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Morado F, Nanda N. A Review of Therapies for Clostridioides difficile Infection. Antibiotics (Basel) 2024; 14:17. [PMID: 39858303 PMCID: PMC11762378 DOI: 10.3390/antibiotics14010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/20/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI.
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Affiliation(s)
- Faiza Morado
- Department of Pharmacy, Keck Medical Center, University of Southern California, Los Angeles, CA 90033, USA;
| | - Neha Nanda
- Division of Infectious Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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2
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Bouza E, Aguado JM, Alcalá L, Almirante B, Alonso-Fernández P, Borges M, Cobo J, Guardiola J, Horcajada JP, Maseda E, Mensa J, Merchante N, Muñoz P, Pérez Sáenz JL, Pujol M, Reigadas E, Salavert M, Barberán J. Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR). REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2020; 33:151-175. [PMID: 32080996 PMCID: PMC7111242 DOI: 10.37201/req/2065.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 01/26/2020] [Indexed: 12/12/2022]
Abstract
This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.
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Affiliation(s)
- E Bouza
- Emilio Bouza MD, PhD, Instituto de Investigación Sanitaria Gregorio Marañón, Servicio de Microbiología Clínica y E. Infecciosas C/ Dr. Esquerdo, 46 - 28007 Madrid, Spain.
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3
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Cheng YW, Fischer M. Clinical management of severe, fulminant, and refractoryClostridioides difficileinfection. Expert Rev Anti Infect Ther 2020; 18:323-333. [DOI: 10.1080/14787210.2020.1730814] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Yao-Wen Cheng
- Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, IN, USA
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4
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Treatment of Severe and Fulminnant Clostridioides difficile Infection. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2019; 17:524-533. [PMID: 31745820 DOI: 10.1007/s11938-019-00262-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI). RECENT FINDINGS Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.
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Abstract
Clostridium difficile infection (CDI) represents one of the most serious nosocomial infections that have grown dramatically over the past decade. Vancomycin and metronidazole are currently used as a standard therapy for CDI. Metronidazole is recommended as a first-line therapy for mild-to-moderate infections and vancomycin is mainly used for severe and/or refractory cases. However, studies have demonstrated that there are quite high CDI relapse rates with both of these medications, which represents a challenge for clinicians. Over the last decade, a number of newer and novel therapeutic options have emerged as promising alternatives to these standard CDI therapies. The following review provides the updated summaries of these newer therapeutic agents and their status in the treatment of CDI.
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6
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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: 1372] [Impact Index Per Article: 196.0] [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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Once Daily High Dose Tigecycline Is Optimal: Tigecycline PK/PD Parameters Predict Clinical Effectiveness. J Clin Med 2018. [PMID: 29522431 PMCID: PMC5867575 DOI: 10.3390/jcm7030049] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE The clinical effectiveness of tigecycline depends on appropriate use, and PK/PD (pharmacokinetic/pharmacodynamic) parameters related to dose and dosing interval. METHODS In our 600-bed university-affiliated teaching hospital, we conducted a tigecycline efficacy review over a three-month period in 34 evaluable patients. Parameters assessed included clinical response, cure or treatment failure, once daily as q12h dosing, maintenance dosing, high dose vs. standard loading regimens, adverse effects, and the effect of infectious disease consultation on outcomes. RESULTS We found once daily high dose tigecycline (HDT) was highly effective in treating serious systemic infections due to MDR Gram-positive/negative pathogens as well as C. difficile colitis. Adverse effects were infrequent and limited to mild nausea/vomiting. Once daily HDT was highly effective, and the few treatment failures were related to suboptimal/split dosing regimens. CONCLUSION Once daily HDT was highly effective when used to treat susceptible pathogens and when optimally dosed, i.e., 200-400 mg (IV) loading dose ×1, followed by a once daily maintenance dose of 100-200 mg (IV) q24h.
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8
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Gil F, Calderón IL, Fuentes JA, Paredes-Sabja D. Clostridioides (Clostridium) difficile infection: current and alternative therapeutic strategies. Future Microbiol 2018; 13:469-482. [PMID: 29464969 DOI: 10.2217/fmb-2017-0203] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Clostridioides difficile (C. difficile) has become a pathogen of worldwide importance considering that epidemic strains are disseminated in hospitals of several countries, where community-acquired infections act as a constant source of new C. difficile strains into hospitals. Despite the advances in the treatment of infections, more effective therapies against C. difficile are needed but, at the same time, these therapies should be less harmful to the resident gastrointestinal microbiota. The purpose of this review is to present a description of issues associated to C. difficile infection, a summary of current therapies and those in developmental stage, and a discussion of potential combinations that may lead to an increased efficacy of C. difficile infection treatment.
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Affiliation(s)
- Fernando Gil
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, 8370035, Chile
| | - Iván L Calderón
- Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, 8370035, Chile
| | - Juan A Fuentes
- Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, 8370035, Chile
| | - Daniel Paredes-Sabja
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, 8370035, Chile
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9
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Marsh JW, Curry SR. Therapeutic Approaches for
Clostridium difficile
Infections. ACTA ACUST UNITED AC 2018; 30:9A.3.1-9A.3.9. [DOI: 10.1002/9780471729259.mc09a03s30] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Jane W. Marsh
- Epidemiology Research Unit, University of Pittsburgh Pittsburgh Pennsylvania
| | - Scott R. Curry
- Epidemiology Research Unit, University of Pittsburgh Pittsburgh Pennsylvania
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10
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Bartoletti M, Tedeschi S, Pascale R, Raumer L, Maraolo AE, Palmiero G, Tumietto F, Cristini F, Ambretti S, Giannella M, Lewis RE, Viale P. Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections. Int J Antimicrob Agents 2018; 51:516-521. [PMID: 29410250 DOI: 10.1016/j.ijantimicag.2018.01.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 12/29/2017] [Accepted: 01/13/2018] [Indexed: 12/19/2022]
Abstract
OBJECTIVES We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen. METHODS We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves. RESULTS We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46). CONCLUSION TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation.
