Olarte
- Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, Costa Rica
| | - Cirle A Warren
- Department of Medicine, Division of Infectious Disease and International Health, University of Virginia, Charlottesville, VA 22908
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Marra F, Ng K. Controversies Around Epidemiology, Diagnosis and Treatment of Clostridium difficile Infection. Drugs 2016; 75:1095-118. [PMID: 26113167 DOI: 10.1007/s40265-015-0422-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Clostridium difficile infection is a major public health problem. However, in recent years the epidemiology, risk factors, diagnosis, and treatment of C. difficile infection have undergone a significant change. The incidence of C. difficile has increased, not only in the healthcare sector but also in the community. Hospital-acquired infection and community-acquired disease have different risk factors, with the latter occurring in children and younger individuals without a history of antibiotic use or previous infections. From a clinician's perspective, a quick efficient diagnosis is required for patient treatment; however, the old method of using enzyme immunoassays is insensitive and not very specific. Recent literature around diagnostic testing for C. difficile infection suggests using PCR or a two-step algorithm to improve sensitivity and specificity. More failures and recurrence with metronidazole have led to treatment algorithms suggesting its use for mild infections and switching to vancomycin if there is no clinical improvement. Alternatively, if signs and symptoms suggest severe infection, then oral vancomycin is recommended as a first-line agent. The addition of a new but costly agent, fidaxomicin, has seen some disparity between the European and North American guidelines with regard to when it should be used. Lastly, rapid developments and good results with fecal microbial transplantation have also left clinicians wondering about its place in therapy. This article reviews the literature around some of the recent controversies in the field of C. difficile infection.
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Affiliation(s)
- Fawziah Marra
- University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada,
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Gerding DN, File TM, McDonald LC. Diagnosis and Treatment of Clostridium difficile Infection (CDI). INFECTIOUS DISEASES IN CLINICAL PRACTICE 2016; 24:3-10. [PMID: 29348706 PMCID: PMC5769958 DOI: 10.1097/ipc.0000000000000350] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Early and accurate diagnosis is essential for optimal treatment of individuals with Clostridium difficile infection (CDI) and for implementation of effective infection control procedures. The decision about which diagnostic test to use is an important one that should be based on test sensitivity, specificity, and predictive value. The challenges of CDI go beyond rapid identification and management of symptomatic patients. Asymptomatic carriage has long been suspected in C. difficile transmission, but it may play a larger role than previously thought. Emerging information also shows that patients treated for CDI remain colonized for many weeks after symptom resolution. In fact, stool culture positivity increases during the first weeks following treatment completion. Treatments that reduce the duration and degree of asymptomatic shedding could have added benefit for reduced transmission.
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Affiliation(s)
- Dale N. Gerding
- Edward Hines Jr VA Hospital, Hines, IL
- Loyola University Chicago Stritch School of Medicine, Chicago, IL
| | - Thomas M. File
- Division of Infectious Disease, Summa Health System, Akron, OH
- Infectious Disease Section, Northeast Ohio Medical University, Rootstown, OH
| | - L. Clifford McDonald
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA
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Vouga M, Greub G. Emerging bacterial pathogens: the past and beyond. Clin Microbiol Infect 2015; 22:12-21. [PMID: 26493844 PMCID: PMC7128729 DOI: 10.1016/j.cmi.2015.10.010] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 09/29/2015] [Accepted: 10/05/2015] [Indexed: 01/03/2023]
Abstract
Since the 1950s, medical communities have been facing with emerging and reemerging infectious diseases, and emerging pathogens are now considered to be a major microbiologic public health threat. In this review, we focus on bacterial emerging diseases and explore factors involved in their emergence as well as future challenges. We identified 26 major emerging and reemerging infectious diseases of bacterial origin; most of them originated either from an animal and are considered to be zoonoses or from water sources. Major contributing factors in the emergence of these bacterial infections are: (1) development of new diagnostic tools, such as improvements in culture methods, development of molecular techniques and implementation of mass spectrometry in microbiology; (2) increase in human exposure to bacterial pathogens as a result of sociodemographic and environmental changes; and (3) emergence of more virulent bacterial strains and opportunistic infections, especially affecting immunocompromised populations. A precise definition of their implications in human disease is challenging and requires the comprehensive integration of microbiological, clinical and epidemiologic aspects as well as the use of experimental models. It is now urgent to allocate financial resources to gather international data to provide a better understanding of the clinical relevance of these waterborne and zoonotic emerging diseases.
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Affiliation(s)
- M Vouga
- Center for Research on Intracellular Bacteria, Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland
| | - G Greub
- Center for Research on Intracellular Bacteria, Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne and University Hospital, Lausanne, Switzerland.
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Baines SD, Wilcox MH. Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection. Antibiotics (Basel) 2015; 4:267-98. [PMID: 27025625 PMCID: PMC4790285 DOI: 10.3390/antibiotics4030267] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Revised: 07/02/2015] [Accepted: 07/03/2015] [Indexed: 12/11/2022] Open
Abstract
Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments.
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Affiliation(s)
- Simon D Baines
- Department of Biological and Environmental Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK.
| | - Mark H Wilcox
- Leeds Institute of Biomedical and Clinical Sciences, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
- Department of Microbiology, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Leeds LS1 3EX, UK.
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Gerding DN, Lessa FC. The epidemiology of Clostridium difficile infection inside and outside health care institutions. Infect Dis Clin North Am 2015; 29:37-50. [PMID: 25582647 PMCID: PMC10924674 DOI: 10.1016/j.idc.2014.11.004] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
This article describes the global changes in Clostridium difficile epidemiology since the late twentieth century and into the twenty-first century when the new epidemic strain BI/NAP1/027 emerged. The article provides an overview of how understanding of C difficile epidemiology has rapidly evolved since its initial association with colitis in 1974. It also discusses how C difficile has spread across the globe, the role of asymptomatic carriers in disease transmission, the increased recognition of C difficile outside health care settings, the changes in epidemiology of C difficile infection in children, and the risk factors for disease.
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Affiliation(s)
- Dale N Gerding
- Department of Medicine, Loyola University Chicago Stritch School of Medicine, 2160 S 1st Avenue, Maywood, IL 60153, USA; Research Service, Edward Hines, Jr. Veterans Affairs Hospital, 5000 South Fifth Avenue, Building 1, Room 347, Hines, IL 60141, USA.
| | - Fernanda C Lessa
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
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Abstract
Antibiotics have significant and long-lasting effects on the intestinal microbiota and consequently reduce colonization resistance against pathogens, including Clostridium difficile. By altering the community structure of the gut microbiome, antibiotics alter the intestinal metabolome, which includes both host- and microbe-derived metabolites. The mechanisms by which antibiotics reduce colonization resistance against C. difficile are unknown yet important for development of preventative and therapeutic approaches against this pathogen. This review focuses on how antibiotics alter the structure of the gut microbiota and how this alters microbial metabolism in the intestine. Interactions between gut microbial products and C. difficile spore germination, growth, and toxin production are discussed. New bacterial therapies to restore changes in bacteria-driven intestinal metabolism following antibiotics will have important applications for treatment and prevention of C. difficile infection.
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Affiliation(s)
- Casey M. Theriot
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27607
| | - Vincent B. Young
- Department of Internal Medicine, Division of Infectious Disease, University of Michigan, Ann Arbor, Michigan 48109
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48109
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