Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.

Antimicrobial resistance is one of the foremost global health concerns of today, and it could offset much of the progress accrued in healthcare over the last century. Excessive antibiotic use accelerates this problem, but it is recognised that specific agents differ in their capacity to promote resistance, a concept recently promoted by the World Health Organisation in the form of its Access, Watch, Reserve (AWaRe) schema. Which, if any, agents should be construed as having a high proclivity for selection of resistance has been contested. The European Antimicrobial Resistance Surveillance Network (EARS-NET) and European Surveillance of Antimicrobial Consumption Network (ESAC-NET) curate population level data over time and throughout the European Economic Area (EEA). EARS-NET monitors resistance to antimicrobials amongst invasive isolates of sentinel pathogens whereas ESAC-NET tracks usage of systemic antimicrobials. Together, data from these networks were interrogated to delineate correlations between antimicrobial consumption and resistance.

Using univariate and multivariate regression analyses, spatiotemporal associations between the use of specific antimicrobial classes and 14 key resistance phenotypes in five sentinel pathogens were assessed methodically for 29 EEA countries.

Use of second and third generation cephalosporins, extended spectrum penicillin/β-lactamase inhibitor combinations, carbapenems, fluoroquinolones, nitroimidazoles and macrolides strongly correlated with key resistance phenotypes, as did overall antimicrobial consumption.

The data obtained mostly support the WHO AWaRe schema with critical caveats. They have the potential to inform antimicrobial stewardship initiatives in the EEA, highlighting obstacles and shortcomings which may be modified in future to minimise positive selection for problematic resistance.

The epidemiological situation of Clostridioides difficile infection (CDI) has dramatically changed over the past 30 years, but few studies have systematically analysed changes in the global epidemic landscape. This study aimed to delineate the global, regional, and national burden of CDI from 1990 to 2021.

CDI data were derived from the Global Burden of Disease Study 2021. Joinpoint regression analysis assessed changes over time and calculated annual percentage change (APC) statistics. An age-period-cohort model was adopted to estimate net/local drifts as well as the age, period, and cohort effects of CDI mortality. The relationship between the sociodemographic index (SDI) and antibiotic use and disease burden was analysed.

The age-standardised death rate (ASDR) increased from 0.10 per 100,000 persons in 1990 to 0.19 per 100,000 persons in 2021, with an estimated annual percentage change of 2.76 (95% confidence interval [CI]: 2.18, 3.33). The ASDR of global CDI exhibited an upward trend from 1990 to 2021, with an AAPC of 2.26 (95% CI: 1.77, 2.76), but a downward trend from 2017 to 2021, with an APC of -2.04 (95% CI: -3.17, -0.90). Antibiotic use was significantly positively associated with CDI burden. The defined daily dose of all antibiotic use per 1000 inhabitants was positively correlated with ASDRs in high, high-middle, and low SDI regions (P< 0.001, P < 0.001, and P< 0.001, respectively).

The burden of CDI has increased globally from 1990 to 2021, revealing significant spatial disparities. Antibiotic use is positively associated with CDI mortality.

To develop, externally validate, and test a series of computer algorithms to accurately predict antibiotic susceptibility test (AST) results at the time of clinical diagnosis, up to 3 days before standard urine culture results become available, with the goal of improving antibiotic stewardship and patient outcomes.

Machine learning algorithms were developed and trained to predict susceptibility or resistance using over 4.7 million discrete AST classifications from urine cultures in a cohort of adult patients from outpatient and inpatient settings from 2012 to 2022. The algorithms were validated on a cohort from a geographically-distant hospital system, ~1931 km (~1200 miles) from the training cohort facilities, from the same time period. Finally, algorithms were clinically validated in a contemporary cohort and compared to the empiric therapy prescribed by clinicians. Appropriateness of the antibiotics selected by clinicians and the algorithm during the clinical validation was compared.

Algorithms were accurate during clinical validation (area under the receiver operating characteristic curve [AUC] 0.71-0.94) for all 11 tested antibiotics. The algorithms' accuracy improved as the organism was identified (AUC 0.79-0.97). In external validation in a geographically-distant cohort, the algorithms remained accurate even without additional training on this group (AUC 0.69-0.87). When the algorithms were trained on the antibiogram from the geographically-distant hospital, the accuracy improved (AUC 0.70-0.93). When algorithms' performances were tested against clinicians in a contemporary cohort for the empiric prescription of oral antibiotics, the drug agent suggested by the algorithms more frequently resulted in adequate empiric coverage.

Machine learning algorithms trained on a large dataset are accurate in prediction of urine culture susceptibility vs resistance up to 3 days prior to urine AST availability. Clinical implementation of such an algorithm could improve both clinical care and antimicrobial stewardship.

Antibiotic consumption is considered an important risk factor for Clostridioides difficile infection (CDI). This ecological analysis investigates the influence of outpatient antibiotic prescriptions in statutory health insurance (SHI) on the admission prevalence of CDI in German hospitals participating in voluntary CDI surveillance through the hospital infection surveillance system (Krankenhaus-Infektions-Surveillance-System; KISS).

