Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea.

OBJECTIVES: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model of C. difficile-associated diarrhoea. METHODS: Omadacycline, clindamycin, tigecycline, vancomycin, and metronidazole minimum inhibitory concentrations (MICs) for the infection-model strain (C. difficile ATCC 43596) were determined. Hamsters were pretreated with subcutaneous clindamycin (10 mg/kg) and infected 24 h later with C. difficile ATCC 43596; 24 h post infection, they received oral omadacycline (50 mg/kg/day), vancomycin (50 mg/kg/day), or vehicle for 5 days. Efficacy was reported as survival. RESULTS: Omadacycline was as active as tigecycline, vancomycin, and metronidazole (MIC 0.06 mg/L); clindamycin showed no activity. Median survival in hamsters was: 12 days, omadacycline; 2 days, vancomycin; 4 days, clindamycin pretreatment only. CONCLUSION: Omadacycline exhibited potent in vitro activity against C. difficile and showed efficacy in a model of C. difficile-associated diarrhoea.

Decreasing Hospital-Acquired Clostridioides Difficile in Patients With Cancer.

Patients with cancer are particularly susceptible to Clostridioides difficile infections because of their exposure to antibiotics, serious underlying chronic illnesses, advancing age, immunocompromising conditions, and extended lengths of stays in the hospital setting. In addition to suboptimal hand hygiene, other potential sources for bacterial transmission in the hospital setting include high-touch surfaces within the patient's immediate environment. Payers, such as the Centers for Medicare and Medicaid Services, continue to prioritize the reduction of healthcare-associated infections.

Defining the decision problem: a scoping review of economic evaluations for Clostridioides difficile interventions.

BACKGROUND: Clostridioides difficile infection is the leading cause of healthcare-associated infectious diarrhoea. Several preventative and treatment interventions exist; however, decisions for their use are typically made independent of other interventions along the care pathway. AIM: To assess how the scope of the decision problem is defined in economic evaluations of C. difficile interventions. METHODS: A scoping review was conducted following the Joanna Briggs Institute framework using a comprehensive literature search with C. difficile and economic evaluation as key search concepts. Study selection and extraction were performed independently by two reviewers. An in-depth analysis of all cost-utility and cost-effectiveness analyses was conducted. Care pathway domains (i.e. infection prevention and control, antimicrobial stewardship programmes, prevention, diagnostics, treatment) were defined iteratively, and each study was classified according to the scope of the decision problem: (i) one intervention, one domain; (ii) one intervention, multiple domains; (iii) multiple interventions, one domain; and (iv) multiple interventions, multiple domains. RESULTS: In total, 3886 studies were identified. Of these, 116 studies were included in the descriptive overview, and 46 were included in the in-depth analysis. Most studies limited the scope of the decision problem to one intervention (43/46; 93%). Only three studies (3/46; 7%) assessed multiple interventions - either as bundled vs standalone interventions for prevention (i.e. a single domain), or as sequences of treatments for initial and recurrent infection (i.e. multiple domains). No study assessed multiple interventions across prevention and treatment domains. CONCLUSIONS: Economic evaluations for C. difficile infection assess narrowly defined decision problems which may have implications for optimal healthcare resource allocation.

The intended purpose and regional patterns of use of antibiotics for managing Clostridioides (Clostridium) difficile infections: An analysis of the National Database of Health Insurance Claims and Specific Health Checkups data of Japan.

