Population pharmacokinetics of flucloxacillin as intermittent bolus infusion in patients with Staphylococcus aureus bloodstream infection.

BACKGROUND: Optimal antibiotic dosing for Staphylococcus aureus bloodstream infections (BSI) is still controversial. One reason is inter-individual variation in pharmacokinetics, which may be influenced by various patient-related factors, particularly in critically ill patients. OBJECTIVES: To describe the population pharmacokinetics (PopPK) of the antibiotic flucloxacillin in patients with S. aureus BSI. Subsequently, we sought to translate the model into a user-friendly app for generating a priori and a posteriori time-concentration curves and dose recommendations to optimize dosing regimens. METHODS: Total and unbound flucloxacillin concentrations were included from 49 patients from a prospective cohort study conducted during clinical routine, including non-critically ill and critically ill individuals who received intermittent bolus applications. These data were analysed using non-linear mixed-effects modelling. RESULTS: Most patients (98%) were treated with 2 g of flucloxacillin every 4 h. We developed a joint model that simultaneously described total and unbound concentrations. The model included an allometric effect of glomerular filtration rate on clearance and albumin on the albumin dissociation constant. The latter was especially important, as in our population the unbound fraction was higher at 11.5% (16.7% for critically ill patients) compared with reported values of approximately 5%. Based on our joint model, we developed a web-based app for optimizing dosing regimens of flucloxacillin. CONCLUSIONS: By utilizing data from clinical routine, we were able to create a predictive PopPK model of flucloxacillin and identify influential covariates. The web-based app is currently being validated in a clinical trial.

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.

Prevention of Hepatitis B Reactivation in Patients Receiving Immunosuppressive Therapy: a Case Series and Appraisal of Society Guidelines.

Hepatitis B (HBV) reactivation (HBVr) is a potentially fatal complication in patients with past HBV exposure receiving immunosuppressive therapy. HBVr can occur in patients with chronic HBV infection as well as in patients with resolved HBV infection. In this article, we present the cases of four patients with resolved hepatitis B who presented with HBVr during or after immunosuppressive treatment, of whom two died as a consequence of HBVr. We then reflect on and summarize the recommendations of four major societies for the screening and management of previously HBV-exposed patients planned to receive immunosuppressive treatment. Current guidelines recommend screening for HBV in all patients planned to receive immunosuppressive therapy. Risk of HBVr is assessed based on the serological status of the patient and the planned immunosuppressive drug regimen. For patients considered to be at low risk of HBVr, management consists of serological monitoring for HBVr and immediate preemptive antiviral therapy in the case of HBVr. For patients considered to be at intermediate or high risk for HBVr, antiviral prophylaxis should be initiated concordantly with the immunosuppressive therapy and continued for up to 18 months after cessation of the immunosuppressive regimen. Areas of uncertainty include the risk of novel and emerging immunosuppressive and immune modulatory drugs and the exact duration of antiviral prophylaxis. Greater awareness is needed among clinicians regarding the risk of HBVr in patients receiving immunosuppressive therapy, especially in low-endemicity settings. Implementation of screening and management programs and decision support tools based on the presented guidelines may improve the management of these patients.

Appropriateness of inpatient intravenous iron therapy in a Swiss tertiary care hospital.

INTRODUCTION: Intravenous (IV) iron replacement is an established treatment for iron deficiency and is recommended in various medical guidelines, but cheaper oral iron formulations remain first-line therapy in several instances. Data on adherence to current prescription standards are lacking in Switzerland. METHODS: Retrospective single center quality control study evaluating the appropriateness of IV iron replacement in 400 inpatients during 2019 and 2021 at a Swiss tertiary care hospital. Appropriateness of IV iron was assessed by expert chart review according to national and international guidelines. RESULTS: IV iron prescriptions were assessed as inappropriate in 147 (37%) of cases (indication lacking in 13%, oral route preferred in 24%). Inappropriate prescribing was more common (p < .001) in surgical wards (66%) compared to medical units (48%) and the gynecologic ward (19%). Iron studies were lacking in 29% of inappropriate IV administrations. Insufficient replacement dosages were chosen in 38% of patients with appropriate prescription. CONCLUSION: Based on current guidelines, inappropriate in-hospital prescription of IV iron was frequently observed. Considerable differences exist between hospital units, which are consistent with conflicting recommendations of professional societies. We recommend increased attention toward the prescription quality to avoid unnecessary, expensive, and potentially harmful use of IV iron.

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.

Free-living core body temperature monitoring using a wrist-worn sensor after COVID-19 booster vaccination: a pilot study.

