Comparative Effectiveness of Biologic Therapies in Preventing Penetrating Complications in Patients With Crohn's Disease.

BACKGROUND & AIMS: Comparative effectiveness of biologics in preventing penetrating disease (PD) in Crohn's disease (CD) is not well established. We compared the risk of developing luminal and perianal PD (LPD and PPD) between biologics used as first-line therapies. METHODS: Adults (>17 years) with CD who initiated their first biologic (anti-tumor necrosis factor [anti-TNF], ustekinumab [UST], or vedolizumab [VDZ]) were identified from Merative Commercial Database (2006 and 2020). We excluded preexisting PD using a minimum look-back period of 1 year. Cohorts were balanced by inverse probability of treatment weighting based on age, sex, comorbidities, prior CD surgery, and CD severity. Pairwise comparisons were performed by Cox proportional hazards models, adjusted for immunomodulator exposure, and with biologic exposure treated as a time-dependent variable based on a medication possession ratio of 0.8. RESULTS: Our analysis included 40,693 patients: 93% anti-TNF, 3% UST, and 4% VDZ. After inverse probability of treatment weighting all comparisons were well balanced. Anti-TNF was protective against LPD (hazard ratio, 0.66; 95% confidence interval, 0.55-0.78; P < .0001) and PPD (hazard ratio, 0.88; 95% confidence interval, 0.80-0.96; P = .0045) compared with VDZ and LPD (hazard ratio, 0.37; 95% confidence interval, 0.30-0.46; P < .0001) compared with UST. There were no significant differences in the risk of LPD and PPD between VDZ and UST. These results were similar after limiting the study period to after 2016. CONCLUSIONS: Anti-TNF therapy was associated with a lower risk of LPD and PPD compared with VDZ, and lower risk of LPD compared with UST. Further studies are needed to validate these findings and to determine potential reasons for these differences.

Costs Attributable to Clostridioides difficile Infection Based on the Setting of Onset.

BACKGROUND: Although hospital-onset Clostridioides difficile infection (CDI) is associated with significant healthcare costs, the economic burden of CDI with onset in other facilities or the community has not been well studied. METHODS: Incident CDI cases were identified using 2011-2017 Medicare fee-for-service data. Controls were randomly selected in a 4:1 ratio matching to the CDI case surveillance definition. Inverse probability of exposure weights were used to balance on measured confounders. One-, 3-, and 5-year cumulative costs attributable to CDI were computed using a 3-part estimator (parametric survival model and pair of 2-part models predicting costs separately in intervals where death did and did not occur). RESULTS: A total of 60 492 CDI cases were frequency-matched to 241 968 controls. One-, 3-, and 5-year adjusted attributable costs were highest for hospital-onset CDI at $14 257, $18 953, and $21 792, respectively, compared with hospitalized controls and lowest for community-associated CDI compared with community controls at $1013, $3161, and $6454, respectively. Adjusted 1-, 3-, and 5-year costs attributable to community-onset healthcare facility-associated CDI were $8222, $13 066, and $16 329 and for other healthcare facility-onset CDI were $5345, $6764, and $7125, respectively. CONCLUSIONS: Economic costs attributable to CDI in elderly persons were highest for hospital-onset and community-onset healthcare facility-associated CDI. Although lower, attributable costs due to CDI were significantly higher in cases with CDI onset in the community or other healthcare facility than for comparable persons without CDI. Additional strategies to prevent CDI in the elderly are needed to reduce morbidity and healthcare expenditures.

Attributable Mortality of Candida Bloodstream Infections in the Modern Era: A Propensity Score Analysis.

BACKGROUND: This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins. METHODS: We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1368-bed tertiary care academic hospital, in Saint Louis, Missouri, from 1 February 2012 to 30 April 2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods-propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile. RESULTS: The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% confidence interval [CI], 1.98-2.25, P < .001). In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (hazard ratio [HR] 3.13 (95% CI, 2.33-4.19). Patients in this lowest risk quintile accounted for 81(61%) of the 130 untreated patients with Candida BSI. Sixty-nine percent of untreated patients (57/83) died versus 35% of (49/127) of treated patients (P < .001). CONCLUSIONS: Patients with Candida BSI continue to experience high mortality. Mortality attributable to Candida BSI was more pronounced in patients at lowest risk to develop Candida BSI. A higher proportion of these low-risk patients went untreated, experienced higher mortality, and should be the target of aggressive interventions to ensure timely, effective treatment.