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Affiliation(s)
- Michele Bartoletti
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
| | - Sara Tedeschi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Renato Pascale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Luigi Raumer
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Alberto Enrico Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy
| | - Giulia Palmiero
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy
| | - Fabio Tumietto
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Francesco Cristini
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Simone Ambretti
- Operative Unit of Clinical Microbiology, S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Maddalena Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Russell Edward Lewis
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
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Fehér C, Soriano A, Mensa J. A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection. Infect Dis Ther 2017; 6:1-35. [PMID: 27910000 PMCID: PMC5336415 DOI: 10.1007/s40121-016-0140-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Indexed: 12/16/2022] Open
Abstract
In spite of increased awareness and the efforts taken to optimize Clostridium difficile infection (CDI) management, with the limited number of currently available antibiotics for C. difficile the halt of this increasing epidemic remains out of reach. There are, however, close to 80 alternative treatment methods with controversial anti-clostridial efficacy or in experimental phase today. Indeed, some of these therapies are expected to become acknowledged members of the recommended anti-CDI arsenal within the next few years. None of these alternative treatment methods can respond in itself to all the major challenges of CDI management, which are primary prophylaxis in the susceptible population, clinical cure of severe cases, prevention of recurrences, and forestallment of asymptomatic C. difficile carriage and in-hospital spread. Yet, the greater the variety of treatment choices on hand, the better combination strategies can be developed to reach these goals in the future. The aim of this article is to provide a comprehensive summary of these experimental and currently off-label therapeutic options.
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Affiliation(s)
- Csaba Fehér
- Department of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain.
| | - Alex Soriano
- Department of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Josep Mensa
- Department of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
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12
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Dumitru IM, Dumitru E, Rugina S, Tuta LA. Toxic Megacolon - A Three Case Presentation. ACTA ACUST UNITED AC 2017; 3:39-44. [PMID: 29967870 PMCID: PMC5769890 DOI: 10.1515/jccm-2017-0008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 01/30/2017] [Indexed: 12/18/2022]
Abstract
Introduction Toxic megacolon is a life-threatening disease and is one of the most serious complications of Clostridium difficile infection (CDI), usually needing prompt surgical intervention. Early diagnosis and adequate medical treatment are mandatory. Cases presentation In the last two years, three Caucasian female patients have been diagnosed with toxic megacolon and treated in the Clinical Infectious Diseases Hospital, Constanta. All patients had been hospitalized for nonrelated conditions. The first patient was in chemotherapy for non-Hodgkin’s lymphoma, the second patient had undergone surgery for colon cancer, and the third patient had surgery for disc herniation. In all cases the toxin test (A+B) was positive and ribotype 027 was present. Abdominal CT examination, both native and after intravenous contrast, showed significant colon dilation, with marked thickening of the wall. Resolution of the condition did not occur using the standard treatment of metronidazole and oral vancomycin, therefore the therapy was altered in two cases using intracolonic administration of vancomycin and intravenous tigecycline. Conclusions In these three cases of CDI, the risk factors for severe evolution were: concurrent malignancy, renal failure, obesity, and immune deficiencies. Ribotype 027, a marker for a virulent strain of CD, was found in all three cases complicated by toxic megacolon. The intracolonic administration of vancomycin, and intravenous tigecycline was successful when prior standard therapy had failed, and surgery was avoided.
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Affiliation(s)
- Irina Magdalena Dumitru
- Discipline of Infectious Diseases, Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania
| | - Eugen Dumitru
- Discipline of Internal Medicine, Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania
| | - Sorin Rugina
- Discipline of Infectious Diseases, Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.,The Academy of Romanian Scientists, Bucharest, Romania
| | - Liliana Ana Tuta
- Discipline of Internal Medicine, Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania
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13
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Diagnosis and treatment of Clostridium difficile (C. diff) colitis: Review of the literature and a perspective in gynecologic oncology. Gynecol Oncol 2017; 144:428-437. [DOI: 10.1016/j.ygyno.2016.11.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 11/08/2016] [Accepted: 11/12/2016] [Indexed: 12/16/2022]
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14
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Liebenstein T, Schulz LT, Viesselmann C, Bingen E, Musuuza J, Safdar N, Rose WE. Effectiveness and Safety of Tigecycline Compared with Other Broad-Spectrum Antimicrobials in Abdominal Solid Organ Transplant Recipients with Polymicrobial Intraabdominal Infections. Pharmacotherapy 2017; 37:151-158. [PMID: 27983753 DOI: 10.1002/phar.1883] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
STUDY OBJECTIVE Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad-spectrum therapies for polymicrobial IAIs in this population. DESIGN Retrospective cohort study. SETTING Large academic medical center with multiple outpatient clinics. PATIENTS A total of 81 adult SOT recipients were included who were treated for confirmed or suspected polymicrobial IAIs from 2007-2012. Of these patients, 27 received tigecycline and 54 received comparator therapy with a broad-spectrum β-lactam (e.g., piperacillin-tazobactam, cefepime, or meropenem) with or without glycopeptide or lipopeptide gram-positive therapy (vancomycin or daptomycin) (comparator group). Patients in the comparator group were matched to tigecycline-treated patients based on transplant type (kidney, combined kidney-pancreas, combined kidney-liver, or solitary pancreas) in a 1:2 ratio (tigecycline-to-other broad-spectrum antibiotics). MEASUREMENTS AND MAIN RESULTS Data on patient demographics, comorbidities, and clinical variables were collected and compared by using bivariate analyses. Clinical outcomes-clinical cure, improvement or failure, and disease recurrence-as well as death within 1 year were analyzed by bivariate analyses and logistic regression. Clinical cure was lower in the tigecycline group versus the comparator group (40.7% vs 72.2%, p=0.008), but cure combined with improvement was similar between the two groups (85.2% vs 88.9%, p=0.724). Multiple logistic regression analysis showed that treatment with comparator antibiotics increased the odds of cure (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.15-12.27) and reduced the odds of treatment failure (OR 0.59, 95% CI 0.07-4.55) and death within 1 year (OR 0.79, 95% CI 0.22-2.86); however, patients receiving comparator antibiotics were more likely to have disease recurrence (OR 1.45, 95% CI 0.33-6.36). Patients receiving tigecycline experienced a higher rate of adverse events than those receiving comparator antibiotics (29.6% vs 9.3%, p=0.026). CONCLUSION Patients receiving tigecycline were less likely to achieve optimal clinical outcomes and had more adverse events. Alternative regimens should be selected over tigecycline for the treatment of polymicrobial IAIs in abdominal SOT recipients until additional studies are completed to examine its role in this population.
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Affiliation(s)
- Tyler Liebenstein
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.,School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin
| | - Lucas T Schulz
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.,School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin
| | - Chris Viesselmann
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.,School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin
| | - Emma Bingen
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.,School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin
| | - Jackson Musuuza
- Division of Infectious Diseases, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin
| | - Nasia Safdar
- Division of Infectious Diseases, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin
| | - Warren E Rose
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.,School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin
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15
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Trubiano JA, Cheng AC, Korman TM, Roder C, Campbell A, May MLA, Blyth CC, Ferguson JK, Blackmore TK, Riley TV, Athan E. Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand. Intern Med J 2017; 46:479-93. [PMID: 27062204 DOI: 10.1111/imj.13027] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 01/19/2016] [Accepted: 01/19/2016] [Indexed: 12/16/2022]
Abstract
The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.
