scholarly journals Corticosteroids Do Not Increase the Likelihood of Primary Clostridioides difficile Infection in the Setting of Broad-spectrum Antibiotic Use

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.

2019 ◽  
Vol 40 (11) ◽  
pp. 1229-1235 ◽  
Author(s):  
Ying P. Tabak ◽  
Arjun Srinivasan ◽  
Kalvin C. Yu ◽  
Stephen G. Kurtz ◽  
Vikas Gupta ◽  
...  

AbstractObjective:Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs).Methods:We analyzed 2016–2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders.Results:The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6–295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24–43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04–1.21; P = .002) after adjusting for confounders.Conclusions:High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.


2019 ◽  
Vol 70 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Sophia V Kazakova ◽  
James Baggs ◽  
L Clifford McDonald ◽  
Sarah H Yi ◽  
Kelly M Hatfield ◽  
...  

Abstract Background Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of US acute care hospitals (ACHs). Methods We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI (008.45), and treatment with metronidazole or oral vancomycin > 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics. Results During 2006–2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10 000 patient-days (PD) (95% confidence interval [CI], 7.1–7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803–820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems, there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a ≥30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67 [95% CI, .47–.96]); ACHs with a ≥20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively. Conclusions At an ecologic level, reductions in total AU, use of fluoroquinolones, and use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S747-S748
Author(s):  
Mauricio Rodriguez ◽  
Surya Chitra ◽  
Kelly Wright ◽  
Thomas Lodise

Abstract Background Real-world evidence studies indicate that around 3% of hospitalized patients with community-acquired pneumonia (CAP) develop Clostridioides difficile infection (CDI; Chalmers et al, J Infect 2016;73:45–53). Factors associated with increased CDI risk include Davis risk score (DRS) ≥ 6, and treatment with high-risk antibiotics such as fluroquinolones (FQ) and ceftriaxone (CTX). Omadacycline (OMC) is indicated for the treatment of community-acquired bacterial pneumonia (CABP) and has demonstrated a low propensity to induce CDI in preclinical and clinical studies. In the phase 3 OPTIC study, 2% of CABP patients who received moxifloxacin (MOX) developed CDI vs 0% for OMC (Stets et al, N Engl J Med 2019;380:517–27); 14% of MOX patients with DRS ≥ 6 developed CDI vs 0% in the OMC group (Table 1; Figure 1). We assessed the economic impact of substituting current CABP treatment (FQ and CTX) with OMC for hospitalized CABP patients with DRS ≥ 6. Table 1 Figure 1 Methods A deterministic healthcare-decision analytic model was performed. Only excess costs associated with each treatment were considered. Base-case model inputs were: yearly CAP admission in US, prevalence of CAP patients with DRS ≥ 6, CDI risk for CAP patients with DRS ≥ 6 with current CABP treatments, CDI costs (initial and recurrent), and OMC cost (Table 2). Efficacy and safety of treatments were assumed to be equal. CDI risk of 0% was assumed for OMC. Costs are reported as USD. Table 2 Results For patients with CABP, total CDI costs were $738M, with first-episode costs of $489M plus recurrence costs of $249M. The cost of 5 days (mean hospital length of stay for CABP) of OMC was $207M. Use of OMC for the estimated 100,000 CABP patients with DRS ≥ 6 would result in a potential cost saving of up to $531M for this patient population, assuming CDI risk of 0% with OMC. As CDI is a risk from any antibiotic use, cost savings can be achieved when OMC is used in place of high-risk antibiotics patients when CDI risk rates exceed 3.9%. Conclusion Our findings suggest prioritizing use of omadacycline over current CABP treatments in hospitalized CABP with a DRS ≥ 6 may substantially reduce attributable CDI costs. These results can serve as a basis for stewardship interventions to reduce hospital CDI rates and associated costs. Disclosures Mauricio Rodriguez, PharmD, BCPS, BCCCP, BCIDP, Paratek Pharmaceuticals, Inc. (Employee) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant)


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S820-S820
Author(s):  
Travis J Carlson ◽  
Melissa F Wilcox ◽  
Sarah G Theriault ◽  
Faris S Alnezary ◽  
Anne J Gonzales-Luna ◽  
...  

