Evaluation of models for prognosing mortality in critical care patients with COVID-19: First- and second-wave data from a German university hospital.

BACKGROUND: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave. METHODS: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave. RESULTS: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy.

Antimicrobial coatings for environmental surfaces in hospitals: a potential new pillar for prevention strategies in hygiene.

Recent reports provide evidence that contaminated healthcare environments represent major sources for the acquisition and transmission of pathogens. Antimicrobial coatings (AMC) may permanently and autonomously reduce the contamination of such environmental surfaces complementing standard hygiene procedures. This review provides an overview of the current status of AMC and the demands to enable a rational application of AMC in health care settings. Firstly, a suitable laboratory test norm is required that adequately quantifies the efficacy of AMC. In particular, the frequently used wet testing (e.g. ISO 22196) must be replaced by testing under realistic, dry surface conditions. Secondly, field studies should be mandatory to provide evidence for antimicrobial efficacy under real-life conditions. The antimicrobial efficacy should be correlated to the rate of nosocomial transmission at least. Thirdly, the respective AMC technology should not add additional bacterial resistance development induced by the biocidal agents and co- or cross-resistance with antibiotic substances. Lastly, the biocidal substances used in AMC should be safe for humans and the environment. These measures should help to achieve a broader acceptance for AMC in healthcare settings and beyond. Technologies like the photodynamic approach already fulfil most of these AMC requirements.

Characterisation and Molecular Analysis of an Unusual Chimeric Methicillin Resistant Staphylococcus Aureus Strain and its Bacteriophages.

In the context of microarray-based epidemiological typing of the clonal organism Staphylococcus aureus/MRSA, a strain was identified that did not belong to known clonal complexes. The molecular analysis by microarray-based typing yielded signals suggesting that it was a mosaic or hybrid strain of two lineages. To verify this result, the isolate was sequenced with both, short-read Illumina and long-read Nanopore technologies and analysed in detail. This supported the hypothesis that the genome of this strain, ST6610-MRSA-IVg comprised of segments originating from two different clonal complexes (CC). While the backbone of the strain's genome, i.e., roughly 2 megabases, belongs to CC8, a continuous insert of 894 kb (approx. 30% of the genome) originated from CC140. Beside core genomic markers in the normal succession and orientation, this insert also included the mecA gene, coding for PbP2a and causing methicillin resistance, localised on an SCCmec IVg element. This particular SCCmec type was also previously observed in CC140 MRSA from African countries. A second conspicuous observation was the presence of the trimethoprim resistance gene dfrG within on a prophage that occupied an attachment site normally used by Panton-Valentine Leucocidin phages. This observation could indicate a role of large-scale chromosomal recombination in the evolution of S. aureus as well as a role of phages in the dissemination of antibiotic resistance genes.

Lower blood pH as a strong prognostic factor for fatal outcomes in critically ill COVID-19 patients at an intensive care unit: A multivariable analysis.

BACKGROUND: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant. METHODS: In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality. RESULTS: Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course.

Impact of the implementation of a standard for preanalytical handling of samples for microbiological diagnostics on the quality of results at a neurocritical care unit.

ABSTRACT: Antibiotic stewardship (ABS) programs intend to improve outcomes of nosocomial infections and to counteract the emergence of further antimicrobial resistances. At the anesthesiologic-neurosurgical intensive care unit (ICU) of the University Medical Center Regensburg (Germany) we implemented a standard operating procedure (SOP) with clear instructions for the preanalytical handling and storage of microbiological samples. We intended to find out whether the instructions given in the SOP led to a higher rate of ideal material being sent to the laboratory and to overall better quality of the received results.We retraced retrospectively all samples taken in cases of suspected pneumonia, urinary tract infection, bloodstream infection, catheter infection associated with a central venous or arterial catheter and ventriculitis due to external ventricular drainage as well as all smears taken for the screening for multi-resistant bacteria within a time period of 1 year before to 1 year after the implementation of the SOP.In the case of suspected pneumonia and urinary tract infection, large amounts of ideal material were sent to the microbiological laboratory. A remarkable improvement after the implementation of the SOP, however, could only be observed regarding the number of urine samples taken from older urinary catheters, which was significantly lower in the "SOP group". Samples for microbiological diagnostics were taken much more often in the daytime, although storage of the probes did not lead to worse results.Concrete instructions enable adequate preanalytical handling of microbiological probes. However, we could not recognize substantial improvements probably due to a preexisting high process quality on the ICU. Microbiological diagnostics during the night shift has to be improved.

Determining amplitude and tilt of a lateral force microscopy sensor.

