Acute grade IV toxic hepatitis due to the e-cigarette.

A 46-year-old woman presented at the emergency department because of acute hepatitis with jaundice. After hepatological work-up including liver biopsy, drug induced liver disease (DILI) was suspected. Patient recovered completely within a few months. One year later she presented again with jaundice due to acute hepatitis. Vaping was the only agent that could be identified as causative agent for DILI. After VAPING cessation, the hepatitis resolved completely. Calculated RUCAM score was 10, making the diagnosis of toxic hepatitis very likely. During follow-up liver tests remained normal. This is the first report of severe DILI secondary to the use of e-cigarettes. In future vaping can be included in the differential diagnosis of DILI.

Human brain mapping using co-registered fUS, fMRI and ESM during awake brain surgeries: A proof-of-concept study.

Accurate, depth-resolved functional imaging is key in both understanding and treatment of the human brain. A new sonography-based imaging technique named functional Ultrasound (fUS) uniquely combines high sensitivity with submillimeter-subsecond spatiotemporal resolution available in large fields-of-view. In this proof-of-concept study we show that: (A) fUS reveals the same eloquent regions as found by fMRI while concomitantly visualizing in-vivo microvascular morphology underlying these functional hemodynamics and (B) fUS-based functional maps are confirmed by Electrocortical Stimulation Mapping (ESM), the current gold-standard in awake neurosurgical practice. This unique cross-modality experiment was performed using motor, visual and language-related functional tasks in patients undergoing awake brain tumor resection. The current work serves as an important milestone towards further maturity of fUS as well as a novel avenue to increase our understanding of hemodynamics-based functional brain imaging.

Hyperferritinemia and non-HFE hemochromatosis: differential diagnosis and workup.

Hyperferritinemia is a common reason for referral to a hepatogastroenterologist. The most frequent causes are not associated with iron overload (e.g. inflammatory diseases, alcohol abuse, metabolic syndrome, etc.). However, hyperferritinemia can also be caused by a genetic variant in one of the iron regulatory genes, called hereditary hemochromatosis, often but not always associated with iron overload. A variation in the human Hemostatic Iron Regulator protein (HFE) gene is the most common genotype, but many other variants have been described. In this paper we discuss two cases of rare hyperferritinemia associated disorders, ferroportin disease and hyperferritinemia-cataract syndrome. We also propose an algorithm for evaluating hyperferritinemia, facilitating a correct diagnosis and preventing potentially unnecessary examinations and therapeutic actions.

Characteristics of mpox positive, versus mpox negative, and mpox unsuspected clients from the Centre of Sexual Health, Public Health Service of Amsterdam, 20 May to 15 September 2022.

BACKGROUND: In May 2022, an outbreak of mpox (monkeypox) in men-who-have-sex-with-men (MSM) emerged and quickly affected over 100 countries. In the early stages of the outbreak, overlap in symptoms with sexually transmitted infections (STI) made triage for mpox testing challenging. More information was needed on whom to screen and the main route of transmission. OBJECTIVES: We aimed to identify characteristics of mpox cases to further strengthen case definitions. We also compared Cycle threshold (Ct) values of the DNA positive mpox samples as a proxy for viral load by body location. METHODS: From 20 May 2022 to 15 September 2022, we tested all MSM who presented with malaise, and/or ulcerative lesions, and/or proctitis and/or a papular-vesicular-pustular eruption attending the Centre of Sexual Health in Amsterdam, the Netherlands, for mpox, with a PCR test. In the same period, 6932 MSM mpox unsuspected clients were not tested. We compared those tested positive for mpox with those tested negative and those unsuspected for mpox. RESULTS: Of the 374 MSM tested, 135 (36%) were positive for mpox. The mpox-positive MSM were older (median age, respectively, 36, 34 and 34 years, p = 0.019) and more often lived with HIV (30% vs. 16% and 7%, p < 0.001). Furthermore, mpox-positive patients more often reported receptive anal sex without a condom, sexualized drug use, more sex partners, and were more often diagnosed with bacterial STI (p < 0.001). Systemic symptoms and anogenital lesions were associated with mpox infection. For mpox-positive patients, anal samples (p = 0.009) and lesional samples (p = 0.006) showed significantly lower median mpox Ct values compared to throat samples. CONCLUSIONS: Mpox-positive patients more often reported receptive anal sex without a condom, had more sex partners and more often lived with HIV. Our results suggest that in the current mpox outbreak among MSM, sexual transmission is the main route.

Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

Diagnostic and prognostic scoring systems for autoimmune hepatitis: a review.

INTRODUCTION: Auto-immune hepatitis (AIH) is a rare condition which primarily affects young women. Several diagnostic scoring systems exist based on clinical, biochemical, immunologic and histologic characteristics of AIH. Additionally, prognostic parameters can be identified. The purpose of this literature review is to compare the clinical value, strengths and limitations of these diagnostic and prognostic scoring systems. METHODS: A literature search was performed in two databases and selected based on diagnostic and prognostic criteria. Only studies concerning AIH in adults were included. RESULTS: The backbone of scoring systems remains the revised AIH criteria published in 1999 and the simplified from 2008. The revised system shows a higher sensitivity, lower specificity and lower diagnostic accuracy compared to the simplified. Limitations to these scoring systems include limited diagnostic accuracy in acute or fulminant liver failure, insufficient inclusion of atypical auto-antibodies and lacking diagnostic power in presence of overlap syndromes. Concerning these overlap syndromes, the Paris criteria show a higher diagnostic accuracy compared to the scoring systems for AIH. Presently, no clinical prognostic scoring systems are available. However, a first system based on response to treatment accurately predicts long-term survival in AIH. CONCLUSION: Diagnostic scoring systems are useful in diagnosing AIH and have complementary value. However, they are no substitute for the gold standard of appropriate clinical assessment and are mostly useful in defining cohorts for research purposes. An evolution towards a more dynamic scoring system, using prognostic parameters and the progression of typical features, seems more valuable than the current diagnostic systems.

[Confusion and abdominal pain after COVID-19 vaccination]. / Verwardheid en buikpijn na covid-19-vaccinatie.

BACKGROUND: Vaccine-induced immune thrombotic trombocytopenia (VITT) is a rare phenomenon, that may present with diffuse and atypical symptoms. CASE DESCRIPTION: We present a case of 63 years old female patient with abdominal pain, confusion and tromboctytopenia. CT scan shows sinustrombosis and trombosis of the vena renalis. The diagnosis VITT was confirmed by a positive HIT test. After initiating treatment with immunoglobulines and a non-heparinoid anticoagulans, symptoms improved and platelet count increased. CONCLUSION: This case illustrates that awareness in case of atypical symptoms and a history of vaccination is important to recognize this phenomenon.

Nephrotoxicity of concomitant piperacillin/tazobactam and teicoplanin compared with monotherapy.

OBJECTIVES: Piperacillin/tazobactam combined with vancomycin has been associated with a decline in renal function when compared with monotherapy. Teicoplanin is a glycopeptide similar to vancomycin. We investigated whether piperacillin/tazobactam combined with teicoplanin is associated with a decline in renal function as well. METHODS: We conducted a single-centre retrospective cohort study with data from our electronic health records from 9 August 2013 to 15 November 2019, including all adult patients that received either piperacillin/tazobactam, teicoplanin or piperacillin/tazobactam + teicoplanin. The incidence of acute kidney injury (AKI) at 48-72 h served as the primary outcome, whereas change in serum creatinine served as a secondary outcome. RESULTS: Of the 4202 included patients, 3188 (75.9%) received piperacillin/tazobactam, 791 (18.8%) received teicoplanin and 223 (5.3%) received piperacillin/tazobactam + teicoplanin. The incidence of AKI at 48-72 h after commencement of antibiotic therapy was 5.4% for piperacillin/tazobactam, 3.4% for teicoplanin and 11.7% for piperacillin/tazobactam + teicoplanin (P < 0.001). However, mean serum creatinine at 48-72 h was slightly higher in the piperacillin/tazobactam + teicoplanin group therapy compared with baseline [+1.61% (95% CI -2.25 to 5.70)], indicating a slight decrease in renal function, and decreased for piperacillin/tazobactam [-1.98% (95% CI -2.73 to -1.22)] and teicoplanin [-8.01% (95% CI -9.54 to -6.45)]. After correcting for significant confounders in a multivariate linear regression analysis, these patterns remained. CONCLUSIONS: Our study suggests that piperacillin/tazobactam + teicoplanin is associated with a higher prevalence of AKI compared with monotherapy. However, as the overall decline in renal function with piperacillin/tazobactam + teicoplanin is very small, its clinical relevance is likely limited. Therefore, piperacillin/tazobactam + teicoplanin can probably be safely combined.