Abstract Background Clostridioides difficile is the most common pathogen causing healthcare-associated infections in the United States and a Centers for Disease Control and Prevention urgent threat-level pathogen. The pathophysiology of C. difficile infection (CDI) involves neutrophil invasion of the colon associated with an inflammatory response. Previous case–control studies investigating an anti-inflammatory corticosteroid (CS) effect on CDI risk demonstrated conflicting results but were unable to control for antibiotic use. We hypothesized that CS use would decrease the risk of CDI in a well-matched, high-risk population. Methods This nested case–control study included hospitalized patients admitted to a single quaternary care hospital in the Texas Medical Center. The case population included adults who were diagnosed with CDI and received at least one dose of an antibiotic of interest (piperacillin–tazobactam, cefepime, or meropenem) in the 90 days prior to CDI diagnosis. The control population included hospitalized adults who received one of the same antibiotics during their hospital stay but did not develop CDI in the 90 days following their first dose. Patients were excluded if they had a documented history of CDI. CS use was defined as ≥ 20 mg prednisone or equivalent administered in the 48 hours prior to CDI diagnosis (cases) or antibiotic start (controls). The primary study outcome was the development of CDI. A logistic regression model was developed modeling CDI diagnosis as a function of available patient covariates. Results A total of 321 patients met the inclusion criteria; 56 patients had a history of CDI, leaving a final study cohort of 265 patients (104 cases and 161 controls). Antibiotic days of therapy were significantly higher in the control group (8 vs. 6 days; P = 0.02). The odds of CDI diagnosis were lower among patients administered CS (OR, 0.17; 95% CI, 0.08–0.38; P < 0.001), which remained protective in the multivariable model after adjusting for age, gender, and invasive GI surgery within 6 months. Conclusion We observed an association between CS use and decreased risk of developing primary CDI in hospitalized patients receiving broad-spectrum antibiotics. Future studies are needed to delineate the dose and duration of CS needed to realize this effect. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S438-S439
Author(s):  
Tanner M Johnson ◽  
Amanda Howard ◽  
Kerry Schwarz ◽  
Lorna Allen ◽  
Misha Huang ◽  
...  

Abstract Background Recurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence. Methods A multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days. Results One-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=&lt; 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group. Conclusion In patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations. Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)


2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Lindsay A Petty ◽  
Valerie M Vaughn ◽  
Scott A Flanders ◽  
Twisha Patel ◽  
Anurag N Malani ◽  
...  

Abstract Background Reducing antibiotic use in patients with asymptomatic bacteriuria (ASB) has been inpatient focused. However, testing and treatment is often started in the emergency department (ED). Thus, for hospitalized patients with ASB, we sought to identify patterns of testing and treatment initiated by emergency medicine (EM) clinicians and the association of treatment with outcomes. Methods We conducted a 43-hospital, cohort study of adults admitted through the ED with ASB (February 2018–February 2020). Using generalized estimating equation models, we assessed for (1) factors associated with antibiotic treatment by EM clinicians and, after inverse probability of treatment weighting, (2) the effect of treatment on outcomes. Results Of 2461 patients with ASB, 74.4% (N = 1830) received antibiotics. The EM clinicians ordered urine cultures in 80.0% (N = 1970) of patients and initiated treatment in 68.5% (1253 of 1830). Predictors of EM clinician treatment of ASB versus no treatment included dementia, spinal cord injury, incontinence, urinary catheter, altered mental status, leukocytosis, and abnormal urinalysis. Once initiated by EM clinicians, 79% (993 of 1253) of patients remained on antibiotics for at least 3 days. Antibiotic treatment was associated with a longer length of hospitalization (mean 5.1 vs 4.2 days; relative risk = 1.16; 95% confidence interval, 1.08–1.23) and Clostridioides difficile infection (CDI) (0.9% [N = 11] vs 0% [N = 0]; P = .02). Conclusions Among hospitalized patients ultimately diagnosed with ASB, EM clinicians commonly initiated testing and treatment; most antibiotics were continued by inpatient clinicians. Antibiotic treatment was not associated with improved outcomes, whereas it was associated with prolonged hospitalization and CDI. For best impact, stewardship interventions must expand to the ED.