In lateral force microscopy (LFM), implemented as frequency-modulation atomic force microscopy, the tip oscillates parallel to the surface. Existing amplitude calibration methods are not applicable for mechanically excited LFM sensors at low temperature. Moreover, a slight angular offset of the oscillation direction (tilt) has a significant influence on the acquired data. To determine the amplitude and tilt we make use of the scanning tunneling microscopy (STM) channel and acquire data without and with oscillation of the tip above a local surface feature. We use a full two-dimensional current map of the STM data without oscillation to simulate data for a given amplitude and tilt. Finally, the amplitude and tilt are determined by fitting the simulation output to the data with oscillation.

[Hygiene in ENT examination: Fluorescence study with overview of current recommendations]. / Hygiene bei der HNO-Untersuchung: Fluoreszenzstudie mit Übersicht der aktuellen Empfehlungen.

Increasing normative demands on patient safety and quality assurance measures, but also the problem of multi-resistant germs and pathogens with a high potential for infection, increase the need for hygienically correct work.In this study, hygienically relevant potential sources of contamination in ENT examinations were to be identified and possible improvement strategies examined.A complete ENT examination was performed by 5 examiners with different professional experience, whose gloves were wetted with fluorescent lotion prior to the examination. Contaminations especially on the examination unit and on the instruments were identified. The potential risk of transmission of pathogens to subsequent patients was assessed using a specially developed score. Various strategies to reduce identified contamination possibilities were developed and thought through.The score of the investigators was very high with an average of 87.4 points (±3.6). The implementation of individual hygiene measures during the examination process would lead to a significant reduction of the score and thus to an improvement in hygiene: No shaking of hands (81.8), additional disinfection of patient's chair (79.8), disinfection of important surfaces (69.8), provision of standard instruments (60.2) or all instruments (32.2), disinfection of all relevant surfaces and provision of all instruments (7.4).The results show very clearly that an ENT examination is a complex procedure from the point of view of hygiene. For reliable protection against possible transmission events, a structured bundling of hygiene measures is therefore necessary.

Utilizing behavioral theories to explain hospital visitors' observed hand hygiene behavior.

BACKGROUND: Hand hygiene is essential for infection prevention. This study aimed to find a suitable theoretical model and identify critical facilitators and barriers to explain hospital visitors' hand hygiene practice. METHODS: Visitors in 4 hospitals were observed and asked to give explanations for using or not using the hand rub dispenser. The written explanations of N = 838 participants were coded according to three theoretical models: Theory of Planned Behavior, Health Action Process Approach (HAPA), and Theoretical Domains Framework (TDF). RESULTS: Self-reported hand hygiene behavior differed from observed behavior, with 15.75% wrongly claiming to have cleaned their hands. Critical facilitators for hand hygiene were attitude toward the behavior,subjective norm, outcome expectancies, risk perception, planning, action control, knowledge and skills, motivation and goals, and social influences. Key barriers included perceived behavioral control; barriers and resources; memory, attention, and decision processes; and environmental context and resources. CONCLUSIONS: Visitors' self-reported hand hygiene behavior is over-reported. Both HAPA and TDF were identified as suitable theoretical models for explaining visitor's hand hygiene practice. Future behavior change interventions should focus on (1) visibility and accessibility of cleaning products; (2) informing laypeople about their role regarding infection prevention; and (3) leveraging social influence processes.

[SARS-CoV-2/COVID-19-epidemiology and prevention]. / SARS-CoV-2/COVID-19 ­ Epidemiologie und Prävention.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally since December 2019. A first wave is visible up to the end of June 2020 in many regions. This article presents a review of the current knowledge on the epidemiology and prevention. The SARS-CoV­2 predominantly replicates in the upper and lower respiratory tracts and is particularly transmitted by droplets and aerosols. The estimate for the basic reproduction number (R0) is between 2 and 3 and the median incubation period is 6 days (range 2-14 days). As with the related SARS-CoV and Middle East respiratory syndrome (MERS-CoV), superspreading events play an important role in the dissemination. A high proportion of infections are uncomplicated but moderate or severe courses develop in 5-10% of infected persons. Pneumonia, cardiac involvement and thromboembolisms are the most frequent manifestations leading to hospitalization. Risk factors for a complicated course are high age, hypertension, diabetes mellitus and chronic cardiovascular and pulmonary diseases as well as immunodeficiency. Currently, the estimation for the infection fatality rate (IFR) is between 0.5% and 1% across all age groups. Outbreaks were limited in many regions with bundles of various measures for reduction of social contacts. The incidence for the first wave in Germany can be estimated as 0.4-1.8% and excess mortality could not be observed.

Epidemiology of SARS-CoV-2.

PURPOSE: SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features. METHODS: Non-systematic review. RESULTS: SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R0) is between 2 and 3, and the median incubation period is 5.7 (range 2-14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5-10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection's fatality rate is 0.5-1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries. CONCLUSIONS: Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

Diphtheria Outbreak in Amerindian Communities, Wonken, Venezuela, 2016-2017.