The annual CDI admission prevalence of a hospital at the federal state level was associated with the outpatient antibiotic consumption of the corresponding federal state. The quantification of outpatient antibiotic prescriptions was determined as the average DDD per 1000 insured persons per day. The risk factors for CDI on hospital admission included the annual consumption of the eight substance groups aminopenicillin combinations/staphylococcal penicillins, basic penicillins, cephalosporins, quinolones, lincosamides/macrolides, nitrofurantoin/fosfomycin/nitroxoline, sulphonamides/trimethoprim and tetracyclines, the type of care provided by the hospital, and the calendar year, and were examined using multivariable regression analyses (generalized estimating equations models).

Between 2011 and 2019, the number of outpatient antibiotic prescriptions decreased from 13.9 to 10.4 DDD per 1000 insured persons per day (-25%), and the CDI admission prevalence decreased from 0.22 to 0.12 per 100 patients (-45%). Basic penicillins and cephalosporins were identified as risk factors for increased CDI admission prevalence, while nitrofurantoin/fosfomycin/nitroxoline and sulphonamides/trimethoprim were associated with decreased CDI admission prevalence.

A decrease in outpatient antibiotic prescriptions with known risk of developing CDI was associated with a decrease in hospital CDI admission prevalence. Our ecological analysis indicates that rational and restrained antibiotic use in the outpatient setting may reduce the incidence of CDI in the population requiring inpatient treatment.

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate with C. difficile susceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate. However, changes in bile salt did not correlate with increased C. difficile susceptibility. Furthermore, bile salts were not required to inhibit C. difficile colonization. We tested whether amino acid fermentation contributed to the persistence of C. difficile in antibiotic-treated communities. C. difficile mutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (prdB-) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. The inability to ferment glycine or leucine as electron acceptors, however, was not sufficient to limit colonization in any communities. The data provide further support for the importance of bile salt-independent mechanisms in regulating the colonization of C. difficile.IMPORTANCEClostridioides difficile is one of the leading causes of hospital-acquired infections and antibiotic-associated diarrhea. Several potential mechanisms through which the microbiota can limit C. difficile infection have been identified and are potential targets for new therapeutics. However, it is unclear which mechanisms of C. difficile inhibition represent the best targets for the development of new therapeutics. These studies demonstrate that in a complex in vitro model of C. difficile infection, colonization resistance is independent of microbial bile salt metabolism. Instead, the ability of C. difficile to colonize is dependent upon its ability to metabolize proline, although proline-dependent colonization is context dependent and is not observed in all disrupted communities. Altogether, these studies support the need for further work to understand how bile-independent mechanisms regulate C. difficile colonization.

Clostridioides difficile infection (CDI) is a common and often nosocomial infection associated with increased mortality and morbidity. Antibiotic use is the most important modifiable risk factor, but many patients require empiric antibiotics. We estimated the increased risk of hospital-onset CDI with one daily dose-equivalent (DDE) of various empiric antibiotics compared to management without that daily dose-equivalent.

Using a multicenter retrospective cohort of adults admitted between March 2, 2020 and February 11, 2021 for the treatment of SARS-CoV-2, we used a series of three-level logistic regression models to estimate the probability of receiving each of several antibiotics of interest. For each antibiotic, we then limited our data set to patient-days at intermediate probability of receipt and used augmented inverse-probability weighted models to estimate the average treatment effect of one daily dose-equivalent, compared to management without that daily dose-equivalent, on the probability of hospital-onset CDI.

In 24,406 patient-days at intermediate probability of receipt, parenteral vancomycin increased risk of hospital-onset CDI, with an average treatment effect of 0.0096 cases per daily dose-equivalent (95% CI: 0.0053-0.0138). In 38,003 patient-days at intermediate probability of receipt, cefepime also increased subsequent CDI risk, with an estimated effect of 0.0074 more cases per daily dose-equivalent (95% CI: 0.0022-0.0126).

Among common empiric antibiotics, parenteral vancomycin and cefepime appeared to increase risk of hospital-onset CDI. Causal inference observational study designs can be used to estimate patient-level harms of interventions such as empiric antimicrobials.

The purpose of this review is to discuss the role of toxin inhibition in select infections and to provide recommendations for appropriate antimicrobial selection when toxin inhibition is indicated.

For select organisms, specifically Clostridioides difficile, Staphylococcus aureus, and Streptococcus pyogenes, toxin production plays an integral role in overall disease pathogenesis and progression. Some expert recommendations include utilization of an antimicrobial with toxin inhibition properties as primary or adjunctive therapy for certain infections due to these organisms, but evolving data have made the choice of antitoxin agent less clear. Clindamycin has been the long-standing standard of care agent for toxin inhibition in necrotizing S. aureus and S. pyogenes infections, but linezolid shows promise as an alternative either in the setting of drug shortages or simply when clindamycin is not optimal, while tetracyclines require further study for this indication. The role for adjunctive toxin inhibition in C. difficile infection (CDI) is less defined, as current first-line therapies already have antitoxin properties.

Toxin inhibition plays a key role in successful management of patients with infections due to toxin-producing organisms. Adjunctive therapy with a tetracycline could be considered in severe, fulminant CDI, but the associated benefit is variable. The benefit of antitoxin treatment for necrotizing S. aureus and S. pyogenes has been more consistently documented. Recent studies support linezolid as an alternative to clindamycin as an adjunctive S. aureus treatment or as monotherapy when appropriate.

