Surveillance of catheter-associated bloodstream infections: development and validation of a fully automated algorithm.

BACKGROUND: Most surveillance systems for catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI) are based on manual chart review. Our objective was to validate a fully automated algorithm for CRBSI and CLABSI surveillance in intensive care units (ICU). METHODS: We developed a fully automated algorithm to detect CRBSI, CLABSI and ICU-onset bloodstream infections (ICU-BSI) in patients admitted to the ICU of a tertiary care hospital in Switzerland. The parameters included in the algorithm were based on a recently performed systematic review. Structured data on demographics, administrative data, central vascular catheter and microbiological results (blood cultures and other clinical cultures) obtained from the hospital's data warehouse were processed by the algorithm. Validation for CRBSI was performed by comparing results with prospective manual BSI surveillance data over a 6-year period. CLABSI were retrospectively assessed over a 2-year period. RESULTS: From January 2016 to December 2021, 854 positive blood cultures were identified in 346 ICU patients. The median age was 61.7 years [IQR 50-70]; 205 (24%) positive samples were collected from female patients. The algorithm detected 5 CRBSI, 109 CLABSI and 280 ICU-BSI. The overall CRBSI and CLABSI incidence rates determined by automated surveillance for the period 2016 to 2021 were 0.18/1000 catheter-days (95% CI 0.06-0.41) and 3.86/1000 catheter days (95% CI: 3.17-4.65). The sensitivity, specificity, positive predictive and negative predictive values of the algorithm for CRBSI, were 83% (95% CI 43.7-96.9), 100% (95% CI 99.5-100), 100% (95% CI 56.5-100), and 99.9% (95% CI 99.2-100), respectively. One CRBSI was misclassified as an ICU-BSI by the algorithm because the same bacterium was identified in the blood culture and in a lower respiratory tract specimen. Manual review of CLABSI from January 2020 to December 2021 (n = 51) did not identify any errors in the algorithm. CONCLUSIONS: A fully automated algorithm for CRBSI and CLABSI detection in critically-ill patients using only structured data provided valid results. The next step will be to assess the feasibility and external validity of implementing it in several hospitals with different electronic health record systems.

Antimicrobial resistance in Enterobacterales infections among children in sub-Saharan Africa: a systematic review and meta-analysis.

Background: The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children. Methods: We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0-18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I2 statistic. The protocol was registered with PROSPERO (CRD42021260157). Findings: After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%-55%; I2: 85.7%, number of isolates (n): 1032) and 84.9% (72.8%-92.2%; I2: 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%-97.9%; I2: 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%-56.5%; I2: 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%-86.3%; I2: 91.6%, n: 1886). Interpretation: High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes. Funding: No funding was received.

Carriage of third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales among children in sub-Saharan Africa: a systematic review and meta-analysis.

Background: The increasing resistance of Enterobacterales to third-generation cephalosporins and carbapenems in sub-Saharan Africa (SSA) is a major public health concern. We did a systematic review and meta-analysis of studies to estimate the carriage prevalence of Enterobacterales not susceptible to third-generation cephalosporins or carbapenems among paediatric populations in SSA. Methods: We performed a systematic literature review and meta-analysis of cross-sectional and cohort studies to estimate the prevalence of childhood (0-18 years old) carriage of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) or carbapenem-resistant Enterobacterales (CRE) in SSA. Medline, EMBASE and the Cochrane Library were searched for studies published from 1 January 2005 to 1 June 2022. Studies with <10 occurrences per bacteria, case reports, and meta-analyses were excluded. Quality and risk of bias were assessed using the Newcastle-Ottawa scale. Meta-analyses of prevalences and odds ratios were calculated using generalised linear mixed-effects models. Heterogeneity was assessed using I2 statistics. The protocol is available on PROSPERO (CRD42021260157). Findings: Of 1111 studies examined, 40 met our inclusion criteria, reporting on the carriage prevalence of Enterobacterales in 9408 children. The pooled carriage prevalence of ESCR-E was 32.2% (95% CI: 25.2%-40.2%). Between-study heterogeneity was high (I2 = 96%). The main sources of bias pertained to participant selection and the heterogeneity of the microbiological specimens. Carriage proportions were higher among sick children than healthy ones (35.7% vs 16.9%). The pooled proportion of nosocomial acquisition was 53.8% (95% CI: 32.1%-74.1%) among the 922 children without ESCR-E carriage at hospital admission. The pooled odds ratio of ESCR-E carriage after antibiotic treatment within the previous 3 months was 3.20 (95% CI: 2.10-4.88). The proportion of pooled carbapenem-resistant for Enterobacterales was 3.6% (95% CI: 0.7%-16.4%). Interpretation: This study suggests that ESCR-E carriage among children in SSA is frequent. Microbiology capacity and infection control must be scaled-up to reduce the spread of those multidrug-resistant microorganisms. Funding: There was no funding source for this study.