In February 2017, a diphtheria outbreak occurred among Amerindians of the Pemón ethnic group in Wonken, Venezuela. A field investigation revealed ≈10 cases; clinical presentation did not include cutaneous or neurologic signs or symptoms. To prevent future outbreaks in Venezuela, Amerindian communities need better access to vaccination and healthcare.

Antibiotic resistance in E. coli isolates from patients with urinary tract infections presenting to the emergency department.

PURPOSE: Escherichia coli urine isolates from patients presenting to the emergency department at a German tertiary care hospital were retrospectively analyzed from January 2015-March 2017 to determine antibiotic resistance patterns and patient risk factors for resistance. METHODS: Uncomplicated urinary tract infection (UTI) was defined as UTI in the otherwise healthy patient without relevant co-morbidities and complications. Patients were assumed to have UTI if diagnosis was made by the attending physician with conclusive dipstick results. For subgroup analysis, only patients with symptoms suggestive for UTI documented in their records were included. RESULTS: 228 patients with a UTI diagnosed by the attending physician with E. coli isolated in urine culture were included. 154/228 patients had documented symptomatic UTI, 57/154 had uncomplicated infection, 76/154 patients had cystitis, and 124/154 were female. Resistance rates of uncomplicated UTI in symptomatic patients were: ciprofloxacin 10.5%, cotrimoxazole 15.8%, amoxicillin/clavulanic acid 5.3%, nitrofurantoin 0% (CLSI MICs). Previous hospitalization in the last 3 months (including patients living in a long-term care facility) was significantly correlated with resistance to ciprofloxacin, cotrimoxazole and amoxicillin/clav. Previous hospitalization was a strong predictor of resistance to ciprofloxacin and cotrimoxazole in multivariate analysis also. Other risk factors correlated with resistance were hematological malignancy (for cotrimoxazole) and renal transplantation (for ciprofloxacin). CONCLUSIONS: Cotrimoxazole is still an alternative for treating uncomplicated cystitis. Previous hospitalization in the last 3 months was a strong predictor of resistance to cotrimoxazole and ciprofloxacin. Other risk factors which might help guide empirical therapy are hematological malignancy and renal transplantation.

UPLC-MS/MS method for therapeutic drug monitoring of 10 antibiotics used in intensive care units.

A large variation in the levels of different ß-lactams and other antibiotics used in critically ill patients has been documented. The aim of this study is to establish and validate a fast, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous analysis of ten antibiotics (Meropenem, Cefepime, Ceftazidime, Piperacillin, Benzylpenicillin, Ampicillin, Flucloxacillin, Linezolid, and Sulfamethoxazole/Trimethoprim) in human plasma according to European Medicines Agency (EMA) guidelines. Protein precipitation with ice-cold methanol containing 9 isotopically labeled internal standards was used for sample clean up. Antibiotics were detected, following a 4-minute gradient separation, in multiple reactions monitoring (MRM) using API 4000 instrument equipped with electrospray source operating in positive ion mode. The lower limit of quantification was 0.1 mg/L for Meropenem, Ceftazidime, Piperacillin, Ampicillin, Flucloxacillin, and Sulfamethoxazole; 0.05 mg/L for Cefepime, Benzylpenicillin, and Trimethoprim; and 0.02 mg/L for Linezolid. The method proved to be precise and accurate and applicable for therapeutic drug monitoring and other pharmacokinetic studies.

Screening of ESBL-producing Enterobacteriacae concomitant with low degree of transmission in intensive care and bone marrow transplant units.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are spreading worldwide in both hospital and community settings. In this study, the molecular epidemiology and the transmission modalities of ESBL-E in intensive care- and bone marrow transplant were investigated. METHODS: All patients included in this study were screened for presence of ESBL-E on admission and weekly. Relevant ß-lactamase genes were identified by PCR and sequencing. RESULTS: A total of 669 patients were included in this study. On admission, ESBL-producing Escherichia coli were detected in 49 (7.3%) patients and ESBL-producing Klebsiella pneumoniae in one patient. The most common ESBL types among E. coli isolates were CTX-M-15 (38.8%) and CTX-M-1 (38.8%). Furthermore, 12 of 49 (24.5%) ESBL-producing E. coli could be assigned to the epidemic clone ST131. A single patient acquired ESBL-producing E. coli during the hospital stay but cross-transmission could not be demonstrated. Among 1095 environmental samples none revealed ESBL. CONCLUSIONS: Our results suggest that early detection of ESBL-producing Enterobacteriaceae and consequent implementation of basic hygiene measures and contact isolation may reduce the transmission rate during the hospital stay.