The COVID-19 pandemic resulted in the enactment of substantial public health measures aimed at reducing the transmission of respiratory viruses. The impact of these measures on gastrointestinal (GI) infections remains unexplored.

To determine whether there was a change in the number of patients presenting to The Royal Melbourne Hospital with GI infections during the COVID-19 pandemic compared to the year prior.

We conducted a retrospective, single-centre case-control study comparing the incidence and characteristics of hospitalisations with GI infections from March to August 2019 and across the same months in 2020, corresponding to periods immediately prior to and during the COVID pandemic.

Of 430 presentations with GI infections across both time periods, there was a 51.9% decrease in hospitalisations with GI infections during the pandemic. Patients admitted during the pandemic were more likely to be admitted to the intensive care unit (0.71% vs 3.4%, P < 0.04) and to be prescribed antibiotics (21.9% vs 36.1%, P < 0.01). Length of stay and mortality were unchanged. There was a decline in the number and proportion of patients with positive faecal cultures in 2020, primarily attributed to a significant reduction in Norovirus cases (28% vs 4%) (odds ratio (OR) = 0.093, P < 0.01). Conversely, the proportion of patients presenting with Clostridioides difficile was higher in 2020 (22% vs 44%) (OR = 2.4, P = 0.01).

There was a substantial decrease in hospital admissions with GI infections, particularly Norovirus, during the COVID-19 pandemic. Admissions because of Clostridioides increased. Stringent public health measures reducing interpersonal contact and increased antibiotic prescribing respectively may explain these changes, while an increased reluctance to seek medical care may also have contributed to the sharp overall decrease in hospitalisations.

Clostridioides difficile is a major cause of antimicrobial-associated colitis. While antimicrobial stewardship has reduced the incidence of C. difficile infection (CDI), managing CDI is challenging because knowledge about preventing it is limited among healthcare professionals. To address this, we examined associations between antimicrobial use and CDI development.

This observational, nested case-controlled study was conducted using the Shizuoka Kokuho Database (SKDB). Individuals with no record of CDI or antimicrobial-associated enterocolitis within 1 year after SKDB enrolment, but who subsequently developed CDI, were included as the Case group. The Control group comprised individuals selected via 1:4 matching sampling without replacement for sex, age, and month of CDI onset. Conditional logistic regression analysis was performed to assess associations between antimicrobial use (number and combination) and CDI development, controlling for matched variables, background factors, and underlying conditions.

Of the 2,398,393 individuals, 4917 were assigned to the Case group and 19,668 to the Control group. The adjusted odds ratios (ORs) for CDI were 3.65 for one antimicrobial and 8.58, 17.3, and 38.9 for combinations of two, three, or four or more agents (all p < 0.001). Penicillins, fourth-generation cephems, and carbapenems exhibited high ORs. Similar results were observed in certain demographic and comorbidity-free subgroups. Several combinations (penicillins + carbapenems, penicillins + cephems + carbapenems, cephems + fluoroquinolones, and penicillins + cephems + carbapenems) were notably associated with CDI development.

CDI prevalence increased with the number of antimicrobial classes used in combination. Certain types or combinations of antimicrobials may increase the OR for CDI.

German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota. Clinical manifestation ranges from asymptomatic colonization over moderate diarrhea to severe pseudomembranous colitis. According to the current German Gastrointestinal Infection Guidelines, fidaxomicin is the preferred treatment option for CDI, especially in patients at high risk of recurrence or those already suffering from recurrence. Vancomycin can also be used as an alternative for initial CDI treatment. Fecal microbiota transplantation is considered a treatment approach for patients with multiple recurrences.

Dentists in the United States and Canada have higher rates of prescribing broad-spectrum spectrum antibiotics than dentists in some other Western countries. The authors provide an overview of dental antibiotic prescribing trends from British Columbia, Canada.

The data include all prescriptions filed from pharmacies in British Columbia from 1996 through 2023. Dental antibiotic prescribing trends were explored visually and stratified according to patient-related characteristics, type of health service area, type of antibiotic, duration of therapy, and dentist's experience. Interrupted time series regression analysis was conducted to investigate the impact of the COVID-19 pandemic on dental antibiotic prescribing.

Dentistry accounted for an increasing proportion of overall antibiotic consumption in British Columbia. Dental prescriptions increased to a peak rate during the COVID-19 pandemic and remained elevated into 2023. The median duration of prescription converged toward a 7-day supply during the study period.

The authors documented how a decreasing trend in dental antibiotic prescribing prepandemic has been interrupted by means of continuously high rates after that event.

Renewed efforts to ensure appropriateness of dental antibiotic prescribing are needed.

Antimicrobial stewardship programs (ASPs) aim to mitigate antimicrobial resistance (AMR) by optimizing antibiotic use including reducing unnecessary broad-spectrum therapy. This study evaluates the impact of ASP funding and resources on the use of broad-spectrum antibiotics in Ontario hospitals.

