scholarly journals Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

Author(s):  
Kevin Zhang ◽  
Patricia Beckett ◽  
Salaheddin Abouanaser ◽  
Marek Smieja

Abstract Objective: Clostridioides difficile infection (CDI) is the leading cause of infectious nosocomial diarrhea. Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists varied recommendations for first-episode non-severe CDI. Given the discrepancy in current treatment guidelines, we sought to evaluate the use of initial vancomycin versus metronidazole for first-episode non-severe CDI. Methods: We conducted a retrospective cohort study of all adult inpatients with first-episode CDI at our institution from January 2013 to May 2018. The initial vancomycin versus initial metronidazole cohorts were examined using a multivariate logistic regression model. Results: The study cohort of 737 patients had a median age of 72.3 years, and 357 of these patients (48.4%) had hospital-acquired infection. Among 326 patients with non-severe CDI, recurrence, new incident infection, and 30-day mortality rates were 16.2%, 10.9%, and 5.3%, respectively, when treated with initial metronidazole, compared to 20.0%, 1.4%, and 10.0%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of initial vancomycin for the treatment of non-severe CDI was associated with a reduction in new incident infection (adjusted odds ratio [ORadj], 0.11; 95% confidence interval [CI], 0.02–0.86; P = .035), compared to initial metronidazole. Conclusions: Initial vancomycin was associated with a reduced rate of new incident infection in the treatment of adult inpatients with first-episode non-severe CDI. These findings support the use of initial vancomycin for all inpatients with CDI, when fidaxomicin is unavailable.

2020 ◽  
Author(s):  
Kevin Zhang ◽  
Patricia Beckett ◽  
Salaheddin Abouanaser ◽  
Marek Smieja

AbstractBackgroundClostridium difficile infection (CDI) is an important cause of nosocomial diarrhea. Given the discrepancy in current treatment guidelines for mild CDI, we sought to evaluate the use of first-line vancomycin for the treatment of non-severe infection.MethodsWe conducted a retrospective cohort study of all adult inpatients with first episode CDI at our institution from January 2013 to May 2018. CDI was defined as a positive C. difficile loop-mediated isothermal amplification assay, in conjunction with ≥3 type 5–7 stools on the Bristol stool scale. To evaluate the impact of first-line vancomycin treatment on adverse clinical outcomes in patients with first episode non-severe CDI, the initial vancomycin vs. initial metronidazole cohorts were first examined in an unadjusted logistic regression analysis for any combination of relapse, recurrence, and all-cause 30-day mortality, followed by an adjusted multivariable analysis.ResultsA total of 737 cases were included. Patients had a median age of 72.3 years (Q1: 61.2, Q3: 83.3) and 628 (85.2%) were classified as non-severe CDI. Among patients with non-severe CDI (n = 628), relapse, recurrence, and mortality rates were 17.4%, 7.0%, and 11.4%, respectively, when treated with initial metronidazole, compared to 18.6%, 3.1%, and 7.8%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of first-line vancomycin for the treatment of non-severe CDI was associated with a reduction in recurrence or 30-day mortality (ORadj: 0.51; 95%CI: 0.28–0.94; P=0.03).ConclusionsInitial vancomycin was associated with reduced recurrence or all-cause 30-day mortality in the treatment of adult inpatients with first episode non-severe CDI. Our findings support the use of initial vancomycin for all C. difficile inpatients, irrespective of disease severity, as recommended by Infectious Diseases Society of America guidelines.


Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 352
Author(s):  
Nicoleta Negrut ◽  
Simona Bungau ◽  
Tapan Behl ◽  
Shamim Ahmad Khan ◽  
Cosmin Mihai Vesa ◽  
...  

Clostridioides difficile (CD) is responsible for nosocomial diarrhea syndrome with possible severe progression. Recurrence of the disease induces higher health system costs, as well as exposes patients to additional health risks. Patients with recurrence of this disease are difficult to identify, so the purpose of this study is to quantify various demographic, clinical, and treatment factors that could prevent further progression to recurrence of the disease. In the period 2018–2019, about 195 patients were diagnosed with more than one episode of CDI in the three months following the first episode. The recurrence rate for CDI was 53.84% (60.95% for one episode and 39.05% for multiple episodes). Most commonly afflicted were 60–69-year-old patients, or those with higher Charlson Comorbidity Index (CCI). Multiple analyses associated cardiovascular (odds ratios (OR) = 3.02, 95% confidence intervals (CI) = 1.23–7.39, p = 0.015), digestive (OR = 3.58, 95% CI = 1.01–12.63, p = 0.047), dementia (OR = 3.26, 95% CI = 1.26–8.41, p = 0.014), immunosuppressive (OR = 3.88, 95% CI = 1.34–11.21, p = 0.012) comorbidities with recurrences. Risk factor identification in the first episode of CDI could lead to the implementation of treatment strategies to improve the patients’ quality of life affected by this disease.


