S0214 The Impact of Acute Diverticulitis on the Outcomes of Hospitalized Patients With Clostridioides difficile Infection

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.

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Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

10.1101/2021.07.16.21260643 ◽

2021 ◽

Author(s):

Ning-Jiun Jan ◽

Noah Oakland ◽

Pankaj Kumar ◽

Girija Ramakrishnan ◽

Brian W. Behm ◽

...

Keyword(s):

Mononuclear Cells ◽

Fecal Microbiota Transplantation ◽

Alpha Diversity ◽

The United States ◽

Fecal Microbiota ◽

Peripheral Blood Mononuclear ◽

Clostridioides Difficile ◽

Rdna Sequencing ◽

Clostridioides Difficile Infection ◽

The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

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An evaluation of toxigenic Clostridioides difficile positivity as a patient outcome metric of antimicrobial stewardship in Saudi Arabia

10.1101/2021.02.23.21252226 ◽

2021 ◽

Author(s):

Christopher A. Okeahialam ◽

Ali A. Rabaan ◽

Albert Bolhuis

Keyword(s):

Patient Outcome ◽

Saudi Arabia ◽

Antimicrobial Stewardship ◽

Laboratory Data ◽

Hospitalized Patients ◽

Antimicrobial Stewardship Program ◽

Repeated Testing ◽

Clostridioides Difficile ◽

Stewardship Program ◽

The Impact

AbstractBackgroundAntimicrobial stewardship has been associated with a reduction in the incidence of health care associated Clostridium difficile infection (HA-CDI). However, CDI remains under-recognized in many low and middle-income countries where clinical and surveillance resources required to identify HA-CDI are often lacking. The rate of toxigenic C. difficile stool positivity in the stool of hospitalized patients may offer an alternative metric for these settings, but its utlity remains largely untested.Aim/ObjectiveTo examine the impact of an antimicrobial stewardship on the rate of toxigenic C. difficile positivity among hospitalized patients presenting with diarrhoeaMethodsA 12-year retrospective review of laboratory data was conducted to compare the rates of toxigenic C. difficile in diarrhoea stool of patients in a hospital in Saudi Arabia, before and after implementation of an antimicrobial stewardship programResultThere was a significant decline in the rate of toxigenic C difficile positivity from 9.8 to 7.4% following the implementation of the antimicrobial stewardship program, and a reversal of a rising trend.DiscussionThe rate of toxigenic C. difficile positivity may be a useful patient outcome metric for evaluating the long term impact of antimicrobial stewardship on CDI, especially in settings with limited surveillance resources. The accuracy of this metric is however dependent on the avoidance of arbitrary repeated testing of a patient for cure, and testing only unformed or diarrhoea stool specimens. Further studies are required within and beyond Saudi Arabia to examine the utility of this metric.

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2373. Impact of a Change in Testing Strategy for Clostridioides difficile Infection on a Publicly Reported Metric and Treatment Days of Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2051 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S818-S819

Author(s):

Ryan Miller ◽

Jose A Morillas ◽

Joanne Sitaras ◽

Jacob Bako ◽

Elizabeth A Neuner ◽

...

Keyword(s):

Health System ◽

Diagnostic Testing ◽

Cleveland Clinic ◽

Public Reporting ◽

Testing Strategy ◽

Clostridioides Difficile ◽

Days Of Therapy ◽

Before And After ◽

Clostridioides Difficile Infection ◽

The Impact

Abstract Background In an effort to optimize diagnostic testing for Clostridioides difficile infection (CDI) our health system changed from stand-alone PCR testing to a “2-step” approach wherein all positive PCR results reflexed to an EIA. We report the effects of this change on publicly reported CDI metrics and treatment days of therapy (DOT). Methods The setting includes 10 Cleveland Clinic Health System hospitals in northeast Ohio and one in Florida. On June 12, 2018, 9 NE Ohio hospitals changed from PCR alone to PCR followed by EIA. Stand-alone PCR testing remained at one and GDH / EIA / PCR for discordant for another. Testing volumes were obtained from the microbiology laboratory. C. difficile LabID event SIRs were obtained from NHSN. Public reporting interpretative categories were identified based on SIR for second half of 2018. DOT for CDI agents were obtained from an antimicrobial stewardship database. Results Among hospitals that changed strategy the volume of PCR testing and the percent PCR + was similar between time periods. EIA positivity ranged from 23% to 53%. 4/11 hospitals improved their public reporting category: 3/9 that changed testing strategy and 1/2 that did not (Table 1). Two of 3 that changed strategy and improved public reporting also had a decrease in DOT. DOT increased in the 2 hospitals that did not change strategy. Conclusion Six months after adopting a 2-step CDI testing strategy 7 of 9 hospitals had a lower SIR with 3 also demonstrating an improvement in public reporting category favorably impacting reputational and reimbursement risk for our healthcare system. CDI agent DOT was similar before and after the change. The impact of choice of test on publicly reported metrics demonstrates the difficulty of utilizing a proxy for hospital onset CDI, the CDI LabID event, as a measure of quality of care provided. Disclosures All authors: No reported disclosures.

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Burden and risk factors for inappropriate Clostridioides Difficile infection testing among hospitalized patients

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2020.115283 ◽

2021 ◽

Vol 99 (4) ◽

pp. 115283

Author(s):

Ellen Axenfeld ◽

William G. Greendyke ◽

Jianhua Li ◽

Daniel A. Green ◽

Susan Whittier ◽

...

