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Introduction: The dose–response relationships of tacrolimus have been primarily assessed through trough concentrations during intermittent administrations. In scenarios where oral administration (PO) is unfeasible, continuous intravenous (IV) administration is advised. Under these circumstances, only steady-state (Css) plasma or blood concentrations are measured, with the absence of distinct trough levels (Cmin). Consequently, the measured concentrations are frequently misinterpreted as trough concentrations, potentially resulting in sub-therapeutic true tacrolimus blood levels. This study employs physiologically based pharmacokinetic modeling (PBPK) to establish the Css/Cmin ratio for tacrolimus across various clinical scenarios. Method: Using a validated PBPK model, the tacrolimus dose (both PO and IV) and the Css/Cmin ratios corresponding to matching area under the blood concentration–time curve during a dosage interval (AUCτ) values were estimated under different conditions, including healthy subjects and individuals exhibiting cytochrome P450 3A (CYP3A) interactions or CYP3A5 polymorphisms, along with a demonstration of a real-life clinical application. Result: In healthy volunteers, the oral/intravenous (PO/IV) dose ratio was found to be 4.25, and the Css/Cmin ratio was 1.40. A specific clinical case substantiated the practical applicability of the Css/Cmin ratio as simulated by PBPK, demonstrating no immediate clinical complications related to the transplant. When considering liver donors versus recipients expressing CYP3A5, the tacrolimus AUCτ was notably affected, yielding a PO/IV dose ratio of 4.00 and a Css/Cmin ratio of 1.75. Furthermore, the concomitant administration of the CYP3A inhibitor itraconazole given PO resulted in a PO/IV ratio of 1.75 with and a Css/Cmin ratio of 1.28. Notably, the inhibitory effect of itraconazole was diminished when administered IV. Conclusions: Through the application of PBPK methodologies, this study estimates the PO/IV dose ratios and Css/Cmin ratios that can enhance dose adjustment and therapeutic drug monitoring during the switch between IV and PO administration of tacrolimus in transplant patients, ultimately guiding clinicians in real-time decision-making. Further validation with in vivo data is recommended to support these findings.

Abstract Introduction Rapid molecular tests could accelerate the control of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenemase-producing organisms (CPO) in intensive care units (ICUs). Objective and methods This interventional 12-month cohort study compared a loop-mediated isothermal amplification (LAMP) assay performed directly on rectal swabs with culturing methods (control period, 6 months), during routine ICU screening. Contact precautions (CP) were implemented for CPO or non-E. coli ESBL-producing Enterobacterales (nEcESBL-PE) carriers. Using survival analysis, we compared the time intervals from admission to discontinuation of unnecessary preemptive CP among patients at-risk and the time intervals from screening to implementation of CP among newly identified carriers. We also compared diagnostic performances, and nEcESBL-PE/CPO acquisition rates. This study is registered, ISRCTN 23588440. Results We included 1043 patients. During the intervention and control phases, 92/147 (62.6%) and 47/86 (54.7%) of patients at-risk screened at admission were candidates for early discontinuation of preemptive CP. The LAMP assay had a positive predictive value (PPV) of 44.0% and a negative predictive value (NPV) of 99.9% for CPO, and 55.6% PPV and 98.2% NPV for nEcESBL-PE. Due to result notification and interpretation challenges, the median time from admission to discontinuation of preemptive CP increased during the interventional period from 80.5 (95% CI 71.5–132.1) to 88.3 (95% CI 57.7–103.7) hours (p = 0.47). Due to the poor PPV, we had to stop using the LAMP assay to implement CP. No difference was observed regarding the incidence of nEcESBL-PE and CPO acquisition. Conclusion A rapid screening strategy with LAMP assays performed directly on rectal swabs had no benefit for infection control in a low-endemicity setting.