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Affiliation(s)
- J A Trubiano
- Infectious Diseases Department, Austin Health, Melbourne, Western Australia.,Infectious Diseases Department, Peter MacCallum Cancer Centre, Melbourne, Western Australia
| | - A C Cheng
- Infectious Diseases Department, Alfred Health, Melbourne, Western Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Western Australia.,Infection Prevention and Healthcare Epidemiology Unit, Alfred Hospital, Melbourne, Western Australia
| | - T M Korman
- Monash Infectious Diseases, Monash Health, Monash University, Melbourne, Western Australia
| | - C Roder
- School of Medicine, Deakin University, Geelong, Victoria, Western Australia.,Geelong Centre for Emerging Infectious Diseases, Barwon Health, Geelong, Victoria, Western Australia
| | - A Campbell
- Infectious Diseases Department, Princess Margaret Hospital for Children, Queen Elizabeth II Medical Centre, Perth, Western Australia
| | - M L A May
- Infection Management and Prevention Service, Lady Cilento Children's Hospital and Sullivan Nicolaides Pathology, Brisbane, Queensland
| | - C C Blyth
- Infectious Diseases Department, Princess Margaret Hospital for Children, Queen Elizabeth II Medical Centre, Perth, Western Australia.,School of Paediatrics and Child Health, The University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Western Australia.,Department of Microbiology, PathWest Laboratory Medicine, Princess Margaret Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia
| | - J K Ferguson
- Pathology North, NSW Pathology, Wellington South, New Zealand.,Immunology and Infectious Diseases Unit, John Hunter Hospital, Wellington South, New Zealand.,Universities of New England and Newcastle, Newcastle, New South Wales, Australia
| | - T K Blackmore
- Laboratory Services, Wellington Regional Hospital, Wellington South, New Zealand
| | - T V Riley
- Microbiology and Immunology, School of Pathology and Laboratory Medicine, The University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Western Australia.,Department of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia
| | - E Athan
- School of Medicine, Deakin University, Geelong, Victoria, Western Australia.,Department of Infectious Disease, Barwon Health, Geelong, Victoria, Western Australia
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16
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Gergely Szabo B, Kadar B, Szidonia Lenart K, Dezsenyi B, Kunovszki P, Fried K, Kamotsay K, Nikolova R, Prinz G. Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study. Clin Microbiol Infect 2016; 22:990-995. [DOI: 10.1016/j.cmi.2016.08.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 07/05/2016] [Accepted: 08/13/2016] [Indexed: 12/11/2022]
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17
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Bandelj P, Golob M, Ocepek M, Zdovc I, Vengust M. Antimicrobial Susceptibility Patterns ofClostridium difficileIsolates from Family Dairy Farms. Zoonoses Public Health 2016; 64:213-221. [DOI: 10.1111/zph.12299] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Indexed: 01/05/2023]
Affiliation(s)
- P. Bandelj
- Veterinary Faculty; University of Ljubljana; Ljubljana Slovenia
| | - M. Golob
- Veterinary Faculty; University of Ljubljana; Ljubljana Slovenia
| | - M. Ocepek
- Veterinary Faculty; University of Ljubljana; Ljubljana Slovenia
| | - I. Zdovc
- Veterinary Faculty; University of Ljubljana; Ljubljana Slovenia
| | - M. Vengust
- Veterinary Faculty; University of Ljubljana; Ljubljana Slovenia
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18
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Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:1744-54. [PMID: 27120571 PMCID: PMC4911291 DOI: 10.1097/mib.0000000000000793] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the U.S. health care system and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges because the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New experimental treatments including vaccines, monoclonal antibodies, and nontoxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed.
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19
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Herzog T, Deleites C, Belyaev O, Chromik AM, Uhl W. [Clostridium difficile in visceral surgery]. Chirurg 2016; 86:781-6. [PMID: 25432576 DOI: 10.1007/s00104-014-2905-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND For surgeons the early identification of patients with clostridium difficile infections (CDI) is important, because the incidence and virulence of this potentially life-threatening disease are increasing. OBJECTIVES The aim of this study was to describe the frequency of CDI among surgical patients, to analyze which treatment was successful and to define which factors were associated with mortality. METHODS A retrospective analysis of patients with CDI was performed. RESULTS From January 2004 to June 2012 the overall incidence of CDI among all departments at the St. Josef Hospital, Ruhr University Bochum was 0.6 % (1669 out of 301,919 patients). In 2004 the number of surgical patients with CDI was 1 which increased to 41 in 2011. Before the diagnosis of CDI was made 84 % (151 out of 179) of patients had received an antibiotic treatment. Conservative management of CDI was performed with metronidazole in 75 % (134 out of 179), 60 % (107 out of 179) received vancomycin, while 44 % (79 out of 179) received a combination of metronidazole and vancomycin, tygecycline or fidaxomidin. The overall mortality was 7 % (12 out of 179). There was a significant association with mortality for patients with sepsis, readmission to the intensive care unit (ICU), requirement for vasopressor therapy and intubation with mechanical ventilation. In 4 % of patients (7 out of 179) colectomy was carried out. Despite maximum intensive care management, 86 % (6 out of 7) of patients who underwent colectomy ultimately died. CONCLUSION Although conservative management is successful for most patients with CDI, the mortality is high for patients who require intensive care management secondary to CDI. Mortality after colectomy for CDI is almost 100 %, mostly because the operation is usually only performed as a last resort in patients with sepsis. The most important risk factor for CDI is a prior antibiotic therapy.
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Affiliation(s)
- T Herzog
- Klinik für Allgemein- und Viszeralchirurgie, St. Josef Hospital, Klinikum der Ruhr Universität Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland
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20
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Abstract
Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value.