Systematic scoping review of automated systems for the surveillance of healthcare-associated bloodstream infections related to intravascular catheters.

INTRODUCTION: Intravascular catheters are crucial devices in medical practice that increase the risk of healthcare-associated infections (HAIs), and related health-economic adverse outcomes. This scoping review aims to provide a comprehensive overview of published automated algorithms for surveillance of catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). METHODS: We performed a scoping review based on a systematic search of the literature in PubMed and EMBASE from 1 January 2000 to 31 December 2021. Studies were included if they evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We assessed the design of the automated systems, including the definitions used to develop algorithms (CLABSI versus CRBSI), the datasets and denominators used, and the algorithms evaluated in each of the studies. RESULTS: We screened 586 studies based on title and abstract, and 99 were assessed based on full text. Nine studies were included in the scoping review. Most studies were monocentric (n = 5), and they identified CLABSI (n = 7) as an outcome. The majority of the studies used administrative and microbiological data (n = 9) and five studies included the presence of a vascular central line in their automated system. Six studies explained the denominator they selected, five of which chose central line-days. The most common rules and steps used in the algorithms were categorized as hospital-acquired rules, infection rules (infection versus contamination), deduplication, episode grouping, secondary BSI rules (secondary versus primary BSI), and catheter-associated rules. CONCLUSION: The automated surveillance systems that we identified were heterogeneous in terms of definitions, datasets and denominators used, with a combination of rules in each algorithm. Further guidelines and studies are needed to develop and implement algorithms to detect CLABSI/CRBSI, with standardized definitions, appropriate data sources and suitable denominators.

[Infectious diseases: what's new in 2023]. / Maladies infectieuses: ce qui a changé en 2023.

The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe community-acquired pneumonia. Administration of doxycycline post-exposure prophylaxis reduced the risk of bacterial sexually transmitted infections at the risk of resistance selection. An herbal preparation decreased mortality in sepsis. A meta-analysis concludes that oseltamivir does not significantly reduce the risk of hospitalisation for influenza. Discontinuation of antibiotic prophylaxis during dental procedures in Sweden did not increase the incidence of viridans group Streptococcus endocarditis. Several studies have led to the introduction of RSV (Respiratory Syncytial Virus (RSV) vaccination. 2023 also saw the resurgence of invasive Group A Streptococcal infections, of which clinicians must be wary.

L'année 2023 est marquée par la publication d'études touchant des domaines variés de l'infectiologie. La mortalité de pneumonies communautaires sévères est diminuée par l'administration de corticostéroïdes. Lors de rapport sexuel à risque, l'administration de doxycycline en prophylaxie postexpositionnelle diminue le risque d'infections sexuellement transmissibles bactériennes, cependant au risque de sélectionner des bactéries résistantes. Une préparation de plantes diminue la mortalité du sepsis. Une méta-analyse conclut que l'oseltamivir ne diminue pas significativement le risque d'hospitalisation lors de grippe. L'arrêt de la prophylaxie antibiotique lors d'intervention dentaire en Suède n'a pas augmenté l'incidence d'endocardite à streptocoques du groupe viridans. Plusieurs études ont mené à l'introduction de la vaccination VRS (virus respiratoire syncytial humain). 2023 a aussi vu la résurgence d'infections invasives à streptocoques du groupe A dont le clinicien doit se méfier.