Abstract Background We investigated the contribution of both occupational and community exposure for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees of a university-affiliated long-term care facility (LTCF), during the 1st pandemic wave in Switzerland (March–June 2020). Methods We performed a nested analysis of a seroprevalence study among all volunteering LTCF staff to determine community and nosocomial risk factors for SARS-CoV-2 seropositivity using modified Poison regression. We also combined epidemiological and genetic sequencing data from a coronavirus disease 2019 (COVID-19) outbreak investigation in a LTCF ward to infer transmission dynamics and acquisition routes of SARS-CoV-2, and evaluated strain relatedness using a maximum likelihood phylogenetic tree. Results Among 285 LTCF employees, 176 participated in the seroprevalence study, of whom 30 (17%) were seropositive for SARS-CoV-2. Most (141/176, 80%) were healthcare workers (HCWs). Risk factors for seropositivity included exposure to a COVID-19 inpatient (adjusted prevalence ratio [aPR] 2.6; 95% CI 0.9–8.1) and community contact with a COVID-19 case (aPR 1.7; 95% CI 0.8–3.5). Among 18 employees included in the outbreak investigation, the outbreak reconstruction suggests 4 likely importation events by HCWs with secondary transmissions to other HCWs and patients. Conclusions These two complementary epidemiologic and molecular approaches suggest a substantial contribution of both occupational and community exposures to COVID-19 risk among HCWs in LTCFs. These data may help to better assess the importance of occupational health hazards and related legal implications during the COVID-19 pandemic.

Abstract Background Escherichia coli sequence type (ST) 131 H30 is an emerging multidrug resistant subclone, known to spread and cause outbreaks in long-term care facilities (LTCFs). Objectives and methods From 2010 through 2020, we performed 11 yearly surveillance studies for determining the prevalence of digestive carriage of ESBL-producing E. coli (ESBL-EC) among residents in a university-affiliated LCTF. Sequencing and genotyping of selected isolates were performed to characterize temporal trends in the prevalence and epidemic potential of ESBL-EC subclones, and for evaluating a potential rebound effect following discontinuation of contact precautions for ESBL-EC carriers in January 2019. Results This study included 2′403 LTCF residents, with 252 (10.5%) positive for ESBL-EC. Among the 236 ESBL-EC isolates available for typing, 58.0% belonged to the ST131 lineage, including 94/137 (68.6%) ST131 H30 isolates. An increasing yearly prevalence was observed for ESBL-EC (from 4.6 to 9.4%; p = 0.11), but not for the ST131 H30 subclone, which peaked in 2015 and declined thereafter. Multiple previously unnoticed ESBL-EC outbreaks occurred in the LTCF. Since 2018, we noted the clonal expansion of a rare ST131 H89 subclone (O16:H5) harboring CTX-M-14 and CTX-M-24. No rebound effect was observed in ESBL-EC prevalence nor in the different subclones following discontinuation of contact precautions for ESBL-EC carriers since 2019. Conclusion Clonal fluctuation was observed for ST131 H30 ESBL-EC with a current decline in prevalence. Surveillance should include the evolution of ST131 non-H30 subclones, which may spread in LTCFs. Our findings suggest that discontinuation of contact precautions for ESBL-EC carriers in LTCFs may be safely implemented, in support of European recommendations to limit ESBL-producing Enterobacteriaceae control measures in endemic settings to non-E. coli.

Abstract Objectives To compile current published reports on nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evaluate the role of healthcare workers (HCWs) in transmission, and evaluate outbreak management practices. Methods Narrative literature review. Short conclusion The coronavirus disease 2019 (COVID-19) pandemic has placed a large burden on hospitals and healthcare providers worldwide, which increases the risk of nosocomial transmission and outbreaks to “non-COVID” patients or residents, who represent the highest-risk population in terms of mortality, as well as HCWs. To date, there are several reports on nosocomial outbreaks of SARS-CoV-2, and although the attack rate is variable, it can be as high as 60%, with high mortality. There is currently little evidence on transmission dynamics, particularly using genomic sequencing, and the role of HCWs in initiating or amplifying nosocomial outbreaks is not elucidated. There has been a paradigm shift in management practices of viral respiratory outbreaks, that includes widespread testing of patients (or residents) and HCWs, including asymptomatic individuals. These expanded testing criteria appear to be crucial in identifying and controlling outbreaks.