A Population-Based Assessment of Depression and Anxiety in Patients With Brachial Plexus Injuries.

PURPOSE: Reactive depression and anxiety are common after major life changes such as brachial plexus injuries (BPI). The purpose of this study was to evaluate the incidence and risk factors for coded depression and coded anxiety among patients with BPI using a national database of commercial insurance claims. METHODS: We used the Truven MarketScan database from 2007 to 2013 to identify commercially insured patients aged 18 to 64 years who underwent BPI surgery. For comparison, a control group without BPI was frequency-matched 10:1 by age group, sex, number of provider visits, and length of insurance enrollment. Using International Classification of Diseases, Ninth Revision diagnosis codes and pharmacy claims, we identified coded depression and coded anxiety in the 12 months before and 12 months after BPI surgery. Multivariable Cox regression models were used to determine risk factors for coded depression or coded anxiety, adjusting for known risk factors for depression or anxiety (eg, alcohol, substance abuse). RESULTS: We identified 1,843 patients with BPI and 18,430 controls. Within the 12 months preceding surgery, coded depression and coded anxiety were present in 38% and 42%, respectively, of the BPI group; both were present in 25% and either was present in 54%. The rate of new-onset/postoperatively coded depression among patients with BPI was 142.1/1,000 person-years (12%) and of new-onset/postoperatively coded anxiety was 273.6/1,000 person-years (20%). Patients with BPI were significantly more likely than controls to develop new-onset/postoperatively coded depression (hazard ratio = 1.3; confidence interval [CI], 1.1-1.5) and new-onset/postoperatively coded anxiety (HR = 2.1 [CI, 1.8-2.4]). CONCLUSIONS: Patients undergoing BPI surgery have a high prevalence of coded depression and coded anxiety in the 12 months before surgery and are at higher risk for developing new-onset/postoperatively coded depression and coded anxiety within 1 year after surgery. These findings can be used by BPI surgeons to inform perioperative counseling, guide emotional recovery from injury, and facilitate coordinated or colocated care with mental health professionals. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The burden of clostridium difficile infection: estimates of the incidence of CDI from U.S. Administrative databases.

BACKGROUND: Many administrative data sources are available to study the epidemiology of infectious diseases, including Clostridium difficile infection (CDI), but few publications have compared CDI event rates across databases using similar methodology. We used comparable methods with multiple administrative databases to compare the incidence of CDI in older and younger persons in the United States. METHODS: We performed a retrospective study using three longitudinal data sources (Medicare, OptumInsight LabRx, and Healthcare Cost and Utilization Project State Inpatient Database (SID)), and two hospital encounter-level data sources (Nationwide Inpatient Sample (NIS) and Premier Perspective database) to identify CDI in adults aged 18 and older with calculation of CDI incidence rates/100,000 person-years of observation (pyo) and CDI categorization (onset and association). RESULTS: The incidence of CDI ranged from 66/100,000 in persons under 65 years (LabRx), 383/100,000 in elderly persons (SID), and 677/100,000 in elderly persons (Medicare). Ninety percent of CDI episodes in the LabRx population were characterized as community-onset compared to 41 % in the Medicare population. The majority of CDI episodes in the Medicare and LabRx databases were identified based on only a CDI diagnosis, whereas almost ¾ of encounters coded for CDI in the Premier hospital data were confirmed with a positive test result plus treatment with metronidazole or oral vancomycin. Using only the Medicare inpatient data to calculate encounter-level CDI events resulted in 553 CDI events/100,000 persons, virtually the same as the encounter proportion calculated using the NIS (544/100,000 persons). CONCLUSIONS: We found that the incidence of CDI was 35 % higher in the Medicare data and fewer episodes were attributed to hospital acquisition when all medical claims were used to identify CDI, compared to only inpatient data lacking information on diagnosis and treatment in the outpatient setting. The incidence of CDI was 10-fold lower and the proportion of community-onset CDI was much higher in the privately insured younger LabRx population compared to the elderly Medicare population. The methods we developed to identify incident CDI can be used by other investigators to study the incidence of other infectious diseases and adverse events using large generalizable administrative datasets.

