Excess Healthcare Costs and Resource Utilisation of Lyme Borreliosis in Germany: A Propensity Score-Matched Cohort Study.

AIM: Lyme borreliosis (LB) is the most common tick-borne disease in Germany; however, data on the economic burden of LB are limited. In this study, we aim to report healthcare costs, healthcare resource utilisation (HCRU) and diagnostic consumption associated with LB by clinical manifestation. METHOD: Using specific case definitions, patients with localised disease (erythema migrans [EM]) or disseminated disease (Lyme arthritis [LA], Lyme neuroborreliosis [LNB] and other rarer manifestations [OTH]) were identified from a claims database in 2016 and followed up for 3 years (2016-2019). After propensity score matching, excess costs and HCRU were calculated as the differences between each LB cohort and the matched control cohort. RESULTS: On a per-patient basis, the excess all-cause healthcare cost was €130 for EM during Quarter 1 of Year 1, and €1539 for LA, €3248 for LNB and €4137 for OTH during Year 1. Only for OTH, additional €1860 was observed in Year 2. No increase in costs was observed in Year 3. When extrapolated to all German patients with statutory health insurance, LB was associated with €64.5 million in excess costs. Although disseminated manifestations only accounted for 7.8% of all LB cases, they were responsible for 66% of overall costs. In addition, LB patients consumed healthcare resources of 1.4 million excess outpatient visits, 13,000 excess hospitalisations, 96,000 ELISAs and 65,000 Western blots. CONCLUSION: This study shows the substantial economic burden of LB to the German healthcare system.

Preferences for a Clostridioides difficile vaccine among adults in the United States.

INTRODUCTION: Clostridioides difficile (C.diff) infection (CDI) causes significant morbidity and mortality among older adults. Vaccines to prevent CDI are in development; however, data on the target population's preferences are needed to inform vaccination recommendations in the United States (US). This study assessed US adults' willingness to receive a C.diff vaccine and examined how vaccine attributes influence their choices. METHODS: A cross-sectional online survey with a discrete choice experiment (DCE) was conducted among US adults aged ≥50 years. DCE attributes included effectiveness, duration of protection, reduction in symptom severity, out-of-pocket (OOP) costs, number of doses, and side effects. The DCE included 11 choice tasks, each with two hypothetical vaccine profiles and an opt-out (i.e., no vaccine). Attribute-level preference weights were estimated using hierarchical Bayesian modeling. Attribute relative importance (RI) was compared between select subgroups. RESULTS: Of 1216 adults in the analyses, 29.9% reported they knew either 'a little' (20.7%) or 'a lot' (9.2%) about C.diff before the study. A C.diff vaccine was chosen 58.0% of the time (vs. opt-out) across choice tasks. It was estimated that up to 75.0% would choose a vaccine when OOP was $0. Those who were immunocompromised/high-risk for CDI (vs. not) more frequently chose a C.diff vaccine. Decreases in OOP costs (RI = 56.1), improvements in vaccine effectiveness (RI = 17.7), and reduction in symptom severity (RI = 10.3) were most important to vaccine choice. The rank ordering of attributes by importance was consistent across subgroups. CONCLUSION: OOP cost, improvements in vaccine effectiveness, and reduction in CDI severity were highly influential to vaccine selection. Most adults aged ≥50 years were receptive to a C.diff vaccine, especially with little-to-no OOP cost, suggesting that mandating insurance coverage of vaccination with no copayment may increase uptake. The limited awareness about C.diff among adults presents an opportunity for healthcare providers to educate their patients about CDI prevention.

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study.

Lyme borreliosis (LB) is the most common tick-borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non-specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically-attended LB by disease manifestation, age group, and federal state for the period 2015-2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD-10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically-attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 - 200.5) to 254.5/100,000 population per year (95% CI, 249.0 - 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5-9 years and in older adults. By federal state, the incidence of medically-attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 - 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 - 417.6) per year in Saxony, whereas for medically-attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 - 24.0] to 35.7 [95% CI, 34.7 - 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically-attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

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.

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.

Healthcare Costs of Clostridioides difficile Infection in Commercially Insured Younger Adults.

In a US adult population aged <65 years, attributable costs due to Clostridioides difficile infection (CDI) were highest in persons with hospital onset and lowest in those with community-associated CDI treated outside a hospital. The economic burden of CDI in younger adults underscores the need for additional CDI-preventive strategies.