We conducted a cross-sectional study of antimicrobial use (AMU) across 63 Ontario hospitals from April 2020 to March 2023. The Ontario ASP Landscape Survey provided data on ASP resourcing and antibiotic utilization. The main outcome was the proportion of all antibiotics that were broad-spectrum, defined as: fluoroquinolones; third-generation cephalosporins; beta-lactam/beta-lactamase inhibitors; carbapenems; clindamycin; and parenteral vancomycin. Secondary outcomes included the proportions of individual antibiotic classes listed above and anti-pseudomonal agents. Statistical analysis involved logistic regression to determine the odds ratio (OR) of the association between ASP funding/resourcing and broad-spectrum antibiotic use.

Among 63 hospitals, 48 reported designated ASP funding/resources. Median broad-spectrum antibiotic use was 52.5%. ASP funding/resources was not associated with overall broad-spectrum antibiotic use (0.97, 95% CI: 0.75-1.25, P = 0.79). However, funding was associated with lower use of fluoroquinolones (OR 0.67, 95% CI: 0.46-0.96, P = 0.03), clindamycin (OR 0.69, 95% CI: 0.47-1.00, P = 0.05), and anti-pseudomonal agents (OR 0.76, 95% CI: 0.59-0.98, P = 0.03).

The presence of designated funding and resources for hospital ASPs is linked to reduced use of specific broad-spectrum antibiotics but not overall broad-spectrum antibiotic use. Enhancing ASP resourcing may be an important factor in limiting targeted antibiotic use, thereby increasing the effectiveness of efforts to mitigate AMR.

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include conversion of conjugated primary bile salts into secondary bile salts toxic to C. difficile growth, and competition between the microbiota and C. difficile for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with six clinically-used antibiotics influenced susceptibility to C. difficile infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate with C. difficile susceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate. However, changes in bile salt did not correlate with increased C. difficile susceptibility. Further, bile salts were not required to inhibit C. difficile colonization. We tested whether amino acid fermentation contributed to persistence of C. difficile in antibiotic-treated communities. C. difficile mutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (prdB-) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. Inability to ferment glycine or leucine as electron acceptors, however, was not sufficient to limit colonization in any communities. This data provides further support for the importance of bile salt-independent mechanisms in regulating colonization of C. difficile.

Antimicrobial use data from inpatients in northern Canada suitable to inform stewardship programs are limited.

As a special project of the Canadian Nosocomial Infection Surveillance Program, to describe antimicrobial use for inpatients in northern Canadian acute care hospitals.

Participating acute care hospitals serving adult or mixed adult and pediatric populations in northern Canada submitted annual data on the use of all systemic antimicrobials from 2019 to 2021. Patient-day denominators were also submitted. Northern Canada was defined as the territories and Statistics Canada's provincial north. Data were analyzed in terms of defined daily doses per 1000 patient days (DDD/1000pd), as per the Anatomical Therapeutic Chemical classification system. Antimicrobials were categorized using the World Health Organization's AWaRe (Access/ Watch/Reserve) classification system.

Each year, 42-47 hospitals participated. More than 90% of participating hospitals were in Alberta or British Columbia. There was large variation in overall antimicrobial use between hospitals (e.g., interquartile range 429 to 779 DDD/1000pd in 2021). From 2019 to 2021, there was a 49% relative increase in antimicrobial use, from 401 to 596 DDD/1000pd (p = 0.11). Over the same period, the use of third- and first-generation cephalosporins increased by 80% and 64%, respectively; antimicrobials in the "Reserve" category increased from 0.4% to 2% of overall use.

This study represents the largest collection of antimicrobial use data for inpatients in northern Canada to date. From 2019 to 2021, there was an increase in antimicrobial use of 195 DDD/1000pd, largely driven by increases in the use of third- and first-generation cephalosporins. The findings should be interpreted with caution, as results may not be generalizable to all northern hospitals.

Previous studies on Clostridioides difficile infection (CDI) in proton pump inhibitor (PPI) users generally enrolled a heterogeneous population and did not include a control group of histamine H2 receptor antagonists (H2RAs) users or adjust for confounding variables, such as previous antibiotics. It is uncertain whether hospitalized patients using PPIs for stress ulcer prophylaxis (SUP) are at a higher risk of CDI compared with those using H2RAs. This study aimed to compare the association between CDI and the usage of antisecretory drugs (ASDs): PPIs and H2RAs, for SUP among hospitalized patients, and the impact of the duration of their use on CDI.

In this nationwide population-based cohort study using the Taiwan National Health Insurance Database, hospitalized patients using ASDs for SUP were identified between 2017 and 2018. A total of 63,266 and 69,269 individuals were included in the PPI and H2RA groups, respectively. The primary endpoint was a 90-day monitoring of CDI occurrence.

The incidences of CDI were 1.6/10,000 and 0.5/10,000 person-days in the PPIs and H2RAs groups, respectively. After adjusting for confounding factors, the risk of infection in the PPIs group remained significantly higher than in the H2RAs group (hazard ratio (HR), 2.49; 95% confidence interval (CI), 1.63-3.81). In the subgroup analysis, during hospitalization, the risk of CDI for patients using high-risk antibiotics or admitted to the intensive care unit (ICU), as well as patients with immunodeficiency, using PPIs for SUP, was higher than using H2RAs. Furthermore, the risk of CDI was higher in patients using ASDs for durations >14 days than in those using them for <7 days (adjusted HR, 3.66; 95% CI, 2.34-5.75).