Increased Peripheral Venous Catheter Bloodstream Infections during COVID-19 Pandemic, Switzerland.

Studies suggest that central venous catheter bloodstream infections (BSIs) increased during the COVID-19 pandemic. We investigated catheter-related BSIs in Switzerland and found peripheral venous catheter (PVC) BSI incidence increased during 2021-2022 compared with 2020. These findings should raise awareness of PVC-associated BSIs and prompt inclusion of PVC BSIs in surveillance systems.

Comparison of clinical outcomes over time of inpatients with healthcare-associated or community-acquired coronavirus disease 2019 (COVID-19): A multicenter, prospective cohort study.

OBJECTIVE: To compare clinical outcomes over time of inpatients with healthcare-associated coronavirus disease 2019 (HA-COVID-19) versus community-acquired COVID-19 (CA-COVID-19). DESIGN: We conducted a multicenter, prospective observational cohort study of inpatients with COVID-19. SETTING: The study was conducted across 16 acute-care hospitals in Switzerland. PARTICIPANTS AND METHODS: We compared HA-COVID-19 cases, defined as patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test > 5 days after hospital admission, with hospitalized CA-COVID-19 cases, defined as those who tested positive within 5 days of admission. The composite primary outcome was patient transfer to an intensive care unit (ICU) or an intermediate care unit (IMCU) and/or all-cause in-hospital mortality. We used cause-specific Cox regression and Fine-Gray regression to model the time to the composite clinical outcome, adjusting for confounders and accounting for the competing event of discharge from hospital. We compared our results to those from a conventional approach using an adjusted logistic regression model where time-varying effects and competitive risk were ignored. RESULTS: Between February 19, 2020, and December 31, 2020, we included 1,337 HA-COVID-19 cases and 9,068 CA-COVID-19 cases. HA-COVID-19 patients were significantly older: median, 80 (interquartile range [IQR], 71-87) versus median 70 (IQR, 57-80) (P < .001). A greater proportion of HA-COVID-19 patients had a Charlson comorbidity index ≥ 5 (79% vs 55%; P < .001) than did CA-COVID-19 patients. In time-varying analyses, between day 0 and 8, HA-COVID-19 cases had a decreased risk of death or ICU or IMCU transfer compared to CA-COVID-19 cases (cause-specific hazard ratio [csHR], 0.43; 95% confidence interval [CI], 0.33-0.56). In contrast, from day 8 to 30, HA-COVID-19 cases had an increased risk of death or ICU or IMCU transfer (csHR, 1.49; 95% CI, 1.20-1.85), with no significant effect on the rate of discharge (csHR, 0.83; 95% CI, 0.61-1.14). In the conventional logistic regression model, HA-COVID-19 was protective against transfer to an ICU or IMCU and/or all-cause in-hospital mortality (adjusted odds ratio [aOR], 0.79, 95% CI, 0.67-0.93). CONCLUSIONS: The risk of adverse clinical outcomes for HA-COVID-19 cases increased substantially over time in hospital and exceeded that for CA-COVID-19. Using approaches that do not account for time-varying effects or competing events may not fully capture the true risk of HA-COVID-19 compared to CA-COVID-19.

Catheter size and risk of short-term peripheral venous catheter-associated bloodstream infections: an observational study.