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Affiliation(s)
- Andrew Ofosu
- Department of Medicine, Jefferson Medical College, Philadelphia, USA
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21
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Erikstrup LT, Aarup M, Hagemann-Madsen R, Dagnaes-Hansen F, Kristensen B, Olsen KEP, Fuursted K. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ Open Gastroenterol 2015; 2:e000038. [PMID: 26568840 PMCID: PMC4641438 DOI: 10.1136/bmjgast-2015-000038] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 09/08/2015] [Indexed: 12/17/2022] Open
Abstract
Objective Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone. Design C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline by oral gavage. After the challenge, the mice were treated with placebo, vancomycin, metronidazole or a combination of vancomycin and metronidazole for 10 days. The mice were monitored for 20 days with weight and a clinical score. Stool samples were examined for C. difficile spore load and presence of C. difficile toxins. Results None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole recovered from CDI faster than mice treated with metronidazole alone. However, after discontinuation of treatment, vancomycin-treated and combination-treated mice succumbed to clinical and bacteriological relapse. Conclusions Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone. A combination of vancomycin and metronidazole did not improve the clinical outcome when compared to treatment with vancomycin alone. Trial registration number The trial registration number from the Danish Experimental Animal Inspectorate is J number 2012-15-2934-00422.
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Affiliation(s)
- Lise Tornvig Erikstrup
- Department of Clinical Microbiology , Aarhus University Hospital , Aarhus , Denmark ; Institute of Clinical Medicine, Aarhus University , Aarhus , Denmark
| | - Mie Aarup
- Department of Clinical Microbiology , Aarhus University Hospital , Aarhus , Denmark ; Department of Biomedicine , Aarhus University , Aarhus , Denmark
| | | | | | - Brian Kristensen
- Department of Microbiology and Infection Control , Statens Serum Institute , Copenhagen , Denmark
| | | | - Kurt Fuursted
- Department of Microbiology and Infection Control , Statens Serum Institute , Copenhagen , Denmark
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22
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Carmo J, Marques S, Chapim I, Túlio MA, Rodrigues JP, Bispo M, Chagas C. Leaping Forward in the Treatment of Clostridium Difficile Infection: Update in 2015. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:259-267. [PMID: 28868417 PMCID: PMC5579984 DOI: 10.1016/j.jpge.2015.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 07/01/2015] [Indexed: 12/15/2022]
Abstract
In recent years, significant advances in the treatment of Clostridium difficile infection (CDI) have risen. We review the most relevant updated recommendations in the current standard of care of CDI and discuss emerging therapies, including antibiotic, alternative therapies (probiotics, toxin-binding resins, immunotherapy) and new data on fecal transplantation. Upcoming surgical options and other rescue therapies for severe refractory disease are also addressed. Although oral metronidazole is a first-line therapy for non-severe CDI, emerging data have demonstrated its inferiority relatively to vancomycin, particularly in the setting of recurrent and/or severe infection. After a CDI recurrence for the first time, fidaxomicin has been shown to be associated with lower likelihood of CDI recurrence compared to vancomycin. Fecal transplantation is now strongly recommended for multiple recurrent CDI and may have a role in refractory disease. Oral, frozen stool capsules may simplify fecal transplantation in the future, with preliminary promising results. Diverting loop ileostomy combined with colonic lavage is a potential alternative to colectomy in severe complicated CDI. Potential alternative therapies requiring further investigation include toxin-binding resins and immunotherapy.
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Affiliation(s)
- Joana Carmo
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
| | - Susana Marques
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
| | - Iolanda Chapim
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
| | - Maria Ana Túlio
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
| | - José Pedro Rodrigues
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
| | - Miguel Bispo
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.,Gastroenterology and Digestive Endoscopy Center, Hospital da Luz, Lisbon, Portugal
| | - Cristina Chagas
- Gastroenterology Department, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
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23
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To KB, Napolitano LM. Clostridium difficile infection: update on diagnosis, epidemiology, and treatment strategies. Surg Infect (Larchmt) 2015; 15:490-502. [PMID: 25314344 DOI: 10.1089/sur.2013.186] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) has increased in incidence and severity over the past quarter century, and is now considered a major cause of healthcare-associated infections. METHODS Review of the pertinent English-language medical literature. RESULTS There has been a substantial change in the management of CDI. The emergence of the NAP1/BI/O27 strain in the early to mid-2000s has been associated with more severe forms of CDI. The pathophysiology, epidemiology, clinical manifestations and diagnosis, as well as new strategies for medical and surgical management are discussed in this review. CONCLUSIONS Clostridium difficile infection can range from benign diarrhea to severe disease associated with substantial morbidity and mortality. Treatment modalities vary based on disease severity and timing of onset. The mainstay of medical treatment remains metronidazole and oral/rectal vancomycin. New management strategies are evolving, including adjunctive treatments such as monoclonal antibodies, vaccination, and fecal transplant. In patients with severe disease or clinical deterioration, early surgical consultation for total colectomy or loop ileostomy may be life-saving. Infection control measures are vital to mitigating the spread of CDI.
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Affiliation(s)
- Kathleen B To
- Department of Surgery, University of Michigan , Ann Arbor, Michigan
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24
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An in vitro combined antibiotic-antibody treatment eliminates toxicity from Shiga toxin-producing Escherichia coli. Antimicrob Agents Chemother 2015; 59:5435-44. [PMID: 26100707 DOI: 10.1128/aac.00763-15] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 06/16/2015] [Indexed: 12/11/2022] Open
Abstract
Treating Shiga toxin-producing Escherichia coli (STEC) gastrointestinal infections is difficult. The utility of antibiotics for STEC treatment is controversial, since antibiotic resistance among STEC isolates is widespread and certain antibiotics dramatically increase the expression of Shiga toxins (Stxs), which are some of the most important virulence factors in STEC. Stxs contribute to life-threatening hemolytic uremic syndrome (HUS), which develops in considerable proportions of patients with STEC infections. Understanding the antibiotic resistance profiles of STEC isolates and the Stx induction potential of promising antibiotics is essential for evaluating any antibiotic treatment of STEC. In this study, 42 O157:H7 or non-O157 STEC isolates (including the "big six" serotypes) were evaluated for their resistance against 22 antibiotics by using an antibiotic array. Tigecycline inhibited the growth of all of the tested STEC isolates and also inhibited the production of Stxs (Stx2 in particular). In combination with neutralizing antibodies to Stx1 and Stx2, the tigecycline-antibody treatment fully protected Vero cells from Stx toxicity, even when the STEC bacteria and the Vero cells were cultured together. The combination of an antibiotic such as tigecycline with neutralizing antibodies presents a promising strategy for future STEC treatments.