Core body temperature (CBT) is a key vital sign and fever is an important indicator of disease. In the past decade, there has been growing interest for vital sign monitoring technology that may be embedded in wearable devices, and the COVID-19 pandemic has highlighted the need for remote patient monitoring systems. While wrist-worn sensors allow continuous assessment of heart rate and oxygen saturation, reliable measurement of CBT at the wrist remains challenging. In this study, CBT was measured continuously in a free-living setting using a novel technology worn at the wrist and compared to reference core body temperature measurements, i.e., CBT values acquired with an ingestible temperature-sensing pill. Fifty individuals who received the COVID-19 booster vaccination were included. The datasets of 33 individuals were used to develop the CBT prediction algorithm, and the algorithm was then validated on the datasets of 17 participants. Mean observation time was 26.4 h and CBT > 38.0 °C occurred in 66% of the participants. CBT predicted by the wrist-worn sensor showed good correlation to the reference CBT (r = 0.72). Bland-Altman statistics showed an average bias of 0.11 °C of CBT predicted by the wrist-worn device compared to reference CBT, and limits of agreement were - 0.67 to + 0.93 °C, which is comparable to the bias and limits of agreement of commonly used tympanic membrane thermometers. The small size of the components needed for this technology would allow its integration into a variety of wearable monitoring systems assessing other vital signs and at the same time allowing maximal freedom of movement to the user.

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

BACKGROUND: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. OBJECTIVE: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. DESIGN: Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). SETTING: 3 Swiss teaching hospitals. PATIENTS: Adult medical patients who were hospitalized. INTERVENTION: Patients were randomly assigned to bedside or outside the room case presentation. MEASUREMENTS: The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. RESULTS: Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001). LIMITATION: Only Swiss hospitals and medical patients were included. CONCLUSION: Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. PRIMARY FUNDING SOURCE: Swiss National Foundation (10531C_ 182422).

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.

Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: a prospective cohort study of unbound plasma and individual MICs.

OBJECTIVES: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the ß-lactam flucloxacillin are scarce. PATIENTS AND METHODS: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively. RESULTS: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01). CONCLUSIONS: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.

Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures.

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively. CONCLUSION: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Next-Generation Digital Biomarkers for Tuberculosis and Antibiotic Stewardship: Perspective on Novel Molecular Digital Biomarkers in Sweat, Saliva, and Exhaled Breath.

The internet of health care things enables a remote connection between health care professionals and patients wearing smart biosensors. Wearable smart devices are potentially affordable, sensitive, specific, user-friendly, rapid, robust, lab-independent, and deliverable to the end user for point-of-care testing. The datasets derived from these devices are known as digital biomarkers. They represent a novel patient-centered approach to collecting longitudinal, context-derived health insights. Adding automated, analytical smartphone applications will enable their use in high-, middle-, and low-income countries. So far, digital biomarkers have been focused primarily on accelerometer data and heart rate due to well-established sensors originating from the consumer market. Novel emerging smart biosensors will detect biomarkers (or compounds) independent of a lab and noninvasively in sweat, saliva, and exhaled breath. These molecular digital biomarkers are a promising novel approach to reduce the burden from 2 major infectious diseases with urgent unmet needs: tuberculosis and infections with multidrug resistant pathogens. Active tuberculosis (aTbc) is one of the deadliest diseases from an infectious agent. However, a simple and reliable test for its detection is still missing. Furthermore, inappropriate antimicrobial use leads to the development of antimicrobial resistance, which is associated with high mortality and health care costs. From this perspective, we discuss the innovative approach of a noninvasive and lab-independent collection of novel biomarkers to detect aTbc, which at the same time may additionally serve as a scalable therapeutic drug monitoring approach for antibiotics. These molecular digital biomarkers are next-generation digital biomarkers and have the potential to shape the future of infectious diseases.

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.

OPAT in Switzerland: single-center experience of a model to treat complicated infections.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) programmes are established in the minority of Swiss hospitals. We aimed to study the OPAT programme at the University Hospital Basel during a 3-year period to evaluate safety and outcome. METHODS: All patients treated in the OPAT programme between 2015 and 2017 were included in the study. Demographic, clinical and OPAT outcome data were extracted from the hospital information system. Differences between treatment periods were analysed and risk factors for readmission and adverse events identified. RESULTS: In total, 462 patients were enrolled from 2015 to 2017. Patient numbers and total treatment days increased by 68% and 116%, respectively. Indications included many complicated infections such as bone and joint (23%) and intravascular infections (13%). Of the identified Gram-negative bacteria, 25% produced extended spectrum beta-lactamases. The percentage of antibiotics administrated with an elastomeric device increased from 11% in 2015 to 29% in 2017, whereas the use of once-daily antimicrobials (such as ceftriaxone) declined. Adverse events were rare (n = 67; 14.6%) including only two severe catheter-related events. Cure was noted in 98% of patients. 30-day unplanned readmission occurred in 46 (10.0%) patients, and intravascular infections and a higher Charlson comorbidity index were identified as independent predictors. CONCLUSION: This study demonstrates the successful implementation of a formal OPAT programme in a Swiss tertiary care hospital. Careful selection of patients and monitoring during treatment are crucial to avoid frequent readmissions. Hence, our data call for an expansion of OPAT services in Switzerland in the near future.