Epidemiology of Clostridioides difficile Infections in Germany, 2010-2019: A Review from Four Public Databases.

INTRODUCTION: Clostridioides difficile infection (CDI) is a recognized global threat especially for vulnerable populations. It is of particular concern to healthcare providers as it is found in both hospital and community settings, with severe courses, frequent recurrence, high mortality and substantial financial impact on the healthcare system. The CDI burden in Germany has been described and compared by analysing data from four different public databases. METHODS: Data on hospital burden of CDI have been extracted, compared, and discussed from four public databases for the years 2010-2019. Hospital days due to CDI were compared to established vaccine preventable diseases, such as influenza and herpes zoster, and also to CDI hospitalisations in the United States (US). RESULTS: All four databases reported comparable incidences and trends. Beginning in 2010, population-based hospitalised CDI incidence increased to a peak of > 137/100,000 in 2013. Then, incidence declined to 81/100,000 in 2019. Hospitalised patients with CDI were predominantly > 50 years of age. The population-based incidence of severe CDI was between 1.4 and 8.4/100,000 per year. Recurrence rates were between 5.9 to 6.5%. More than 1,000 CDI deaths occurred each year, with a peak of 2,666 deaths in 2015. Cumulative CDI patient days (PD) were between 204,596 and 355,466 each year, which exceeded cumulated PD for influenza and herpes zoster in most years, though year-to-year differences were observed. Finally, hospitalized CDI incidence was higher in Germany than in the US, where the disease is well recognized as a public health threat. CONCLUSIONS: All four public sources documented a decline in CDI cases since 2013, but the disease burden remains substantial and warrants continued attention as a severe public health challenge.

Incidence, Attributable Mortality, and Healthcare and Out-of-Pocket Costs of Clostridioides difficile Infection in US Medicare Advantage Enrollees.

BACKGROUND: US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018. METHODS: This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched cohort using 2018 as the index year. Outcome analyses were stratified by infection acquisition and hospitalization status. RESULTS: From 2012 to 2019, overall annual CDI incidence declined from 609 to 442 per 100 000 person-years. Although the incidence of healthcare-associated CDI declined overall (2012, 53.2%; 2019, 47.2%), community-associated CDI increased (2012, 46.8%; 2019, 52.8%). The 1-year attributable mortality was 7.9% (CDI cases, 26.3%; non-CDI controls, 18.4%). At the 2-month follow-up, CDI-associated excess mean total healthcare and out-of-pocket costs were $13 476 and $396, respectively. Total excess mean healthcare costs were greater among hospitalized (healthcare-associated, $28 762; community-associated, $28 330) than nonhospitalized CDI patients ($5704 and $2320, respectively), whereas total excess mean out-of-pocket cost was highest among community-associated hospitalized CDI patients ($970). CONCLUSIONS: CDI represents an important public health burden in the MAE population. Preventive strategies and treatments are needed to improve outcomes and reduce costs for healthcare systems and this growing population of older US adults.

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.

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.

Staphylococcus aureus infections after elective pediatric surgeries.

OBJECTIVE: To determine the 180-day cumulative incidence of culture-confirmed Staphylococcus aureus infections after elective pediatric surgeries. DESIGN: Retrospective cohort study utilizing the Premier Healthcare database (PHD). SETTING: Inpatient and hospital-based outpatient elective surgical discharges. PATIENTS: Pediatric patients <18 years who underwent surgery during elective admissions between July 1, 2010, and June 30, 2015, at any of 181 PHD hospitals reporting microbiology results. METHODS: In total, 74 surgical categories were defined using ICD-9-CM and CPT procedure codes. Microbiology results and ICD-9-CM diagnosis codes defined S. aureus infection types: bloodstream infection (BSI), surgical site infection (SSI), and other types (urinary tract, respiratory, and all other). Cumulative postsurgical infection incidence was calculated as the number of infections divided by the number of discharges with qualifying elective surgeries. RESULTS: Among 11,874 inpatient surgical discharges, 180-day S. aureus infection incidence was 1.79% overall (1.00% SSI, 0.35% BSI, 0.45% other). Incidence was highest among children <2 years of age (2.76%) and lowest for those 10-17 years (1.49%). Among 50,698 outpatient surgical discharges, incidence was 0.36% overall (0.23% SSI, 0.05% BSI, 0.08% others); it was highest among children <2 years of age (0.57%) and lowest for those aged 10-17 years (0.30%). MRSA incidence was significantly higher after inpatient surgeries (0.68%) than after outpatient surgeries (0.14%; P < .0001). Overall, the median days to S. aureus infection was longer after outpatient surgery than after inpatient surgery (39 vs. 31 days; P = .0116). CONCLUSIONS: These findings illustrate the burden of postoperative S. aureus infections in the pediatric population, particularly among young children. These results underscore the need for continued infection prevention efforts and longer-term surveillance after surgery.