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25
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Hung YP, Lee JC, Lin HJ, Liu HC, Wu YH, Tsai PJ, Ko WC. Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection. Antibiotics (Basel) 2015; 4:216-29. [PMID: 27025622 PMCID: PMC4790331 DOI: 10.3390/antibiotics4020216] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Revised: 04/25/2015] [Accepted: 06/15/2015] [Indexed: 12/29/2022] Open
Abstract
Clostridium difficile infection (CDI) is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin) is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not the standard therapeutic choices for CDI, they may serve as an alternative or a component of combination therapy. Previous tetracycline or doxycycline usage had been shown to have less association with CDI development. Tigecycline, a broad-spectrum glycylcycline with potency against many gram-positive or gram-negative pathogens, had been successfully used to treat severe or refractory CDI. The in vitro susceptibility of C. difficile clinical isolates to tigecycline in many studies showed low minimal inhibitory concentrations. Tigecycline can suppress in vitro toxin production in both historical and hypervirulent C. difficile strains and reduce spore production in a dose-dependent manner. Tetracycline compounds such as doxycycline, minocycline, and tigecycline possess anti-inflammatory properties that are independent of their antibiotic activity and may contribute to their therapeutic effect for CDI. Although clinical data are limited, doxycycline is less likely to induce CDI, and tigecycline can be considered one of the therapeutic choices for severe or refractory CDI.
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Affiliation(s)
- Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 70043, Taiwan.
- Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan 70403, Taiwan.
- Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan 70403, Taiwan.
| | - Jen-Chieh Lee
- Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan 70403, Taiwan.
| | - Hsiao-Ju Lin
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 70043, Taiwan.
- Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan 70403, Taiwan.
- Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan 70403, Taiwan.
| | - Hsiao-Chieh Liu
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 70043, Taiwan.
- Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan 70102, Taiwan.
| | - Yi-Hui Wu
- Department of Internal Medicine, E-da Hospital, Kaohsiung 82445, Taiwan.
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan 70102, Taiwan.
- Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 70102, Taiwan.
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan 70403, Taiwan.
- Department of Medicine, National Cheng Kung University, Medical College, Tainan 70102, Taiwan.
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26
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Di Bella S, Gouliouris T, Petrosillo N. Fecal microbiota transplantation (FMT) for Clostridium difficile infection: focus on immunocompromised patients. J Infect Chemother 2015; 21:230-237. [PMID: 25703532 DOI: 10.1016/j.jiac.2015.01.011] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 01/15/2015] [Accepted: 01/16/2015] [Indexed: 12/18/2022]
Abstract
Clostridium difficile infection (CDI) is an emerging problem worldwide associated with significant morbidity, mortality, recurrence rates and healthcare costs. Immunosuppressed patients, including HIV-seropositive individuals, solid organ transplant recipients, patients with malignancies, hematopoietic stem cell transplant recipients, and patients with inflammatory bowel disease are increasingly recognized as being at higher risk of developing CDI where it may be associated with significant complications, recurrence, and mortality. Fecal microbiota transplantation (FMT) has proven to be an effective and safe procedure for the treatment of recurrent or refractory CDI in immunocompetent patients by restoring the gut microbiota and resistance to further recurrences. During the last two years the first data on FMT in immunocompromised patients began to appear in the medical literature. Herein we summarize the use of FMT for the treatment of CDI with a focus on immunocompromised patients.
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Affiliation(s)
- Stefano Di Bella
- 2nd Division, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
| | - Theodore Gouliouris
- Department of Infectious Diseases, Cambridge University Hospitals, Cambridge, United Kingdom
| | - Nicola Petrosillo
- 2nd Division, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
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27
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Abstract
IMPORTANCE Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years). EVIDENCE REVIEW Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI). CONCLUSIONS AND RELEVANCE Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.
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Affiliation(s)
- Natasha Bagdasarian
- Division of Infectious Disease and Department of Infection Control, St John Hospital and Medical Center, Detroit, Michigan
- Wayne State University, Department of Internal Medicine, Detroit, Michigan
| | - Krishna Rao
- University of Michigan Medical School, Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Health System, Ann Arbor, Michigan
- Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
| | - Preeti N. Malani
- University of Michigan Medical School, Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Health System, Ann Arbor, Michigan
- Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
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28
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Fantin F, Manica A, Soldani F, Bissoli L, Zivelonghi A, Zamboni M. Use of tigecycline in elderly patients forClostridium difficileinfection. Geriatr Gerontol Int 2015; 15:230-1. [DOI: 10.1111/ggi.12336] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- Francesco Fantin
- Department of Medicine, Section of Geriatrics; University of Verona; Verona Italy
| | - Angela Manica
- Department of Medicine, Section of Geriatrics; University of Verona; Verona Italy
| | - Fabio Soldani
- Department of Pathology and Diagnostics; Section of Infectious Diseases; Azienda Ospedaliera Universitaria Integrata; Policlinico “G. B. Rossi”; Verona Italy
| | - Luisa Bissoli
- Department of Medicine, Section of Geriatrics; University of Verona; Verona Italy
| | | | - Mauro Zamboni
- Department of Medicine, Section of Geriatrics; University of Verona; Verona Italy
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29
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Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 2014; 20 Suppl 2:1-26. [PMID: 24118601 DOI: 10.1111/1469-0691.12418] [Citation(s) in RCA: 792] [Impact Index Per Article: 72.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 09/22/2013] [Accepted: 09/27/2013] [Indexed: 12/11/2022]
Abstract
In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended.
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30
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Tigecycline for severe Clostridium difficile infection. Int J Infect Dis 2014; 26:171-2. [DOI: 10.1016/j.ijid.2014.04.025] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Revised: 03/31/2014] [Accepted: 04/26/2014] [Indexed: 01/27/2023] Open
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31
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Aldape MJ, Heeney DD, Bryant AE, Stevens DL. Tigecycline suppresses toxin A and B production and sporulation in Clostridium difficile. J Antimicrob Chemother 2014; 70:153-9. [PMID: 25151204 DOI: 10.1093/jac/dku325] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) is mediated by potent extracellular toxins and is spread largely via bacterial spores. We and others have shown that some antibiotics stimulate C. difficile toxin production in a strain-specific manner; however, the effects of newer anti-C. difficile antibiotics on this process remain to be investigated. METHODS The effects of the protein synthesis inhibitor tigecycline on sporulation and toxin A and toxin B production were compared in historical (strain 9689) and hypervirulent BI/NAP1/027 (strain 5325) isolates of C. difficile in vitro. RESULTS Tigecycline at 1/4× MIC stimulated an increased and earlier toxin A and/or B gene expression in both the historical and the hypervirulent strains, although a commensurate increase in toxin protein production was observed only in the 9689 strain. In fact, in the hypervirulent 5325 strain, toxin production was dramatically suppressed. By comparison, subinhibitory concentrations of vancomycin and metronidazole also stimulated increased protein toxin production by the historical, but not the hypervirulent, strain. In addition, tigecycline dose-dependently reduced viable spore production by both the 9689 and 5325 strains. Vancomycin treatment also suppressed spore formation in both C. difficile strains; however, metronidazole, while reducing spore formation in the 9689 strain, stimulated a near 2 log increase in spore production by the 5325 isolate. CONCLUSIONS In summary, these findings suggest that the treatment of CDI patients with tigecycline could effectively both control disease progression and limit its spread by disrupting sporulation.
