Antibiotic and Nonantibiotic Drugs Associated With Clostridioides difficile Infection Risk: a Pharmacopoeia-Wide Case-Cohort Study.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

A history of Clostridioides difficile infection portends infection recurrence and worse outcomes after stoma reversal

Background:Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. Significant risk factors for CDI include antibiotic use and healthcare exposure. Antibiotics are often administered before, during and/or after surgery to prevent postsurgical infection. The contribution of surgery-related antibiotics to the overall CDI burden has not been well described, and assessment of the appropriateness of surgical antibiotic use is complicated by complex clinical guidelines. We have described surgical antibiotic prophylaxis history among adult with CDI in Minnesota in 2018. Method: The Minnesota Department of Health (MDH) performs 5-county active population- and laboratory-based CDI surveillance as a CDC Emerging Infections Program site. Incident CDI was defined as stool positive for C. difficile by toxin or molecular assay from a person aged ≥18 years with no positive test in the preceding 8 weeks. History of CDI was defined as having had a previous CDI episode in the 2009–2018 surveillance data set. Medical records were reviewed for 12 weeks prior to incident CDI test date to identify antibiotic prescriptions. Antibiotics with documented indication for surgical-site infection prevention or surgical prophylaxis were classified as “surgical antibiotic prophylaxis” (SPPX). SPPX type (eg, intraoperative, postoperative), appropriateness of SPPX, and clinical guideline adherence were not assessed. Results: During 2018, 812 incident CDIs were reported to MDH among 736 patients. SPPX preceded 84 (10.3%) cases, non-SPPX antibiotic use preceded 465 cases (57.3%), and 263 cases (32.4%) had no documented prior antibiotic use. The median age of incident CDIs with preceding SPPX was 68 years (IQR, 54–79.5). In 25 incident CDI cases with preceding SPPX (29.8%), there were no other antibiotic exposures. Among incident CDIs with preceding SPPX, 11 (13.1%) had >1 surgery event with SPPX. Prior CDI was identified for 13 (15.7%) with SPPX. Among 99 procedures with preceding SPPX, orthopedic surgeries (n = 27, 27.3%), gastrointestinal surgeries (n = 26, 26.3%), and cardiovascular surgeries (n = 22, 22.2%) were most common. In total 18 SPPX prescriptions (18.2%) originated in outpatient settings. SPPX drugs included cefazolin (n = 67, 67.7%), ceftriaxone (n = 7, 7.1%), ertapenem (n = 6, 6.1%), and clindamycin (n = 6, 6.1%). Median SPPX duration was 1 day (IQR, 1–2), and the median number days between surgery and specimen collection date was 19 (IQR, 7–49). Conclusions: Antibiotic stewardship programs should assess surgical prescribing, including in outpatient centers. Even short antibiotic duration for surgery could put patients at risk for CDI. More data are needed to evaluate the appropriateness of SPPX prescribing and to describe the impact of SPPX on CDI.Funding: NoneDisclosures: None

BackgroundPediatric oncology and hematopoietic stem cell transplant patients (POTP) are at increased risk for Clostridioides difficile infection (CDI) and recurrence. It is unknown whether recurrent CDI is related to the same C. difficile strain as the initial CDI. We describe genomic relatedness of C. difficile strains in patients with multiple CDI using whole-genome sequencing (WGS).MethodsThis was a retrospective cohort study of CDI in POTP in 2016. CDI cases were identified by electronic medical record search for positive C. difficile toxin PCR tests. Patients with multiple CDI episodes were identified. CDI episodes were classified as incident, duplicate or recurrent using National Healthcare Safety Network (NHSN) definitions. Retrieved residual stool specimens were cultured anaerobically, toxin-producing C. difficile isolates were determined using a cell culture cytotoxicity assay with neutralization and WGS was performed followed by core genome MLST (cgMLST). Variability of the isolates was summarized by strain type (ST), and a minimum spanning tree was constructed, defining genomically related isolates as those with <7 allele difference.ResultsEighteen patients had 51 positive C. difficile samples. CDI were classified as incident in 31 (61%) episodes, recurrent in 18 (36%), and duplicate in 2 (3%). Isolates from 47 (92%) samples were sequenced, identifying 14 different strain types (ST) in 41 (87%) isolates. Of the 31 incident CDI, 13 (42%) episodes occurred 8 weeks or more after the initial incident CDI. Among those 13 incident CDI, 7 (54%) had prior CDI due to a related isolate. Of the 18 recurrent CDIs, 10 (55%) were due to an isolate related to the previous incident CDI and 5 (28%) were due to an isolate unrelated to the incident CDI. The relatedness of the remaining 3 recurrent episodes could not be evaluated because no isolate was available for sequence analysis.ConclusionCDI classification of incident vs. recurrent infection using NHSN definition might be not applicable in POTP. WGS showed that more than half of CDI episodes classified as incident were actually a recurrence of a previous C. difficile strain. Similarly, some CDI episodes classified as recurrent were actually re-infection with a different stain.DisclosuresRandall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board