2021 ◽  
Vol 14 ◽  
pp. 175628482110119
Author(s):  
Abdelkader Chaar ◽  
Paul Feuerstadt

Clostridioides difficile infection (CDI) has been an epidemic for many years. Our biggest challenge in treating CDI is preventing recurrence, which is seen in approximately 25% of patients with initial infection and in 40–60% of those with subsequent episodes. Given the major disease burden of this infection, appropriate data-driven treatment remains essential. Clinical treatment guidelines provide an unbiased critical analysis of the literature, integrating the quality of the available data to make recommendations. As CDI has been evolving and more research has become available, the frequency of guideline issue from various global societies has increased, as has the detail of the recommendations to fit more relevant clinical scenarios. In this review, we will discuss clinical guideline recommendations over three time periods: The Initial Guidelines 1995–1997, The Second Wave 2009–2013, and The Modern Era 2014–present. We see the changing recommendations from metronidazole or vancomycin for initial infection during earlier times to preferential treatment with fidaxomicin within the Infectious Diseases Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) joint guidelines provisional update in late 2020. The recommended treatments for first recurrence were initially with the same antimicrobial as the first episode but have since changed to having multiple options for one or more recurrences. We have also seen the addition of immune boosting treatments, including fecal microbiota transplantation (FMT)/microbiota restoration therapy (MRT) and bezlotoxumab in the more modern recommendations. As the guidelines are evolving with the times, it remains important to understand the differences among them so we can apply this information clinically and optimize patient outcomes.


Author(s):  
Ryan Goon Hon Au

Clostridioides difficile (C. diff.) is a leading cause of nosocomial infections worldwide and is a major challenge to public health. Widespread use of antibiotic agents have caused increasing incidence rates of C. diff. infections and the emergence of antibiotic-resistant strains of the potentially-deadly bacteria. The current treatment guidelines include the use of various antibiotics, which further contributes to the problem of antibiotic resistance. There is an urgent need for novel treatment methods in order to halt the emergence of even more antibiotic-resistant bacteria. This review discusses the pathogenesis of C. diff. infections, current treatment strategies, and possible alternative treatment strategies based on breakthrough scientific research.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S441-S442
Author(s):  
Xing Tan ◽  
Andrew M Skinner ◽  
Benjamin Sirbu ◽  
Larry H Danziger ◽  
Dale N Gerding ◽  
...  

Abstract Background There is a paucity of data assessing outcomes of alternate fidaxomicin strategies in patients with recurrent Clostridioides difficile infection (rCDI). The objective of our study is to evaluate a tapered-pulsed (T-P) fidaxomicin regimen that was administered immediately following a course of CDI treatment with initial symptom resolution in patients with multiple rCDI. Methods We reviewed the characteristics and outcomes of 46 consecutive patients who received T-P fidaxomicin between January 1, 2014-June 30, 2019 in a specialty CDI clinic. The first episode in which fidaxomicin T-P was administered was analyzed. Failure was defined as the persistence of diarrhea and/or the need for additional CDI treatment at any time on T-P fidaxomicin. Sustained clinical cure (SCC) was defined as resolution of diarrhea without recurrence. Recurrence was defined as the return of diarrhea requiring retreatment with CDI therapy after completion of T-P fidaxomicin. Both SCC and recurrence were evaluated at 30 and 90 days after completion of T-P fidaxomicin. Results The mean±SD age of the 46 patients was 63.2±19.9 years, 71.7% were female, and the mean±SD CDI episodes within the past year was 3±1.4 . Most patients (73.9%) had previously failed a vancomycin tapered and/or pulsed regimen. Prior to administering T-P fidaxomicin, a treatment regimen was given to ensure resolution of symptoms. The CDI treatment most commonly used (58.7%) was vancomycin. The T-P fidaxomicin regimen used consisted of 200 mg given once daily for 7 days followed by 200 mg every other day for a median (min-max) duration of 33 (6-120) days. Two patients (4%) failed to respond to T-P fidaxomicin; 34 (74%) and 28 (61%) achieved SCC at 30 and 90 days, respectively. Among the 44 patients that successfully completed the T-P fidaxomicin regimen, recurrence developed in 10 (22.7%) and 16 (36.4%) of patients at 30 and 90 days, respectively, with a median (min-max) time to recurrence of 20 (3-87) days (Figure 1). Four patients with recurrence had received subsequent systemic antibiotics. Figure 1. Course of CDI therapy and follow-up Conclusion A tapered-pulsed fidaxomicin strategy may be effective in patients with multiply rCDI who are refractory to other treatments, including a vancomycin tapered and pulsed regimen. Disclosures Larry H. Danziger, PharmD, Merck (Speaker’s Bureau)


2021 ◽  
Vol 10 (13) ◽  
pp. 2957
Author(s):  
Shira Buchrits ◽  
Anat Gafter-Gvili ◽  
Jihad Bishara ◽  
Alaa Atamna ◽  
Gida Ayada ◽  
...  