INTRODUCTION: We previously showed the trend of antimicrobial use (AMU) for Clostridioides (Clostridium) difficile infection (CDI) using sales data. However, the details of the prescribing medical institutions and regional characteristics are unknown. Therefore, the purpose of this study was to clarify the details of the medical institutions where antibiotics for CDI were prescribed, and evaluate the AMU for CDI and the regional characteristics. METHODS: Antibiotics for CDI, including oral vancomycin (VCM), oral metronidazole (MNZ), and intravenous (IV) MNZ, were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) between 2013 and 2016. The PID (patients/1000 inhabitants/day) was used as an evaluation index for AMU. The PID was calculated using the claim types: inpatient, outpatient, dental, and pharmacy. The PID of each prefecture was calculated for inpatient claims in 2016. RESULTS: The AMU of oral VCM and IV MNZ were observed mainly in the inpatient claims. For oral MNZ, the total AMU in the outpatient and pharmacy claims accounted for approximately 80% per year throughout the study period. For inpatient claims of each prefecture in 2016, the PID of the antibiotics used for CDIs was approximately 3.5 times the difference between the highest and lowest prefectures. CONCLUSIONS: The AMU for CDI that takes into account the purpose of use was clarified by using the information of the prescribed medical institutions that were included in the NDB. Oral MNZ was used frequently in outpatients, and attention should be paid to the acquisition of resistance.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Level of Knowledge of Medical Staff on the Basis of the Survey in Terms of Risk Management, Associated with Clostridioides difficile Infections.

Infections caused by the toxigenic strains of Clostridioides difficile in the hospital environment pose a serious public health problem. The progressive increase in hospital infections in Poland indicates that risk management is a tool that is not used in an effective way and significantly differs from the goals set by the Leading Authorities, the Ministry of Health and its subordinate units. Systematic education of medical personnel constitutes the basic element of rational risk management aimed at reducing the number of infections as it allows for the transfer of knowledge, development of appropriate organizational procedures, and improves internal communication. This paper presents the results of a survey conducted in hospital facilities throughout Poland. The study dealt with what medical personnel know about channels of transmission and prevention of Clostridioides difficile infections in the hospital setting, professional training and risk management in terms of reducing the number of infections. The survey reveals that Clostridioides difficile continues to be a serious problem in the inpatient care system. Procedures and management strategies implemented by hospitals in order to limit the spread of the pathogen are predominantly focused on short-term action, which does not lead to a real improvement in terms of hospitalized patients' safety. The infection risk management system was assessed at a fairly low level. The obtained research results confirmed the research hypotheses that had been formulated.

Costs Associated with the Treatment of Clostridioides Difficile Infections.

BACKGROUND: Clostridioides difficile, as the main cause of infectious diarrhoea in hospitalised patients, is a considerable challenge for medical personnel (hospital environment) who have direct contact with the patient, as well as being of interest to public health specialists. Financial issues related to the occurrence of the above-mentioned micro-organism are being increasingly raised. Due to the scale of the phenomenon, we are beginning to pay attention to the significant system costs caused by the diagnosis and treatment of CDI infection and its complications. Studies indicate that the nosocomial infection of C. difficile complicates hospitalisation, by increasing the cost by more than half and extending patient's stay by an average of 3.6 days. MATERIAL AND METHODS: The aim of this study was to attempt to calculate the estimated costs associated with the prolonged hospitalisation of patients with nosocomial CDI infection, using the example of a hospital in Lodz. A total of 53 completed hospitalisations of patients treated in the period of January-August 2018 were analysed, during which hospital Clostridioides difficile infection was identified. For the purposes of this study, statistical data collected in the hospital's IT system were also analysed, covering 44,868 hospitalisations in the Jan-Aug 2018 period, during which no hospital infection occurred. They was a control group, in which the analysed cases were compared. The obtained data in the study determined how long each patient with Clostridioides difficile infection stayed in the hospital (from the moment infection was diagnosed until the day of hospital discharge), and which diagnosis related groups (DRG) (according to National Health Fund guidelines) were assigned. The average length of patient stay without infection within a given DRG group in each hospital ward was also determined. The collected materials became the initial point for the final analysis of hospital costs and the length of hospital stay caused by Clostridioides difficile infection. RESULTS: Clostridioides difficile infection extended the hospital stay by an average of almost 12 days. The average cost of prolonged hospitalisation due to CDI infection (according to the average cost per person-day) was about PLN 7148 (1664 EUR), which gave a total value of about PLN 378,860.6 (88,240.5 EUR) in the examined period. At the same time, the average expenditure from the National Health Fund for hospitalisation due to CDI infections increased by about PLN 6627 (1542.8 EUR), which in the analysed period translated into over PLN 351,232.0 (81,505.5 EUR) (according to settlements with the National Health Fund). The outcome indicates that there is a clear relation between CDI and the anticipated length of hospitalisation of patients without an infection.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Evaluation of a risk assessment model to predict infection with healthcare facility-onset Clostridioides difficile.

