Hand hygiene compliance in nursing home wards: The effects of feedback with lights on alcohol-based hand rub dispensers.

BACKGROUND: Hand hygiene (HH) among health care workers (HCWs) is crucial in preventing infections in nursing homes. However, HH compliance (HHC) among HCWs remains low. This study aimed to investigate the effect of feedback lights on HCWs' HHC. METHODS: A 5-month interventional study was conducted in 3 wards in a nursing home in Denmark. During the intervention period, a green light with a smiley appeared on the alcohol-based hand rub (ABHR) dispensers when HCWs used the ABHR, acknowledging HCWs for using the ABHR. HHC was monitored using an automatic HH monitoring system (AHHMS). RESULTS: A total of 64 HCWs were enrolled. The AHHMS collected 23,696 HH opportunities in apartments and dirty utility rooms. Overall, HHC in the apartments increased from 50% at baseline (95% CI: 48, 53) to 56% (95% CI: 54, 58) during the intervention. However, the increased HHC level was not sustained during follow-up. CONCLUSIONS: The AHHMS enabled the assessment of the intervention. We found a significant effect of light-guided feedback in the apartments. However, the increased HHC was not sustained after the light was switched off.

Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010-2019.

The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010-13, 2.6%; 2014-16, 6.3%; 2017-19; 9.4%). Mortality (HR 1.08, 95%CI 0.90-1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75-1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18-2.96). There was no interaction between time from admission to BSI (1-2, 3-14, and >14 days) and HR of death (P = 0.14) or discharge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.

Revisiting the personal protective equipment components of transmission-based precautions for the prevention of COVID-19 and other respiratory virus infections in healthcare.

The COVID-19 pandemic highlighted some potential limitations of transmission-based precautions. The distinction between transmission through large droplets vs aerosols, which have been fundamental concepts guiding infection control measures, has been questioned, leading to considerable variation in expert recommendations on transmission-based precautions for COVID-19. Furthermore, the application of elements of contact precautions, such as the use of gloves and gowns, is based on low-quality and inconclusive evidence and may have unintended consequences, such as increased incidence of healthcare-associated infections and spread of multidrug-resistant organisms. These observations indicate a need for high-quality studies to address the knowledge gaps and a need to revisit the theoretical background regarding various modes of transmission and the definitions of terms related to transmission. Further, we should examine the implications these definitions have on the following components of transmission-based precautions: (i) respiratory protection, (ii) use of gloves and gowns for the prevention of respiratory virus infections, (iii) aerosol-generating procedures and (iv) universal masking in healthcare settings as a control measure especially during seasonal epidemics. Such a review would ensure that transmission-based precautions are consistent and rationally based on available evidence, which would facilitate decision-making, guidance development and training, as well as their application in practice.

Findings in Danish long-term care facilities in the first year of the SARS-CoV-2 pandemic.

PURPOSE: To describe the occurrence of SARS-CoV-2 infections, deaths and outbreaks among residents in Danish long-term care facilities (LTCFs) from February 2020 to February 2021. METHODS: Danish COVID-19 national register data from a newly implemented automated surveillance system was used to describe incidence rate and deaths (per 1000 residents' years), number of tests, SARS-CoV-2 infections and outbreaks among LTCF residents. A case was defined as a LTCF resident with a positive SARS-CoV-2 PCR test. An outbreak was defined as two or more cases in one LTCF within a 14-day period, and considered closed if no new cases had occurred within 28 days. Death was defined as occurring within 30-days of a positive test. RESULTS: A total of 55,359 residents living in 948 LTCFs were included. The median age of the residents was 85 years and 63% were female. There was a total of 3712 cases found among residents across 43% of all LTCFs. Nearly all (94%) cases were linked to outbreaks. Higher numbers of cases and outbreaks were seen in Denmark's Capital Region compared to other regions. Overall, 22 SARS-CoV-2 deaths and 359 deaths (non-SARS-CoV-2) per 1000 resident years were identified in the study period. CONCLUSION: Less than half of LTCFs identified any cases. The majority of cases were linked to outbreaks, emphasizing the importance of preventing introductions of SARS-CoV-2 into the facilities. Furthermore, it highlights the need to invest efforts into infrastructures, routine procedures and monitoring of SARS-CoV-2 in LTCFs to limit the introduction and the spread of SARS-CoV-2.