Keyword(s):

Risk Factors ◽

Hospitalized Patients ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection

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2440. Using a geospatially explicit agent-based model of a regional healthcare network to assess varied antibiotic risk on Clostridioides difficile infection incidence

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2118 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S843-S844

Author(s):

Sarah Rhea ◽

Kasey Jones ◽

Georgiy Bobashev ◽

Breda Munoz ◽

James Rineer ◽

...

Keyword(s):

Acute Care ◽

Acute Care Hospital ◽

Care Hospital ◽

Healthcare Facilities ◽

Agent Based ◽

Healthcare Network ◽

Clostridioides Difficile ◽

Unit Increase ◽

Clostridioides Difficile Infection ◽

The Impact

Abstract Background Different antibiotic classes are associated with different Clostridioides difficile infection (CDI) risk. The impact of varied antibiotic risk on CDI incidence can be explored using agent-based models (ABMs). ABMs can simulate complete systems (e.g., regional healthcare networks) comprised of discrete, unique agents (e.g., patients) which can be represented using a synthetic population, or model-generated representation of the population. We used an ABM of a North Carolina (NC) regional healthcare network to assess the impact of increasing antibiotic risk ratios (RRs) across network locations on healthcare-associated (HA) and community-associated (CA) CDI incidence. Methods The ABM describes CDI acquisition and patient movement across 14 network locations (i.e., nodes) (11 short-term acute care hospitals, 1 long-term acute care hospital, 1 nursing home, and the community). We used a sample of 2 million synthetic NC residents as ABM microdata. We updated agent states (i.e., location, antibiotic exposure, C. difficile colonization, CDI status) daily. We applied antibiotic RRs of 1, 5, 8.9 (original model RR), 15, and 20 to agents across the network to simulate varied risk corresponding to different antibiotic classes. We determined network HA-CDI and CA-CDI incidence and percent mean change for each RR. Results In this simulation study, HA-CDI incidence increased with increasing antibiotic risk, ranging from 11.3 to 81.4 HA-CDI cases/100,000 person-years for antibiotic RRs of 1 to 20, respectively. On average, the per unit increase in antibiotic RR was 33% for HA-CDI and 6% for CA-CDI (figure). Conclusion We used a geospatially explicit ABM to simulate increasing antibiotic risk, corresponding to different antibiotic classes, and to explore the impact on CDI incidence. The per unit increase in antibiotic risk was greater for HA-CDI than CA-CDI due to the higher probability of receiving antibiotics and higher concentration of agents with other CDI risk factors in the healthcare facilities of the ABM. These types of analyses, which demonstrate the interconnectedness of network healthcare facilities and the associated community served by the network, might help inform targeted antibiotic stewardship efforts in certain network locations. Disclosures All authors: No reported disclosures.

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Clostridioides difficile infection in immunocompromised hospitalized patients is associated with a high recurrence rate

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2019.10.028 ◽

2020 ◽

Vol 90 ◽

pp. 237-242 ◽

Cited By ~ 2

Author(s):

Tomer Avni ◽

Tanya Babitch ◽

Haim Ben-Zvi ◽

Rabab Hijazi ◽

Gida Ayada ◽

...

Keyword(s):

Recurrence Rate ◽

Hospitalized Patients ◽

High Recurrence Rate ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection

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Loss of IL-10 signaling promotes IL-22 dependent host defenses against acute Clostridioides difficile infection

Infection and Immunity ◽

10.1128/iai.00730-20 ◽

2021 ◽

Author(s):

Emily S. Cribas ◽

Joshua E. Denny ◽

Jeffrey R. Maslanka ◽

Michael C. Abt

Keyword(s):

Defense Mechanisms ◽

Intestinal Inflammation ◽

Bacterial Pathogen ◽

Survival Advantage ◽

Protective Mechanisms ◽

Genetic Ablation ◽

Proinflammatory Mediators ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

The Impact

Infection with the bacterial pathogen Clostridioides difficile causes severe damage to the intestinal epithelium that elicits a robust inflammatory response. Markers of intestinal inflammation accurately predict clinical disease severity. However, determining the extent to which host-derived proinflammatory mediators drive pathogenesis versus promote host protective mechanisms remains elusive. In this report, we employed Il10-/- mice as a model of spontaneous colitis to examine the impact of constitutive intestinal immune activation, independent of infection, on C. difficile disease pathogenesis. Upon C. difficile challenge, Il10-/- mice exhibited significantly decreased morbidity and mortality compared to littermate Il10 heterozygote (Il10HET) control mice, despite a comparable C. difficile burden, innate immune response, and microbiota composition following infection. Similarly, antibody-mediated blockade of IL-10 signaling in wild-type C57BL/6 mice conveyed a survival advantage if initiated three weeks prior to infection. In contrast, no advantage was observed if blockade was initiated on the day of infection, suggesting that constitutive activation of inflammatory defense pathways prior to infection mediated host protection. IL-22, a cytokine critical in mounting a protective response against C. difficile infection, was elevated in the intestine of uninfected, antibiotic-treated Il10-/- mice, and genetic ablation of the IL-22 signaling pathway in Il10-/- mice negated the survival advantage following C. difficile challenge. Collectively, these data demonstrate that constitutive loss of IL-10 signaling, via genetic ablation or antibody blockade, enhances IL-22 dependent host defense mechanisms to limit C. difficile pathogenesis.

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