PURPOSE: We evaluated a previously published risk model (Novant model) to identify patients at risk for healthcare facility-onset Clostridioides difficile infection (HCFO-CDI) at 2 hospitals within a large health system and compared its predictive value to that of a new model developed based on local findings. METHODS: We conducted a retrospective case-control study including adult patients admitted from July 1, 2016, to July 1, 2018. Patients with HCFO-CDI who received systemic antibiotics were included as cases and were matched 1 to 1 with controls (who received systemic antibiotics without developing HCFO-CDI). We extracted chart data on patient risk factors for CDI, including those identified in prior studies and those included in the Novant model. We applied the Novant model to our patient population to assess the model's utility and generated a local model using logistic regression-based prediction scores. A receiver operating characteristic area under the curve (ROC-AUC) score was determined for each model. RESULTS: We included 362 patients, with 161 controls and 161 cases. The Novant model had a ROC-AUC of 0.62 in our population. Our local model using risk factors identifiable at hospital admission included hospitalization within 90 days of admission (adjusted odds ratio [OR], 3.52; 95% confidence interval [CI], 2.06-6.04), hematologic malignancy (adjusted OR, 12.87; 95% CI, 3.70-44.80), and solid tumor malignancy (adjusted OR, 4.76; 95% CI, 1.27-17.80) as HCFO-CDI predictors and had a ROC-AUC score of 0.74. CONCLUSION: The Novant model evaluating risk factors identifiable at admission poorly predicted HCFO-CDI in our population, while our local model was a fair predictor. These findings highlight the need for institutions to review local risk factors to adjust modeling for their patient population.

Assessment of Prehospital Monitor/Defibrillators for Clostridioides difficile Contamination.

OBJECTIVES: The purpose of this study was to determine if Clostridioides difficile (C. diff) was present on the electrocardiogram (ECG) right arm leads, blood pressure cuffs, and fingertip pulse oximetry sensors of monitor/defibrillators used in the prehospital setting. METHODS: On March 22, 2019, a total of 20 prehospital monitor/defibrillators located at an Emergency Medical Service (EMS) station in Alabama (USA) were assessed for C. diff. The inside area of the fingertip pulse oximetry sensor, patient contact side of the blood pressure cuff, and right arm ECG lead of monitor/defibrillators (n = 60) were swabbed using a sterile cotton-tipped applicator saturated in a 0.85% Sodium Chloride solution. These cotton-tipped applicators were then inserted, scored, and released into Banana Broth vials. The vials were then sealed tightly and immediately transported to the laboratory, where they were incubated at 36°C for 72 hours. Colorimetric change from red to yellow was considered a positive indication for the presence of C. diff. RESULTS: Of 20 blood pressure cuffs, 15 had C. diff contamination (75%); C. diff was also present on 19 of 20 fingertip pulse oximeter sensors (95%) and 20 of 20 ECG right arm monitor leads (100%). CONCLUSION: Prehospital monitor/defibrillators may represent a significant reservoir of C. diff and other pathogenic bacteria. Improved disinfection protocols for reusable monitoring equipment and transition to disposable monitoring equipment used in the prehospital setting may reduce the risk of patient and EMS provider infection.