EBV : not your Everyday Benign Virus.

BACKGROUND: Epstein-Barr virus infection is common, with seroprevalence of 90% in adults. Clinical presentation of primary EBV infection can be variable and atypical. It is often subclinical or can result in infectious mononucleosis. Clinical course is mostly benign, but in rare cases serious short- and long-term complications may occur. CASE PRESENTATION: We present a case of a 19-year-old woman who was admitted to the hospital with general malaise, fever, dyspnea, icterus, vomiting and diarrhea, with acute left upper quadrant pain. She was diagnosed with acute EBV-infection with hepatitis, splenomegaly and spontaneous splenic rupture. CONCLUSIONS: Spontaneous splenic rupture is an uncommon, but potentially fatal complication of infectious mononucleosis. In a patient with suspicion of EBV infection and abdominal pain, we should always be aware of the possibility of spontaneous splenic rupture and emphasis should be put on appropriate counseling.

Recommendations for antibacterial therapy in adults with COVID-19 e an evidence based guideline

The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

Atypical and fulminant presentations of pneumococcal infections: A case series in a tertiary intensive care unit.

With the introduction of conjugate pneumococcal vaccines, changes in causative serotypes and clinical presentations of Streptococcus pneumoniae infections are occurring. During the 2017-2018 winter, an unusual number of patients with a severe manifestation of pneumococcal disease was admitted to a tertiary care intensive care unit (ICU) in the Netherlands. We describe some of the cases in depth. Given our observed change in infecting serotypes and extreme clinical manifestations of pneumococcal disease, a systematic clinical registry of pneumococcal infections in the ICU may be a valuable addition to pneumococcal disease surveillance.

Proxy indicators to estimate the appropriateness of medications prescribed by paediatricians in infectious diseases: a cross-sectional observational study based on reimbursement data.

BACKGROUND: We previously developed proxy indicators (PIs) that can be used to estimate the appropriateness of medications used for infectious diseases (in particular antibiotics) in primary care, based on routine reimbursement data that do not include clinical indications. OBJECTIVES: To: (i) select the PIs that are relevant for children and estimate current appropriateness of medications used for infectious diseases by French paediatricians and its variability while using these PIs; (ii) assess the clinimetric properties of these PIs using a large regional reimbursement database; and (iii) compare performance scores for each PI between paediatricians and GPs in the paediatric population. METHODS: For all individuals living in north-eastern France, a cross-sectional observational study was performed analysing National Health Insurance data (available at prescriber and patient levels) regarding antibiotics prescribed by their paediatricians in 2017. We measured performance scores of the PIs, and we tested their clinimetric properties, i.e. measurability, applicability and room for improvement. RESULTS: We included 116 paediatricians who prescribed a total of 44 146 antibiotic treatments in 2017. For all four selected PIs (seasonal variation of total antibiotic use, amoxicillin/second-line antibiotics ratio, co-prescription of anti-inflammatory drugs and antibiotics), we found large variations between paediatricians. Regarding clinimetric properties, all PIs were measurable and applicable, and showed high improvement potential. Performance scores did not differ between these 116 paediatricians and 3087 GPs. CONCLUSIONS: This set of four proxy indicators might be used to estimate appropriateness of prescribing in children in an automated way within antibiotic stewardship programmes.

Management of infected pancreatic necrosis in the intensive care unit: a narrative review.

BACKGROUND: Severe acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team-with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control-is essential in the treatment of this complex disease. OBJECTIVES: To address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU. SOURCES: A literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s). CONTENT: This narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU. IMPLICATIONS: In pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.

Nationwide survey of hospital antibiotic stewardship programs in France.

