CDC's Hospital-Onset Clostridioides difficile Prevention Framework in a Regional Hospital Network.

Importance: Despite modest reductions in the incidence of hospital-onset Clostridioides difficile infection (HO-CDI), CDI remains a leading cause of health care-associated infection. As no single intervention has proven highly effective on its own, a multifaceted approach to controlling HO-CDI is needed. Objective: To assess the effectiveness of the Centers for Disease Control and Prevention's Strategies to Prevent Clostridioides difficile Infection in Acute Care Facilities Framework (hereafter, the Framework) in reducing HO-CDI incidence. Design, Setting, and Participants: This quality improvement study was performed within the Duke Infection Control Outreach Network from July 1, 2019, through March 31, 2022. In all, 20 hospitals in the network participated in an implementation study of the Framework recommendations, and 26 hospitals did not participate and served as controls. The Framework has 39 discrete intervention categories organized into 5 focal areas for CDI prevention: (1) isolation and contact precautions, (2) CDI confirmation, (3) environmental cleaning, (4) infrastructure development, and (5) antimicrobial stewardship engagement. Exposures: Monthly teleconferences supporting Framework implementation for the participating hospitals. Main Outcomes and Measures: Primary outcomes were HO-CDI incidence trends at participating hospitals compared with controls and postintervention HO-CDI incidence at intervention sites compared with rates during the 24 months before the intervention. Results: The study sample included a total of 2184 HO-CDI cases and 7 269 429 patient-days. In the intervention cohort of 20 participating hospitals, there were 1403 HO-CDI cases and 3 513 755 patient-days, with a median (IQR) HO-CDI incidence of 2.8 (2.0-4.3) cases per 10 000 patient-days. The first analysis included an additional 3 755 674 patient-days and 781 HO-CDI cases among the 26 controls, with a median (IQR) HO-CDI incidence of 1.1 (0.7-2.7) case per 10 000 patient-days. The second analysis included an additional 2 538 874 patient-days and 1751 HO-CDI cases, with a median (IQR) HO-CDI incidence of 5.9 (2.7-8.9) cases per 10 000 patient-days, from participating hospitals 24 months before the intervention. In the first analysis, intervention sites had a steeper decline in HO-CDI incidence over time relative to controls (yearly incidence rate ratio [IRR], 0.79 [95% CI, 0.67-0.94]; P = .01), but the decline was not temporally associated with study participation. In the second analysis, HO-CDI incidence was declining in participating hospitals before the intervention, and the rate of decline did not change during the intervention. The degree to which hospitals implemented the Framework was associated with steeper declines in HO-CDI incidence (yearly IRR, 0.95 [95% CI, 0.90-0.99]; P = .03). Conclusions and Relevance: In this quality improvement study of a regional hospital network, implementation of the Framework was not temporally associated with declining HO-CDI incidence. Further study of the effectiveness of multimodal prevention measures for controlling HO-CDI is warranted.

Implementation of a diagnostic stewardship intervention to improve blood-culture utilization in 2 surgical ICUs: Time for a blood-culture change.

OBJECTIVE: We compared the number of blood-culture events before and after the introduction of a blood-culture algorithm and provider feedback. Secondary objectives were the comparison of blood-culture positivity and negative safety signals before and after the intervention. DESIGN: Prospective cohort design. SETTING: Two surgical intensive care units (ICUs): general and trauma surgery and cardiothoracic surgery. PATIENTS: Patients aged ≥18 years and admitted to the ICU at the time of the blood-culture event. METHODS: We used an interrupted time series to compare rates of blood-culture events (ie, blood-culture events per 1,000 patient days) before and after the algorithm implementation with weekly provider feedback. RESULTS: The blood-culture event rate decreased from 100 to 55 blood-culture events per 1,000 patient days in the general surgery and trauma ICU (72% reduction; incidence rate ratio [IRR], 0.38; 95% confidence interval [CI], 0.32-0.46; P < .01) and from 102 to 77 blood-culture events per 1,000 patient days in the cardiothoracic surgery ICU (55% reduction; IRR, 0.45; 95% CI, 0.39-0.52; P < .01). We did not observe any differences in average monthly antibiotic days of therapy, mortality, or readmissions between the pre- and postintervention periods. CONCLUSIONS: We implemented a blood-culture algorithm with data feedback in 2 surgical ICUs, and we observed significant decreases in the rates of blood-culture events without an increase in negative safety signals, including ICU length of stay, mortality, antibiotic use, or readmissions.