Neurofibromatosis type 1 and chronic neurological conditions in the United States: an administrative claims analysis.

PURPOSE: Neurofibromatosis type 1 has been linked to several neurological conditions, including epilepsy, Parkinson disease, headache, multiple sclerosis, and sleep disturbances, predominantly through case reports and patient series that lack comparison groups. Our objective was to assess whether specific neurological conditions occur more frequently in individuals with neurofibromatosis type 1 versus those without neurofibromatosis type 1. METHODS: We used the 2006-2010 MarketScan Commercial Claims and Encounters database to examine associations between neurological conditions and neurofibromatosis type 1. The neurofibromatosis type 1 group was identified through ≥2 International Classification of Diseases, Ninth Revision, Clinical Modification neurofibromatosis codes (237.70, 237.71) occurring ≥30 days apart or one inpatient neurofibromatosis code. A nonneurofibromatosis type 1 comparison group was frequency matched to the neurofibromatosis type 1 group on age and enrollment length at a 10:1 ratio. Unconditional logistic regression was employed to calculate adjusted odds ratios and 95% confidence intervals for associations between neurofibromatosis and neurological conditions. RESULTS: Compared with the nonneurofibromatosis type 1 group (n = 85,790), the neurofibromatosis type 1 group (n = 8,579) had significantly higher odds of health insurance claims for epilepsy (odds ratio: 7.3; 95% confidence interval: 6.4-8.3), Parkinson disease (odds ratio: 3.1; 95% confidence interval: 1.3-7.5), headache (odds ratio: 2.9; 95% confidence interval: 2.6-3.1), multiple sclerosis (odds ratio: 1.9; 95% confidence interval: 1.2-2.9), and sleep disturbances/disorder (odds ratio: 1.4; 95% confidence interval: 1.2-3.6). CONCLUSION: This large study provides strong evidence for positive associations between several neurological conditions and neurofibromatosis type 1.

Effect of surgical fixation timing on in-hospital mortality and morbidity of distal femur fractures.

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data. METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications. RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in the fragility cohort and 2.56 % in the polytrauma cohort. Multivariate analysis of the fragility cohort showed that fixation greater than 48 h from time of presentation was associated with increased mortality compared to fixation within 24 h (OR 1.89, CI: 1.26-2.83, p=0.002) and between 24 and 48 h (OR 1.63, CI: 1.23-2.15, p<0.001). In the polytrauma cohort, multivariate analysis showed no significant mortality differences between fixation timing groups. Multivariate analysis of morbidity outcomes in both cohorts showed that fixation greater than 48 h was associated with increased LOS, ICU LOS, ventilator days, and complications compared to fixation within 24 h. In the polytrauma cohort, fixation between 24 and 48 h was associated with decreased LOS, ICU LOS, and complications compared to the other two timing groups. CONCLUSIONS: Fixation of distal femur fractures before 48 h from presentation may lead to improved mortality and morbidity in older, lower injury severity patients. No significant mortality benefit was observed in younger, polytrauma fractures. Further prospective work is needed to validate these findings.

Evaluation of obesity and age as a predictive factor of lower extremity compartment syndrome: A national trauma data bank analysis.