Assessment of public health notification thresholds for Clostridioides difficile in acute-care hospitals-Colorado and Tennessee, 2018.

OBJECTIVES: We aimed to identify a threshold number of Clostridioides difficile infections (CDI) for acute-care hospitals (ACHs) to notify public health agencies of outbreaks and we aimed to determine whether thresholds can be used with existing surveillance strategies to further infection reduction goals. DESIGN: Descriptive analysis of laboratory-identified CDI reported to the National Healthcare Safety Network by Colorado and Tennessee ACH inpatient units in 2018. METHODS: Threshold levels of ≥2, ≥3, and ≥4 CDI events per calendar month per unit (unit month) were assessed to identify units that would trigger facility reporting to public health. Values meeting thresholds were defined as alerts. Recurrent alerts were defined as alerts from units meeting the threshold ≥2 times within 12 months. The presence of alerts was compared to the number of excess infections to identify high-burden facilities. RESULTS: At an alert threshold of ≥2 CDI events per unit month, 204 alerts occurred among 43 Colorado ACHs and 290 among 78 Tennessee ACHs. At a threshold of ≥3, there were 59 and 61 alerts, and at a threshold of ≥4, there were 17 and 10 alerts in Colorado and Tennessee, respectively. In both Colorado and Tennessee, at a threshold of ≥3 nearly 50% of alerts were recurrent, and facilities with at least one alert in 2018 accounted for ∼85% of the statewide excess infections. CONCLUSIONS: An alert threshold of ≥3 CDI events per unit month is feasible for rapid identification of outbreaks in ACHs. This threshold can facilitate earlier assessments and interventions in high-burden facilities.

Economic burden of recurrent Clostridioides difficile infection in adults admitted to Spanish hospitals. A multicentre retrospective observational study.

OBJECTIVE: Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). METHODS: Observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. RESULTS: We included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was €10,877 (9,499-12,777), of which the hospital stay accounted for 92.56. CONCLUSIONS: There is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System.

Using diagnostic stewardship to reduce rates, healthcare expenditures and accurately identify cases of hospital-onset Clostridioides difficile infection.

OBJECTIVE: Lack of judicious testing can result in the incorrect diagnosis of Clostridioides difficile infection (CDI), unnecessary CDI treatment, increased costs and falsely augmented hospital-acquired infection (HAI) rates. We evaluated facility-wide interventions used at the VA San Diego Healthcare System (VASDHS) to reduce healthcare-onset, healthcare-facility-associated CDI (HO-HCFA CDI), including the use of diagnostic stewardship with test ordering criteria. DESIGN: We conducted a retrospective study to assess the effectiveness of measures implemented to reduce the rate of HO-HCFA CDI at the VASDHS from fiscal year (FY)2015 to FY2018. INTERVENTIONS: Measures executed in a stepwise fashion included a hand hygiene initiative, prompt isolation of CDI patients, enhanced terminal room cleaning, reduction of fluoroquinolone and proton-pump inhibitor use, laboratory rejection of solid stool samples, and lastly diagnostic stewardship with C. difficile toxin B gene nucleic acid amplification testing (NAAT) criteria instituted in FY2018. RESULTS: From FY2015 to FY2018, 127 cases of HO-HCFA CDI were identified. All rate-reducing initiatives resulted in decreased HO-HCFA cases (from 44 to 13; P ≤ .05). However, the number of HO-HCFA cases (34 to 13; P ≤ .05), potential false-positive testing associated with colonization and laxative use (from 11 to 4), hospital days (from 596 to 332), CDI-related hospitalization costs (from $2,780,681 to $1,534,190) and treatment cost (from $7,158 vs $1,476) decreased substantially following the introduction of diagnostic stewardship with test criteria from FY2017 to FY2018. CONCLUSIONS: Initiatives to decrease risk for CDI and diagnostic stewardship of C. difficile stool NAAT significantly reduced HO-HCFA CDI rates, detection of potential false-positives associated with laxative use, and lowered healthcare costs. Diagnostic stewardship itself had the most dramatic impact on outcomes observed and served as an effective tool in reducing HO-HCFA CDI rates.