Background:Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy.Methods:A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated.Results:Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p < 0.00001). Significant heterogeneity was seen with I2 = 59%.Discussion:Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI.

Introduction: Clostridioides difficile infection (CDI) is a significant concern in patients undergoing acid-suppressive therapy. This study aimed to evaluate and compare the risk of CDI in patients treated with proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2RAs), and potassium-competitive acid blockers (tegoprazan). Methods: This retrospective observational cohort study evaluated 606,460 individuals who were prescribed PPIs, H2RAs, or tegoprazan for more than 7 days, resulting in 22,431 matched individuals after propensity score matching. The primary outcome was CDI incidence within 12 weeks of medication use. Results: Patients receiving PPIs exhibited a significantly higher relative risk (RR) (RR: 1.86; 95% confidence interval [CI]: 1.18–2.91) of developing CDI than those receiving H2RAs. Tegoprazan showed no significant increase in CDI risk (RR: 1.07; 95% CI: 0.64–1.79) compared to H2RAs. The risk of CDI increased with a longer duration of acid suppressant use. No dose-dependent differences in CDI occurrence were observed across PPI doses and no significant differences were found in the incidence of severe CDI among the groups. Conclusions: PPIs are associated with a higher risk of CDI than H2RAs. These findings highlight the need for careful selection of acid-suppressive therapies, particularly in high-risk populations.

To examine the incidence and risk factors of Clostridioides difficile infection (CDI) after otolaryngologic surgery. A retrospective cohort study of subjects undergoing otolaryngologic surgery was performed using the 2016 to 2021 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). The incidence of CDI and potential risk factors were assessed. One-hundred eighty-five surgical encounters experienced postoperative CDI out of 149 960, with a CDI incidence of 0.12% (8.8 cases per 10,000 patient-days). The greatest number of postoperative CDI was observed in head and neck reconstructive surgeries. On bivariate analysis, risk factors significantly and practically associated with the occurrence of CDI after otolaryngologic surgery were older age and longer operating times. Multiple logistic regression revealed that the CDI rate did not differ among otolaryngology subspecialties but was influenced by age, functional status, and operating times after controlling for relevant confounders. CDI after otolaryngologic surgery is a serious, costly complication with an incidence comparable to the national CDI rate. Knowledge of the preoperative risk factors associated with CDI may aid in the prevention of such infection after otolaryngologic procedures, thus decreasing patient morbidity and healthcare cost.

Risk of Healthcare-Associated Clostridioides difficile Infection During Pandemic Preparation: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) may be a surrogate for poor patient health. As such, a history of CDI before THA may be used to identify patients at higher risk for postoperative CDI and complications after THA. Investigations into the associations between CDI before THA and postoperative CDI and complications are lacking. We compared the (1) frequency and potential risk factors for CDI after THA, (2) the frequency of 90-day complications after THA in patients with and without a history of CDI, and (3) the length of stay and frequency of readmissions in patients experiencing CDIs more than 6 months before THA, patients experiencing CDIs in the 6 months before THA, and patients without a history of CDI. Patients undergoing primary THA from 2010 to 2019 were identified in the PearlDiver database using ICD and Current Procedural Terminology codes (n = 714,185). This analysis included Medicare, Medicaid, and private insurance claims across the United States with the ability to perform longitudinal and costs analysis using large patient samples to improve generalizability and reduce error rates. Patients with a history of CDI before THA (n = 5196) were stratified into two groups: those with CDIs that occurred more than 6 months before THA (n = 4003, median 2.2 years [interquartile range 1.2 to 3.6]) and those experiencing CDIs within the 6 months before THA (n = 1193). These patients were compared with the remaining 708,989 patients without a history of CDI before THA. Multivariable logistic regression was used to evaluate the association of risk factors and incidence of 90-day postoperative CDI in patients with a history of CDI. Variables such as antibiotic use, proton pump inhibitor use, chemotherapy, and inflammatory bowel disease were included in the models. Chi-square and unadjusted odds ratios with 95% confidence intervals were used to compare complication frequencies. A Bonferroni correction adjusted the p value significance threshold to < 0.003. Prior CDI during either timespan was associated with higher unadjusted odds for postoperative CDI (CDI > 6 months before THA: OR 8.44 [95% CI 6.95 to 10.14]; p < 0.001; CDI ≤ 6 months before THA: OR 49.92 [95% CI 42.26 to 58.54]; p < 0.001). None of the risk factors included in the regression were associated with increased odds for postoperative CDI in patients with preoperative history of CDI. Patients with a history of CDI before THA were associated with higher unadjusted odds for every 90-day complication compared with patients without a history of CDI before THA. CDI during either timespan was associated with longer lengths of stay (no CDI before THA: 3.8 days; CDI > 6 months before THA: 4.5 days; CDI ≤ 6 months before THA: 5.3 days; p < 0.001) and 90-day readmissions (CDI > 6 months before THA: OR 2.21 [95% CI 1.98 to 2.47]; p < 0.001; CDI ≤ 6 months before THA: OR 3.39 [95% CI 2.85 to 4.02]; p < 0.001). Having CDI before THA was associated with higher odds of postoperative CDI compared with patients without a history of CDI. A history of CDI within the 6 months before THA was associated with the greatest odds for postoperative complications and readmissions. Providers should strongly consider delaying THA until 6 months after CDI, if possible, to provide adequate time for patient recovery and eradication of infection. Level III, therapeutic study.