BACKGROUND: Risk factors of acute compartment syndrome (ACS) of the leg include tibial fractures followed by soft tissue injuries. METHODS: Data collected from the National Trauma Data Bank (NTDB) between 2017 and 2019 were analyzed for adult patients with lower extremity fractures, including proximal tibia, tibial shaft, and distal tibia. The primary outcome was a diagnosis of ACS. RESULTS: There were 1052/220,868 patients with lower extremity fractures with a concomitant diagnosis of compartment syndrome. Our study has shown that patients with a BMI of ≥30 had a lower incidence of compartment syndrome when compared with patients with a BMI of 25-29 and controlled for fracture type. Increased age ≥55 in males, and females between 65 and 84, also demonstrated a decreased risk. Proximal tibial fractures (n â€‹= â€‹54,696) were significantly associated with ACS compared to midshaft (n â€‹= â€‹42,153) and distal (n â€‹= â€‹100,432), p â€‹< â€‹0.0001. CONCLUSION: We found that being overweight decreases risk for development of compartment syndrome in patients with lower extremity fractures. This big data study aids in establishing risk factors for development of ACS in adult trauma patients.

Clostridioides difficile infection across the lifespan: Estimation using life tables.

Using a life tables approach with 2011-2017 claims data, we calculated lifetime risks of Clostridioides difficile infection (CDI) beginning at age 18 years. The lifetime CDI risk rates were 32% in female patients insured by Medicaid, 10% in commercially insured male patients, and almost 40% in females with end-stage renal disease.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

Modeling asthma exacerbations through lung function in children.

BACKGROUND: Formal economic evaluation using a model-based approach is playing an increasingly important role in health care decision making. OBJECTIVE: To develop a model by using an objective measure of lung function-- prebronchodilator FEV(1) as a percent of predicted (FEV(1)% predicted)--as the primary independent factor to predict the frequency of adverse events related to the exacerbation of asthma on a population level. METHODS: We developed a Markov simulation model of childhood asthma by using data from the Childhood Asthma Management Program. The primary outcomes were the result of asthma exacerbations defined as hospitalizations, emergency department (ED) visits, and the need for oral corticosteroid therapy. Predicted monthly frequencies for each acute event were based on negative binomial regression equations estimated from the placebo arm of the Childhood Asthma Management Program with covariates of age, prebronchodilator FEV(1)% predicted, time in study, prior hospitalizations, and prior nocturnal awakenings. RESULTS: Simulated versus observed mean number of acute events were similar within the placebo and treatment groups. While the trial demonstrated treatment effects of 48% reduction in hospitalizations, 46% reduction in ED visits, and 44% reduction in the need for oral corticosteroid therapy at 48 months, the model simulated similar reductions of 49% in hospitalizations, 41% in ED visits, and 46% in the need for oral corticosteroid therapy. CONCLUSIONS: Our findings suggest that longitudinal intervention effects may be modeled through FEV(1)% predicted to estimate hospitalizations, ED visits, and need for oral corticosteroid therapy in childhood asthma for planning and evaluation purposes.

State of the Union: Timeliness to Antibiotics in Open Fractures.

OBJECTIVE: In open fractures, early administration of systemic antibiotics has recently been recognized as a universal recommendation, with the current American College of Surgeons Trauma Center Verification recommendation for administration within 1 hour of facility arrival. We sought to quantify the baseline rate of timely antibiotic administration and the various factors associated with delay. METHODS: Data from the National Trauma Data Bank were obtained for all patients treated for open fractures in 2019. 65,552 patients were included. Univariate and multivariate analyses were performed, first for patient, prehospital, and hospital factors compared with rate of antibiotic administration within 1 hour of hospital arrival, then with a multivariate analysis of factors affecting these times. RESULTS: The overall rate of antibiotic administration within 1 hour of arrival was 47.6%. Patient factors associated with lower rates of timely antibiotics include increased age, Medicare status, and a higher number of comorbidities. Associated prehospital factors included non-work-related injuries, fixed-wing air or police transport, and walk-in arrival method. Patients with lower extremity open fractures were more likely to receive antibiotics within 1 hour of arrival than those with upper extremity open fractures. Traumatic amputations had a higher rate of timely administration (67.3%). ACS trauma Level II (52.5%) centers performed better than Level III (48.3%), Level I (45.5%), and Level IV (34.5%) centers. Multivariate analysis confirmed the findings of the univariate analysis. CONCLUSIONS: Despite current clinical standards, rates of adherence to rapid antibiotic administration are low. Certain patient, facility, and environmental factors are associated with delays in antibiotic administration and can be a focus for quality improvement processes. We plan to use these data to evaluate how focus on antibiotic administration as this quality standard changes practice over time. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increased Incidence and Risk of Septicemia and Urinary Tract Infection After Clostridioides difficile Infection.