Effects of light-guided nudges on health care workers' hand hygiene behavior.

BACKGROUND: Hospital-acquired infections are the most frequent adverse events in health care and can be reduced by improving the hand hygiene compliance (HHC) of health care workers (HCWs). We aimed to investigate the effect of nudging with sensor lights on HCWs' HHC. METHODS: An 11-month intervention study was conducted in 2 inpatient departments at a university hospital. An automated monitoring system (Sani NudgeTM) measured the HHC. Reminder and feedback nudges with lights were displayed on alcohol-based hand rub dispensers. We compared the baseline HHC with HHC during periods of nudging and used the follow-up data to establish if a sustained effect had been achieved. RESULTS: A total of 91 physicians, 135 nurses, and 15 cleaning staff were enrolled in the study. The system registered 274,085 hand hygiene opportunities in patient rooms, staff restrooms, clean rooms, and unclean rooms. Overall, a significant, sustained effect was achieved by nudging with lights in relation to contact with patients and patient-near surroundings for both nurses and physicians. Furthermore, a significant effect was observed on nurses' HHC in restrooms and clean rooms. No significant effect was found for the cleaning staff. CONCLUSIONS: Reminder or feedback nudges with light improved and sustained physicians' and nurses' HHC, and constitute a new way of changing HCWs' hand hygiene behavior.

Contaminated dicloxacillin capsules as the source of an NDM-5/OXA-48-producing Enterobacter hormaechei ST79 outbreak, Denmark and Iceland, 2022 and 2023.

From October 2022 through January 2023, nine patients with NDM-5/OXA-48-carbapenemase-producing Enterobacter hormaechei ST79 were detected in Denmark and subsequently one patient in Iceland. There were no nosocomial links between patients, but they had all been treated with dicloxacillin capsules. An NDM-5/OXA-48-carbapenemase-producing E. hormaechei ST79, identical to patient isolates, was cultured from the surface of dicloxacillin capsules in Denmark, strongly implicating them as the source of the outbreak. Special attention is required to detect the outbreak strain in the microbiology laboratory.

Excess length of stay and readmission following hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach.

OBJECTIVES: Population-based estimates of excess length of stay after hospital-acquired bacteraemia (HAB) are few and prone to time-dependent bias. We investigated the excess length of stay and readmission after HAB. METHODS: This population-based cohort study included the North Denmark Region adult population hospitalized for ≥48 hours, from 2006 to 2018. Using a multi-state model with 45 days of follow-up, we estimated adjusted hazard ratios (aHRs) for end of stay and discharge alive. The excess length of stay was defined as the difference in residual length of stay between infected and uninfected patients, estimated using a non-parametric approach with HAB as time-dependent exposure. Confounder effects were estimated using pseudo-value regression. Readmission after HAB was investigated using the Cox regression. RESULTS: We identified 3457 episodes of HAB in 484 291 admissions in 205 962 unique patients. Following HAB, excess length of stay was 6.6 days (95% CI, 6.2-7.1 days) compared with patients at risk. HAB was associated with decreased probability of end of hospital stay (aHR, 0.60; 95% CI, 0.57-0.62) driven by the decreased hazard for discharge alive; the aHRs ranged from 0.30 (95% CI, 0.23-0.40) for bacteraemia stemming from 'heart and vascular' source to 0.72 (95% CI, 0.69-0.82) for the 'urinary tract'. Despite increased post-discharge mortality (aHR, 2.76; 95% CI, 2.38-3.21), HAB was associated with readmission (aHR, 1.42; 95% CI, 1.31-1.53). CONCLUSION: HAB was associated with considerably excess length of hospital stay compared with hospitalized patients without bacteraemia. Among patients discharged alive, HAB was associated with increased readmission rates.

Clinical evaluation of an electronic hand hygiene monitoring system.