2020 ◽  
Vol 41 (S1) ◽  
pp. s136-s136
Author(s):  
Cindy Hou ◽  
Nikunj Vyas ◽  
Marianne Kraemer ◽  
David Condoluci

Background: A system of 3 community hospitals in New Jersey has actively engaged in antimicrobial stewardship since November 2014. Consultations with infectious diseases specialists are mandatory for patients with sepsis, severe sepsis, septic shock, patients on 3 or more antibiotics, and for those diagnosed with Clostridioides difficile infection (CDI). A multidisciplinary team meets monthly and has begun to improve the appropriateness of antibiotics use and to reduce antibiotic days of therapy per 1,000 patient days. Recently, we participated in a targeted assessment program (TAP) for CDI, and we identified areas of opportunity for antimicrobial stewardship. Methods: The TAP survey was emailed to a wide distribution of employees in the hospital, primarily nurses, physicians, and others with a variable range of experience and for those working in the intensive care units and on the wards. Ultimately, the numbers of responses were 60 in hospital A, 88 in hospital B, and 124 in hospital C. Results: In hospital A, most respondents were nurses or nurse assistants or technicians (63%), and most of the total individuals surveyed worked outside the intensive care unit setting. In hospital B, nurses or nurse assistants or technicians comprised 69% of all responses. Hospital C had the highest percentage of physicians who responded (31%). One theme for all hospitals was that a little more than half of those surveyed felt that for patients with new or recent CDI infections, antibiotics prescribed for infections were reviewed by clinicians. Less than half of respondents believed that education was being given to patients and families about the risks of CDI from antibiotics. With regard to high-risk CDI antibiotics, there was a general lack of knowledge that these were being monitored. For example, survey respondents felt that this was always monitored on clindamycin by only 33% of respondents in hospital A, 40% in hospital B, and 42% in hospital C. With regard to strategies to reduce the unnecessary use of fluoroquinolones, the response of “always” ranged from 35% to 47% of the time. Conclusions: Even though hospitals may have robust antimicrobial stewardship programs, it is important to survey frontline staff. Although all of the antimicrobial stewardship interventions, such as monitoring high-risk-CDI antibiotics, reducing high-risk CDI antibiotics, among others, are performed, there may be lack of knowledge that these initiatives are even being implemented. In this TAP against CDI, we found opportunities to share data with respondents to increase awareness of antimicrobial stewardship to further combat hospital-acquired infections.Funding: NoneDisclosures: None


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S437-S437
Author(s):  
Kerui Xu ◽  
Andrea L Benin ◽  
Hsiu Wu ◽  
Jonathan R Edwards ◽  
Qunna Li ◽  
...  

Abstract Background Clostridioides difficile infections (CDIs) are an urgent public health threat, accounting for 223,900 infections and 12,800 deaths in hospitalized patients annually. In early 2018, the Infectious Disease Society of America (IDSA) recommended oral vancomycin or fidaxomicin as the first-line antibiotics for CDIs. To track the uptake of IDSA’s recommendations, we evaluated the association between CDI prevalence and use of first-line antibiotics in hospitals reporting to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN). Methods We matched 2018 hospital-level, NHSN data on laboratory-identified CDIs with NHSN antimicrobial use (AU) data for the same time period. Hospitals that submitted &lt; 6 months of either data type in 2018 were excluded. The association between quarterly hospital-level CDI prevalence rates per 100 patient-admissions and use of CDI antibiotics (oral vancomycin plus fidaxomicin) per 1,000 days-present was evaluated using Pearson’s linear correlation coefficient and using Goodman and Kruskal’s gamma (G) on ordinal quartiles to assess rates of discordant pairs. Results Among the 2735 hospital-level quarters based on 714 hospitals included in the study, CDI prevalence (median: 0.46 per 100 patient-admissions) and CDI antibiotic use (median: 8.85 antibiotic-days per 1,000 days-present) demonstrated only a moderately positive correlation (r = 0.48). Among hospitals in the highest quartile for CDI prevalence, 5.1% were in the lowest quartile for antibiotic use. Among hospitals in the highest quartile for antibiotic use, 5.3% were in the lowest quartile for CDI prevalence, and 54.2% were in the highest quartile for CDI prevalence (G = 0.60; 95% CI: 0.57–0.63). Correlation of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in U.S. acute care hospitals, 2018 Distribution of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in ordinal quartiles (Q1–Q4) to access rates of discordant pairs Conclusion The moderate correlation and discordant rates suggest that vancomycin and fidaxomicin are less frequently used as primary antibiotics in some hospitals; whereas in others, CDI antibiotic use is occurring in the absence of positive laboratory tests for CDI. To further investigate this discordance, there is a need to assess hospitals’ prescribing and testing practices in an ongoing manner. These findings may be useful to serve as baseline for measuring progress of appropriateness of treatment and testing for CDIs. Disclosures All Authors: No reported disclosures


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