Disinfection efficacy of Oxivir TB wipe residue on severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

We assessed Oxivir Tb wipe disinfectant residue in a controlled laboratory setting to evaluate low environmental contamination of SARS-CoV-2. Frequency of viral RNA detection was not statistically different between intervention and control arms on day 3 (P=0.14). Environmental contamination viability is low; residual disinfectant did not significantly contribute to low contamination.

Assessing the Impact of 2-Step Clostridioides difficile Testing at the Healthcare Facility Level.

BACKGROUND: Two-step testing for Clostridioides difficile infection (CDI) aims to improve diagnostic specificity but may also influence reported epidemiology and patterns of treatment. Some providers fear that 2-step testing may result in adverse outcomes if C. difficile is underdiagnosed. METHODS: Our primary objective was to assess the impact of 2-step testing on reported incidence of hospital-onset CDI (HO-CDI). As secondary objectives, we assessed the impact of 2-step testing on C. difficile-specific antibiotic use and colectomy rates as proxies for harm from underdiagnosis or delayed treatment. This longitudinal cohort study included 2 657 324 patient-days across 8 regional hospitals from July 2017 through March 2022. Impact of 2-step testing was assessed by time series analysis with generalized estimating equation regression models. RESULTS: Two-step testing was associated with a level decrease in HO-CDI incidence (incidence rate ratio, 0.53 [95% confidence interval {CI}, .48-.60]; P < .001), a similar level decrease in utilization rates for oral vancomycin and fidaxomicin (utilization rate ratio, 0.63 [95% CI, .58-.70]; P < .001), and no significant level (rate ratio, 1.16 [95% CI, .93-1.43]; P = .18) or trend (rate ratio, 0.85 [95% CI, .52-1.39]; P = .51) change in emergent colectomy rates. CONCLUSIONS: Two-step testing is associated with decreased reported incidence of HO-CDI, likely by improving diagnostic specificity. The parallel decrease in C. difficile-specific antibiotic use offers indirect reassurance against underdiagnosis of C. difficile infections still requiring treatment by clinician assessment. Similarly, the absence of any significant change in colectomy rates offers indirect reassurance against any rise in fulminant C. difficile requiring surgical management.

Using clinical decision support to improve urine testing and antibiotic utilization.

OBJECTIVE: Urine cultures collected from catheterized patients have a high likelihood of false-positive results due to colonization. We examined the impact of a clinical decision support (CDS) tool that includes catheter information on test utilization and patient-level outcomes. METHODS: This before-and-after intervention study was conducted at 3 hospitals in North Carolina. In March 2021, a CDS tool was incorporated into urine-culture order entry in the electronic health record, providing education about indications for culture and suggesting catheter removal or exchange prior to specimen collection for catheters present >7 days. We used an interrupted time-series analysis with Poisson regression to evaluate the impact of CDS implementation on utilization of urinalyses and urine cultures, antibiotic use, and other outcomes during the pre- and postintervention periods. RESULTS: The CDS tool was prompted in 38,361 instances of urine cultures ordered in all patients, including 2,133 catheterized patients during the postintervention study period. There was significant decrease in urine culture orders (1.4% decrease per month; P < .001) and antibiotic use for UTI indications (2.3% decrease per month; P = .006), but there was no significant decline in CAUTI rates in the postintervention period. Clinicians opted for urinary catheter removal in 183 (8.5%) instances. Evaluation of the safety reporting system revealed no apparent increase in safety events related to catheter removal or reinsertion. CONCLUSION: CDS tools can aid in optimizing urine culture collection practices and can serve as a reminder for removal or exchange of long-term indwelling urinary catheters at the time of urine-culture collection.

Optimizing reflex urine cultures: Using a population-specific approach to diagnostic stewardship.

BACKGROUND: Clinicians and laboratories routinely use urinalysis (UA) parameters to determine whether antimicrobial treatment and/or urine cultures are needed. Yet the performance of individual UA parameters and common thresholds for action are not well defined and may vary across different patient populations. METHODS: In this retrospective cohort study, we included all encounters with UAs ordered 24 hours prior to a urine culture between 2015 and 2020 at 3 North Carolina hospitals. We evaluated the performance of relevant UA parameters as potential outcome predictors, including sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria and used receiver operating curves to identify the 5 best-performing models for predicting significant bacteriuria (≥100,000 colony-forming units of bacteria/mL). RESULTS: In 221,933 encounters during the 6-year study period, no single UA parameter had both high sensitivity and high specificity in predicting bacteriuria. Absence of leukocyte esterase and pyuria had a high NPV for significant bacteriuria. Combined UA parameters did not perform better than pyuria alone with regard to NPV. The high NPV ≥0.90 of pyuria was maintained among most patient subgroups except females aged ≥65 years and patients with indwelling catheters. CONCLUSION: When used as a part of a diagnostic workup, UA parameters should be leveraged for their NPV instead of sensitivity. Because many laboratories and hospitals use reflex urine culture algorithms, their workflow should include clinical decision support and or education to target symptomatic patients and focus on populations where absence of pyuria has high NPV.