BACKGROUND: We aimed to test the accuracy of an electronic hand hygiene monitoring system (EHHMS) during daily clinical activities in different wards and with varying health care professions. METHODS: The accuracy of an EHHMS (Sani Nudge) was assessed during real clinical conditions by comparing events registered by two observers in parallel with events registered by the EHHMS. The events were categorized as true-positive, false-positive, and false-negative registrations. Sensitivity and positive predictive value (PPV) were calculated. RESULTS: A total of 103 events performed by 25 health care workers (9 doctors, 11 nurses, and 5 cleaning assistants) were included in the analyses. The EHHMS had a sensitivity of 100% and a PPV of 100% when measuring alcohol-based hand rub. When looking at the hand hygiene opportunities of all health care workers combined taking place in the patient rooms and working rooms, the sensitivity was 75% and the PPV 95%. For doctors' and nurses' taking care of patients in their beds the EHHMS had a sensitivity of 100% and a PPV of 94%. CONCLUSIONS: The objective accuracy measures demonstrate that this EHHMS can capture hand hygiene behavior under clinical conditions in different settings with clinical health care workers but show less accuracy with cleaning assistants.

Increased transmission of SARS-CoV-2 in Denmark during UEFA European championships.

Denmark hosted four games during the 2020 UEFA European championships (EC2020). After declining positive SARS-CoV-2 test rates in Denmark, a rise occurred during and after the tournament, concomitant with the replacement of the dominant Alpha lineage (B.1.1.7) by the Delta lineage (B.1.617.2), increasing vaccination rates and cessation of several restrictions. A cohort study including 33 227 cases was conducted from 30 May to 25 July 2021, 14 days before and after the EC2020. Included was a nested cohort with event information from big-screen events and matches at the Danish national stadium, Parken (DNSP) in Copenhagen, held from 12 June to 28 June 2021. Information from whole-genome sequencing, contact tracing and Danish registries was collected. Case-case connections were used to establish transmission trees. Cases infected on match days were compared to cases not infected on match days as a reference. The crude incidence rate ratio (IRR) of transmissions was 1.55, corresponding to 584 (1.76%) cases attributable to EC2020 celebrations. The IRR adjusted for covariates was lower (IRR 1.41) but still significant, and also pointed to a reduced number of transmissions from fully vaccinated cases (IRR 0.59). These data support the hypothesis that the EC2020 celebrations contributed to the rise of cases in Denmark in the early summer of 2021.

Incidence and mortality of hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach.

OBJECTIVE: The effect of hospital-acquired bacteraemia on mortality is sparsely investigated. We investigated the incidence and hospital-acquired bacteraemia impact on mortality. METHODS: We conducted a 13-year population-based cohort study using the North Denmark Bacteraemia Research Database and Danish health registries. The population comprised all adult patients with a hospital admission lasting ≥48 hr. We used Poisson regression to estimate trends in incidence. The 30-day mortality of hospital-acquired bacteraemia was estimated using an illness-death multistate model with recovery using the population at risk of hospital-acquired bacteraemia as reference. RESULTS: We identified 3588 episodes of hospital-acquired bacteraemia in 484 264 admissions. The incidence increased proportionally by 1.02 episodes yearly (95% CI 1.01-1.03) between 2006 and 2018. Hospital-acquired bacteraemia was associated with increased mortality (adjusted hazard ratio (aHR) 4.32, 95% CI 3.95-4.72), especially hospital-acquired bacteraemia with unknown source (aHR 6.42 (95% CI 5.67-7.26), "thoracic incl. pneumonia" (aHR 5.89, 95% CI 3.45-10.12) and abdominal source (aHR 4.33, 95% CI 3.27-5.74). The relative impact on mortality diminished with age (aHR 5.66, 95% CI 2.00-16.01 in 18-40 years old vs. 3.69, 95% CI 3.14-4.32 in 81-105 years old) and comorbidity (aHR 5.75, 95% CI 4.45-7.42 in low vs. 3.55, 95% CI 3.16-3.98 in high comorbidity), and was higher in elective admissions (aHR 9.09, 95% CI 7.14-11.57 vs. aHR of 4.03, 95% CI 3.67-4.42). DISCUSSION: Hospital-acquired bacteraemia is associated with high mortality, especially when the source is unknown or originating from the thoracic cavity.

Risk factors for hospital-acquired bacteraemia - an explorative case-control study of hospital interventions.