The risk of occurrence CDI for hospitalized patients using PPIs for SUP was higher than using H2RAs. It is recommended not to exceed 14 days of any gastric ASDs for SUP during hospitalization, especially for patients who have used high-risk antibiotics, have been admitted to the ICU, or have immunodeficiency.

Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI) compared with those without IBD, which is worsened with antibiotic usage. While prior studies have shown a correlation between CDI development and certain classes of antibiotics, the IBD population has not been well represented. This study evaluates the rates of CDI with outpatient antibiotic use in patients with IBD.

We conducted a retrospective cohort study composed of patients with IBD and compared the incidence of CDI in patients who received an outpatient prescription for antibiotics (6694 patients) against those without prescriptions (6025 patients) from 2014 to 2020 at our institution. We compared CDI rates based on nine antibiotic classes: penicillins, cephalosporins, sulfonamides, tetracyclines, macrolides, quinolones, clindamycin, metronidazole, and nitrofurantoin.

The risk of CDI was low (0.7%) but significantly higher for those with antibiotic exposure (0.9% vs 0.5%, P = 0.005) and had a positive correlation with a smoking history. The increased risk of CDI in the IBD population was attributable to the clindamycin and metronidazole classes (odds ratio = 4.7, 95% confidence interval: 1.9-11.9, P = 0.001; odds ratio = 3.6, 95% confidence interval: 2.1-6.2, P < 0.0001, respectively).

The use of clindamycin or metronidazole prescribed in an outpatient setting was associated with a statistically significant increased risk of CDI in patients with IBD. Although the association between clindamycin and CDI is a well-established and common finding, the association between metronidazole and CDI is unique in this study.

To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.

Retrospective cohort study.

Community health system.

Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10-14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.

Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.

The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07-0.56, p < 0.002).

Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

Antibiotic utilization stands as the strongest modifiable determinant for Clostridioides difficile infection (CDI). However, previous studies have relied on aggregated antibiotic categories, leaving prescribers without detailed comparative risk information for individual antibiotics. The objective of this study was to estimate the risk of CDI comprehensively across specific antibiotics.

Two methodologies were integrated to access and rank the risk of CDI associated with individual antibiotics or classes. Initially, a network comparison was conducted by analysing data from randomized controlled trials (RCTs). Subsequently, a real-world disproportionality analysis using the Food and Drug Adverse Event Reporting System (FAERS) database complemented and enriched the findings from RCTs.

The network comparison, encompassing 61 RCTs with 25,931 patients, revealed that exposure to cefepime [odds ratio (OR) 2.56, 95% confidence interval (CI) 1.20-5.44; P=0.02] and imipenem/cilastatin (OR 3.86, 95% CI 1.61-9.29; P=0.003) exhibited higher frequencies of CDI compared with piperacillin/tazobactam. No significant differences were observed between the carbapenems, albeit a trend indicating higher incidence of CDI with imipenem/cilastatin compared with meropenem (OR 3.89, 95% CI 0.94-16.09). In the FAERS disproportionality analysis, nearly all antibiotics displayed associations with CDI, and CDI risk signals often clustered within the majority of antibiotic classes. Among these, lincomycin demonstrated the strongest association (OR 112.17, 95% CI 51.68-243.43). Additionally, oral third-generation cephalosporins tended to exhibit higher CDI risk signals than other antibiotics.

The findings unveiled substantial diversity in the risk of CDI, both within and between antibiotic classes, providing valuable guidance for clinicians in antibiotic prescription decisions and for initiatives aimed at antibiotic stewardship.

Findings from research and recommendations from the World Health Organization favor restrictive use of episiotomy, but whether this guidance is being followed in India, and factors associated with its use, are not known. This study sought to document trends in use of episiotomy over a five-year period (2014-2018); to examine its relationship to maternal, pregnancy, and health-system characteristics; and to investigate its association with other obstetric interventions.

We conducted a secondary analysis of data collected by the Maternal Newborn Health Registry, a prospective population-based pregnancy registry established in Central India (Nagpur, Eastern Maharashtra). We examined type of birth and use of episiotomy in vaginal deliveries from 2014 to 2018, as well as maternal and birth characteristics, health systems factors, and concurrent obstetric interventions associations with its use with multivariable Poisson regression models.

During the five-year interval, the rate of episiotomy in vaginal birth rose from 13 to 31% despite a decline in assisted vaginal birth. Associations with episiotomy were found for the following factors: prior birth, multiple gestations, seven or more years of maternal education, higher gestational age, higher birthweight, delivery by an obstetrician (as compared to midwife or general physician), and birth in hospital (as compared to clinic or health center). After adjusting for these factors, year over year rise in episiotomy was significant with an adjusted incidence rate ratio (AIRR) of 1.10 [95% confidence interval (CI) 1.08-1.12; p = 0.002]. We found an association between episiotomy and several other obstetric interventions, with the strongest relationship for maternal treatment with antibiotics (AIRR 4.23, 95% CI 3.12-5.73; p = 0.001).

Episiotomy in this population-based sample from central India steadily rose from 2014 to 2018. This increase over time was observed even after adjusting for patient characteristics, obstetric risk factors, and health system features, such as specialty of the birthing provider. Our findings have important implications for maternal-child health and respectful maternity care given that most women prefer to avoid episiotomy; they also highlight a potential target for antibiotic stewardship as part of global efforts to combat antimicrobial resistance.

