Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

INTRODUCTION: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB. METHODS AND ANALYSIS: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study. ETHICS AND DISSEMINATION: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL8347 (the Netherlands Trial Register).

Comparative effectiveness of ß-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naïve individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA).

To the authors' knowledge, there is currently no literature or guidance recommendation regarding whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and compared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretroviral therapy within <24 h of enrolment: DTG 50 mg BID, DRV/r 800/100 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs thereafter (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration-time profile of 0-24 h (AUC0-24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90-2.55). Total exposure during DTG BID increased but did not double [AUC0-24h GMR 1.65 (90% CI 1.50-1.81) h.mg/L]. DTG glucuronidation MR increased by approximately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads ≤40 copies/mL. The drug-drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.

The effect of the acute phase of infection on absorption of and exposure to orally administered antibiotics in non-critically ill, hospitalized patients.

OBJECTIVES: During the acute phase of infection, IV antibiotics are preferred to ensure adequate systemic exposure. To assess whether adequate exposure may also be achieved with oral antibiotics, we investigated exposure to oral antibiotics and PTA during the acute phase of infection and after defervescence. METHODS: We enrolled hospitalized, non-critically ill febrile patients treated with IV antibiotics other than amoxicillin or ciprofloxacin. The study consisted of two visits: when patients had received <24 h IV treatment; and when patients had become afebrile. On both visits, patients received one additional dose of 750 mg amoxicillin, or 500 mg ciprofloxacin, depending on the presumed infection, after which serial blood samples were obtained. The primary endpoint was the ratio of the AUC during the febrile and the afebrile phase. The AUCs were considered to be equivalent when the ratio of the mean AUCs and its 90% CI was contained within the acceptance interval of 80%-125%. The secondary endpoint was PTA. RESULTS: Forty-four patients (15 amoxicillin, 29 ciprofloxacin) completed both study visits. The median time between the two study visits was 65.8 h (range 33.8-427.4). The ratio of the mean AUCs (study visit 1/study visit 2) was 97% (90% CI of 80%-117%) for amoxicillin and 112% (90% CI of 108%-116%) for ciprofloxacin. The PTA for amoxicillin and ciprofloxacin did not differ between the two phases and was adequate to treat common pathogens. CONCLUSIONS: The acute phase of infection in non-critically ill febrile patients does not influence the exposure to, or PTA of, orally administered amoxicillin and ciprofloxacin. This might justify earlier IV-to-oral switching.

Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

[18F]FDG-PET/CT in Staphylococcus aureus bacteremia: a systematic review.

OBJECTIVES: [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB. METHODS: We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley's Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case-control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers. RESULTS: We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed. DISCUSSION: We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions.

Yield of Adding chest CT to Abdominal CT to Detect COVID-19 in Patients Presenting With Acute Gastrointestinal Symptoms (SCOUT-3): Multicenter Study.

OBJECTIVE: To determine the incremental yield of standardized addition of chest CT to abdominal CT to detect COVID-19 in patients presenting with primarily acute gastrointestinal symptoms requiring abdominal imaging. Summary Background Data: Around 20% of patients with COVID-19 present with gastrointestinal symptoms. COVID-19 might be neglected in these patients, as the focus could be on finding abdominal pathology. During the COVID-19 pandemic, several centers have routinely added chest CT to abdominal CT to detect possible COVID-19 in patients presenting with gastrointestinal symptoms. However, the incremental yield of this strategy is unknown. METHODS: This multicenter study in 6 Dutch centers included consecutive adult patients presenting with acute nontraumatic gastrointestinal symptoms, who underwent standardized combined abdominal and chest CT between March 15, 2020 and April 30, 2020. All CT scans were read for signs of COVID-19 related pulmonary sequelae using the СО-RADS score. The primary outcome was the yield of high COVID-19 suspicion (СО-RADS 4-5) based on chest CT. RESULTS: A total of 392 patients were included. Radiologic suspicion for COVID-19 (СО-RADS 4-5) was present in 17 (4.3%) patients, eleven of which were diagnosed with COVID-19. Only 5 patients with СО-RADS 4-5 presented without any respiratory symptoms and were diagnosed with COVID-19. No relation with community prevalence could be detected. CONCLUSION: The yield of adding chest CT to abdominal CT to detect COVID-19 in patients presenting with acute gastrointestinal symptoms is extremely low with an additional detection rate of around 1%.

A multicentre cluster-randomized clinical trial to improve antibiotic use and reduce length of stay in hospitals: comparison of three measurement and feedback methods.