[Hematochezia and right-sided upper abdominal pain after puncture of a liver abscess in a 75-year-old male]. / Hämatochezie und rechtsseitiger Oberbauchschmerz nach Punktion eines Leberabszesses bei einem 75-Jährigen.

This article presents the case of a 75-year-old male patient, who underwent a percutaneous abscess puncture of a liver abscess. A few days after the puncture and drainage there was a sudden onset of right upper quadrant abdominal pain accompanied by hematochezia. The patient presented with markedly elevated liver enzyme levels and a significant drop in hemoglobin concentration. After gastroscopy and abdominal computed tomography (CT) in the portal venous phase no bleeding source could be identified. A false aneurysm of the cystic artery was identified only after a CT angiography of the abdomen. Due to spontaneous cessation of the bleeding a cholecystectomy was subsequently performed for definitive treatment of the false aneurysm.

Zwischen Traum und Trauma - Aufbau und Betrieb einer Kohortenstation für Patient_innen mit COVID-19 in einem Akutspital - Eine Fallstudie.

Between dream and distress - Setting up and running a cohort ward for COVID-19 Patients at an acute hospital - A case study Abstract. Background: In the context of the pandemic, hospitals must be able to care for COVID-19 patients within a very short timeframe. OBJECTIVE: Description of the setting up of a cohort ward for patients with COVID-19 on a surgical ward including the development of the nursing team. METHODS: The intrinsic retrospective case study describes the situation, identifies special phenomena in a reflective manner and links them to existing knowledge. Data were anecdotal, routine data were collected in the context of nursing practice development. RESULTS: Setting up the cohort ward in a Swiss hospital consisted of structural and technical planning, infection control measures, the establishment of interprofessional structures, and internal communication. During the four-week operation, 71 patients were treated. The use of practice development methodology initiated a cultural change. The reflection describes a field of tension between "dream and distress": As a dream, the lived experience of optimal care, with well-functioning processes, sufficient material, sufficient personnel and a very good interprofessional cooperation was evaluated. Distress in the form of high infection rates as well as psychological and physical stress did not occur. After the cohort ward was closed, there was a risk working back in normal operations based on existing economical and organizational conditions, with the knowledge that a different cooperation and organization is possible. CONCLUSIONS: Positive experiences from the "crisis mode" should be used to further develop essential operations during normal times.

Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy.

Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).

Prosthetic valve endocarditis caused by Pseudomonas aeruginosa with variable antibacterial resistance profiles: a diagnostic challenge.

BACKGROUND: Infective endocarditis (IE) caused by gram-negative bacilli is rare. However, the incidence of this severe infection is rising because of the increasing number of persons at risk, such as patients with immunosuppression or with cardiac implantable devices and prosthetic valves. The diagnosis of IE is often difficult, particularly when microorganisms such as Pseudomonas aeruginosa, which rarely cause this infection, are involved. One of the mainstays for the diagnosis of IE are persistently positive blood cultures with the same bacteria, while polymicrobial bacteremia usually points to another cause, e.g. an abscess. The antimicrobial resistance profile of some P. aeruginosa strains may change, falsely suggesting an infection with several strains, thus further increasing the diagnostic difficulties. CASE PRESENTATION: A 66-year old male patient who had a transcatheter aortic valve implantation (TAVI) one year previously developed fever seven days after an elective inguinal hernia repair. During the following four weeks, P. aeruginosa with different antibiotic resistance profiles was repeatedly isolated from blood cultures. Repeated trans-esophageal echocardiograms (TEE) were negative and an infection by different P. aeruginosa strains was suspected. Extensive diagnostic workup for an infectious focus was performed with no results. Finally, an oscillating mass on the aortic valve was detected by TEE five weeks after the initial positive blood cultures. P. aeruginosa endocarditis was confirmed by culture of the surgically removed valve. Whole genome sequencing of the last two P. aeruginosa isolates (valve and blood culture) revealed identical strains, with genome mutations for AmpR, AmpD and OprD. CONCLUSIONS: The diagnosis of prosthetic valve endocarditis is particularly difficult for several reasons. The modified Duke criteria have a lower sensitivity for patients with prosthetic valve endocarditis and the infection may be caused by "unusual" pathogens such as P. aeruginosa. Patients with repeatedly positive blood cultures should make clinicians suspicious for endocarditis even if imaging studies are negative and if isolated pathogens are "unusual". Repeatedly positive blood cultures for P. aeruginosa should be considered as "persistent bacteremia" (suspicious for IE) even in the presence of different antibiotic susceptibility patterns, since P. aeruginosa might rapidly activate or deactivate resistance mechanisms depending on antibiotic exposition.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

OBJECTIVE: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. STUDY SELECTION: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. DATA SOURCES: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. DATA EXTRACTION: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. DATA SYNTHESIS: Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). CONCLUSIONS: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.