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.

Community-acquired pneumonia (CAP) is a leading cause of hospitalizations and mortality in the US. Overuse of extended spectrum antibiotics (ESA) for CAP contributes to antimicrobial resistance. The 2019 Infectious Diseases Society of America/American Thoracic Society CAP guidelines emphasize de-escalation of ESA following negative cultures, early switch to oral (PO) antibiotics, and limited duration of therapy (DOT). This study describes clinicians’ acceptance of an infectious diseases-trained (ID) pharmacist-led stewardship recommendations in hospitalized patients with CAP.

This prospective, single-arm, cohort study included adults admitted with a diagnosis of pneumonia to six Cleveland Clinic hospitals receiving ID pharmacist-led stewardship recommendations. The ID pharmacist provided recommendations for ESA de-escalation, DOT, intravenous (IV) to PO transition, and antimicrobial discontinuation. Descriptive statistics were used to describe clinician acceptance rates.

From November 1, 2022, to January 31, 2024, the ID pharmacist made recommendations for 685 patient encounters to 327 clinicians. Of these patients, 52% received an ESA and 15% had severe CAP. There were 959 recommendations: ESA de-escalation (19%), DOT (46%), IV to PO transition (19%), antimicrobial discontinuation (13%), and other (3%). Clinicians accepted 693 recommendations (72%): IV to PO transition (148/184, 80%), ESA de-escalation (141/181 78%), antimicrobial discontinuation (94/128, 73%), DOT (286/437, 65%), and other (24/29, 83%).

Clinicians were generally receptive to ID pharmacist-led CAP recommendations with an overall acceptance rate of 72%. Prescribers were most receptive to recommendations for IV to PO conversion and least receptive to limiting DOT.

Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity.

Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity.

Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27–11.46), severe CAP on admission (OR 1.76, 95% CI 1.56–1.98), substance abuse (OR 1.57, 95% CI 1.27–1.93), smoking (OR 1.23, 95% CI 1.09–1.39), and hyponatremia (OR 1.35, 95% CI 1.17–1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52–0.82), congestive heart failure (OR 0.72, 95% CI 0.63–0.83), obesity (OR 0.71, 95% CI 0.60–0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45–0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests.

Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship.

To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility–onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years).

CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain.

Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST.

Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias.

The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.

To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy.

We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures.

This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals.

Adults hospitalized for CAP.

Risk factors for resistant infection.

Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%–30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model.

Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI.

We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens.

Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70–1.38).

Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

We investigated the quality of life (QoL) of patients hospitalized with C. difficile infection (CDI).

Prospective survey study.

US tertiary-care referral center, acute-care setting.

Adults hospitalized with a diagnosis of CDI, defined as ≥3 episodes of unformed stool in 24 hours and a positive laboratory test for C. difficile.

We surveyed patients from July 2019 to March 2020 using the disease-specific Cdiff32 questionnaire and the generic PROMIS GH survey. We compared differences in Cdiff32 scores among demographic and clinical subgroups (including CDI severity, CDI recurrence, and various comorbidities) using 2-sample t tests. We compared PROMIS GH scores to the general population T score of 50 using 1-sample t tests. We performed multivariable linear regression to identify predictors of Cdiff32 scores.

In total, 100 inpatients (mean age, 58.6 ±17.1 years; 53.0% male; 87.0% white) diagnosed with CDI completed QoL surveys. PROMIS GH physical health summary scores (T = 37.3; P < .001) and mental health summary scores (T = 43.4; P < .001) were significantly lower than those of the general population. In bivariate analysis, recurrent CDI, severe CDI, and number of stools were associated with lower Cdiff32 scores. In multivariable linear regression, recurrent CDI, severe CDI, and each additional stool in the previous 24 hours were associated with significantly decreased Cdiff32 scores.

Patients hospitalized with CDI reported low scores on the Cdiff32 and PROMIS GH, demonstrating a negative impact of CDI on QoL in multiple health domains. The Cdiff32 questionnaire is particularly sensitive to QoL changes in patients with recurrent or severe disease.

Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.

We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.

Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).

In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI.

Retrospective cohort study.

Single tertiary-care hospital.

Adult patients diagnosed with hospital-onset, healthcare facility–associated CDI from June 2014 to September 2015.

We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality.

Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe–complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23–40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72–0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90–1.09) or recurrence (OR, 0.88; 95% CI, 0.77–1.00).

Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.

Viruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization.

Retrospective cohort study.

The study included 179 US hospitals.

Adults admitted with pneumonia between July 2010 and June 2015.

We assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients.

Among 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001).

A minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.

To identify risk factors for asymptomatic Clostridioides difficile colonization among hospitalized adults utilizing a meta-analysis, which may enable early identification of colonized patients at risk of spreading C. difficile.

Meta-analysis and systematic review.

We systematically searched MEDLINE, Scopus, Web of Science, and EMBASE from January 1, 1975, to February 15, 2020, for articles related to C. difficile colonization among hospitalized adults. Studies with multivariable analyses evaluating risk factors for asymptomatic colonization were eligible.