BACKGROUND: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS). OBJECTIVES: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention. METHODS: Three methods were randomly allocated to 42 clusters from 21 Dutch hospitals: (1) feedback on quantity of antibiotic use [DDD, days-of-therapy (DOT) from hospital pharmacy data], versus feedback on (2) validated, or (3) non-validated quality indicators from point prevalence studies. Using this feedback together with an implementation tool, stewardship teams systematically developed and performed improvement strategies. The hospital length of stay (LOS) was the primary outcome and secondary outcomes included DOT, ICU stay and hospital mortality. Data were collected before (February-May 2015) and after (February-May 2017) the intervention period. RESULTS: The geometric mean hospital LOS decreased from 9.5 days (95% CI 8.9-10.1, 4245 patients) at baseline to 9.0 days (95% CI 8.5-9.6, 4195 patients) after intervention (P < 0.001). No differences in effect on LOS or secondary outcomes were found between methods. Feedback on quality of antibiotic use was used more often to identify improvement targets and was preferred over feedback on quantity of use. Consistent use of the implementation tool seemed to increase effectiveness of the AMS intervention. CONCLUSIONS: The decrease in LOS versus baseline likely reflects improvement in the quality of antibiotic use with the stewardship intervention. While the outcomes with the three methods were otherwise similar, stewardship teams preferred data on the quality over the quantity of antibiotic use.

Sensitivity of C-Reactive Protein and Procalcitonin Measured by Point-of-Care Tests to Diagnose Urinary Tract Infections in Nursing Home Residents: A Cross-Sectional Study.

BACKGROUND: Diagnosing urinary tract infections (UTIs) in nursing home residents is complex, as specific urinary symptoms are often absent and asymptomatic bacteriuria (ASB) is prevalent. The aim of this study was to assess the sensitivity of blood C-reactive protein (CRP) and procalcitonin (PCT), measured by point-of-care tests (PoCTs), to diagnose UTIs in this setting. METHODS: Elderly residents (≥65 years old) with a suspected UTI were recruited from psychogeriatric, somatic, or rehabilitation wards across 13 participating nursing homes. CRP and PCT were tested simultaneously in the same study participants. To assess the tests' sensitivities, a stringent definition of "true" UTI was used that included the presence of symptoms, urinary leucocytes, a positive urine culture, and symptom resolution during antibiotic treatment covering isolated uropathogen(s). The original sample size was 440 suspected UTI episodes, in order to detect a clinically relevant sensitivity of at least 65% when calculated using the matched analysis approach to compare both PoCTs. RESULTS: After enrollment of 302 episodes (68.6% of the planned sample size), an unplanned and funder-mandated interim analysis was done, resulting in premature discontinuation of the study for futility. For 247 of 266 eligible episodes, all mandatory items required for the true UTI definition (92.9%) were available. In total, 49 episodes fulfilled our stringent UTI definition (19.8%). The sensitivities of CRP (cut-off, 6.5 mg/L) and PCT (cut-off, 0.025 ng/mL) were 52.3% (95% confidence interval [CI], 36.7-67.5%) and 37.0% (95% CI, 23.2-52.5%), respectively. CONCLUSIONS: Our results indicate that CRP and PCT are not suitable tests for distinguishing UTI and ASB in nursing home residents. CLINICAL TRIALS REGISTRATION: Netherlands Trial Registry NL6293.

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial.

OBJECTIVES: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. METHODS: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. RESULTS: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). CONCLUSIONS: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.

Anal Squamous Intraepithelial Lesions (SILs) in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men: Incidence and Risk Factors of SIL and of Progression and Clearance of Low-Grade SILs.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs). METHODS: HIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level. RESULTS: Of 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs. CONCLUSION: Incident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.

Exhaled Breath Profiles Before, During and After Exacerbation of COPD: A Prospective Follow-Up Study.

Many patients with chronic obstructive lung disease (COPD) experience exacerbations. The diagnosis of an exacerbation is solely based on symptoms. We hypothesized that exhaled breath profiles, measured by Gas Chromatography-Mass Spectrometry (GC-MS) or electronic nose (eNose), are different between stable disease and exacerbations and may have the potential to serve as biomarkers for COPD exacerbations. In this prospective follow-up study, breath samples were taken during stable COPD, during a subsequent exacerbation and after recovery. Samples were analyzed by GC-MS and eNose. CCQ symptom scores were associated with univariate outcomes of GC-MS and eNose using analysis of covariance (ANCOVA). After multivariate modeling by Principal Component Analysis (PCA), paired student t-tests were performed. Sixty-eight patients were included, 31 had an exacerbation and 16 patients had breath sampled at all three time points. Significant differences were found in breathprints taken during exacerbation as compared to baseline and recovery for both GC-MS and eNose. Breath profiles obtained by GC-MS as well as by eNose showed a correct classification of 71% (10/14) for baseline vs exacerbation and of 78% (11/14) for exacerbation vs recovery. These results provide proof of principle that exhaled breath can serve as a noninvasive biomarker for the diagnosis of COPD exacerbations.

Comparison of antimicrobial stewardship programmes in acute-care hospitals in four European countries: A cross-sectional survey.

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.