Are Rates of Methicillin-Resistant Staphylococcus aureus and Clostridioides difficile Associated With Quality and Clinical Outcomes in US Acute Care Hospitals?

The purpose of this study was to examine the association between rates of methicillin-resistant Staphylococcus aureus (MRSA)/Clostridioides difficile and quality and clinical outcomes in US acute care hospitals. The population was all Medicare-certified US acute care hospitals with MRSA/C difficile standardized infection ratio (SIR) data available from 2013 to 2017. Hospital-level data from the Centers for Medicare & Medicaid Services were used to estimate hospital and time fixed effects models for 30-day hospital readmissions, length of stay, 30-day mortality, and days in the intensive care unit. The key explanatory variables were SIR for MRSA and C difficile. No association was found between MRSA or C difficile rates and any of the 4 outcomes. The null results add to the mixed evidence in the field, but there are likely residual confounding factors. Future research should use larger samples of patient-level data and appropriate methods to provide evidence to guide efforts to tackle antimicrobial resistance.

Impact of California's mandate for antimicrobial stewardship programs on rates of methicillin-resistant Staphylococcus aureus and Clostridioides difficile infection in acute-care hospitals.

OBJECTIVE: To estimate the impact of California's antimicrobial stewardship program (ASP) mandate on methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile infection (CDI) rates in acute-care hospitals. POPULATION: Centers for Medicare and Medicaid Services (CMS)-certified acute-care hospitals in the United States. DATA SOURCES: 2013-2017 data from the CMS Hospital Compare, Provider of Service File and Medicare Cost Reports. METHODS: Difference-in-difference model with hospital fixed effects to compare California with all other states before and after the ASP mandate. We considered were standardized infection ratios (SIRs) for MRSA and CDI as the outcomes. We analyzed the following time-variant covariates: medical school affiliation, bed count, quality accreditation, number of changes in ownership, compliance with CMS requirements, % intensive care unit beds, average length of stay, patient safety index, and 30-day readmission rate. RESULTS: In 2013, California hospitals had an average MRSA SIR of 0.79 versus 0.94 in other states, and an average CDI SIR of 1.01 versus 0.77 in other states. California hospitals had increases (P < .05) of 23%, 30%, and 20% in their MRSA SIRs in 2015, 2016, and 2017, respectively. California hospitals were associated with a 20% (P < .001) decrease in the CDI SIR only in 2017. CONCLUSIONS: The mandate was associated with a decrease in CDI SIR and an increase in MRSA SIR.

Hospital-acquired Clostridioides difficile infection among patients at an urban safety-net hospital in Philadelphia: Demographics, neighborhood deprivation, and the transferability of national statistics.

OBJECTIVE: To investigate associations between healthcare-associated Clostridioides difficile infection and patient demographics at an urban safety-net hospital and compare findings with national surveillance statistics. METHODS: Study participants were selected using a case-control design using medical records collected between August 2014 and May 2018 at Hahnemann University Hospital in Philadelphia. Controls were frequency matched to cases by age and length of stay. Final sample included 170 cases and 324 controls. Neighborhood-level factors were measured using American Community Survey data. Multilevel models were used to examine infection by census tract, deprivation index, race/ethnicity, insurance type, referral location, antibiotic use, and proton-pump inhibitor use. RESULTS: Patients on Medicare compared to private insurance had 2.04 times (95% CI, 1.31-3.20) the odds of infection after adjusting for all covariables. Prior antibiotic use (2.70; 95% CI, 1.64-4.46) was also associated with infection, but race or ethnicity and referral location were not. A smaller proportion of hospital cases occurred among white patients (25% vs 44%) and patients over the age of 65 (39% vs 56%) than expected based on national surveillance statistics. CONCLUSIONS: Medicare and antibiotics were associated with Clostridioides difficile infection, but evidence did not indicate association with race or ethnicity. This finding diverges from national data in that infection is higher among white people compared to nonwhite people. Furthermore, a greater proportion of hospital cases were aged <65 years than expected based on national data. National surveillance statistics on CDI may not be transportable to safety-net hospitals, which often disproportionately serve low-income, nonwhite patients.