Few studies evaluate the epidemiology and risk factors of Clostridioides difficile infection (CDI) in Asian patients with inflammatory bowel disease (IBD). We investigated the year-end prevalence, cumulative incidence and risk factors of CDI in Asian patients with IBD using a large-scale population-based cohort in Korea. Using the National Health Insurance Service database, we identified patients with IBD and sex- and age-matched controls without IBD between 2008 and 2018. The year-end prevalence and cumulative incidence of CDI were compared among patients with Crohn's disease (CD) and ulcerative colitis (UC) with controls. The risk factors for CDI were evaluated. Among the 54,836 patients with IBD and 109,178 controls, CDI occurred in 293 patients with IBD and 87 controls. The annual year-end prevalence of CDI in patients with IBD increased from 8.6/10,000 persons in 2008 to 22.3/10,000 persons in 2018. The risk of CDI was higher in both patients with CD and UC than that in the matched controls (hazard ratio [HR], 7.285; 95% confidence interval [CI], 5.388-9.851; P < 0.001 and HR, 7.487; 95% CI, 5.796-9.670; P < 0.001, respectively). Among patients with IBD, the risk factors for CDI included older age, female sex, high Charlson comorbidity index score, and IBD-related medications including oral 5-aminosalicylic acid, immunomodulatory agents, biologics, and steroids used for > 90 days. The risk of CDI in Korean patients with IBD was approximately seven times higher than that in controls without IBD, and the annual year-end prevalence of CDI continuously increased from 2008 to 2018.

Background and AimsAdverse outcomes associated with the treatment of Helicobacter pylori remain poorly understood. We investigated whether H pylori treatment was associated with an increased risk of Clostridioides difficile infection (CDI).MethodsThis retrospective cohort study included all adult members who tested positive for H pylori between January 1, 2000, and December 31, 2020, at Kaiser Permanente Northern California. We measured the incidence of CDI after H pylori treatment and evaluated the predictors of CDI using multivariable logistic regression.ResultsOf 139,226 individuals who tested positive for H pylori, the incidence of CDI was 5.9/10,000 within 3 months (P = .02) and 7.0/10,000 (P = .003) within 6 months after H pylori treatment, compared with 2.7/10,000 among untreated individuals. The adjusted odds ratio (aOR) (95% confidence interval) for CDI within 3 months after H pylori treatment was 2.00 (1.02–3.90) overall, 3.15 (1.14–8.70) for concomitant therapy, and 6.34 (2.75–14.59) for bismuth quadruple therapy. Inflammatory bowel disease (IBD) (aOR, 7.89 [2.38–26.21]) and history of CDI (aOR, 8.27 [1.92–35.62]) had the strongest association with CDI, while Asians/Pacific Islanders (aOR, 0.22 [0.09–0.55] and non-English language preference (aOR, 0.30 [0.12–0.72]) were associated with a lower risk.ConclusionIn a large, diverse, community-based population, treatment of H pylori was associated with an increased risk of CDI, although the overall incidence was very low. History of IBD and prior CDI were the strongest predictors of CDI. These findings support the safety of H pylori treatment, although caution should be exercised when treating H pylori among individuals with IBD or a prior history of CDI.