OBJECTIVES: Short-term peripheral venous catheter-associated bloodstream infections (PVC-associated BSI) are disregarded in the literature because of their relatively low incidence. No data are available on the association between PVC diameter size and the risk of PVC-associated BSI. METHODS: Using a prospective database, we performed an observational study at the University of Geneva Hospitals from 1 January 2020 to 31 December 2021, including all patients with a PVC. We used univariable and multivariable marginal Cox regression models for clustered data to investigate the association between catheter size and PVC-associated BSI. The main variable of interest 'catheter size' was forced into our multivariable models. Confounders, which are thought to influence the risk of PVC-associated BSI, were used as adjustment factors. RESULTS: A total of 206 804 PVCs were included. In all, 10 806 of 201 413 (5.4%), 80 274 of 201 413 (39.9%), 93 047 of 201 413 (46.2%) and 17 286 of 201 413 (8.6%) PVCs measured ≤16G, 18G, 20G and ≥22G, respectively. The univariable analysis showed that diameters of ≤16G were significantly associated with a higher risk of PVC-associated BSI (hazard ratio [HR] 4.52, 95% CI, 1.14-18.00). Multivariable models confirmed these results (HR 4.65, 95% CI, 1.19-18.20). Sensitivity analyses including PVC inserted only in 2021 (HR 4.80, 95% CI, 1.21-19.10), for dwell time >2 days (HR 3.67, 95% CI, 0.92-14.65) and only in adults (HR 3.97, 95% CI, 0.97-15.39) showed similar results. DISCUSSION: Larger PVC size may increase the risk of PVC-associated BSI. Diameter size should be considered when selecting PVCs to reduce the burden of PVC-associated BSI.

[Surgical site infection after lower limb arterial reconstruction: can we improve prevention?] / Infections postchirurgie artérielle des membres inférieurs : peut-on mieux faire?

Infections associated with arterial reconstructions of the lower limbs are associated with high morbidity. This article reviews the risk factors for infection associated with this surgery and the preventive measures. These include smoking cessation and glycemic control preoperatively; avoiding unnecessary exposure to antibiotics or corticosteroids; optimal peripheral wound care; rigorous antisepsis and antibiotic prophylaxis in the operating theatre ; and finally, meticulous post-operative wound monitoring. The benefit of Staphylococcus aureus decolonization in vascular surgery is less clearly established than in cardiac and thoracic surgery, but it is still recommended in cases of implant placement or where there is a high risk of S. aureus infection, depending on the planned approach and type of surgery.

Les infections associées aux reconstructions artérielles des membres inférieurs sont grevées d'une morbidité élevée. Cet article revoit les facteurs de risque d'infection associés à cette chirurgie et les mesures de prévention. Ces dernières incluent l'arrêt du tabac et le contrôle glycémique en préopératoire ; l'absence d'exposition inutile aux antibiotiques ou aux corticostéroïdes ; les soins de plaies périphériques optimaux ; une antisepsie et une antibioprophylaxie au bloc opératoire rigoureuses et, finalement, un suivi de plaie postopératoire minutieux. Le bénéfice de la décolonisation à Staphylococcus aureus dans le cadre de la chirurgie vasculaire est moins clairement établi qu'en chirurgies cardiaque et thoracique, mais celle-ci reste recommandée en cas de mise en place d'implant ou de risque élevé d'infection à S. aureus, selon la voie d'abord et le type de chirurgie prévue.

[Computerized support to improve antimicrobial prescribing: myth or reality?] / Aide informatique pour mieux prescrire des antimicrobiens : mythe ou réalité?

Antimicrobial stewardship programmes aim to improve antimicrobial prescribing with the final aim to improve patient care, while limiting the emergence and spread of resistant bacteria. Two main categories of digital tools are currently available in this area: stand-alone mobile applications and tools directly integrated into electronic health records. The former are easy to implement and less costly, but offer limited support as they do not take into account individual patient data. Their impact depends on the clinician's willingness to use them regularly. Integrated systems are based on more sophisticated, individualised algorithms and offer the possibility of intervening with a variety of techniques (restriction, reassessment, feedback, alerts), sometimes before the prescription occurs. They are costly and complex to implement and require an appropriate IT infrastructure. Both systems, as in other areas of digital medicine, have a low level of evidence regarding their clinical impact. In this review we examine the two types of tools, the benefits and challenges associated with each, and the available data on effectiveness.