Background: Although increased occurrence of septicemia in persons with Clostridioides difficile infection (CDI) has been reported, incidence rates and risk of septicemia and urinary tract infection (UTI) after CDI are unclear. Methods: The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population. Results: The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and 19.5%, respectively) and lowest in those with community-associated CDI (3.8%, 4.3%, and 8.3%, respectively). In contrast, the incidence of UTI was highest in those with other healthcare facility onset CDI in all 3 populations (32.1%, 24.2%, and 18.1%, respectively). Hospital-onset CDI was associated with highest risk of septicemia compared with uninfected controls in all 3 populations. In the younger populations, risk of septicemia was more uniform across the CDI surveillance definitions. The risk of UTI was significantly higher in all CDI surveillance categories compared to uninfected controls, and among CDI cases it was lowest in those with community-associated CDI. Conclusions: The incidence of septicemia is high after CDI, particularly after hospital-onset infection. Additional preventive measures are needed to reduce infectious complications of CDI.

Trends in the incidence of Clostridioides difficile infection in adults and the elderly insured by Medicaid compared to commercial insurance or Medicare only.

OBJECTIVE: Few data are available to quantify the Clostridioides difficile infection (CDI) burden in US adults depending on Medicaid insurance status; thus, we sought to contribute to this body of information. METHODS: Retrospective cohort study to identify adults with codes for CDI from 2011 to 2017 in MarketScan commercial and Medicaid databases (for those aged 25-64 years) and the CMS Medicare database (for those aged ≥65 years). CDI was categorized as healthcare-facility-associated (HCA-CDI) and community-associated CDI (CA-CDI). CDI incidence rates were compared by year, insurer, and age group. RESULTS: The overall CDI incidence in the elderly was 3.1-fold higher in persons insured by Medicare plus Medicaid than in those insured by Medicare only (1,935 vs 618 per 100,000 person years (PY)), and the CDI incidence was 2.7-fold higher in younger adults with Medicaid compared to commercial insurance (195 vs 73 per 100,000 PY). From 2011 to 2017, HCA-CDI rates declined in the younger Medicaid population (124.0 to 95.2 per 100,000 PY; P < .001) but were stable in those commercially insured (25.9 to 24.8 per 100,000 PY; P = .33). In the elderly HCA-CDI rates declined from 2011 to 2017 in the Medicare-only population (403 to 318 per 100,000 PY; P < .001) and the Medicare plus Medicaid population (1,770 to 1,163 per 100,000 PY; P < .002). Persons with chronic medical conditions and those with immunocompromising conditions insured by Medicaid had 2.8- and 2.7-fold higher CDI incidence compared to the commercially insured population, respectively. The incidence of CDI was lowest in Medicaid and commercially insured younger adults without chronic medical or immunosuppressive conditions (67.5 and 45.6 per 100,000 PY, respectively). CONCLUSIONS: Although HCA-CDI incidence decreased from 2011 to 2017 in elderly and younger adults insured by Medicaid, the burden of CDI remains much higher in low-income adults insured by Medicaid.

Impact of the Severe acute respiratory syndrome coronavirus 2 pandemic on mortality associated with healthcare-associated infections.