The study was registered at ClinicalTrials.gov under reference number NCT01073475.

First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative. Current recommendations for clinical management often rely on observational studies, given the limited number of well conducted randomised controlled trials studying infective endocarditis due to the rarity of the disease. In this Seminar, we provide a comprehensive overview of optimal clinical practices in infective endocarditis, highlighting key aspects of pathophysiology, pathogens, diagnosis, management, prevention, and multidisciplinary approaches, providing updates on recent research findings and addressing remaining controversies in diagnostic accuracy, prevention strategies, and optimal treatment.

Patients' expectations are a major contributor to the unnecessary prescribing of antibiotics, yet limited research has examined how physicians can calibrate these expectations. The studies we conducted tested how varying messages could impact patients' expectations for antibiotics and their experience of medical appointments. All the participants read a short scenario about an appointment for mild sinusitis symptoms, with the patient's expectation of antibiotics. In Study 1, the participants (n = 1069) were randomly assigned to read a positively framed, neutral, or negatively framed message regarding unnecessary antibiotics. In Study 2, the participants (n = 1073) read a message emphasizing either the societal or personal harms of unnecessary antibiotics, or a message without additional rationale. None of our pre-registered hypotheses were supported, but our exploratory analyses indicated that the societal message increased concern about antibiotic resistance. The participants who were more concerned about resistance were less likely to ask for antibiotics, more satisfied when the physician did not prescribe them, and more likely to recommend the physician to a friend. Discussing the consequences of the different courses of action did not appear to negatively impact physician-patient rapport. These studies demonstrate an inexpensive method with which to pre-test various messages about antibiotic consumption, and suggest that such messages are not negatively received by patients.

Inappropriate or overuse of antibiotic prescribing in primary care highlights an opportunity for antimicrobial stewardship (AMS) programs aimed at reducing unnecessary use of antimicrobials through education, policies and practice audits that optimize antibiotic prescribing. Evidence from the early part of the pandemic indicates a high rate of prescribing of antibiotics for patients with COVID-19. It is crucial to surveil antibiotic prescribing by primary care providers from the start of the pandemic and into its endemic stage to understand the effects of the pandemic and better target effective AMS programs.

This was a matched pair population-based cohort study that used electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Participants included all patients that visited their primary care provider and met the inclusion criteria for COVID-19, respiratory tract infection (RTI), or non-respiratory or influenza-like-illness (negative). Four outcomes were evaluated (a) receipt of an antibiotic prescription; (b) receipt of a non-antibiotic prescription; (c) a subsequent primary care visit (for any reason); and (d) a subsequent primary care visit with a bacterial infection diagnosis. Conditional logistic regression was used to evaluate the association between COVID-19 and each of the four outcomes. Each model was adjusted for location (rural or urban), material and social deprivation, smoking status, alcohol use, obesity, pregnancy, HIV, cancer and number of chronic conditions.

The odds of a COVID-19 patient receiving an antibiotic within 30 days of their visit is much lower than for patients visiting for RTI or for a non-respiratory or influenza-like-illnesses (AOR = 0.08, 95% CI[0.07, 0.09] compared to RTI, and AOR = 0.43, 95% CI[0.38, 0.48] compared to negatives). It was found that a patient visit for COVID-19 was much less likely to have a subsequent visit for a bacterial infection at all time points.

Encouragingly, COVID-19 patients were much less likely to receive an antibiotic prescription than patients with an RTI. However, this highlights an opportunity to leverage the education and attitude change brought about by the public health messaging during the COVID-19 pandemic (that antibiotics cannot treat a viral infection), to reduce the prescribing of antibiotics for other viral RTIs and improve antibiotic stewardship.

There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics.

To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence.

In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE).

Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11-14) and 20 days (16-26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1).

Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

In July 2021, as part of a planned multiyear broad and long-term organizational realignment, the general medicine service assumed continuous care of residents at a Community Living Center (CLC), which are nursing homes within the Veterans Affairs (VA) health care system. We hypothesized that practitioners accustomed to caring for patients in acute care would be more likely to prescribe antibiotics to long-term care residents.

Retrospective cohort study.

Residents of a 105-bed CLC associated with a large VA medical center.

Our cohort included CLC residents between July 1, 2020, and June 30, 2022. We used administrative data to assess resident demographics and medical conditions in the 1 year before and after the change of practitioners. We also compared antibiotics agents prescribed and the following antibiotic use metrics in the year before and after the change: days of therapy (DOT) per 1000 bed days of care (BDOC), antibiotic starts/1000 BDOC, and mean length of therapy in days.

Resident characteristics and overall antibiotic use metrics were similar before and after the change in staffing. The specific agents prescribed differed, with a decrease in fluoroquinolones (14.3 to 5.8 DOT/1000 BDOC; P < .01) and an increase doxycycline (7.4 vs 19.1 DOT/1000 BDOC; P < .01) after the staff change. Rates of Clostridioides difficile infection also decreased, from 6.23 to 3.41 cases/10,000 BDOC after the change in staffing.

The comparable antibiotic use metrics before and after the general medical service assumed care of the CLC residents may be explained by constancy in resident population and other facility-related factors. Differences in the types of agents used suggests that antibiotic stewardship efforts can be tailored not only to the setting and patient population but also to the practitioners' discipline.