Incidence and burden of Staphylococcus aureus infection after orthopedic surgeries.

OBJECTIVE: To assess the 180-day incidence of Staphylococcus aureus infections following orthopedic surgeries using microbiology cultures. DESIGN: Retrospective observational epidemiology study. SETTING: National administrative hospital database. PATIENTS: Adult patients with an elective admission undergoing orthopedic surgeries in the inpatient and hospital-based outpatient settings discharged between July 1, 2010, and June 30, 2015. METHODS: Patients were identified from 181 hospitals reporting microbiology results to the Premier Healthcare Database. Orthopedic surgeries were defined using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure and current procedural terminology (CPT) codes. Microbiology cultures and ICD-9/10 diagnosis codes identified surgical site infections (SSIs), bloodstream infections (BSIs), and other infections associated postoperatively (eg, respiratory and urinary tract infections). RESULTS: Among 359,268 inpatient orthopedic surgical encounters, the S. aureus infection incidence was 1.13%: SSI, 0.68%; BSI, 0.28%; and other types, 0.17%. Among 292,011 outpatient encounters, the S. aureus incidence was 0.78%: SSI, 0.55%; BSI, 0.12%; and other types, 0.11%. Methicillin-resistant S. aureus (MRSA) infections accounted for 46% and 44% in the respective settings. Plastic/hand-limb reattachment and amputation had the highest overall S. aureus incidence in both settings. S. aureus was the most commonly isolated microorganism among culture-confirmed SSIs (48.0%) and BSIs (35.0%), followed by other Enterobacteriaceae (14.0%) for SSIs and Escherichia spp (12.5%) for BSIs. CONCLUSIONS: These findings suggest that S. aureus infections continue to be an important contributor to the burden of postoperative infections after inpatient and outpatient orthopedic procedures.

A Risk Score to Predict Clostridioides difficile Infection.

BACKGROUND: Clostridioides difficile infection (CDI) is a major cause of severe diarrhea. In this retrospective study, we identified CDI risk factors by comparing demographic and clinical characteristics for Kaiser Permanente Northern California members ≥18 years old with and without laboratory-confirmed incident CDI. METHODS: We included these risk factors in logistic regression models to develop 2 risk scores that predict future CDI after an Index Date for Risk Score Assessment (IDRSA), marking the beginning of a period for which we estimated CDI risk. RESULTS: During May 2011 to July 2014, we included 9986 CDI cases and 2 230 354 members without CDI. The CDI cases tended to be older, female, white race, and have more hospitalizations, emergency department and office visits, skilled nursing facility stays, antibiotic and proton pump inhibitor use, and specific comorbidities. Using hospital discharge as the IDRSA, our risk score model yielded excellent performance in predicting the likelihood of developing CDI in the subsequent 31-365 days (C-statistic of 0.848). Using a random date as the IDRSA, our model also predicted CDI risk in the subsequent 31-365 days reasonably well (C-statistic 0.722). CONCLUSIONS: These results can be used to identify high-risk populations for enrollment in C difficile vaccine trials and facilitate study feasibility regarding sample size and time to completion.

Assessing risk factors, mortality, and healthcare utilization associated with Clostridioides difficile infection in four Latin American countries

ABSTRACT Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. Methods: This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 − 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. Results: The study included 481 cases and 962 controls. Mean age and sex were similar between cases and controls, but mean Charlson comorbidity index (4.3 vs 3.6; p< 0.001) and recent hospital admission (35.3% vs 18.8%; p< 0.001) were higher among cases. By multivariable analyses, CDI risk was associated with prior hospital admission within 3 months (odds ratio [OR], 2.08; 95% CI: 1.45, 2.97), recent antibiotic use (ie, carbapenem; OR, 2.85; 95% CI: 1.75, 4.64), acid suppressive therapy use (OR, 1.71; 95% CI: 1.14, 2.58), and medical conditions (ie, renal disease; OR, 1.48; 95% CI: 1.19, 1.85). In-hospital mortality rate (18.7% vs 6.9%; p< 0.001) and mean overall LOS (33.5 vs 18.8 days; p< 0.001) were higher and longer, respectively, in cases versus controls. Conclusion: Antibiotic exposure, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries.