Objective: To determine the relationship between severe acute respiratory syndrome coronavirus 2 infection, hospital-acquired infections (HAIs), and mortality. Design: Retrospective cohort. Setting: Three St. Louis, MO hospitals. Patients: Adults admitted ≥48 hours from January 1, 2017 to August 31, 2020. Methods: Hospital-acquired infections were defined as those occurring ≥48 hours after admission and were based on positive urine, respiratory, and blood cultures. Poisson interrupted time series compared mortality trajectory before (beginning January 1, 2017) and during the first 6 months of the pandemic. Multivariable logistic regression models were fitted to identify risk factors for mortality in patients with an HAI before and during the pandemic. A time-to-event analysis considered time to death and discharge by fitting Cox proportional hazards models. Results: Among 6,447 admissions with subsequent HAIs, patients were predominantly White (67.9%), with more females (50.9% vs 46.1%, P = .02), having slightly lower body mass index (28 vs 29, P = .001), and more having private insurance (50.6% vs 45.7%, P = .01) in the pre-pandemic period. In the pre-pandemic era, there were 1,000 (17.6%) patient deaths, whereas there were 160 deaths (21.3%, P = .01) during the pandemic. A total of 53 (42.1%) coronavirus disease 2019 (COVID-19) patients died having an HAI. Age and comorbidities increased the risk of death in patients with COVID-19 and an HAI. During the pandemic, Black patients with an HAI and COVID-19 were more likely to die than White patients with an HAI and COVID-19. Conclusions: In three Midwestern hospitals, patients with concurrent HAIs and COVID-19 were more likely to die if they were Black, elderly, and had certain chronic comorbidities.

Corticosteroids Increase the Risk of Invasive Fungal Infections More Than Tumor Necrosis Factor-Alpha Inhibitors in Patients With Inflammatory Bowel Disease.

Background: Invasive fungal infections are a devastating complication of inflammatory bowel disease (IBD) treatment. We aimed to determine the incidence of fungal infections in IBD patients and examine the risk with tumor necrosis factor-alpha inhibitors (anti-TNF) compared with corticosteroids. Methods: In a retrospective cohort study using the IBM MarketScan Commercial Database we identified US patients with IBD and at least 6 months enrollment from 2006 to 2018. The primary outcome was a composite of invasive fungal infections, identified by ICD-9/10-CM codes plus antifungal treatment. Tuberculosis (TB) infections were a secondary outcome, with infections presented as cases/100 000 person-years (PY). A proportional hazards model was used to determine the association of IBD medications (as time-dependent variables) and invasive fungal infections, controlling for comorbidities and IBD severity. Results: Among 652 920 patients with IBD, the rate of invasive fungal infections was 47.9 cases per 100 000 PY (95% CI 44.7-51.4), which was more than double the TB rate (22 cases [CI 20-24], per 100 000 PY). Histoplasmosis was the most common invasive fungal infection (12.0 cases [CI 10.4-13.8] per 100 000 PY). After controlling for comorbidities and IBD severity, corticosteroids (hazard ratio [HR] 5.4; CI 4.6-6.2) and anti-TNFs (HR 1.6; CI 1.3-2.1) were associated with invasive fungal infections. Conclusions: Invasive fungal infections are more common than TB in patients with IBD. The risk of invasive fungal infections with corticosteroids is more than double that of anti-TNFs. Minimizing corticosteroid use in IBD patients may decrease the risk of fungal infections.

Microbiology Clinical Culture Diagnostic Yields and Antimicrobial Resistance Proportions before and during the COVID-19 Pandemic in an Indian Community Hospital and Two US Community Hospitals.

Studies comparing the impact of the COVID-19 pandemic on diagnostic microbiology culture yields and antimicrobial resistance proportions in low-to-middle-income and high-income countries are lacking. A retrospective study using blood, respiratory, and urine microbiology data from a community hospital in India and two community hospitals (Hospitals A and B) in St. Louis, MO, USA was performed. We compared the proportion of cultures positive for selected multi-drug-resistant organisms (MDROs) listed on the WHO's priority pathogen list both before the COVID-19 pandemic (January 2017-December 2019) and early in the COVID-19 pandemic (April 2020-October 2020). The proportion of blood cultures contaminated with coagulase-negative Staphylococcus (CONS) was significantly higher during the pandemic in all three hospitals. In the Indian hospital, the proportion of carbapenem-resistant (CR) Klebsiella pneumoniae in respiratory cultures was significantly higher during the pandemic period, as was the proportion of CR Escherichia coli in urine cultures. In the US hospitals, the proportion of methicillin-resistant Staphylococcus aureus in blood cultures was significantly higher during the pandemic period in Hospital A, while no significant increase in the proportion of Gram-negative MDROs was observed. Continuity of antimicrobial stewardship activities and better infection prevention measures are critical to optimize outcomes and minimize the burden of antimicrobial resistance among COVID-19 patients.