Les programmes d'antimicrobial stewardship visent à optimiser la prescription d'antimicrobiens, dans l'objectif d'améliorer les soins aux patients, tout en limitant l'émergence et la dissémination des bactéries résistantes. Deux grandes catégories d'outils digitaux sont aujourd'hui disponibles : les applications mobiles « stand alone ¼ et les outils intégrés au dossier patient informatisé. Les premiers, faciles à implémenter et moins coûteux, offrent cependant une aide plus limitée, ne prenant pas en compte des données individuelles. Les systèmes intégrés reposent sur des algorithmes plus élaborés, et offrent la possibilité d'intervenir par des moyens variés (restriction, réévaluation, feedback, alertes), parfois en amont de la prescription. Leur implémentation est coûteuse et nécessite une infrastructure informatique adéquate. Nous passons ici en revue les deux types d'outils, les avantages et les défis associés à chacun ainsi que les données d'efficacité disponibles.

Predictive performance of automated surveillance algorithms for intravascular catheter bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Intravascular catheter infections are associated with adverse clinical outcomes. However, a significant proportion of these infections are preventable. Evaluations of the performance of automated surveillance systems for adequate monitoring of central-line associated bloodstream infection (CLABSI) or catheter-related bloodstream infection (CRBSI) are limited. OBJECTIVES: We evaluated the predictive performance of automated algorithms for CLABSI/CRBSI detection, and investigated which parameters included in automated algorithms provide the greatest accuracy for CLABSI/CRBSI detection. METHODS: We performed a meta-analysis based on a systematic search of published studies in PubMed and EMBASE from 1 January 2000 to 31 December 2021. We included studies that evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We estimated the pooled sensitivity and specificity of algorithms for accuracy and performed a univariable meta-regression of the different parameters used across algorithms. RESULTS: The search identified five full text studies and 32 different algorithms or study populations were included in the meta-analysis. All studies analysed central venous catheters and identified CLABSI or CRBSI as an outcome. Pooled sensitivity and specificity of automated surveillance algorithm were 0.88 [95%CI 0.84-0.91] and 0.86 [95%CI 0.79-0.92] with significant heterogeneity (I2 = 91.9, p < 0.001 and I2 = 99.2, p < 0.001, respectively). In meta-regression, algorithms that include results of microbiological cultures from specific specimens (respiratory, urine and wound) to exclude non-CRBSI had higher specificity estimates (0.92, 95%CI 0.88-0.96) than algorithms that include results of microbiological cultures from any other body sites (0.88, 95% CI 0.81-0.95). The addition of clinical signs as a predictor did not improve performance of these algorithms with similar specificity estimates (0.92, 95%CI 0.88-0.96). CONCLUSIONS: Performance of automated algorithms for detection of intravascular catheter infections in comparison to manual surveillance seems encouraging. The development of automated algorithms should consider the inclusion of results of microbiological cultures from specific specimens to exclude non-CRBSI, while the inclusion of clinical data may not have an added-value. Trail Registration Prospectively registered with International prospective register of systematic reviews (PROSPERO ID CRD42022299641; January 21, 2022). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299641.

Digitalizing Clinical Guidelines: Experiences in the Development of Clinical Decision Support Algorithms for Management of Childhood Illness in Resource-Constrained Settings.