Evaluation of hospital blood culture utilization rates to identify opportunities for diagnostic stewardship.

OBJECTIVES: To evaluate the pattern of blood-culture utilization among a cohort of 6 hospitals to identify potential opportunities for diagnostic stewardship. METHODS: We completed a retrospective analysis of blood-culture utilization during adult inpatient or emergency department (ED) encounters in 6 hospitals from May 2019 to April 2020. We investigated 2 measures of blood-culture utilization rates (BCURs): the total number of blood cultures, defined as a unique accession number per 1,000 patient days (BCX) and a new metric of blood-culture events per 1,000 patient days to account for paired culture practices. We defined a blood-culture event as an initial blood culture and all subsequent samples for culture drawn within 12 hours for patients with an inpatient or ED encounter. Cultures were evaluated by unit type, positivity and contamination rates, and other markers evaluating the quality of blood-culture collection. RESULTS: In total, 111,520 blood cultures, 52,550 blood culture events, 165,456 inpatient admissions, and 568,928 patient days were analyzed. Overall, the mean BCUR was 196 blood cultures per 1,000 patient days, with 92 blood culture events per 1,000 patient days (range, 64-155 among hospitals). Furthermore, 7% of blood-culture events were single culture events, 55% began in the ED, and 77% occurred in the first 3 hospital days. Among all blood cultures, 7.7% grew a likely pathogen, 2.1% were contaminated, and 5.9% of first blood cultures were collected after the initiation of antibiotics. CONCLUSIONS: Blood-culture utilization varied by hospital and was heavily influenced by ED culture volumes. Hospital comparisons of blood-culture metrics can assist in identifying opportunities to optimize blood-culture collection practices.

SARS-CoV-2 reinfection across a spectrum of immunological states.

Purpose: Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved understanding of the risk factors for reinfection and the character and duration of the serological responses to infection and vaccination is critical for managing the coronavirus disease 2019 (COVID-19) pandemic. Methods: We described four cases of SARS-CoV-2 reinfection in individuals representing a spectrum of healthy and immunocompromised states, including (1) a healthy 41-year-old pediatrician, (2) an immunocompromised 31-year-old with granulomatosis with polyangiitis, (3) a healthy 26-year-old pregnant woman, and (4) a 50-year-old with hypertension and hyperlipidemia. We performed confirmatory quantitative reverse transcription-polymerase chain reaction and qualitative immunoglobulin M and quantitative IgG testing on all available patient samples to confirm the presence of infection and serological response to infection. Results: Our analysis showed that patients 1 and 2, a healthy and an immunocompromised patient, both failed to mount a robust serologic response to the initial infection. In contrast, patients 3 and 4, with minimal comorbid disease, both mounted a strong serological response to their initial infection, but were still susceptible to reinfection. Conclusion: Repeat episodes of COVID-19 are capable of occurring in patients regardless of the presence of known risk factors for infection or level of serological response to infection, although this did not trigger critical illness in any instance.

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.

Envisioning Future Urinary Tract Infection Diagnostics.

Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

In pursuit of the holy grail: Improving C. difficile testing appropriateness with iterative electronic health record clinical decision support and targeted test restriction.