BACKGROUND: Knowledge on hospital-related interventions as risk factors for hospital-acquired bacteraemia (HAB) is sparse. AIM: We aimed to investigate hospital interventions as risk factors for HAB. METHODS: Prospectively through one year, we identified episodes of HAB in a single tertiary hospital. We used a matched incidence density sampled case-control design. Matching on sex and age group, we sampled controls (1:2) from the adult hospital population with ongoing hospitalization for ≥48 h. Using conditional logistic regression, we estimated odds ratios (OR) with 95% confidence intervals (CI). For adjusted ORs (aOR), adjustments were made for length of hospital stay, type and urgency of admission, and Charlson Comorbidity Index score level. FINDINGS: From 15th October 2019 through 14th October 2020, we identified 115 incident episodes of HAB and matched them with 230 controls. HAB patients were more often admitted as 'medicine or emergency surgery'-patients (94% vs 87%) and had a longer hospital stay before inclusion (median days 20 vs 12). They were more frequently categorized as having a 'low level comorbidity' (58% vs 39%) but had higher prevalence of haematologic (15% vs 6%) or metastatic cancer (13% vs 10%). Our estimates for central venous catheters were aOR of 3.46 (95% CI 1.92-6.23), haemodialysis; aOR 5.05 (95% CI 1.41-18.06), immunosuppressive treatment including chemotherapy; aOR of 1.72 (95% CI 1.00-2.96). CONCLUSION: Central venous catheters and haemodialysis were the most prominent risk factors. Immunosuppressive treatment including therapy may play an important role in the development of HAB.

Information technology aspects of large-scale implementation of automated surveillance of healthcare-associated infections.

INTRODUCTION: Healthcare-associated infections (HAI) are a major public health concern. Monitoring of HAI rates, with feedback, is a core component of infection prevention and control programmes. Digitalization of healthcare data has created novel opportunities for automating the HAI surveillance process to varying degrees. However, methods are not standardized and vary widely between different healthcare facilities. Most current automated surveillance (AS) systems have been confined to local settings, and practical guidance on how to implement large-scale AS is needed. METHODS: This document was written by a task force formed in March 2019 within the PRAISE network (Providing a Roadmap for Automated Infection Surveillance in Europe), gathering experts in HAI surveillance from ten European countries. RESULTS: The document provides an overview of the key e-health aspects of implementing an AS system of HAI in a clinical environment to support both the infection prevention and control team and information technology (IT) departments. The focus is on understanding the basic principles of storage and structure of healthcare data, as well as the general organization of IT infrastructure in surveillance networks and participating healthcare facilities. The fundamentals of data standardization, interoperability and algorithms in relation to HAI surveillance are covered. Finally, technical aspects and practical examples of accessing, storing and sharing healthcare data within a HAI surveillance network, as well as maintenance and quality control of such a system, are discussed. CONCLUSIONS: With the guidance given in this document, along with the PRAISE roadmap and governance documents, readers will find comprehensive support to implement large-scale AS in a surveillance network.

PRAISE: providing a roadmap for automated infection surveillance in Europe.

INTRODUCTION: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. METHODS: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. RESULTS: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. CONCLUSIONS: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists.

Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020.

In June-November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25-30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.

Characterisation of recombinant factor IX before and after GlycoPEGylation.

The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX. Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, ß-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP. Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously. For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio. Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP. The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX. Furthermore, the pH dependent degradation was reduced due to the GlycoPEGylation of rFIX. GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).

Surveillance of OXA-244-producing Escherichia coli and epidemiologic investigation of cases, Denmark, January 2016 to August 2019.

BackgroundCarbapenemase-producing Escherichia coli are increasing worldwide. In recent years, an increase in OXA-244-producing E. coli isolates has been seen in the national surveillance of carbapenemase-producing organisms in Denmark.AimMolecular characterisation and epidemiological investigation of OXA-244-producing E. coli isolates from January 2016 to August 2019.MethodsFor the epidemiological investigation, data from the Danish National Patient Registry and the Danish register of civil registration were used together with data from phone interviews with patients. Isolates were characterised by analysing whole genome sequences for resistance genes, MLST and core genome MLST (cgMLST).ResultsIn total, 24 OXA-244-producing E. coli isolates were obtained from 23 patients. Among the 23 patients, 13 reported travelling before detection of the E. coli isolates, with seven having visited countries in Northern Africa. Fifteen isolates also carried an extended-spectrum beta-lactamase gene and one had a plasmid-encoded AmpC gene. The most common detected sequence type (ST) was ST38, followed by ST69, ST167, ST10, ST361 and ST3268. Three clonal clusters were detected by cgMLST, but none of these clusters seemed to reflect nosocomial transmission in Denmark.ConclusionImport of OXA-244 E. coli isolates from travelling abroad seems likely for the majority of cases. Community sources were also possible, as many of the patients had no history of hospitalisation and many of the E. coli isolates belonged to STs that are present in the community. It was not possible to point at a single country or a community source as risk factor for acquiring OXA-244-producing E. coli.