Incidence of Staphylococcus aureus Infections After Elective Surgeries in US Hospitals.

BACKGROUND: Although Staphylococcus aureus is a leading cause of postsurgical infections, national estimates of these infections after elective surgeries based on microbiology data are limited. This study assessed cumulative 180-day postsurgical S. aureus incidence in real-world hospital settings. METHODS: A retrospective study of adults (≥18 years) undergoing inpatient or hospital-based outpatient elective surgeries from 1/7/2010-30/6/2015 at hospitals (N = 181) reporting microbiology results in the Premier Healthcare Database (PHD). 86 surgical categories were identified from the National Healthcare Safety Network procedures. We classified positive S. aureus cultures using a hierarchy (bloodstream [BSI], surgical site [SSI], and all other types [urinary tract, respiratory, other/unknown site]) and calculated incidence (number of infections divided by the number of elective surgery discharges). We estimated national infection case volumes by multiplying incidence by national inpatient elective surgical discharge estimates using the entire PHD and weights based on hospital characteristics. RESULTS: Following 884 803 inpatient elective surgical discharges, 180-day S. aureus infection incidence was 1.35% (0.30% BSI, 0.74% SSI no BSI, 0.32% all other types only). Among 1 116 994 hospital-based outpatient elective surgical discharges, 180-day S. aureus incidence was 1.19% (0.25% BSI, 0.75% SSI no BSI, 0.19% all other types only). Methicillin resistance was observed in ~45% of the S. aureus infections. We estimated 55 764 S. aureus postsurgical infections occurred annually in the US following 4.2 million elective inpatient surgical discharges. CONCLUSIONS: The high burden of S. aureus infections after both inpatient and outpatient elective surgeries highlights the continued need for surveillance and novel infection prevention efforts.

Identification of patients at risk of Clostridioides difficile infection for enrollment in vaccine clinical trials.

BACKGROUND: Clostridioides difficile infection (CDI) is an important cause of diarrheal disease associated with increasing morbidity and mortality. Efforts to develop a preventive vaccine are ongoing. The goal of this study was to develop an algorithm to identify patients at high risk of CDI for enrollment in a vaccine efficacy trial. METHODS: We conducted a 2-stage retrospective study of patients aged ≥ 50 within the US Department of Veterans Affairs Health system between January 1, 2009 and December 31, 2013. Included patients had at least 1 visit in each of the 2 years prior to the study, with no CDI in the past year. We used multivariable logistic regression with elastic net regularization to identify predictors of CDI in months 2-12 (i.e., days 31 - 365) to allow time for antibodies to develop. Performance was measured using the positive predictive value (PPV) and the area under the curve (AUC). RESULTS: Elements of the predictive algorithm included age, baseline comorbidity score, acute renal failure, recent infections or high-risk antibiotic use, hemodialysis in the last month, race, and measures of recent healthcare utilization. The final algorithm resulted in an AUC of 0.69 and a PPV of 3.4%. CONCLUSIONS: We developed a predictive algorithm to identify a patient population with increased risk of CDI over the next 2-12 months. Our algorithm can be used prospectively with clinical and administrative data to facilitate the feasibility of conducting efficacy studies in a timely manner in an appropriate population.

Assessing risk factors, mortality, and healthcare utilization associated with Clostridioides difficile infection in four Latin American countries.

BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. METHODS: This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 - 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. RESULTS: The study included 481 cases and 962 controls. Mean age and sex were similar between cases and controls, but mean Charlson comorbidity index (4.3 vs 3.6; p < 0.001) and recent hospital admission (35.3% vs 18.8%; p < 0.001) were higher among cases. By multivariable analyses, CDI risk was associated with prior hospital admission within 3 months (odds ratio [OR], 2.08; 95% CI: 1.45, 2.97), recent antibiotic use (ie, carbapenem; OR, 2.85; 95% CI: 1.75, 4.64), acid suppressive therapy use (OR, 1.71; 95% CI: 1.14, 2.58), and medical conditions (ie, renal disease; OR, 1.48; 95% CI: 1.19, 1.85). In-hospital mortality rate (18.7% vs 6.9%; p < 0.001) and mean overall LOS (33.5 vs 18.8 days; p < 0.001) were higher and longer, respectively, in cases versus controls. CONCLUSION: Antibiotic exposure, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries.