Healthcare-associated infections (HAIs) during the coronavirus disease 2019 (COVID-19) pandemic: A time-series analysis.

Objective: To use interrupted time-series analyses to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs). We hypothesized that the pandemic would be associated with higher rates of HAIs after adjustment for confounders. Design: We conducted a cross-sectional study of HAIs in 3 hospitals in Missouri from January 1, 2017, through August 31, 2020, using interrupted time-series analysis with 2 counterfactual scenarios. Setting: The study was conducted at 1 large quaternary-care referral hospital and 2 community hospitals. Participants: All adults ≥18 years of age hospitalized at a study hospital for ≥48 hours were included in the study. Results: In total, 254,792 admissions for ≥48 hours occurred during the study period. The average age of these patients was 57.6 (±19.0) years, and 141,107 (55.6%) were female. At hospital 1, 78 CLABSIs, 33 CAUTIs, and 88 VAEs were documented during the pandemic period. Hospital 2 had 13 CLABSIs, 6 CAUTIs, and 17 VAEs. Hospital 3 recorded 11 CLABSIs, 8 CAUTIs, and 11 VAEs. Point estimates for hypothetical excess HAIs suggested an increase in all infection types across facilities, except for CLABSIs and CAUTIs at hospital 1 under the "no pandemic" scenario. Conclusions: The COVID-19 era was associated with increases in CLABSIs, CAUTIs, and VAEs at 3 hospitals in Missouri, with variations in significance by hospital and infection type. Continued vigilance in maintaining optimal infection prevention practices to minimize HAIs is warranted.

Early coronavirus disease 2019 (COVID-19) pandemic effects on individual-level risk for healthcare-associated infections in hospitalized patients.

OBJECTIVE: We compared the individual-level risk of hospital-onset infections with multidrug-resistant organisms (MDROs) in hospitalized patients prior to and during the coronavirus disease 2019 (COVID-19) pandemic. We also quantified the effects of COVID-19 diagnoses and intrahospital COVID-19 burden on subsequent MDRO infection risk. DESIGN: Multicenter, retrospective, cohort study. SETTING: Patient admission and clinical data were collected from 4 hospitals in the St. Louis area. PATIENTS: Data were collected for patients admitted between January 2017 and August 2020, discharged no later than September 2020, and hospitalized ≥48 hours. METHODS: Mixed-effects logistic regression models were fit to the data to estimate patients' individual-level risk of infection with MDRO pathogens of interest during hospitalization. Adjusted odds ratios were derived from regression models to quantify the effects of the COVID-19 period, COVID-19 diagnosis, and hospital-level COVID-19 burden on individual-level hospital-onset MDRO infection probabilities. RESULTS: We calculated adjusted odds ratios for COVID-19-era hospital-onset Acinetobacter spp., P. aeruginosa and Enterobacteriaceae spp infections. Probabilities increased 2.64 (95% confidence interval [CI], 1.22-5.73) times, 1.44 (95% CI, 1.03-2.02) times, and 1.25 (95% CI, 1.00-1.58) times relative to the prepandemic period, respectively. COVID-19 patients were 4.18 (95% CI, 1.98-8.81) times more likely to acquire hospital-onset MDRO S. aureus infections. CONCLUSIONS: Our results support the growing body of evidence indicating that the COVID-19 pandemic has increased hospital-onset MDRO infections.

Risk factors for hospital-onset Clostridioides difficile infections before and during the severe acute respiratory syndrome coronavirus 2 pandemic.

In this retrospective cohort from 3 Missouri hospitals from January 2017 to August 2020, hospital-onset Clostridioides difficile infections were more common during the severe acute respiratory syndrome coronavirus 2 pandemic at the tertiary care hospital. Risk factors associated with hospital-onset C difficile infection included the year of hospitalization, age, high-risk antibiotic use, acid-reducing medications, chronic comorbidities, and severe acute respiratory syndrome coronavirus 2 infection.