Clinical decision support systems (CDSSs) can strengthen the quality of integrated management of childhood illness (IMCI) in resource-constrained settings. Several IMCI-related CDSSs have been developed and implemented in recent years. Yet, despite having a shared starting point, the IMCI-related CDSSs are markedly varied due to the need for interpretation when translating narrative guidelines into decision logic combined with considerations of context and design choices. Between October 2019 and April 2021, we conducted a comparative analysis of 4 IMCI-related CDSSs. The extent of adaptations to IMCI varied, but common themes emerged. Scope was extended to cover a broader range of conditions. Content was added or modified to enhance precision, align with new evidence, and support rational resource use. Structure was modified to increase efficiency, improve usability, and prioritize care for severely ill children. The multistakeholder development processes involved syntheses of recommendations from existing guidelines and literature; creation and validation of clinical algorithms; and iterative development, implementation, and evaluation. The common themes surrounding adaptations of IMCI guidance highlight the complexities of digitalizing evidence-based recommendations and reinforce the rationale for leveraging standards for CDSS development, such as the World Health Organization's SMART Guidelines. Implementation through multistakeholder dialogue is critical to ensure CDSSs can effectively and equitably improve quality of care for children in resource-constrained settings.

Incidence of healthcare-associated coronavirus disease 2019 (COVID-19) in the state of Geneva.

An examination of all coronavirus disease 2019 (COVID-19) cases and patient movements in Geneva indicated important disease activity within the healthcare system since the beginning of the pandemic. We estimate that 4.3% of all COVID-19 cases were likely acquired within the healthcare system, contributing to 62% of the COVID-19-related deaths.

Impact of interactive computerised decision support for hospital antibiotic use (COMPASS): an open-label, cluster-randomised trial in three Swiss hospitals.

BACKGROUND: Computerised decision-support systems (CDSSs) for antibiotic stewardship could help to assist physicians in the appropriate prescribing of antibiotics. However, high-quality evidence for their effect on the quantity and quality of antibiotic use remains scarce. The aim of our study was to assess whether a computerised decision support for antimicrobial stewardship combined with feedback on prescribing indicators can reduce antimicrobial prescriptions for adults admitted to hospital. METHODS: The Computerised Antibiotic Stewardship Study (COMPASS) was a multicentre, cluster-randomised, parallel-group, open-label superiority trial that aimed to assess whether a multimodal computerised antibiotic-stewardship intervention is effective in reducing antibiotic use for adults admitted to hospital. After pairwise matching, 24 wards in three Swiss tertiary-care and secondary-care hospitals were randomised (1:1) to the CDSS intervention or to standard antibiotic stewardship measures using an online random sequence generator. The multimodal intervention consisted of a CDSS providing support for choice, duration, and re-evaluation of antimicrobial therapy, and feedback on antimicrobial prescribing quality. The primary outcome was overall systemic antibiotic use measured in days of therapy per admission, using adjusted-hurdle negative-binomial mixed-effects models. The analysis was done by intention to treat and per protocol. The study was registered with ClinicalTrials.gov (identifier NCT03120975). FINDINGS: 24 clusters (16 at Geneva University Hospitals and eight at Ticino Regional Hospitals) were eligible and randomly assigned to control or intervention between Oct 1, 2018, and Dec 31, 2019. Overall, 4578 (40·2%) of 11 384 admissions received antibiotic therapy in the intervention group and 4142 (42·8%) of 9673 in the control group. The unadjusted overall mean days of therapy per admission was slightly lower in the intervention group than in the control group (3·2 days of therapy per admission, SD 6·2, vs 3·5 days of therapy per admission, SD 6·8; p<0·0001), and was similar among patients receiving antibiotics (7·9 days of therapy per admission, SD 7·6, vs 8·1 days of therapy per admission, SD 8·4; p=0·50). After adjusting for confounders, there was no statistically significant difference between groups for the odds of an admission receiving antibiotics (odds ratio [OR] for intervention vs control 1·12, 95% CI 0·94-1·33). For admissions with antibiotic exposure, days of therapy per admission were also similar (incidence rate ratio 0·98, 95% CI 0·90-1·07). Overall, the CDSS was used at least once in 3466 (75·7%) of 4578 admissions with any antibiotic prescription, but from the first day of antibiotic treatment for only 1602 (58·9%) of 2721 admissions in Geneva. For those for whom the CDSS was not used from the first day, mean time to use of CDSS was 8·9 days. Based on the manual review of 1195 randomly selected charts, transition from intravenous to oral therapy was significantly more frequent in the intervention group after adjusting for confounders (154 [76·6%] of 201 vs 187 [87%] of 215, +10·4%; OR 1·9, 95% CI 1·1-3·3). Consultations by infectious disease specialists were less frequent in the intervention group (388 [13·4%] of 2889) versus the control group (405 [16·9%] of 2390; OR 0·84, 95% CI 0·59-1·25). INTERPRETATION: An integrated multimodal computerised antibiotic stewardship intervention did not significantly reduce overall antibiotic use, the primary outcome of the study. Contributing factors were probably insufficient uptake, a setting with relatively low antibiotic use at baseline, and delays between ward admission and first CDSS use. FUNDING: Swiss National Science Foundation. TRANSLATIONS: For the French and Italian translations of the abstract see Supplementary Materials section.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