OBJECTIVE: We aimed to evaluate the current state of antibiotic stewardship (ABS) in French public and private acute care hospitals. METHODS: We conducted a cross-sectional online questionnaire survey. The selection of participating hospitals was performed through a stratified random sampling procedure among all French public and private hospitals with acute care beds. RESULTS: 97/215 (45%) hospitals participated. A formal ABS program was implemented in 84% (80/95) of hospitals. A person officially in charge of this program (i.e., ABS program leader) was present in almost all participating hospitals (99%, 95/96) and s/he coordinated a multidisciplinary ABS team in 42% (40/96) of cases. The median time spent on ABS activities was 1.7, 1.6, and 0.8hours/week/100 acute care beds for infectious disease (ID) specialists, pharmacists, and microbiologists respectively; 27% (7/26) of ID specialists/other clinicians, 58% (15/26) of pharmacists, and 80% (16/20) of microbiologists received no salary support for the stewardship activities conducted as part of the team. Local guidelines (94%, 88/94), electronic medical records (85%, 80/94), and an antibiotic restriction policy (92%, 82/89) were implemented in almost all hospitals. Reports on antibiotic consumption and local resistance rates were available in 100% (91/91) and 84% (76/91) of hospitals, respectively. CONCLUSION: Despite the existence of national requirements, hospital ABS programs are not fully implemented in France, mainly because of inadequate institutional support and funding.

Comparison of antimicrobial stewardship programmes in acute-care hospitals in four European countries: A cross-sectional survey.

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.

How to measure quantitative antibiotic use in order to support antimicrobial stewardship in acute care hospitals: a retrospective observational study.

A cornerstone of antimicrobial stewardship programs (ASPs) is monitoring quantitative antibiotic use. Frequently used metrics are defined daily dose (DDD) and days of therapy (DOT). The purpose of this study was (1) to explore for the hospital setting the possibilities of quantitative data retrieval on the level of medical specialty and (2) to describe factors affecting the usability and interpretation of these quantitative metrics. We performed a retrospective observational study, measuring overall systemic antibiotic use at specialty level over a 1-year period, from December 1st 2014 to December 1st 2015, in one university and 13 non-university hospitals in the Netherlands. We distinguished surgical and non-surgical adult specialties. The association between DDDs, calculated from aggregated dispensing data, and DOTs, calculated from patient-level prescription data, was explored descriptively and related to organizational factors, data sources (prescription versus dispensing data), data registration, and data extraction. Twelve hospitals were able to extract dispensing data (DDD), three of which on the level of medical specialty; 13 hospitals were able to extract prescription data (DOT), 11 of which by medical specialty. A large variation in quantitative antibiotic use was found between hospitals and the correlation between DDDs and DOTs at specialty level was low. Differences between hospitals related to organizational factors, data sources, data registration, and data extraction procedures likely contributed to the variation in quantitative use and the low correlation between DDDs and DOTs. The differences in healthcare organization, data sources, data registration, and data extraction procedures contributed to the variation in reported quantitative use between hospitals. Uniform registration and extraction procedures are necessary for appropriate measurement and interpretation and benchmarking of quantitative antibiotic use.

A survey on antimicrobial stewardship prerequisites, objectives and improvement strategies: systematic development and nationwide assessment in Dutch acute care hospitals.

Background: Stewardship guidelines define three essential building blocks for successful hospital antimicrobial stewardship programmes (ASPs): stewardship prerequisites, stewardship objectives and improvement strategies. Objectives: We systematically developed a survey, based on these building blocks, to evaluate the current state of antimicrobial stewardship in hospitals. We tested this survey in 64 Dutch acute care hospitals. Methods: We performed a literature review on surveys of antimicrobial stewardship. After extraction and categorization of survey questions, five experts merged and rephrased questions during a consensus meeting. After a pilot study, the survey was sent to 80 Dutch hospitals. Results: The final survey consisted of 46 questions, categorized into hospital characteristics, stewardship prerequisites, stewardship objectives and stewardship strategies. The response rate was 80% (n = 64). Ninety-four percent of hospitals had established an antimicrobial stewardship team, consisting of at least one hospital pharmacist and one clinical microbiologist. An infectious diseases specialist was present in 68% of the teams. Nine percent had dedicated IT support. Forty-one percent of the teams were financially supported, with a median of 0.6 full-time equivalents (FTE; 0.1-1.8). The majority of hospitals performed monitoring of restricted antibiotic agents (91%), dose optimization (65%), bedside consultation (56%) and intravenous-to-oral switch (53%). Fifty-eight percent of the hospitals provided education to residents and 28% to specialists. Conclusions: The survey provides information on the progress that is being made in hospitals regarding the three building blocks of a successful ASP, and provides clear aims to strengthen ASPs. Ultimately, these data will be related to national data on antibiotic consumption and resistance.