Clostridium paraputrificum bacteremia is very rare, and its clinical importance is poorly understood. An 86-year-old man was receiving lascufloxacin therapy for acute pharyngolaryngitis before presenting to our emergency department with a recurrent fever. Two sets of blood cultures on admission revealed C. paraputrificum. A stool culture showed a reduced presence of intestinal commensal bacteria. After admission, the patient's fever resolved without antibiotics. Colonoscopy revealed a rectal tumor. Rectal tumor and microbial substitutions caused by antibiotics may have led to bacteremia. When treating C. paraputrificum bacteremia, physicians should be mindful of coexisting gastrointestinal disorders and a history of antibiotic administration.

Clostridioides difficile infection (CDI) burdens hospitalized patients, particularly those with comorbidities. Colon cancer may worsen CDI severity and outcomes. We aimed to assess CDI outcomes in hospitalized colon cancer patients.

A retrospective analysis of 2016 to 2020 National Inpatient Survey data identified adults with CDI, categorized by the presence of colon cancer. Hospitalization characteristics, comorbidities, and outcomes were compared between groups. Primary outcomes included in-hospital mortality, length of stay, and total hospital charges. The secondary outcomes were CDI complications. Multivariate logistic regression analysis was performed, with P values ≤0.05 indicating statistical significance.

Among 1,436,860 CDI patients, 14,085 had colon cancer. Patients with colon cancer had a longer length of stay (10.77 vs 9.98 days; P < 0.001). After adjustment for confounders, colon cancer patients exhibited higher odds of acute peritonitis (adjusted odds ratio [aOR] 2.37; P = 0.009), bowel perforation (aOR 5.49; P < 0.001), paralytic ileus (aOR 2.12; P = 0.003), and colectomy (aOR 36.99; P < 0.001), but lower risks of mortality, sepsis, septic shock, acute kidney injury, cardiac arrest, and mechanical ventilation (all P < 0.001).

Colon cancer significantly impacts CDI outcomes in hospitalized patients, highlighting the need for improved management strategies to reduce morbidity and mortality.

Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.

Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors.

A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created. Unformed stool samples positive for both glutamate dehydrogenase antigen by enzyme immunoassay and tcdB gene by polymerase chain reaction were classified as TCdD positive. The TCdD Model was created using logistic regression and was modified to the TCdD Risk Score to facilitate its use.

8.1% of patients were TCdD positive. TCdD risk increased with abdominal pain (adjusted odds ratio 1.3; 95% CI, 1.0-1.8), previous C. difficile diarrhea (2.5, 1.1-6.1), and prior antibiotic exposure, especially when sampled in the emergency department (4.2, 2.5-7.0) versus the hospital (1.7, 1.3-2.3). TCdD risk also increased when testing occurred earlier during the hospitalization encounter, when age and white cell count increased concurrently, and with decreased eosinophil count. In internal validation, the TCdD Model had moderate discrimination (optimism-corrected C-statistic 0.65, 0.62-0.68) and good calibration (optimism-corrected Integrated Calibration Index [ICI] 0.017, 0.001-0.022). Performance decreased slightly for the TCdD Risk Score (C-statistic 0.63, 0.62-0.63; ICI 0.038, 0.004-0.038).

TCdD risk can be predicted using readily available clinical risk factors with modest accuracy.

Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI).

iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis.

Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI.

Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

Antimicrobial stewardship programs (ASPs) have the potential to effectively deescalate unnecessary methicillin-resistant Staphylococcus aureus (MRSA) coverage. This review summarizes literature published from 2014 through 2021 describing contemporary ASP methods and their resulting effectiveness at reducing anti-MRSA agent use (ie vancomycin, linezolid, daptomycin, ceftaroline, and clindamycin). This review of the literature examined the following strategies, which had reports of success in either decreasing the use or duration of anti-MRSA agents: prospective review and feedback, antibiotic timeouts, health system or department protocol changes, polymerase chain reaction (PCR) and rapid testing of patient samples. Most of the current literature continue to support most ASP interventions including antibiotic timeouts, pathways, and molecular testing including MRSA nasal PCRs and rapid diagnostic testing can be successful at reducing unnecessary anti-MRSA use.