OBJECTIVE: To determine the impact of electronic health record (EHR)-based interventions and test restriction on Clostridioides difficile tests (CDTs) and hospital-onset C. difficile infection (HO-CDI). DESIGN: Quasi-experimental study in 3 hospitals. SETTING: 957-bed academic (hospital A), 354-bed (hospital B), and 175-bed (hospital C) academic-affiliated community hospitals. INTERVENTIONS: Three EHR-based interventions were sequentially implemented: (1) alert when ordering a CDT if laxatives administered within 24 hours (January 2018); (2) cancellation of CDT orders after 24 hours (October 2018); (3) contextual rule-driven order questions requiring justification when laxative administered or lack of EHR documentation of diarrhea (July 2019). In February 2019, hospital C implemented a gatekeeper intervention requiring approval for all CDTs after hospital day 3. The impact of the interventions on C. difficile testing and HO-CDI rates was estimated using an interrupted time-series analysis. RESULTS: C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR], 0.79; 95% CI, 0.72-0.87) and did not decrease further with the EHR interventions. The laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline, 0.85; 95% CI, 0.75-0.96) at hospitals A and B. The gatekeeper intervention at hospital C was associated with level (IRR, 0.50; 95% CI, 0.42-0.60) and trend reductions in C. difficile testing (annual change in IR, 0.91; 95% CI, 0.85-0.98) and level (IRR 0.42; 95% CI, 0.22-0.81) and trend reductions in HO-CDI (annual change in IR, 0.68; 95% CI, 0.50-0.92) relative to the baseline period. CONCLUSIONS: Test restriction was more effective than EHR-based clinical decision support to reduce C. difficile testing in our 3-hospital system.

Deconstructing the urinalysis: A novel approach to diagnostic and antimicrobial stewardship.

The extensive use of the urinalysis for screening and monitoring in diverse clinical settings usually identifies abnormal urinalysis parameters in patients with no suspicion of urinary tract infection, which in turn triggers urine cultures, inappropriate antimicrobial use, and associated harms like Clostridioides difficile infection. We highlight how urinalysis is misused, and suggest deconstructing it to better align with evolving patterns of clinical use and the differential diagnosis being targeted. Reclassifying the urinalysis components into infectious and non-infectious panels and interpreting urinalysis results in the context of individual patient's pretest probability of disease is a novel approach to promote proper urine testing and antimicrobial stewardship, and achieve better outcomes.

Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience.

OBJECTIVE: For the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs. METHODS: This retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection. RESULTS: Fifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARS-CoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen's k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively. CONCLUSIONS: BAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high.

Uncovering the Harms of Treating Clostridioides difficile Colonization.

Patients with toxin-negative Clostridioides difficile-positive diarrhea are often treated with oral vancomycin with the assumption that treatment is more beneficial than harmful. However, this hypothesis has never been formally tested, and recent studies suggest that most such patients recover quickly without treatment and can be colonized rather than infected. Fishbein et al. conducted a prospective, placebo-controlled randomized trial to systematically evaluate the effects, risks, and benefits of oral vancomycin in these patients (S. R. S. Fishbein, T. Hink, K. A. Reske, C. Cass, et al., mSphere 6:e00936-20, 2020, https://doi.org/10.1128/mSphere.00936-20). Although small, the results are intriguing and suggest the adverse antibiotic-induced effects of vancomycin outweigh the clinical benefit when colonization is more likely than disease.

Early experience with universal preprocedural testing for SARS-CoV-2 in a relatively low-prevalence area.

We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload.

Environmental and Aerosolized Severe Acute Respiratory Syndrome Coronavirus 2 Among Hospitalized Coronavirus Disease 2019 Patients.

During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The agreement between NP swab and saliva positivity was high (89.5%; κ = 0.79). Two NP swabs collected from patients on days 1 and 7 post-symptom onset had evidence of infectious virus (2 passages over 14 days in Vero E6 cells). In summary, the low molecular prevalence and lack of viable SARS-CoV-2 virus in fomites and air samples implied low nosocomial risk of SARS-CoV-2 transmission through inanimate objects or aerosols.

Healthcare associated diarrhea, not Clostridioides difficile.

PURPOSE OF REVIEW: The aim of this article is to review the epidemiology, cause, diagnostic evaluation, and management of healthcare-associated diarrhea (HCAD) with particular attention to current epidemiology and recent developments in diagnostics. RECENT FINDINGS: Multiplex polymerase chain reaction gastrointestinal panels allow rapid detection of a wide array of potential enteropathogens but the role, yield, and utility of these tests have not been systematically assessed in patients with HCAD. Recent epidemiologic studies reaffirm that HCAD is predominantly a noninfectious condition most often caused by medications or underlying medical conditions, sometimes Clostridioides difficile, and occasionally viruses. Other infections are rare. SUMMARY: Clinical assessment remains fundamental to the evaluation of HCAD and targeted testing for C. difficile is sufficient in most patients. Multiplex gastrointestinal panels may have a role in immunocompromised patients but more study is needed. Medication-induced diarrhea is common and underappreciated and not limited to antibiotics, laxatives, and enemas.