Abstract Background Social media may provide a tool, when coupled with a patient-included™ conference, to enhance the engagement among the general public. We describe authors and potential readers of Twitter content surrounding a patient-included™ scientific congress, the International Consortium for Prevention and Infection Control (ICPIC) 2019. Methods Retrospective observational analysis of Twitter users posting with the #ICPIC2019 hashtag during the conference. Tweet authors, overall followers, and active followers were categorized according to their Twitter biographies using unsupervised learning. Diversity of professional backgrounds of Tweet authors and their followers was explored. Network analysis explored connectedness between the reach of authors. Results In total, 1264 participants attended ICPIC 2019, of which 28 were patients. From September 7 to 16, 2019, we were able to categorize 235′620 (41%) followers linked to 474 (76%) authors. Among authors and followers, respectively 34% and 14% were healthcare workers, 11% and 15% were from industry representatives, 8% and 7% were academic researchers. On average, 23% (range 9–39%) followers belonged to the same categories as authors. Among all followers categorized, only 582/235 620 (0.25%) interacted with original messages, including healthcare workers (37%), global and public health (12%), academic research (11%) and those from industry (11%). Though the similarity between Tweet authors and followers was supported by network analysis, we also observed that non-healthcare workers (including patients) appeared to have more diverse followers. Conclusions We observed the participation of numerous Tweet authors and followers from diverse professional backgrounds potentially supporting the benefit of including patients in conferences to reach a more general, non-specialized public.

Abstract As emergence and spread of multi-drug resistant organisms (MDRO) requires a standardized preventive approach, we aimed to evaluate current MDRO admission screening practices in Swiss hospitals and to identify potential barriers impeding their implementation. In early 2018, all Swiss public and private healthcare institutions providing inpatient care were contacted with a 34-item questionnaire to investigate current MDRO admission screening policies. Among 139 respondents representing 180 institutions (response rate, 79%), 83% (149) of institutions implemented MDRO admission screening, while 28% of private and 9% of public institutions did not perform any screening. Targeted high-risk screening included carbapenemase producers, extended-spectrum beta-lactamase producers and methicillin-resistant Staphylococcus aureus at the institutional level for respectively 78% (115), 81% (118) and 98% (145) of screening institutions. Vancomycin-resistant enterococci (44% of institutions), multi-resistant Acinetobacter baumanii (41%) and Pseudomonas aeruginosa (37%) were systematically searched only by a minority of screening institutions. A large diversity of risk factors for targeted screening and some heterogeneity in body sites screened were also observed. Admission-screening practices were mostly impeded by a difficulty to identify high-risk patients (44%) and non-compliance of healthcare workers (35%). Heterogeneous practices and gaps in small and privately-owned institutions, as well as a mismatch between current epidemiologic MDRO trends and screening practices were noticed. These results highlight the need for uniform national MDRO screening standards.

The current global systemic crisis reveals how globalised societies are unprepared to face a pandemic. Beyond the dramatic loss of human life, the COVID-19 pandemic has triggered widespread disturbances in health, social, economic, environmental and governance systems in many countries across the world. Resilience describes the capacities of natural and human systems to prevent, react to and recover from shocks. Societal resilience to the current COVID-19 pandemic relates to the ability of societies in maintaining their core functions while minimising the impact of the pandemic and other societal effects. Drawing on the emerging evidence about resilience in health, social, economic, environmental and governance systems, this paper delineates a multisystemic understanding of societal resilience to COVID-19. Such an understanding provides the foundation for an integrated approach to build societal resilience to current and future pandemics.

