Factors associated with non-carbapenemase mediated carbapenem resistance of Gram-negative bacteria: a retrospective case-control study.

Infections with carbapenemase-producing Gram-negative bacteria are related to increased morbidity and mortality, yet little is known regarding infections caused by non-beta-lactamase mediated carbapenem-resistant bacteria. Our objective was to identify risk factors for, and the clinical impact of infections caused by carbapenem-resistant carbapenemase-negative Enterobacterales and Pseudomonas aeruginosa. This retrospective matched case-control study was performed at the University Hospital of Basel, Switzerland, in 2016. We focused on other resistance mechanisms by excluding laboratory-confirmed carbapenemase-positive cases. Carbapenem resistance was set as the primary endpoint, and important risk factors were investigated by conditional logistic regression. The clinical impact of carbapenem resistance was estimated using regression models containing the resistance indicator as explanatory factor and adjusting for potential confounders. Seventy-five cases of infections with carbapenem-resistant, carbapenemase-negative bacteria were identified and matched with 75 controls with carbapenem-susceptible infections. The matched data set was well-balanced regarding age, gender, and comorbidity. Duration of prior carbapenem treatment (OR 1.15, [1.01, 1.31]) correlated with resistance to carbapenems. Our study showed that patients with carbapenem-resistant bacteria stayed 1.59 times (CI [0.81, 3.14]) longer in an ICU. The analyzed dataset did not provide evidence for strong clinical implications of resistance to carbapenems or increased mortality. The duration of prior carbapenem treatment seems to be a strong risk factor for the development of carbapenem resistance. The higher risk for a longer ICU stay could be a consequence of a carbapenem resistance. In contrast to carbapenemase-producers, the clinical impact of carbapenamase-negative, carbapenem-resistant strains may be limited. Trial registration: The study design was prospectively approved by the local Ethics Commission on 10.08.2017 (EKNZ BASEC 2017-00222).

Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections.

PURPOSE: Cefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates. METHODS: This retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020. Primary outcomes included in-hospital death, renal impairment and neurologic adverse events; secondary outcomes included length of hospital stay and recurrent infection. RESULTS: Two hundred and seventy episodes of AmpC-PE BSI were included, 162, 77 and 31 were treated with a carbapenem, cefepime and other antibiotics, respectively. Patients treated with carbapenems were more likely to be transferred to the ICU on admission and more frequently had central venous catheter as a source of infection. In uni- and multivariable analyses, primary and secondary outcomes did not differ between the two treatment groups, except for more frequent occurrence of neurological adverse events among patients treated with carbapenems and shorter length of hospital stay among survivors treated with cefepime. CONCLUSION: After excluding isolates with phenotypic ESBL-co-production, cefepime was not associated with adverse outcomes compared to carbapenems when used to treat BSIs caused by AmpC-PE. Our study provides evidence to support the use of cefepime as a safe treatment strategy for AmpC-PE BSI, particularly in clinically stable patients without initial renal impairment or increased susceptibility to neurological adverse events.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection.

BACKGROUND: Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline. OBJECTIVE: The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej . CONCLUSION: This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders. Guideline registration number PREPARE-2023CN045.

Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019.

There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616.

Air temperature and incidence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

BACKGROUND: Higher outdoor temperature may be related to an increase in antibiotic resistant bacteria. We investigated the association between local outdoor air temperature and the incidence of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) correcting for known drivers of antibiotic resistance. METHODS: We performed a time-series regression study using prospectively collected weekly surveillance data on all ESBL-PE isolated from in- and outpatients of the University Hospital Basel, a tertiary care center in Switzerland, between 01/2008-12/2017. Temperature was measured hourly at the meteorological institute of the University Basel next to our institution over this time period. A time-series approach using a Poisson regression model and different lag terms for delayed exposure effects was performed to assess associations between minimal, mean and maximal weekly temperature and the number of ESBL-PE recovered. RESULTS: Over 10 years, recovery of ESBL-PE increased (annual incidence rate ratio [IRR] 1.14, 95%CI 1.13-1.16), while mean weekly temperature measures remained stable. In multivariable analyses, increasing temperature was associated with higher recovery rates of ESBL-PE after three to four weeks, correcting for potential confounders, such as the number of admissions, proportion of long-term nursing facility- and ICU-admissions, age, Charlson comorbidity index and consumption of antimicrobials (IRRs per 10 °C ranging from 1.14 to 1.22, 95%CIs 1.07-1.33). These trends remained when analyzing correlations between temperature with the proportion of extended spectrum cephalosporin resistance of all recovered Enterobacteriaceae. CONCLUSIONS: Higher outdoor temperature may be associated with an increase of ESBL-PE-incidence, independent of important confounders, such as antimicrobial consumption and thus should be considered for future resistance-trajectories.

