scholarly journals Assessment of Kidney Injury as a Severity Criteria for Clostridioides Difficile Infection

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
Kimberly Nebo ◽  
Hannah Y Chan ◽  
Ngoc-Linh T Tran ◽  
...  

Abstract Background The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) revised their Clostridioides difficile infection (CDI) severity classification criteria in 2017 to include an absolute serum creatinine (SCr) value above a threshold (≥1.5 mg/dL) rather than a relative increase from baseline (≥1.5 times the premorbid level). To date, how to best define kidney injury as a CDI disease severity marker has not been validated to assess severe outcomes associated with CDI. Methods This multicenter cohort study included adult hospitalized patients with CDI. Patients were assessed for the presence of acute kidney injury (AKI), chronic kidney disease (CKD), and CDI severity using the 2010 and 2017 IDSA/SHEA CDI guidelines. Primary outcome was all-cause inpatient mortality. Results The final study cohort consisted of 770 CDI episodes from 705 unique patients aged 65 ± 17 years (female, 54%; CKD, 36.5%; AKI, 29.6%). Eighty-two episodes (10.6%) showed discordant severity classification results due to the inclusion of more patients with preexisting CKD in the severe disease category using an absolute SCr threshold criterion. The absolute SCr criterion better correlated with all-cause mortality (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.76–9.28; P = .001) than the relative increase in SCr (OR, 1.34; 95% CI, 0.62–2.89; P = .46). This corresponded to an increased likelihood of the 2017 CDI severity classification criteria to predict mortality (OR, 5.33; 95% CI, 1.81–15.72; P = .002) compared with the 2010 criteria (OR, 2.71; 95% CI, 1.16–6.32; P = .02). Conclusions Our findings support the 2017 IDSA/SHEA CDI severity classification criteria of a single pretreatment SCr in future CDI guideline updates.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S441-S441
Author(s):  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
Kimberly Nebo ◽  
Hannah Y Chan ◽  
Ngoc-Linh T Tran ◽  
...  

Abstract Background The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) revised their Clostridioides difficile infection (CDI) severity classification criteria in 2017 to include a serum creatinine (SCr) value above a threshold (≥ 1.5 mg/dL) rather than a relative increase from baseline (≥ 1.5 times the premorbid level). To date, these criteria have not been validated and may overestimate the number of severe CDI cases in patients with underlying renal insufficiency. Methods This multicenter, retrospective cohort study included all patients ≥ 18 years of age with CDI diagnosed in two large health systems in the Houston, Texas area between 2016 and 2018. Patients were assessed for presence of acute kidney injury (AKI) and chronic kidney disease (CKD), defined per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and IDSA/SHEA CDI severity classification criteria per the 2010 and 2017 CDI guidelines. The primary outcome was all-cause inpatient mortality. Results The study cohort consisted of 770 CDI episodes from 12 hospitals. A large proportion of episodes occurred in patients with preexisting CKD (36.5%) and concomitant AKI (29.6%). Eighty-two episodes (10.6%) showed discordant results when applying the 2017 revised severity classification criteria due to the identification of patients with preexisting CKD. However, the 2017 severity classification criteria were better correlated with all-cause mortality (OR, 5.40; 95% CI, 1.84-15.86; P = 0.002) than were the 2010 severity classification criteria (OR, 3.12; 95% CI, 1.35-7.19; P = 0.008) as the 2017 SCr criterion was an independent predictor of mortality (OR, 3.66; 95% CI, 1.66-8.05; P = 0.001) while the 2010 SCr criterion was not (OR, 1.47; 95% CI, 0.71-3.08; P = 0.30). Conclusion Our findings support the inclusion of the 2017 IDSA/SHEA CDI severity classification criteria in future CDI guideline updates. Disclosures Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)


2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Richard L Hengel ◽  
Timothy E Ritter ◽  
Ramesh V Nathan ◽  
Lucinda J Van Anglen ◽  
Claudia P Schroeder ◽  
...  

Abstract Background Bezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited. Methods Records of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting ≥2 days resulting in treatment, was assessed 90 days postbezlotoxumab. Results The study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n = 173) had prior CDI episodes and 79% (n = 158) had ≥2 risk factors for rCDI. SoC antibiotics included vancomycin (n = 137, 68%), fidaxomicin (n = 60, 30%), and metronidazole (n = 3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with ≥2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14–6.76; P = .025). Conclusions This real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.


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.