Many previous studies of Clostridioides difficile infection (CDI) epidemiology have used hospital discharge data codes, which can have limited accuracy. We used a data set of laboratory-confirmed cases of CDI in the province of Manitoba, Canada, to describe the epidemiology of CDI over a decade. We conducted a population-based historical cohort study using Manitoba Health's population-wide laboratory-based CDI data set linked to administrative health databases. All individuals living in Manitoba and experiencing a CDI episode between 2005 and 2015 were included (n = 8471) and followed up from CDI diagnosis. We assessed time trends of CDI, incidence and predictors of recurrence and severe outcomes, and health care encounters after CDI diagnosis. CDI episodes were stratified by community versus hospital site of acquiring CDI. Between 2005 and 2009, overall CDI diagnoses decreased by an average of 12.6% per year (95% confidence interval [CI] -4.4 to -20.0), with no statistically significant change from 2010 to 2015. In stratified analysis, incident and recurrent CDI had a similar decrease in the initial study time period and then stabilized. The proportion of community-associated CDI cases increased by an average of 4.8% per year (95% CI 2.8 to 6.8) during the study period. CDI acquired in a health care facility had a higher recurrence rate and more severe outcomes. Recurrence of CDI increased the likelihood of admission to hospital. Between 2005 and 2015, the rates of overall laboratory-confirmed CDI, incident CDI, recurrent CDI and severe outcomes following CDI initially decreased before stabilizing, and an increasing proportion of CDI cases were community-associated. There is an increasing need to test for CDI among outpatients with diarrhea and to increase efforts to prevent recurrent CDI.

BackgroundPatients with multiple recurrences of Clostridioides difficile infection (CDI) have longer hospital stays and lower quality of life. Recent changes in therapies and strains of CDI make understanding recurrent CDI in the general population critical as these patients may benefit from microbiota restoring therapies rather than antibiotics alone.MethodsGeorgia’s Emerging Infections Program (supported by CDC) conducts CDI surveillance in 8 counties around metropolitan Atlanta, GA (population ∼4 million). CDI is defined as any C. difficile-positive specimen with no positive test in the prior 2 weeks. We evaluated CDI between Jan 2015 through Dec 2019 and captured recurrent CDI (CDI test date 2-52 weeks following previous CDI) for 2016-2019 which were categorized as single episode only, recurrent (2 episodes ≤ 1 year) or multiple recurrent (>2 episodes ≤ 1 year). Year was attributed to date of final episode. Census data was used to determine crude and age-specific incidence. Bivariate and multivariable logistic regression was used to estimate odds for multiple recurrent compared to single recurrent CDI with demographic, comorbidity and treatment related covariates.ResultsOver 4 years 13,745 patients had at least one episode of CDI, 2,930 (20%) had ≥ 1 recurrence and 916 (30%) of these progressed to multiple recurrence. Between 2016 to 2019, incidence of single CDI decreased 25% from 93/100,000 to 69/100,000 (P< 0.01). Multiple recurrent CDI decreased 45% from 9/100,000 to 5/100,000) (P< 0.01); incidence in the 80+ age group was highest and where decreased incidence was most dramatic during the study period (Figures). Time between 1st and 2nd episode was longer among patients with single recurrent than multiple recurrent CDI (median 12 weeks vs. 9 weeks, P< 0.01).. Independent predictors of multiple recurrence were fewer days (< 90) between episodes (aOR: 1.87 P< 0.01) and chronic renal disease (aOR: 1.59 , P< 0.01).Figure 1:Annual Incidence of CDI by age group.A) Incidence of CDI among patients with only a single episode of CDI within 365 days. B) Incidence of CDI among patients with three or more episodes (two or more recurrence) within 365 days. RR documented compares 2016 to 2018 incidence in the 80+ age groupConclusionTime between 1st and 2nd CDI most strongly predicts likelihood of progression to multiple recurrences. Of all measured comorbid conditions, renal disease was most predictive. These findings may help to identify patients at high risk for progression for advanced interventions such as microbiota modifying therapies.DisclosuresScott Fridkin, MD, Pfizer: Grant/Research Support Colleen Kraft, MD MS, Rebiotix Inc: Advisor/Consultant|SERES: Advisor/Consultant.

Clostridioides difficile infection after pneumonia in elderly patients: which antibiotic is at lower risk?