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During Clostridium difficile infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota. We set out to determine the impact of antibiotic-induced disruption of the microbiome on ILC function. Our goal was to understand antibiotic-induced changes in ILC function on susceptibility to C. difficile colitis in a mouse model. We utilized high-throughput single-cell RNAseq to investigate the phenotypic features of colonic ILC at baseline, after antibiotic administration with or without IL-33 treatment. We identified a heterogeneous landscape of colonic ILCs with gene signatures of inflammatory, anti-inflammatory, migratory, progenitor, plastic, and antigen-presenting ILCs. Antibiotic treatment decreased ILC2 while coordinately increasing ILC1 and ILC3 phenotypes. Notably, Ifng+, Ccl5+, and Il23r+ ILC increased after antibiotics. IL-33 treatment counteracted the antibiotic effect by downregulating ILC1 and ILC3 and activating ILC2. In addition, IL-33 treatment markedly induced the expression of type 2 genes, including Areg and Il5. Finally, we identified amphiregulin, produced by ILC2, as protective during C. difficile infection. Together, our data expand our understanding of how antibiotics induce susceptibility to C. difficile colitis through their impact on ILC subsets and function.IMPORTANCEClostridium difficile infection (CDI) accounts for around 500,000 symptomatic cases and over 20,000 deaths annually in the United States alone. A major risk factor of CDI is antibiotic-induced dysbiosis of the gut. Microbiota-regulated IL-33 and innate lymphoid cells (ILCs) are important in determining the outcomes of C. difficile infection. Understanding how antibiotic and IL-33 treatment alter the phenotype of colon ILCs is important to identify potential therapeutics. Here, we performed single-cell RNAseq of mouse colon ILCs collected at baseline, after antibiotic treatment, and after IL-33 treatment. We identified heterogeneous subpopulations of all three ILC subtypes in the mouse colon. Our analysis revealed several potential pathways of antibiotic-mediated increased susceptibility to intestinal infection. Our discovery that Areg is abundantly expressed by ILCs, and the protection of mice from CDI by amphiregulin treatment, suggests that the amphiregulin-epidermal growth factor receptor pathway is a potential therapeutic target for treating intestinal colitis.

Clostridioides Difficile Infection (CDI) is a serious antibiotic related complication that has been reported among children undergoing treatment of appendicitis. CDI likelihood amongst different empiric antibiotic regimens for appendicitis remains unclear but likely has important implications for antibiotic stewardship.

A retrospective cohort study of the Pediatric Health Information System was used to examine patients ages 1 through 18 who received operative management of acute appendicitis. Common empiric antibiotic regimens 1) Ceftriaxone & Metronidazole (CM) 2) Piperacillin & Tazobactam (PT) and 3) Cefoxitin were compared. Study outcomes were CDI within 28 days post-appendectomy and 30-day post-appendectomy percutaneous drainage procedures. Subset analyses were repeated to only include hospitals that standardized empiric antibiotic choice.

Of 105,911 patients, 220 (0.21 %) developed CDI. CDI was more common in patients that received CM (CM 0.29 % vs PT 0.15 % vs Cefoxitin 0.18 %; P < 0.01). On adjusted analysis, PT was associated with a lower likelihood of CDI (OR, 0.48; 95%CI, 0.31-0.74) compared to CM which was consistent in hospitals with standardized antibiotic choice. Exposure to more unique antibiotic regimens (OR, 1.70; 95 % CI, 1.50-1.93) and higher total antibiotic days (OR, 1.17; 95 % CI 1.13-1.21) were associated with an increased likelihood of CDI. There was no significant difference in the likelihood of post-appendectomy percutaneous drainage between antibiotic regimens.

CDI is rare following appendectomy for pediatric appendicitis. While PT was associated with statistically lower rates of CDI compared to CM, antibiotic stewardship efforts to avoid mixed regimens and decrease overall antibiotic exposure warrant exploration.

Level III.

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.

To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.

Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.

Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.

Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Necrotizing otitis externa (NOE) is an aggressive and fast-evolving infection of the external auditory canal. Late diagnoses and untreated cases can lead to severe, even fatal consequences and so early diagnosis and treatment are paramount. NOE is a notoriously challenging diagnosis to make. It is therefore important to understand what diagnostic modalities are available and how otolaryngologists can use them to accurately treat such an aggressive disease. This review aims to evaluate the different diagnostic options available in NOE and discuss their advantages and limitations, thus, providing an up-to-date picture of the multimodal approach required in the diagnosis of this disease.

This study's objective was to develop a risk-prediction model to identify hospitalized patients at risk of Clostridioides difficile infection (CDI) who had received at least one dose of systemic antibiotics in a large tertiary hospital.

This was a retrospective case-control study that included patients hospitalized for more than 2 days who received antibiotic therapy during hospitalization. The study included two groups: patients diagnosed with hospital CDI and controls without hospital CDI. Cases were matched 1:3 with assigned controls by age and sex. Descriptive statistics were used to identify the study population by comparing cases with controls. Continuous variables were stated as the means and standard deviations. A multivariate analysis was built to identify the significantly associated covariates between cases and controls for CDI.

A total of 364 patients were included and distributed between the two groups. The control group included 273 patients, and the case group included 91 patients. The risk factors for CDI were investigated, with only significant risks identified and included in the risk assessment model: age older than 70 years (p = 0.034), chronic kidney disease (p = 0.043), solid organ transplantation (p = 0.021), and lymphoma or leukemia (p = 0.019). A risk score of ≥2 showed the best sensitivity, specificity, and accuracy of 78.02%, 45.42%, and 78.02, respectively, with an area under the curve of 0.6172.

We identified four associated risk factors in the risk-prediction model. The tool showed good discrimination that might help predict, identify, and evaluate hospitalized patients at risk of developing CDI.

Among 100 propensity score-matched emergency department patients receiving ≤14 days doxycycline versus cephalexin monotherapy for outpatient treatment of nonpurulent (presumed streptococcal) skin and soft tissue infection, a low rate of 14-day clinical failure was observed [6% each group; odds ratio (OR), 1.34 (0.21-8.69); P = 0.745], defined as hospital admission, i.v. antibiotic therapy, or change in oral antibiotic. Doxycycline may represent a reasonable therapeutic alternative for this indication in regions with low tetracycline resistance.