Clostridioides difficile infection surveillance in intensive care units and oncology wards using machine learning.

OBJECTIVE: Screening individuals admitted to the hospital for Clostridioides difficile presents opportunities to limit transmission and hospital-onset C. difficile infection (HO-CDI). However, detection from rectal swabs is resource intensive. In contrast, machine learning (ML) models may accurately assess patient risk without significant resource usage. In this study, we compared the effectiveness of swab surveillance to daily risk estimates produced by an ML model to identify patients who will likely develop HO-CDI in the intensive care unit (ICU) setting. DESIGN: A prospective cohort study was conducted with patient carriage of toxigenic C. difficile identified by rectal swabs analyzed by anaerobic culture and polymerase chain reaction (PCR). A previously validated ML model using electronic health record data generated daily risk of HO-CDI for every patient. Swab results and risk predictions were compared to the eventual HO-CDI status. PATIENTS: Adult inpatient admissions taking place in University of Michigan Hospitals' medical and surgical intensive care units and oncology wards between June 6th and October 8th, 2020. RESULTS: In total, 2,979 admissions, representing 2,044 patients, were observed over the course of the study period, with 39 admissions developing HO-CDIs. Swab surveillance identified 9 true-positive and 87 false-positive HO-CDIs. The ML model identified 9 true-positive and 226 false-positive HO-CDIs; 8 of the true-positives identified by the model differed from those identified by the swab surveillance. CONCLUSION: With limited resources, an ML model identified the same number of HO-CDI admissions as swab-based surveillance, though it generated more false-positives. The patients identified by the ML model were not yet colonized with C. difficile. Additionally, the ML model identifies at-risk admissions before disease onset, providing opportunities for prevention.

Clostridioides difficile toxin is infrequently detected in inflammatory bowel disease and does not associate with clinical outcomes.

INTRODUCTION: Clostridioides difficile infection (CDI) rates and outcomes can vary based on differences in testing strategy. Our aim was to assess the prevalence of toxin detection in inflammatory bowel disease (IBD) when compared to those without IBD. Secondly, the clinical outcomes of CDI in IBD were assessed using two-step testing strategies. METHODS: We included patients undergoing CDI testing from four academic centers in the United States between January 1, 2018 and June 30, 2020. First the prevalence of toxin detection was compared between individuals with IBD and those without IBD. Secondly, among patients with IBD a primary composite outcome of abdominal colectomy, admission to an intensive care unit (ICU) or death within 30 days of C. difficile testing was assessed across the three categorical groups (screen positive/toxin positive, screen positive/toxin negative and screen negative assay) resulting from the two-step testing strategy. RESULTS: When comparing individuals with a positive screening assay, patients with IBD were less likely to have toxin detected by enzyme immunoassay (EIA) as compared to the non-IBD population (22/145 (15.2%) vs. 413/1144 (36.1%), p < 0.0001). Among all patients with IBD (n = 300), twenty-five (8.3%) had a screen positive assay/toxin positive assay, 136 (45.3%) had a screen positive/toxin negative assay and 139 (46.3%) had a negative screening assay. No significant difference in the primary composite outcome was detected across the three groups (p = 0.566). CONCLUSION: When compared to those without IBD, patients with IBD have a reduced proportion of cases of C. difficile with toxin positivity. Differences in clinical outcomes among patients with IBD were not detected and limited by the infrequent detection of expressed toxin.

Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection.

Members of the Klebsiella pneumoniae species complex frequently colonize the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases (N = 85), where colonizing and invasive isolates were identical strain types, were matched to asymptomatically colonizing controls (N = 160). Thirty-seven genes are associated with infection, 27 of which remain significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes are not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many genes are plasmid borne, and for some, the relationship with infection is mediated by gut dominance. Five genes were validated in a geographically-independent cohort of colonized patients. This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella.

Non-steroidal anti-inflammatory drugs are not associated with increased risk of Clostridioides difficile infection: A propensity-score-matched case-control study.