Infections in Patients Colonized With Extended-spectrum Beta-Lactamase-Producing Enterobacterales: A Retrospective Cohort Study.

We investigated relative proportions of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) versus non-ESBL-PE (nESBL-PE) infections in ESBL-PE colonized patients. ESBL-PE are not causative for the majority of infections in hospitalized patients colonized with ESBL-PE. Site of infection and patient-level exposures may be useful predictors of nESBL-PE infections, potentially guiding empiric treatment recommendations.

Identification of a Cluster of Extended-spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Sequence Type 101 Isolated From Food and Humans.

We report a cluster of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sequence type 101, derived from 1 poultry and 2 clinical samples collected within the setting of a prospective study designed to determine the diversity and migration of ESBL-producing Enterobacterales between humans, foodstuffs, and wastewater.

Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients with and without Laboratory-Confirmed SARS-CoV-2 Infection.

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.

Accuracy of urine flow cytometry and urine test strip in predicting relevant bacteriuria in different patient populations.

BACKGROUND: Urinary tract infection (UTI) is diagnosed combining urinary symptoms with demonstration of urine culture growth above a given threshold. Our aim was to compare the diagnostic accuracy of Urine Flow Cytometry (UFC) with urine test strip in predicting bacterial growth and in identifying contaminated urine samples, and to derive an algorithm to identify relevant bacterial growth for clinical use. METHODS: Species identification and colony-forming unit (CFU/ml) quantification from bacterial cultures were matched to corresponding cellular (leucocytes/epithelial cells) and bacteria counts per µl. Results comprise samples analysed between 2013 and 2015 for which urine culture (reference standard) and UFC and urine test strip data (index tests, Sysmex UX-2000) were available. RESULTS: 47,572 urine samples of 26,256 patients were analysed. Bacteria counts used to predict bacterial growth of ≥105 CFU/ml showed an accuracy with an area under the receiver operating characteristic curve of > 93% compared to 82% using leukocyte counts. The relevant bacteriuria rule-out cut-off of 50 bacteria/µl reached a negative predictive value of 98, 91 and 89% and the rule-in cut-off of 250 bacteria/µl identified relevant bacteriuria with an overall positive predictive value of 67, 72 and 73% for microbiologically defined bacteriuria thresholds of 105, 104 or 103 CFU/ml, respectively. Measured epithelial cell counts by UFC could not identify contaminated urine. CONCLUSIONS: Prediction of a relevant bacterial growth by bacteria counts was most accurate and was a better predictor than leucocyte counts independently of the source of the urine and the medical specialty ordering the test (medical, surgical or others).

Delirium in Meningitis and Encephalitis: Emergence and Prediction in a 6-Year Cohort.

BACKGROUND/OBJECTIVE: Data regarding delirium in patients presenting with infections of the central nervous system, such as meningitis and/or encephalitis (ME), are scarce. We aimed to determine the frequency and early predictors of delirium in the acute phase of ME. METHODS: We assessed clinical, radiologic, and laboratory data of patients with ME at a Swiss academic medical center from 2011 to 2017. The highest Intensive Care Delirium Screening Checklist (ICDSC) score was assessed within 24 hours around lumbar puncture. Multivariable logistic regression was performed to identify predictors of delirium (ICDSC ≥4). RESULTS: Among 330 patients with ME, infectious pathogens were identified in 41%. An ICDSC >1 was found in 28% with and 19% without identified infectious pathogens. Delirium was diagnosed in 18% with and 14% without infectious pathogens and significantly associated with prolonged in-hospital treatment and mechanical ventilation, more frequent administration of neuroleptics and anesthetics (in 96% with delirium vs 35% without), complications, and less recovery to premorbid functional baseline. Low serum albumin at presentation was the only independent predictor of delirium (area under the receiver-operating curve [AUROC] = 0.792) in patients with pathogens. In patients with infections, the AUROC was smallest for encephalitis (AUROC = 0.641) and larger for patients with meningeal infections (meningitis AUROC = 0.807; meningoencephalitis AUROC = 0.896). CONCLUSIONS: Delirium in the context of ME is seen in almost every fifth patient and linked to prolonged treatment, complications, and incomplete recovery. Among clinical, radiologic, and laboratory parameters, the good calibration and discrimination of low albumin serum concentrations for the prediction of delirium in patients with ME seem promising, especially if meninges are affected.