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Affiliation(s)
- Michael John Aldape
- Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA
| | - Dustin Delaney Heeney
- Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA
| | - Amy Evelyn Bryant
- Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA
| | - Dennis Leroy Stevens
- Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA
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Zhu S, Zhang H, Zhang X, Wang C, Fan G, Zhang W, Sun G, Chen H, Zhang L, Li Z. Investigation of toxin gene diversity and antimicrobial resistance of Clostridium difficile strains. Biomed Rep 2014; 2:743-748. [PMID: 25054021 DOI: 10.3892/br.2014.311] [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: 05/16/2014] [Accepted: 06/26/2014] [Indexed: 01/05/2023] Open
Abstract
The incidence of Clostridium difficile infection (CDI) has been previously reported in a number of studies. However, data collected from the Chinese population is limited. In the present study, the diversity of the toxin genes, tcdA and tcdB, of 57 Clostridium difficile (C. difficile) isolates from a Chinese population were investigated by polymerase chain reaction (PCR) (38 A+B+, 14 A-B+ and 5 A-B-). Quantitative PCR was used to check the expression of these two genes and it was found that the genes were not expressed by all the strains. The absence of tcdA or tcdB expression in certain strains could be due to the lower expression of tcdD and the higher expression of tcdC, which are positive and negative regulators for these two toxin genes, respectively. In addition, the antimicrobial susceptibilities of 57 isolates were investigated. Therefore, these data would aid in the future prevention of CDI outbreaks and improve the understanding of the infection.
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Affiliation(s)
- Shanshan Zhu
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Huaping Zhang
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Xinsheng Zhang
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Chao Wang
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Guangming Fan
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Weifeng Zhang
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Gang Sun
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Huihong Chen
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Liming Zhang
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
| | - Zhaoyun Li
- Central Hospital of Taizhou City, Taizhou, Zhejiang 318000, P.R. China
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Abstract
Clostridium difficile infection (CDI) is the leading health care-associated illness. Both human and animal models have demonstrated the importance of the gut microbiota's capability of providing colonization resistance against C. difficile. Risk factors for disease development include antibiotic use, which disrupts the gut microbiota, leading to the loss of colonization resistance and subsequent CDI. Identification of the specific microbes capable of restoring this function remains elusive. Future studies directed at how microbial communities influence the metabolic environment may help elucidate the role of the microbiota in disease development. These findings will improve current biotherapeutics for patients with CDI, particularly those with recurrent disease.
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Treatment of Clostridium difficile Infection With Tigecycline. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2014. [DOI: 10.1097/ipc.0000000000000113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Turner RB, Smith CB, Martello JL, Slain D. Role of doxycycline in Clostridium difficile infection acquisition. Ann Pharmacother 2014; 48:772-6. [PMID: 24682682 DOI: 10.1177/1060028014528792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To evaluate and review the literature surrounding the potential protective benefit of tetracyclines, particularly doxycycline, in reducing Clostridium difficile infection (CDI) acquisition. DATA SOURCES MEDLINE/PubMed, Google Scholar, and International Pharmaceutical Abstracts were searched through January 2014 using the search terms doxycycline, tetracycline, and Clostridium difficile. STUDY SELECTION AND DATA EXTRACTION Relevant studies, case reports, and review articles were screened for inclusion. Bibliographies of articles were extensively reviewed for additional sources. DATA SYNTHESIS Doxycycline is a second-generation tetracycline antibiotic indicated for use in a variety of clinical syndromes and has activity against aerobic Gram-positive and -negative, anaerobic, and atypical bacteria as well as protozoan parasites. Although not used therapeutically to treat CDI, doxycycline may prevent or attenuate the virulence factors of toxigenic C difficile. Current literature does not indicate an increased risk of development of CDI with doxycycline use. In 3 retrospective studies, the use of doxycycline was associated with a protective effect. CONCLUSIONS Doxycycline has been shown to have potential protective effects against the development of CDI. Although further randomized placebo-controlled studies are needed, available data suggest that the use of doxycycline in place of alternative antimicrobials, when appropriate, may be a useful antimicrobial stewardship strategy aimed at reducing the incidence of CDI.
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Affiliation(s)
- R Brigg Turner
- Pacific University Oregon School of Pharmacy, Hillsboro, OR, USA
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Abstract
PURPOSE OF REVIEW Clostridium difficile infections (CDIs) are of increasing concern in healthcare due to increasing incidence as well as suboptimal response to standard therapies. This review focuses on current updates in chemotherapeutic treatment options for primary CDI as well as for relapse. RECENT FINDINGS Metronidazole and vancomycin remain the standard therapy for mild and severe CDI, respectively. Fidaxomicin was approved for use in CDI by the US Food and Drug Administration in 2011 and new studies have shown a decreased rate of recurrence as compared with vancomycin as well as potential promise for use as a chaser. Rifaximin may be useful in salvage therapy for recurrent CDI as well as for a chaser. Tigecycline, teicoplanin, doxycycline, linezolid, nitazoxanide, amixicile, LFF571, and CB-183 315 have in-vitro activity and are under different stages of study. Monoclonal antitoxin antibodies for prevention of relapse of CDI are currently under evaluation in a phase 3 clinical trial. SUMMARY A variety of promising new treatment options for Clostridium difficile are under development, although further studies are necessary to determine the efficacy of these newer treatments for cure and preventing disease relapse.
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IV ECO, III ECO, Johnson DA. Clinical update for the diagnosis and treatment of Clostridium difficile infection. World J Gastrointest Pharmacol Ther 2014; 5:1-26. [PMID: 24729930 PMCID: PMC3951810 DOI: 10.4292/wjgpt.v5.i1.1] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Revised: 10/06/2013] [Accepted: 12/09/2013] [Indexed: 02/06/2023] Open
Abstract
Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.
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Garneau JR, Valiquette L, Fortier LC. Prevention of Clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam. BMC Infect Dis 2014; 14:29. [PMID: 24422950 PMCID: PMC3897887 DOI: 10.1186/1471-2334-14-29] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 01/08/2014] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro. METHODS The reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic. RESULTS All strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates. CONCLUSIONS The capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.