Given rising antibiotic resistance and increasing use of delayed prescription for uncomplicated lower urinary tract infections (UTI), patients at risk for treatment failure should be identified early. We assessed risk factors for clinical and microbiological failure in women with lower UTI. This case-control study nested within a randomized clinical trial included all women in the per-protocol population (PPP), those in the PPP with microbiologically confirmed UTI, and those in the PPP with UTI due to Escherichia coli. Cases were women who experienced clinical and/or microbiologic failure; controls were those who did not. Risk factors for failure were assessed using multivariate logistic regression. In the PPP, there were 152 clinical cases for 307 controls. Among 340 women with microbiologically confirmed UTI, 126 and 102 cases with clinical and microbiological failure were considered with, respectively, 214 and 220 controls. Age ≥52 years was independently associated with clinical (adjusted OR 3.01; 95%CI 1.84-4.98) and microbiologic failure (aOR 2.55; 95%CI 1.54-4.25); treatment with fosfomycin was associated with clinical failure (aOR 2.35; 95%CI 1.47-3.80). The association with age persisted among all women, and women with E. coli-related UTI. Diabetes was not an independent risk factor, nor were other comorbidities. Postmenopausal age emerged as an independent risk factor for both clinical and microbiological treatment failure in women with lower UTI and should be considered to define women at-risk for non-spontaneous remission, and thus for delayed antibiotic therapy; diabetes mellitus was not associated with failure.

Using computerized time-stamps, we compared the turnaround-times (TAT) for urine samples and screening ESwabs of MRSA, VRE, and ESBL carriage in the bacteriology laboratory of Geneva University Hospitals between January and December 2017 (period preceding the implementation of the WASPLabTM) with the same specimen types analyzed between January and December 2019 (period after the implementation of the automation). During both 1-year periods, a total of 98'380 specimens were analyzed (48'158 in 2017 vs. 50'222 in 2019). On the WASPLabTM, all culture plates were imaged at defined intervals each day of incubation, but the processing of the cultures (i.e., pathogen identification and antimicrobial susceptibility testing) was only performed during day shift hours (~8:00 A.M. to 4:30 P.M.). The median TAT for negative reports decreased by almost half for urine samples from 52.1 (2017) to 28.3 h (2019) (p < 0.001), and for MRSA screening specimens from 50.7 to 26.3 h (p < 0.001). The difference in median TAT for negative reports was less pronounced for screening of ESBL (50.2 vs. 43.0 h) (p < 0.001) and VRE (50.6 vs. 45.7 h) (p < 0.001). Despite a trend toward shorter result delivery for positive samples, there was no significant change in the median TAT. These results suggest that TAT for negative samples immediately benefit from automation, whereas TAT for positive samples also depend on the laboratory hours of operation and daily human resource management.

Candida auris, a globally emerging pathogen, has been repeatedly introduced into European healthcare settings, leading to large and long-lasting nosocomial outbreaks. The pathogen has already been isolated in Switzerland, requiring clinicians and microbiologists to become alert. This is the first comprehensive guidance document on prevention and control of C. auris in Swiss acute care hospitals. It brings to light the most recent evidence from published original articles and reviews. We emphasise the importance of quickly identifying this yeast by means of screening in order to prevent an outbreak that could be difficult to contain. Key containment strategies include reinforcing early detection, hand hygiene, application of strict contact precautions for colonised and infected patients, and thorough specific environmental cleaning and disinfection.

Abstract Sepsis is estimated to affect more than 30 million patients with potentially five million deaths every year worldwide. Prevention of sepsis, as well as early recognition, diagnosis and treatment, can’t be overlooked to mitigate this global public health threat. World Health Organization (WHO) promotes hand hygiene in health care through its annual global campaign, SAVE LIVES: Clean Your Hands campaign on 5 May every year. The 2018 campaign targets sepsis with the overall theme “It’s in your hands; prevent sepsis in health care”.