In search of lost time: A timing evaluation of antimicrobial prescribing with and without a computerized decision support system using clinical vignettes.

BACKGROUND: We implemented a computerized decision support system (CDSS) integrated in the in-house computerized physician order entry (CPOE) system to assist physicians with antimicrobial prescribing decisions in the context of the multicenter cluster-randomized COMPASS trial (NCT03120975). Some physicians in the intervention wards complained about the perceived extra-time associated with the use of the CDSS compared with routine prescribing through CPOE. The aim of this study was to compare the time needed to prescribe antimicrobials with and without the CDSS. METHODS: Physicians with and without previous experience with the COMPASS CDSS working at our hospital in Geneva, Switzerland, were recruited to prescribe antimicrobials using clinical vignettes. Physicians without experience received a brief explanation of the CDSS. Each physician received 2 groups of 5-7 clinical vignettes randomly selected from a pool of 28. Each group of vignettes included prescriptions with different levels of complexity (empiric versus targeted or pre-defined treatment, dose adjustment for renal function, oral switch, treatments for which COMPASS does not provide recommendations or where a deviation was necessary). Prescriptions were completed using the standard CPOE (first set), then using COMPASS (second set). A print version of the local antimicrobial guidelines was available for consultation. Time to complete each prescription was recorded (including time needed to consult paper guidelines). The Mann-Whitney test was used for comparisons. Consultation of guidelines booklet and concordance with local guidelines were assessed. RESULTS: Twenty-five physicians were recruited. Thirteen (52%) had previously used COMPASS. Among them, 11 (85%) estimated the extra-time being above 1 min. We evaluated a total of 296 vignettes. Overall, the median time to complete a prescription was 55.5 s (IQR 38-86) using COMPASS and 50 s (IQR 31-88) using the standard CPOE (p = 0.24). Concordance of prescriptions with local guidelines was similar with the 2 systems (127/148, 85.8% for both), but consultation of paper guidelines was more frequent when prescribing without the CDSS (49.3% (73/148) vs 22.3% (33/148)). CONCLUSIONS: The increased time required for prescribing using COMPASS is overestimated by end-users. Information collected in the study will be used to streamline the prescribing process via COMPASS and increase acceptance.

Methicillin-Resistant Staphylococcus aureus: An Update on Prevention and Control in Acute Care Settings.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health-care-associated infections. Controversies regarding the effectiveness of various control strategies have contributed to varying approaches to MRSA control. However, new evidence from large-scale studies has emerged, particularly concerning screening and decolonization. Importantly, implementation and outcomes of control measures in practice are not only influenced by scientific evidence, but also economic, administrative, and political factors, as demonstrated by decreasing MRSA rates in a number of countries after concerted and coordinated efforts at a national level. Flexibility to adapt measures based on local epidemiology and resources is essential for successful MRSA control.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Outbreak of Pseudomonas aeruginosa producing VIM carbapenemase in an intensive care unit and its termination by implementation of waterless patient care.

BACKGROUND: Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa. METHODS: We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir. RESULTS: Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention. DISCUSSION: Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.