Clinical experiences with a new system for automated hand hygiene monitoring: A prospective observational study.

BACKGROUND: Hand hygiene compliance (HHC) among health care workers remains suboptimal, and good monitoring systems are lacking. We aimed to evaluate HHC using an automated monitoring system. METHODS: A prospective, observational study was conducted at 2 Danish university hospitals employing a new monitoring system (Sani nudge). Sensors were located on alcohol-based sanitizers, health care worker name tags, and patient beds measuring hand hygiene opportunities and sanitations. RESULTS: In total, 42 nurses were included with an average HHC of 52% and 36% in hospitals A and B, respectively. HHC was lowest in patient rooms (hospital A: 45%; hospital B: 29%) and highest in staff toilets (hospital A: 72%; hospital B: 91%). Nurses sanitized after patient contact more often than before, and sanitizers located closest to room exits and in hallways were used most frequently. There was no association found between HHC level and the number of beds in patient rooms. The HHC level of each nurse was consistent over time, and showed a positive correlation between the number of sanitations and HHC levels (hospital A: r = 0.69; hospital B: r = 0.58). CONCLUSIONS: The Sani nudge system can be used to monitor HHC at individual and group levels, which increases the understanding of compliance behavior.

National Automated Surveillance of Hospital-Acquired Bacteremia in Denmark Using a Computer Algorithm.

BACKGROUND In 2015, Denmark launched an automated surveillance system for hospital-acquired infections, the Hospital-Acquired Infections Database (HAIBA). OBJECTIVE To describe the algorithm used in HAIBA, to determine its concordance with point prevalence surveys (PPSs), and to present trends for hospital-acquired bacteremia SETTING Private and public hospitals in Denmark METHODS A hospital-acquired bacteremia case was defined as at least 1 positive blood culture with at least 1 pathogen (bacterium or fungus) taken between 48 hours after admission and 48 hours after discharge, using the Danish Microbiology Database and the Danish National Patient Registry. PPSs performed in 2012 and 2013 were used for comparison. RESULTS National trends showed an increase in HA bacteremia cases between 2010 and 2014. Incidence was higher for men than women (9.6 vs 5.4 per 10,000 risk days) and was highest for those aged 61-80 years (9.5 per 10,000 risk days). The median daily prevalence was 3.1% (range, 2.1%-4.7%). Regional incidence varied from 6.1 to 8.1 per 10,000 risk days. The microorganisms identified were typical for HA bacteremia. Comparison of HAIBA with PPS showed a sensitivity of 36% and a specificity of 99%. HAIBA was less sensitive for patients in hematology departments and intensive care units. Excluding these departments improved the sensitivity of HAIBA to 44%. CONCLUSIONS Although the estimated sensitivity of HAIBA compared with PPS is low, a PPS is not a gold standard. Given the many advantages of automated surveillance, HAIBA allows monitoring of HA bacteremia across the healthcare system, supports prioritizing preventive measures, and holds promise for evaluating interventions. Infect Control Hosp Epidemiol 2017;38:559-566.

Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination.

OBJECTIVE: Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone. DESIGN: C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline by oral gavage. After the challenge, the mice were treated with placebo, vancomycin, metronidazole or a combination of vancomycin and metronidazole for 10 days. The mice were monitored for 20 days with weight and a clinical score. Stool samples were examined for C. difficile spore load and presence of C. difficile toxins. RESULTS: None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole recovered from CDI faster than mice treated with metronidazole alone. However, after discontinuation of treatment, vancomycin-treated and combination-treated mice succumbed to clinical and bacteriological relapse. CONCLUSIONS: Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone. A combination of vancomycin and metronidazole did not improve the clinical outcome when compared to treatment with vancomycin alone. TRIAL REGISTRATION NUMBER: The trial registration number from the Danish Experimental Animal Inspectorate is J number 2012-15-2934-00422.