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Affiliation(s)
| | | | - Louis-Charles Fortier
- Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3201 rue Jean Mignault, Sherbrooke, Québec J1E 4K8, Canada.
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Tsutsumi LS, Owusu YB, Hurdle JG, Sun D. Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review. Curr Top Med Chem 2014; 14:152-75. [PMID: 24236721 PMCID: PMC3921470 DOI: 10.2174/1568026613666131113154753] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 09/06/2013] [Accepted: 09/15/2013] [Indexed: 02/07/2023]
Abstract
Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.
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Affiliation(s)
| | | | | | - Dianqing Sun
- Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
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40
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Bass S, Bauer S, Neuner E, Lam S. Comparison of treatment outcomes with vancomycin alone versus combination therapy in severe Clostridium difficile infection. J Hosp Infect 2013; 85:22-7. [DOI: 10.1016/j.jhin.2012.12.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Accepted: 12/11/2012] [Indexed: 10/26/2022]
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Pant C, Deshpande A, Altaf MA, Minocha A, Sferra TJ. Clostridium difficile infection in children: a comprehensive review. Curr Med Res Opin 2013; 29:967-84. [PMID: 23659563 DOI: 10.1185/03007995.2013.803058] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To provide a comprehensive review of the literature relating to Clostridium difficile (C. difficile) infection (CDI) in the pediatric population. METHODS Two investigators conducted independent searches of PubMed, Web of Science, and Scopus until March 31st, 2013. All databases were searched using the terms 'Clostridium difficile infection', 'Clostridium difficile associated diarrhea' 'antibiotic associated diarrhea', 'C. difficile', in combination with 'pediatric' and 'paediatric'. Articles which discussed pediatric CDI were reviewed and relevant cross references also read and evaluated for inclusion. Selection bias could be a possible limitation of this approach. FINDINGS There is strong evidence for an increased incidence of pediatric CDI. Increasingly, the infection is being acquired from the community, often without a preceding history of antibiotic use. The severity of the disease has remained unchanged. Several medical conditions may be associated with the development of pediatric CDI. Infection prevention and control with antimicrobial stewardship are of paramount importance. It is important to consider the age of the child while testing for CDI. Traditional therapy with metronidazole or vancomycin remains the mainstay of treatment. Newer antibiotics such as fidaxomicin appear promising especially for the treatment of recurrent infection. Conservative surgical options may be a life-saving measure in severe or fulminant cases. CONCLUSIONS Pediatric providers should be cognizant of the increased incidence of CDI in children. Early and judicious testing coupled with the timely institution of therapy will help to secure better outcomes for this disease.
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Affiliation(s)
- Chaitanya Pant
- Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Chaparro-Rojas F, Mullane KM. Emerging therapies for Clostridium difficile infection - focus on fidaxomicin. Infect Drug Resist 2013; 6:41-53. [PMID: 23843696 PMCID: PMC3702225 DOI: 10.2147/idr.s24434] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The epidemiology of Clostridium difficile infections (CDI) has evolved during the last decades, with an increase in the reported incidence, severity of cases, and rate of mortality and relapses. These increases have primarily affected some special populations including the elderly, patients requiring concomitant antibiotic therapy, patients with renal failure, and patients with cancer. Until recently, the treatment of CDI was limited to either metronidazole or vancomycin. New therapeutic options have emerged to address the shortcomings of current antibiotic therapy. Fidaxomicin stands out as the first-in-class oral macrocyclic antibiotic with targeted activity against C. difficile and minimal collateral damage on the normal colonic flora. Fidaxomicin has demonstrated performance not inferior to what is considered the "gold standard" available therapy for CDI, vancomycin, in two separate Phase III clinical trials, but with significant advantages, including fewer recurrences and higher rates of sustained clinical cures. Fidaxomicin constitutes an important development in targeted antibiotic therapy for CDI and must be considered as a first-line agent for patients with risk factors known to portend relapse and severe infection.
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Affiliation(s)
- Fredy Chaparro-Rojas
- Department of Medicine, Section of Infectious Diseases, University of Chicago, Chicago, IL, USA
| | - Kathleen M Mullane
- Department of Medicine, Section of Infectious Diseases, University of Chicago, Chicago, IL, USA
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Analysis of anti-Clostridium difficile activity of thuricin CD, vancomycin, metronidazole, ramoplanin, and actagardine, both singly and in paired combinations. Antimicrob Agents Chemother 2013; 57:2882-6. [PMID: 23571539 DOI: 10.1128/aac.00261-13] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Due to the ongoing problem of recurrence of Clostridium difficile-associated diarrhea following antibiotic treatment, there is an urgent need for alternative treatment options. We assessed the MICs of five antimicrobials singly and in combinations against a range of C. difficile clinical isolates. Ramoplanin-actagardine combinations were particularly effective, with partial synergistic/additive effects observed against 61.5% of C. difficile strains tested.
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Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108:478-98; quiz 499. [PMID: 23439232 DOI: 10.1038/ajg.2013.4] [Citation(s) in RCA: 1184] [Impact Index Per Article: 98.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratified depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mild-to-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classification of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI.
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Affiliation(s)
- Christina M Surawicz
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
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Kleger A, Schnell J, Essig A, Wagner M, Bommer M, Seufferlein T, Härter G. Fecal transplant in refractory Clostridium difficile colitis. DEUTSCHES ARZTEBLATT INTERNATIONAL 2013; 110:108-15. [PMID: 23468820 DOI: 10.3238/arztebl.2013.0108] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 11/27/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clostridium difficile infections are becoming more common, more severe, and more likely to recur. Conventional treatment with antibiotics often fails to eradicate the infection; even when it succeeds, recurrent infection is common. Complementary treatment with probiotic agents to reconstitute the physiological intestinal flora does not yield any consistent benefit. In recent years, fecal transplantation has been used in the English-speaking countries with cure rates of about 87%, but the available evidence is limited to large case series. No randomized controlled trials have been performed. We present the case of a 73-year-old woman with intractable, recurrent enterocolitis due to Clostridium difficile who was successfully treated with fecal transplantation via colonoscopy. CASE DESCRIPTION Upon the completion of antibiotic treatment for a second recurrence of enterocolitis, stool in liquid suspension was introduced into the patient's colon through a colonoscope. Prior testing had shown the stool donor to be free of acute infection or stool pathogens. The patient was given loperamide to prolong contact of the stool transplant with the colonic mucosa. She was also treated with Saccharomyces cerevisiae for four weeks. COURSE There was no clinical or microbiological evidence of a further recurrence of enterocolitis for 6 months after transplantation. Stool transplantation had no adverse effects. CONCLUSION This patient had a lasting remission of enterocolitis due to Clostridium difficile after the treatment described above. Fecal transplantation seems to be a safe and highly effective treatment for recurrent Clostridium difficile infection. It is unclear whether the administration of Saccharomyces cerevisiae confers any additional benefit.