2019 ◽  
Vol 54 (7) ◽  
pp. 662-668 ◽  
Author(s):  
Lynn Chan ◽  
Noreen H. Chan-Tompkins ◽  
James Como ◽  
Anthony J. Guarascio

Background: Nafcillin or cefazolin are drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Prior studies indicate a higher incidence of acute kidney injury (AKI) with nafcillin, although AKI classification and time to occurrence is not well described. Objective: To characterize the incidence and time to adverse drug events for nafcillin versus cefazolin in the inpatient setting. Methods: A retrospective cohort study evaluated hospitalized, adult patients receiving intravenous nafcillin or cefazolin for treatment of MSSA infection. Incidence and time to AKI based on RIFLE criteria were measured. Secondary end points included antibiotic discontinuation and incidence of neutropenia, thrombocytopenia, elevated transaminases, and Clostridioides difficile infection (CDI). Results: Of 324 patients who received nafcillin (n = 119) or cefazolin (n = 205), higher rates of AKI were found for nafcillin versus cefazolin (19% vs 2%, respectively; P < 0.0001). Median time to AKI with nafcillin was 6.5 days (range, 3-14 days). The majority of patients were classified as RIFLE “Risk” stratum. Nafcillin treatment discontinuations were more frequent than for cefazolin (17.6% vs 0.9%, respectively; P < 0.0001). Nafcillin was an independent predictor of AKI (odds ratio = 12.4; 95% CI = 4.14-47.60, P < 0.0001). No differences in neutropenia, thrombocytopenia, elevated transaminases, or CDI were observed. Conclusion and Relevance: Nafcillin displayed higher rates of AKI at a median of 1 week of therapy, which provides a framework for clinician monitoring and consideration of antibiotic modification. Most patients developed “Risk” class AKI (RIFLE classification), which may be reversible with prompt intervention.


2019 ◽  
Vol 7 (10) ◽  
pp. 435 ◽  
Author(s):  
Hamo ◽  
Azrad ◽  
Nitzan ◽  
Peretz

The high risk of complications and death following Clostridioides difficile infection (CDI) requires identifying patients with severe disease and treating them accordingly. We characterized the immune response of CDI patients in relation to infection severity. Concentrations of 28 cytokines and chemokines were measured in serum samples, obtained from 54 CDI patients within a median timeframe of 24–48 h after laboratory confirmation of C. difficile infection. Demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined by “Score indices for Clostridioides difficile infection severity”. Of 54 patients (mean age, 76.6 years, 61.1% female), 38 (70.4%) had mild disease and 16 (29.6%) had moderate disease. Seven cytokines were associated with a more severe CDI: granulocyte-macrophage colony-stimulating factor (p = 0.0106), interleukin (IL)-1β (p = 0.004), IL-8 (p = 0.0098), IL-12p70 (p = 0.0118), interferon-α (p = 0.0282), IL-15 (p = 0.0015), and IL-2 (p = 0.0031). Additionally, there was an increased T-helper 1 response in more severe cases of CDI. Cytokines may serve as biomarkers for early prediction of CDI severity. Better and earlier assessment of illness severity will contribute to the adjustment of medical treatment, including monitoring and follow-up.


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.


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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Hsin Lai ◽  
Bo-Yang Tsai ◽  
Chih-Yu Hsu ◽  
Yi-Hsuan Chen ◽  
Po-Han Chou ◽  
...  

BackgroundClostridioides difficile is the leading cause of nosocomial infectious diarrhea. Toll-like receptors (TLRs) are the major components of innate immunity that sense pathogens. The relationship between TLRs and C. difficile infection (CDI) was analyzed in clinical patients and a mouse model.Materials and MethodsA prospective investigation was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, from January 2011 to January 2013. Adult patients were followed up for the development of CDI. Single nucleotide polymorphisms (SNPs) of TLR2 and TLR4 were analyzed to assess the relationship between genetic polymorphisms and the development of CDI. A mouse model of CDI was used to investigate the pathogenic role of TLRs in CDI, TLR2 and TLR4 knockout (Tlr2-/- and Tlr4-/-) mice.ResultsIn the prospective study, 556 patients were enrolled, and 6.5% (36) of patients, accounting for 3.59 episodes per 1000 patient-days, developed CDI. Of 539 patients with available blood samples, the TLR2 rs3804099 polymorphism was more often noted in those with CDI than in those without CDI (64.5% vs. 46.1%; P = 0.046) but was not significant in multivariate analysis. Because the TLR2 rs3804099 polymorphism was moderately associated with CDI, the role of TLR2 and TLR4 was further evaluated in a mouse model. Both Tlr2-/- and Tlr4-/- mice showed more severe CDI disease than wild-type mice in terms of body weight change and fecal content five days after oral challenge with C. difficile. Furthermore, Tlr2-/- mice suffered from more severe disease than Tlr4-/- mice, as evidenced by stool consistency, cecum weight, and survival rate.ConclusionThe TLR2 rs3804099 polymorphism is marginally associated with the development of CDI, and the pathogenic role of TLR2 is further supported by a mouse model.


Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1357
Author(s):  
Massimo Sartelli ◽  
Federico Coccolini ◽  
Angeloantonio Carrieri ◽  
Francesco M. Labricciosa ◽  
Enrico Cicuttin ◽  
...  

Surgical antibiotic prophylaxis (SAP) is one of the peri-operative measures for preventing surgical site infections (SSIs). Its goal is to counteract the proliferation of bacteria in the surgical site during intervention in order to reduce the risk of SSIs. SAP should be administered for surgical interventions where the benefit expected (prevention of SSIs) is higher compared to the risk (serious side effects, such as acute kidney injury, Clostridioides difficile infection, and the spread of antimicrobial resistance). In prescribing SAP, surgeons should have both the awareness necessary “to handle antibiotics with care”, and the knowledge required to use them appropriately.


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