The Economic Burden of Clostridioides difficile in Denmark: A Retrospective Cohort Study.

Objectives: The aim of this study was to make a comprehensive economic assessment of the costs of hospital-acquired C. difficile infections (CDI). Methods: We carried out a retrospective matched cohort study utilizing Danish registry data with national coverage to identify CDI cases and matched reference patients without CDI (controls) for economic burden assessment in Denmark covering 2011-2014. Health care costs and public transfer costs were obtained from national registries, and calculated for 1 year prior to, and 2 years after index admission using descriptive statistics and regression analysis. Results: The study included 12,768 CDI patients and 23,272 matched controls. The total health care cost was significantly larger for CDI cases than controls throughout all periods. During the index admission period, cost was €12,867 per CDI case compared to €4,522 (p < 0.001) for controls, which increased to an average of €31,388 and €19,512 (p < 0.001) in Year 1 for the two groups, respectively. Excess costs were found both among infections with onset in hospitals and in the community. Diagnosis compatible with complications increased costs to on average >€91,000 per case. The regression analysis showed that CDI adds a substantial economic burden, but only explains about 1/3 of the crude difference observed in the matched analysis. Discussion: The major economic impact of hospital-acquired CDI with complications underlines the importance of preventing complications in these patients. Our study provides an informed estimate of the potential economic gain per patient by successful intervention, which is likely to be relatively comparable across countries.

Quantifying bacterial spore germination by single-cell impedance cytometry for assessment of host microbiota susceptibility to Clostridioides difficile infection.

The germination of ingested spores is often a necessary first step required for enabling bacterial outgrowth and host colonization, as in the case of Clostridioides difficile (C. difficile) infection. Spore germination rate in the colon depends on microbiota composition and its level of disruption by antibiotic treatment since secretions by commensal bacteria modulate primary to secondary bile salt levels to control germination. Assessment of C. difficile spore germination typically requires measurement of colony-forming units, which is labor intensive and takes at least 24 h to perform but is regularly required due to the high recurrence rates of nosocomial antibiotic-associated diarrhea. We present a rapid method to assess spore germination by using high throughput single-cell impedance cytometry (>300 events/s) to quantify live bacterial cells, by gating for their characteristic electrophysiology versus spores, so that germination can be assessed after just 4 h of culture at a detection limit of ~100 live cells per 50 µL sample. To detect the phenotype of germinated C. difficile bacteria, we utilize its characteristically higher net conductivity versus that of spore aggregates and non-viable C. difficile forms, which causes a distinctive high-frequency (10 MHz) impedance phase dispersion within moderately conductive media (0.8 S/m). In this manner, we can detect significant differences in spore germination rates within just 4 h, with increasing primary bile salt levels in vitro and using ex vivo microbiota samples from an antibiotic-treated mouse model to assess susceptibility to C. difficile infection. We envision a rapid diagnostic tool for assessing host microbiota susceptibility to bacterial colonization after key antibiotic treatments.

Incorporating preauthorization into antimicrobial stewardship pharmacist workflow reduces Clostridioides difficile and gastrointestinal panel testing.

OBJECTIVE: To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea. DESIGN: Single center, quasi-experimental before-and-after study. SETTING: Tertiary-care, academic medical center in Ann Arbor, Michigan. PATIENTS: Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours. INTERVENTION: A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained. RESULTS: An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56-0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37-0.77; P = .001), respectively. CONCLUSIONS: We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.