How to measure quantitative antibiotic use in order to support antimicrobial stewardship in acute care hospitals: a retrospective observational study.

A cornerstone of antimicrobial stewardship programs (ASPs) is monitoring quantitative antibiotic use. Frequently used metrics are defined daily dose (DDD) and days of therapy (DOT). The purpose of this study was (1) to explore for the hospital setting the possibilities of quantitative data retrieval on the level of medical specialty and (2) to describe factors affecting the usability and interpretation of these quantitative metrics. We performed a retrospective observational study, measuring overall systemic antibiotic use at specialty level over a 1-year period, from December 1st 2014 to December 1st 2015, in one university and 13 non-university hospitals in the Netherlands. We distinguished surgical and non-surgical adult specialties. The association between DDDs, calculated from aggregated dispensing data, and DOTs, calculated from patient-level prescription data, was explored descriptively and related to organizational factors, data sources (prescription versus dispensing data), data registration, and data extraction. Twelve hospitals were able to extract dispensing data (DDD), three of which on the level of medical specialty; 13 hospitals were able to extract prescription data (DOT), 11 of which by medical specialty. A large variation in quantitative antibiotic use was found between hospitals and the correlation between DDDs and DOTs at specialty level was low. Differences between hospitals related to organizational factors, data sources, data registration, and data extraction procedures likely contributed to the variation in quantitative use and the low correlation between DDDs and DOTs. The differences in healthcare organization, data sources, data registration, and data extraction procedures contributed to the variation in reported quantitative use between hospitals. Uniform registration and extraction procedures are necessary for appropriate measurement and interpretation and benchmarking of quantitative antibiotic use.

A survey on antimicrobial stewardship prerequisites, objectives and improvement strategies: systematic development and nationwide assessment in Dutch acute care hospitals.

Background: Stewardship guidelines define three essential building blocks for successful hospital antimicrobial stewardship programmes (ASPs): stewardship prerequisites, stewardship objectives and improvement strategies. Objectives: We systematically developed a survey, based on these building blocks, to evaluate the current state of antimicrobial stewardship in hospitals. We tested this survey in 64 Dutch acute care hospitals. Methods: We performed a literature review on surveys of antimicrobial stewardship. After extraction and categorization of survey questions, five experts merged and rephrased questions during a consensus meeting. After a pilot study, the survey was sent to 80 Dutch hospitals. Results: The final survey consisted of 46 questions, categorized into hospital characteristics, stewardship prerequisites, stewardship objectives and stewardship strategies. The response rate was 80% (n = 64). Ninety-four percent of hospitals had established an antimicrobial stewardship team, consisting of at least one hospital pharmacist and one clinical microbiologist. An infectious diseases specialist was present in 68% of the teams. Nine percent had dedicated IT support. Forty-one percent of the teams were financially supported, with a median of 0.6 full-time equivalents (FTE; 0.1-1.8). The majority of hospitals performed monitoring of restricted antibiotic agents (91%), dose optimization (65%), bedside consultation (56%) and intravenous-to-oral switch (53%). Fifty-eight percent of the hospitals provided education to residents and 28% to specialists. Conclusions: The survey provides information on the progress that is being made in hospitals regarding the three building blocks of a successful ASP, and provides clear aims to strengthen ASPs. Ultimately, these data will be related to national data on antibiotic consumption and resistance.

Human resources required for antimicrobial stewardship teams: a Dutch consensus report.

SCOPE: Antimicrobial stewardship teams are responsible for implementing antimicrobial stewardship programmes (ASP). However, in many countries, lack of funding challenges this obligation. A consensus procedure was performed to investigate which structural activities need to be performed by Dutch stewardship teams and how much time (and thus full-time equivalent (FTE) labor) is needed to perform these activities. METHODS: In 2015, an electronic survey, based on a nonsystematic literature search and interviews with seven experienced stewardship teams, was sent to 21 stewardship teams that performed an ASP. This was followed by a semistructured face-to-face consensus meeting. Fourteen stewardship teams completed the survey (18% of Dutch acute-care hospitals), and 13 participated in the consensus meeting. RECOMMENDATIONS: The hours needed each year are dependent on hospital size and number of stewardship objectives monitored. If all activities are performed at a minimal base (one stewardship objective; minimal staffing standard), time investment was estimated to be 1393 to 2680 hours annually in the early phase, corresponding with 0.87 (300 beds) to 1.68 FTE (1200 beds), with a further increase to minimally 1.25 to 3.18 FTE in the following years with three stewardship objectives monitored (optimal staffing standards during the first few years of implementing an ASP). This consensus on required human resources provides a directive for structural financial support of stewardship teams in the Dutch context. Some stewardship activities (and related time investments) might be specific to the Dutch context and hospital setting. To develop standards for other settings, our methodology could be applied.

A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

Objectives: To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. Methods: A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. Results: During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. Conclusions: This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.