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Affiliation(s)
- Alexander Kleger
- Ulm University Hospital Medical Center, Department of Internal Medicine I, Germany
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46
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Beauduy C, MacDougall C. Update on Management of Clostridium difficileInfection. Hosp Pharm 2013. [DOI: 10.1310/hpj4802-s7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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47
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Berg AM, Kelly CP, Farraye FA. Clostridium difficile infection in the inflammatory bowel disease patient. Inflamm Bowel Dis 2013; 19:194-204. [PMID: 22508484 DOI: 10.1002/ibd.22964] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Clostridium difficile infection (CDI) has been increasing in frequency and severity in patients with inflammatory bowel disease (IBD). Population based and single center studies have shown worse clinical outcomes in concomitant CDI and IBD, with several reporting longer length of hospital stay, higher colectomy rates and increased mortality. Clinically, CDI may be difficult to distinguish from an IBD flare and may range from an asymptomatic carrier state to severe life threatening colitis. The traditional risk factors for CDI have included hospitalization, antibiotic use, older age and severe co-morbid disease but IBD patients have several distinct characteristics including younger age, community acquisition, lack of antibiotic exposure, colonic IBD and steroid use. CDI can occur in the small bowel and specifically in ulcerative colitis patients who have had a colectomy and an ileal pouch anal anastomosis. PCR based assays and combination Elisa algorithms have improved the sensitivity and specificity of testing, though in IBD patients have raised clinical questions about how to best manage diarrhea in the setting of possible C. difficile colonization. Treatment modalities for CDI have not been examined in randomized clinical trials in the IBD population. Newer antibiotics, immunotherapy and fecal microbiota transplantation may alter current treatment strategies. This review will focus on the unique epidemiology of CDI in IBD patients, detail clinical disease states, and provide updated diagnostic strategies, prevention and treatment options.
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Affiliation(s)
- Adam M Berg
- Section of Gastroenterology, Boston Medical Center, Boston, Massachusetts 02118-2338, USA.
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48
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Badger VO, Ledeboer NA, Graham MB, Edmiston CE. Clostridium difficile: epidemiology, pathogenesis, management, and prevention of a recalcitrant healthcare-associated pathogen. JPEN J Parenter Enteral Nutr 2012; 36:645-62. [PMID: 22577120 DOI: 10.1177/0148607112446703] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Clostridium difficile is the leading cause of healthcare-associated infectious diarrhea. Although C difficile is part of normal flora in some healthy individuals, patients with selective risk factors are often vulnerable to the toxigenic potential of this virulent healthcare pathogen. The spectrum of C difficile infection (CDI) is highly variable, ranging from mild to severe illness, presenting with single to multiple disease recurrences. Current approaches to treatment are based on severity of illness, number of recurrences, and clinical presentation. Oral vancomycin and metronidazole have formed the foundation for treatment of CDI, but therapeutic failures are commonly reported, especially involving hypervirulent clones. Alternative therapies, including newer antimicrobials, probiotics, immunotherapy, and fecal transplantation, have all met with varying degrees of efficacy. Although toxigenic culture (TC) testing from anaerobic culture remains the gold standard, newer technologies, including enzyme immunoassay, common antigen (glutamate dehydrogenase) testing, and real-time polymerase chain reaction (PCR) are less time-consuming and rapid. However, TC and PCR have reported high specificity and sensitivity when compared with other laboratory tests. Because of the significant morbidity and mortality associated with CDI, a high index of suspicion is warranted. Prevention and eradication of CDI require a multidisciplinary approach, including early disease recognition through appropriate surveillance, implementation of effective contact isolation strategies, adherence to environmental controls, judicious hand hygiene, evidence-based treatment, and management that includes antibiotic stewardship, continuous education of healthcare workers, and administrative support.
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Affiliation(s)
- Victor O Badger
- Department of Internal Medicine, Division of Infection Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
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Vardakas KZ, Polyzos KA, Patouni K, Rafailidis PI, Samonis G, Falagas ME. Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence. Int J Antimicrob Agents 2012; 40:1-8. [PMID: 22398198 DOI: 10.1016/j.ijantimicag.2012.01.004] [Citation(s) in RCA: 204] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 01/04/2012] [Accepted: 01/05/2012] [Indexed: 12/30/2022]
Abstract
The objective of this review was to evaluate the frequency of treatment failure and recurrence of Clostridium difficile infection (CDI) following treatment with vancomycin or metronidazole in recently performed studies (last 10 years). Searches in PubMed and Scopus were performed by two reviewers independently. Data regarding treatment failure and recurrence following metronidazole and vancomycin treatment were extracted and analysed. In total, 39 articles (7005 patients) were selected for inclusion in the systematic review. The reported treatment failure was 22.4% with metronidazole (16 studies) and 14.2% with vancomycin (8 studies). Recurrence of CDI occurred in 27.1% of patients following metronidazole treatment (18 studies) and 24.0% of patients following vancomycin treatment (8 studies). Mean treatment failure and recurrence in the selected studies was 22.3% (24 studies) and 22.1% (37 studies). The reported outcomes depended on the study design (higher in prospective and retrospective cohort studies than in randomised controlled trials), geographic location of the study (higher in North America than in Europe and Asia), funding (higher in studies funded by non-profit organisations than pharmaceutical companies), mean age of the studied population (higher in older patients) and duration of follow-up (higher in studies with follow-up >1 month). In conclusion, infection with C. difficile is associated with 22.4% and 14.2% treatment failure and 27.1% and 24.0% recurrence after treatment with metronidazole and vancomycin, respectively. The variation in the reported outcomes amongst studies depends on the study design, location, funding, age and follow-up period.
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Hooper MH, Kelly UM, Marik PE. An overview of the diagnosis and management of Clostridium difficile infection. Hosp Pract (1995) 2012; 40:119-129. [PMID: 22406887 DOI: 10.3810/hp.2012.02.952] [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: 05/31/2023]
Abstract
The diagnosis and treatment of Clostridium difficile infection are becoming increasingly complex with the introduction of novel diagnostic techniques and new pharmacologic and nonpharmacologic treatments. The integration of these new approaches with older, established methods is a challenge to individual clinicians and hospital systems. This article provides an overview of the current methods for the diagnosis and treatment of C difficile infection.
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Affiliation(s)
- Michael H Hooper
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
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