Multicentre investigation of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in German hospitals.

Aim of this study was to determine the incidence and molecular epidemiology of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Germany. E. coli and K. pneumoniae isolates from clinical samples which were non-susceptible to carbapenems were collected in laboratories serving 20 hospitals throughout Germany from November 2013 to April 2014. The isolates were tested for the presence of carbapenemases by PCR and phenotypic methods and typed by multilocus sequence typing. Risk factors including a previous hospitalization abroad were analysed. Carbapenemases were detected in 24 isolates from 22 patients out of 464,514 admissions. Carbapenemases included OXA-48 (n=14), KPC-2 (n=8) and NDM-1 (n=2). Except for two K. pneumoniae isolates with ST101, all OXA-48 producing strains belonged to different clones. In contrast, half of KPC-2 producing K. pneumoniae were of ST258 and both NDM-1 producing strains were of ST11. Compared to carbapenem-susceptible controls, patients with carbapenemase-producing strains differed by a significantly higher proportion of males, a higher proportion of isolates from wound samples and a more frequent previous stay abroad in univariate analysis. This multicentre study demonstrated an incidence of carbapenemase-producing E. coli and K. pneumoniae from clinical samples in Germany of 0.047 cases per 1000 admissions. OXA-48 was more frequent than KPC-2 and NDM-1 and showed a multiclonal background.

Risk of infection due to medical interventions via central venous catheters or implantable venous access port systems at the middle port of a three-way cock: luer lock cap vs. luer access split septum system (Q-Syte).

BACKGROUND: Many cancer patients receive a central venous catheter or port system prior to therapy to assure correct drug administration. Even appropriate hygienic intervention maintenance carries the risk of contaminating the middle port (C-port) of a three-way cock (TWC), a risk that increases with the number of medical interventions. Because of the complexity of the cleaning procedure with disconnection and reconnection of the standard luer lock cap (referred as "intervention"), we compared luer lock caps with a "closed access system" consisting of a luer access split septum system with regard to process optimization (work simplification, process time), efficiency (costs) and hygiene (patient safety). METHODS: For determination of process optimization the workflow of an intervention according to the usual practice and risks was depicted in a process diagram. For determining the actual process costs, we analyzed use of material and time parameters per intervention and used the process parameters for programming the process into a simulation run (n = 1000) to determine the process costs as well as their differences (ACTUAL vs. NOMINAL) within the framework of a discrete event simulation.Additionally cultures were carried out at the TWC C-ports to evaluate possible contamination. RESULTS: With the closed access system, the mean working time of 5.5 minutes could be reduced to 2.97 minutes. The results for average process costs (labour and material costs per use) were 3.92 € for luer lock caps and 2.55 € for the closed access system. The hypothesis test (2-sample t-test, CI 0.95, p-value<0.05) confirmed the significance of the result.In 50 reviewed samples (TWC's), the contamination rate for the luer lock cap was 8% (4 out of 50 samples were positive), the contamination rate of the 50 samples with the closed access system was 0%.Possible hygienic risks (related to material, surroundings, staff handling) could be reduced by 65.38%. CONCLUSIONS: In the present research, the closed access system with a divided split septum was superior to conventional luer lock caps. The advantage of the closed access system lies in the simplified handling for staff, which results in a reduced risk of patient infection due to improved clinical hygiene.

Cerebellar cysticercosis caused by larval Taenia crassiceps tapeworm in immunocompetent woman, Germany.

Human cysticercosis caused by Taenia crassiceps tapeworm larvae involves the muscles and subcutis mostly in immunocompromised patients and the eye in immunocompetent persons. We report a successfully treated cerebellar infection in an immunocompetent woman. We developed serologic tests, and the parasite was identified by histologic examination and 12s rDNA PCR and sequencing.

Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment.

AIM: Cold atmospheric plasma (CAP) has already proven efficient at disinfection of microorganisms including biofilms. The objective of the present study is to assess the efficacy of CAP against the dermatophytes Trichophyton rubrum and Microsporum canis in vitro. MATERIALS & METHODS: T. rubrum and M. canis were exposed to CAP for different treatment times and time intervals in vitro. Treatment with ciclopirox olamine or UVC radiation (0.120 J/cm(2)) served as controls. CAP was generated by the surface microdischarge technology. Fungal colony growth was measured upon CAP treatment. RESULTS: Repeated daily CAP treatments of 10 min demonstrated an inhibition of growth during the treatment period of 9 days. Single CAP treatment sessions for 5, 8 and 10 min, as well as treatments for 5 or 8 min daily, resulted in less fungal growth inhibition. UVC radiation treatment failed, but not ciclopirox olamine. CONCLUSION: CAP shows promising potential for future application in the treatment of dermatophyte infections.