Among 5,506 studies identified in the search, 19 studies met the inclusion criteria. Included studies reported 20,334 adult patients of whom 1,588 were asymptomatically colonized with C. difficile. Factors associated with an increased risk of colonization were hospitalization in the previous 6 months (OR, 2.18; 95% CI, 1.86–2.56; P < .001), use of gastric acid suppression therapy within the previous 8 weeks (OR, 1.42; 95% CI, 1.17–1.73; P < .001), tube feeding (OR, 2.02; 95% CI, 1.06–3.85; P = .03), and corticosteroid use in the previous 8 weeks (OR, 1.58; 95% CI, 1.14–2.17; P = .006). Receipt of antibiotics in the previous 3 months (OR, 1.37; 95% CI, 0.94–2.01; P = .10) was not associated with statistically significant effects on risk of colonization.

C. difficile colonization was significantly associated with previous hospitalization, gastric acid suppression, tube feeding, and corticosteroid use. Recognition of these risk factors may assist in identifying asymptomatic carriers of C. difficile and taking appropriate measures to reduce transmission.

To summarize risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) in hospitalized pediatric patients as determined by previous observational studies.

Meta-analysis and systematic review.

Studies evaluating risk factors for CDI in pediatric inpatients were eligible for inclusion.

We systematically searched MEDLINE, Web of Science, Scopus, and EMBASE for subject headings and text words related to CDI and pediatrics from 1975 to 2017. Two of the investigators independently screened studies, extracted and compiled data, assessed study quality, and performed the meta-analysis.

Of the 2,033 articles screened, 14 studies reporting 10,531,669 children met the inclusion criteria. Prior antibiotic exposure (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31–3.52) and proton pump inhibitor (PPI) use (OR, 1.33; 95% CI, 1.07–1.64) were associated with an increased risk of CDI in children. Subgroup analyses using studies reporting only adjusted results suggested that prior antibiotic exposure is not a significant risk factor for CDI. H2 receptor antagonist (H2RA) use (OR, 1.36; 95% CI, 0.31–5.98) and that female gender (OR, 0.87; 95% CI, 0.74–1.03) did not play a significant role as a risk factor for developing CDI.

Prior antibiotic exposure appears to be an important risk factor for CDI based on the combined analysis but not significant using adjusted studies. PPI use was associated with an increased risk of CDI. Judicious and appropriate use of antibiotics and PPIs may help reduce the risk of CDI in this vulnerable population.

Multiple studies have demonstrated that daily chlorhexidine gluconate (CHG) bathing is associated with a significant reduction in infections caused by gram-positive pathogens. However, there are limited data on the effectiveness of daily CHG bathing on gram-negative infections. The aim of this study was to determine whether daily CHG bathing is effective in reducing the rate of gram-negative infections in adult intensive care unit (ICU) patients.

We searched MEDLINE and 3 other databases for original studies comparing daily bathing with and without CHG. Two investigators extracted data independently on baseline characteristics, study design, form and concentration of CHG, incidence, and outcomes related to gram-negative infections. Data were combined using a random-effects model and pooled relative risk ratios (RRs), and 95% confidence intervals (CIs) were derived.

In total, 15 studies (n = 34,895 patients) met inclusion criteria. Daily CHG bathing was not significantly associated with a lower risk of gram-negative infections compared with controls (RR, 0.89; 95% CI, 0.73–1.08; P = .24). Subgroup analysis demonstrated that daily CHG bathing was not effective for reducing the risk of gram-negative infections caused by Acinetobacter, Escherichia coli, Klebsiella, Enterobacter, or Pseudomonas spp.

The use of daily CHG bathing was not associated with a lower risk of gram-negative infections. Further, better designed trials with adequate power and with gram-negative infections as the primary end point are needed.

Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear.

We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider.

We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs.

We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies.

The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment.

Infect Control Hosp Epidemiol 2018;39:412–424

Contaminated hands of healthcare workers (HCWs) are an important source of transmission of healthcare-associated infections. Alcohol-based hand sanitizers, while effective, do not provide sustained antimicrobial activity. The objective of this study was to compare the immediate and persistent activity of 2 hand hygiene products (ethanol [61% w/v] plus chlorhexidine gluconate [CHG; 1.0% solution] and ethanol only [70% v/v]) when used in an intensive care unit (ICU).

Prospective, randomized, double-blinded, crossover study

Three ICUs at a large teaching hospital

In total, 51 HCWs involved in direct patient care were enrolled in and completed the study.

All HCWs were randomized 1:1 to either product. Hand prints were obtained immediately after the product was applied and again after spending 4–7 minutes in the ICU common areas prior to entering a patient room or leaving the area. The numbers of aerobic colony-forming units (CFU) were compared for the 2 groups after log transformation. Each participant tested the alternative product after a 3-day washout period.

On bare hands, use of ethanol plus CHG was associated with significantly lower recovery of aerobic CFU, both immediately after use (0.27 ± 0.05 and 0.88 ± 0.08 log10 CFU; P = .035) and after spending time in ICU common areas (1.81 ± 0.07 and 2.17 ± 0.05 log10 CFU; P<.0001). Both the antiseptics were well tolerated by HCWs.

In comparison to the ethanol-only product, the ethanol plus CHG sanitizer was associated with significantly lower aerobic bacterial counts on hands of HCWs, both immediately after use and after spending time in ICU common areas.

Clinicaltrials.gov identifier NCT02258412

Infect Control Hosp Epidemiol 2018;39:267–271