Background: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. Methods: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. Results: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01–3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01–2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. Conclusions: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.


mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Jhansi L. Leslie ◽  
Matthew L. Jenior ◽  
Kimberly C. Vendrov ◽  
Alexandra K. Standke ◽  
Madeline R. Barron ◽  
...  

ABSTRACT Clostridioides difficile, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for C. difficile infection (CDI), as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative C. difficile. To date, the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is nontoxigenic C. difficile. Using multiple infection models, we determined that precolonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of C. difficile, surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain of C. difficile, is sufficient to decrease germination of the second strain, thereby limiting colonization by the lethal strain. IMPORTANCE Antibiotic-associated colitis is often caused by infection with the bacterium Clostridioides difficile. In this study, we found that reduction of the amino acid glycine by precolonization with a less virulent strain of C. difficile is sufficient to decrease germination of a second strain. This finding demonstrates that the axis of competition for nutrients can include multiple life stages. This work is important, as it is the first to identify a possible mechanism through which precolonization with C. difficile, a current clinical therapy, provides protection from reinfection. Furthermore, our work suggests that targeting nutrients utilized by all life stages could be an improved strategy for bacterial therapeutics that aim to restore colonization resistance in the gut.


Author(s):  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
Melissa F Wilcox ◽  
Sarah G Theriault ◽  
Faris S Alnezary ◽  
...  

Abstract Objectives The pathogenesis of Clostridioides difficile infection (CDI) involves a significant host immune response. Generally, corticosteroids act by suppressing the host inflammatory response, and their anti-inflammatory effects are used to treat gastrointestinal disorders. Although previous investigations have demonstrated mixed results regarding the effect of corticosteroids on CDI, we hypothesized that the anti-inflammatory effect of corticosteroids would decrease the risk of CDI in hospitalized patients. Methods This was a case-control study of hospitalized adults. The case population included patients diagnosed with primary CDI who received at least one dose of a high-risk antibiotic (cefepime, meropenem, or piperacillin-tazobactam) in the 90 days prior to CDI diagnosis. The control population included patients who received at least one dose of the same high-risk antibiotic but did not develop CDI in the 90 days following their first dose of antibiotic. The primary study outcome was the development of CDI based on receipt of corticosteroids. Results The final study cohort consisted of 104 cases and 153 controls. Those who received corticosteroids had a lower odds of CDI after adjusting for age, proton-pump inhibitor use, and antibiotic days of therapy (OR, 0.54; 95% CI, 0.30 to 0.97; P=0.04). We did not observe an association between corticosteroid dose or duration and CDI. Conclusions We demonstrated a 46% relative reduction in the odds of developing CDI in patients who received corticosteroids in the past 90 days. We believe that our results provide the best clinical evidence to further support mechanistic studies underlying this phenomenon.


Author(s):  
María Esteban-Rihuete ◽  
Luis Moreno-Borraz ◽  
Diego Rodríguez-Gascón ◽  
Julio César García-Herrero ◽  
Juan Manuel García-Lechuz ◽  
...  

Objective. The aim of the study was to know the characteristics and risk factors of Clostridioides difficile infection (CDI) in a long-term hospital is key to improve its management. Material and methods. Retrospective study with 37 patients, along 43 months. We describe demographic variables, clinical data, time to diagnosis, treatment, and evolution. Results. Analysis of 46 episodes (37 patients, mean age=82.2 years). 77.8% were absolutely dependent, 41.7% had chronic kidney disease, 64.9% had received antibiotics in the previous three months, 40.5% received antibiotics at diagnosis. It was the first episode in 78.4%, and first recurrence in 21.6%. Therapy was started in the first 24 hours after diagnosis in 89.2%, mostly metronidazole. 83.3% recovered, 3 patients died from CDI, diagnosis was registered in the discharge report in 91.1%. Conclusions. Previous antibiotic therapy, high grade of dependency and renal failure were the main risk factors. There is room for improvement in CDI management at our hospital.


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