Risk Factors for Primary Clostridium difficile Infection; Results From the Observational Study of Risk Factors for Clostridium difficile Infection in Hospitalized Patients With Infective Diarrhea (ORCHID).

Background: There are inconsistent data on the risk factors for Clostridium difficile infection (CDI) in the literature. Aims: To use two C. difficile infection (CDI) case-control study groups to compare risk factors in hospitalized patients with diarrhea across different countries. Methods: A multi-center group of CDI cases/controls were identified by standardized testing from seven countries from the prior EUropean, multi-center, prospective bi-annual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhea (EUCLID). A second group of CDI cases/controls was identified from a single center in Germany [parallel study site (PSS)]. Data were extracted from the medical notes to assess CDI risk factors. Univariate analyses and multivariate logistic regression models were used to identify and compare risk factors between the two groups. Results: There were 253 and 158 cases and 921 and 584 controls in the PSS and EUCLID groups, respectively. Significant variables from univariate analyses in both groups were age ≥65, number of antibiotics (OR 1.2 for each additional antibiotic) and prior hospital admission (all p < 0.001). Congestive heart failure, diabetes, admission from assisted living or Emergency Department, proton pump inhibitors, and chronic renal disease were significant in PSS (all p < 0.05) but not EUCLID. Dementia and admitted with other bacterial diseases were significant in EUCLID (p < 0.05) but not PSS. Following multivariate analyses, age ≥ 65, number of antibiotics and prior hospital admission were consistently identified as CDI risk factors in each individual group and combined datasets. Conclusion: Our results show that the same CDI risk factors were identified across datasets. These were age ≥ 65 years, antibiotic use and prior hospital admission. Importantly, the odds of developing CDI increases with each extra antibiotic prescribed.

Modeling the potential impact of administering vaccines against Clostridioides difficile infection to individuals in healthcare facilities.

BACKGROUND: A vaccine against Clostridioides difficile infection (CDI) is in development. While the vaccine has potential to both directly protect those vaccinated and mitigate transmission by reducing environmental contamination, the impact of the vaccine on C. difficile colonization remains unclear. Consequently, the transmission-reduction effect of the vaccine depends on the contribution of symptomatic CDI to overall transmission of C. difficile. METHODS: We designed a simulation model of CDI among patients in a network of 10 hospitals and nursing homes and calibrated the model using estimates of transmissibility from whole genome sequencing studies that estimated the fraction of CDI attributable to transmission from other CDI patients. We assumed the vaccine reduced the rate of progression to CDI among carriers by 25-95% after completion of a 3-dose vaccine course administered to randomly chosen patients at facility discharge. We simulated the administration of this vaccination campaign and tallied effects over 5 years. RESULTS: We estimated 30 times higher infectivity of CDI patients compared to other carriers. Simulations of the vaccination campaign produced an average reduction of 3-16 CDI cases per 1000 vaccinated patients, with 2-11 of those cases prevented among those vaccinated and 1-5 prevented among unvaccinated patients. CONCLUSIONS: Our findings demonstrate potential for a vaccine against CDI to reduce transmissions in healthcare facilities, even with no direct effect on carriage susceptibility. The vaccine's population impact will increase if received by individuals at risk for CDI onset in high-transmission settings.

Synthesis of novel multifunctional carbazole-based molecules and their thermal, electrochemical and optical properties.

Two novel carbazole-based compounds 7a and 7b were synthesised as potential candidates for application in organic electronics. The materials were fully characterised by NMR spectroscopy, mass spectrometry, FTIR, thermogravimetric analysis, differential scanning calorimetry, cyclic voltammetry, and absorption and emission spectroscopy. Compounds 7a and 7b, both of which were amorphous solids, were stable up to 291 °C and 307 °C, respectively. Compounds 7a and 7b show three distinctive absorption bands: high and mid energy bands due to locally excited (LE) transitions and low energy bands due to intramolecular charge transfer (ICT) transitions. In dichloromethane solutions compounds 7a and 7b gave emission maxima at 561 nm and 482 nm with quantum efficiencies of 5.4% and 97.4% ± 10%, respectively. At positive potential, compounds 7a and 7b gave two different oxidation peaks, respectively: quasi-reversible at 0.55 V and 0.71 V, and reversible at 0.84 V and 0.99 V. At negative potentials, compounds 7a and 7b only exhibited an irreversible reduction peak at -1.86 V and -1.93 V, respectively.