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs. METHODS: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2. RESULTS: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%). CONCLUSIONS: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland.

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.

What is new with hand hygiene?

PURPOSE OF REVIEW: Healthcare-associated infections (HAIs) challenge healthcare systems worldwide. As healthcare workers' hands are considered the main vector for transmission of pathogens, effective hand hygiene is the single most important action to prevent HAIs. We sought to highlight new developments and advances in hand hygiene. RECENT FINDINGS: Hand hygiene compliance averages at 38%. A sustained increase of compliance with a subsequent decrease of HAIs may be achieved by national, systematic and rigorous education, and auditing programs. Periodically deployed self-operating hand hygiene surveillance systems coupled with personalized reminders could facilitate such efforts. Alcohol-based hand-rub (ABHR) solutions remain the hand hygiene gold standard, but are modified in texture and composition to better meet healthcare workers' preferences. Modifications of the hand hygiene procedure have been proposed targeting both time and technique of hand rub application. Reducing rub-time from 30 to 15 s and simplifying the technique to consist of three rather than six steps yielded encouraging results in terms of microbiological efficacy and higher compliance. SUMMARY: Implementation and promotion of compliance are the major concerns of today's research on hand hygiene. Developments towards better surveillance and systematic education, improved ABHR formulation and streamlining of hand hygiene actions are paving the way ahead.

Diagnostic and therapy of severe Clostridioides difficile infections in the ICU.

PURPOSE OF REVIEW: The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU. RECENT FINDINGS: In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications. SUMMARY: Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.

Predictors of infectious meningitis or encephalitis: the yield of cerebrospinal fluid in a cross-sectional study.

BACKGROUND: Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis. METHODS: Consecutive patients with meningitis and/or encephalitis form 2011-17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome. For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7-0.8 was defined as "good", 08-0.9 as "excellent", and > 0.9 as "outstanding". Calibration was defined as "good" if the goodness of fit tests revealed insignificant p-values. RESULTS: Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens were Streptococcus pneumoniae, Varicella zoster, and Herpes simplex 1&2. While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration. CONCLUSIONS: Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio are is the most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03856528. Registered on February 26th 2019.

Independent, external validation of clinical prediction rules for the identification of extended-spectrum ß-lactamase-producing Enterobacterales, University Hospital Basel, Switzerland, January 2010 to December 2016.

BackgroundAlgorithms for predicting infection with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) on hospital admission or in patients with bacteraemia have been proposed, aiming to optimise empiric treatment decisions.AimWe sought to confirm external validity and transferability of two published prediction models as well as their integral components.MethodsWe performed a retrospective case-control study at University Hospital Basel, Switzerland. Consecutive patients with ESBL-producing Escherichia coli or Klebsiella pneumoniae isolated from blood samples between 1 January 2010 and 31 December 2016 were included. For each case, three non-ESBL-producing controls matching for date of detection and bacterial species were identified. The main outcome measure was the ability to accurately predict infection with ESBL-PE by measures of discrimination and calibration.ResultsOverall, 376 patients (94 patients, 282 controls) were analysed. Performance measures for prediction of ESBL-PE infection of both prediction models indicate adequate measures of calibration, but poor discrimination (area under receiver-operating curve: 0.627 and 0.651). History of ESBL-PE colonisation or infection was the single most predictive independent risk factor for ESBL-PE infection with high specificity (97%), low sensitivity (34%) and balanced positive and negative predictive values (80% and 82%).ConclusionsApplying published prediction models to institutions these were not derived from, may result in substantial misclassification of patients considered as being at risk, potentially leading to wrong allocation of antibiotic treatment, negatively affecting patient outcomes and overall resistance rates in the long term. Future prediction models need to address differences in local epidemiology by allowing for customisation according to different settings.