Prior research identified an increased risk for Clostridioides difficile infection (CDI) following exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use. NSAID use was not associated with an increased risk of CDI.

Measurement of Klebsiella Intestinal Colonization Density To Assess Infection Risk.

Klebsiella pneumoniae and the closely related species K. variicola and K. quasipneumoniae are common causes of health care-associated infections, and patients frequently become infected with their intestinal colonizing strain. To assess the association between Klebsiella colonization density and subsequent infections, a case-control study was performed. A multiplex quantitative PCR (qPCR) assay was developed and validated to quantify Klebsiella (K. pneumoniae, K. variicola, and K. quasipneumoniae combined) relative to total bacterial DNA copies in rectal swabs. Cases of Klebsiella infection were identified based on clinical definitions and having a clinical culture isolate and a preceding or coincident colonization isolate with the same wzi capsular sequence type. Controls were colonized patients without subsequent infection and were matched 2:1 to cases based on age, sex, and rectal swab collection date. qPCR from rectal swab samples was used to measure the association between the relative abundance of Klebsiella and subsequent infections. The Klebsiella relative abundance by qPCR was highly correlated with 16S sequencing (ρ = 0.79; P < 0.001). The median Klebsiella relative abundance was higher in cases (15.7% [interquartile range {IQR}, 0.93 to 52.6%]) (n = 83) than in controls (1.01% [IQR, 0.02 to 12.8%]) (n = 155) (P < 0.0001). Adjusting for multiple clinical covariates using inverse probability of treatment weighting, a Klebsiella relative abundance of >22% was associated with infection overall (odds ratio [OR], 2.87 [95% confidence interval {CI}, 1.64 to 5.03]) (P = 0.0003) and with bacteremia in a secondary analysis (OR, 4.137 [95% CI, 1.448 to 11.818]) (P = 0.0084). Measurement of colonization density by qPCR could represent a novel approach to identify hospitalized patients at risk for Klebsiella infection. IMPORTANCE Colonization by bacterial pathogens often precedes infection and offers a window of opportunity to prevent these infections in the first place. Klebsiella colonization is significantly and reproducibly associated with subsequent infection; however, factors that enhance or mitigate this risk in individual patients are unclear. This study developed an assay to measure the density of Klebsiella colonization, relative to total fecal bacteria, in rectal swabs from hospitalized patients. Applying this assay to 238 colonized patients, a high Klebsiella density, defined as >22% of total bacteria, was significantly associated with subsequent infection. Based on widely available PCR technology, this type of assay could be deployed in clinical laboratories to identify patients at an increased risk of Klebsiella infections. As novel therapeutics are developed to eliminate pathogens from the gut microbiome, a rapid Klebsiella colonization density assay could identify patients who would benefit from this type of infection prevention intervention.

Risk Factors for Klebsiella Infections among Hospitalized Patients with Preexisting Colonization.

Klebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of health care-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear. A cohort study was performed, in which intensive care and hematology/oncology patients with Klebsiella colonization based on rectal swab culture were enrolled and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in a bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing. Among 2,087 hospitalizations from 1,978 colonized patients, 90 cases of infection (4.3%) were identified. The mean time to infection was 20.6 ± 24.69 (range, 0 to 91; median, 11.5) days. Of 86 typed cases, 68 unique wzi types were identified, and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression, and low albumin levels at the time of rectal swab collection were independently associated with subsequent Klebsiella infection (i.e., cases). Despite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates, and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at an increased risk of subsequent Klebsiella infection. IMPORTANCE Klebsiella is a leading cause of health care-associated infections. Patients who are intestinally colonized with Klebsiella are at a significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1,978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin levels in a blood test were more likely to develop infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The clinical variables associated with infection are readily available in the medical record and could serve as the foundation for developing an integrated risk assessment of Klebsiella infection in hospitalized patients.