HIV transmission by human bite: a case report and review of the literature—implications for post-exposure prophylaxis

We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case

Anakinra for the treatment of COVID-19 patients: a systematic review and meta-analysis

Background At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin‑1 (IL‑1) receptor antagonist Anakinra for the treatment of COVID‑19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID‑19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS‑CoV‑2 infection. Methods We searched the Cochrane COVID‑19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID‑19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS‑CoV‑2 infection. Results We included five RCTs with 1,627 patients (nAnakinra = 888, ncontrol = 739, mean age 59.63 years, 64% male). Random‑effects meta‑analysis was used to pool data. We found that Anakinra makes little or no difference to all‑cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64–1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I2 = 49%; low certainty of evidence). Conclusions Anakinra has no effect on adult hospitalized patients with SARS‑CoV‑2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone. Trial Registration: PROSPERO Registration Number: CRD42021257552.Peer Reviewe

Outpatient decolonization after recurrent skin infection with Panton-Valentine leukocidin (PVL)-producing S. aureus - The importance of treatment repetition

Background: Recurrent skin abscesses are often associated with Panton-Valentine leukocidin-producing strains of S. aureus (PVL-SA). Decolonization measures are required along with treatment of active infections to prevent re-infection and spreading. Even though most PVL-SA patients are treated as outpatients, there are few studies that assess the effectiveness of outpatient topical decolonization in PVL-SA patients. Methods: We assessed the results of topical decolonization of PVL-SA in a retrospective review of patient files and personal interviews. Successful decolonization was defined as the absence of any skin abscesses for at least 6 months after completion of the final decolonization treatment. Clinical and demographic data was assessed. An intention-to-treat protocol was used. Results: Our cohort consisted of 115 symptomatic patients, 66% from PVL-positive MSSA and 19% from PVL-positive MRSA. The remaining 16% consisted of symptomatic patients with close contact to PVL-SA positive index patients but without detection of PVL-SA. The majority of patients were female (66%). The median age was 29.87% of the patients lived in multiple person households. Our results showed a 48% reduction in symptomatic PVL-SA cases after the first decolonization treatment. The results also showed that the decrease continued with each repeated decolonization treatment and reached 89% following the 5th treatment. A built multivariable Cox proportional-hazards model showed that the absence of PVL-SA detection (OR 2.0) and living in single person households (OR 2.4) were associated with an independently increased chance of successful decolonization. Conclusion: In our cohort, topical decolonization was a successful preventive measure for reducing the risk of PVL-SA skin abscesses in the outpatient setting. Special attention should be given to patients living in multiple person households because these settings could confer a risk that decolonization will not be successful

Development of a Model-Informed Dosing Tool to Optimise Initial Antibiotic Dosing - A Translational Example for Intensive Care Units

The prevalence and mortality rates of severe infections are high in intensive care units (ICUs). At the same time, the high pharmacokinetic variability observed in ICU patients increases the risk of inadequate antibiotic drug exposure. Therefore, dosing tailored to specific patient characteristics has a high potential to improve outcomes in this vulnerable patient population. This study aimed to develop a tabular dosing decision tool for initial therapy of meropenem integrating hospital-specific, thus far unexploited pathogen susceptibility information. An appropriate meropenem pharmacokinetic model was selected from the literature and evaluated using clinical data. Probability of target attainment (PTA) analysis was conducted for clinically interesting dosing regimens. To inform dosing prior to pathogen identification, the local pathogen-independent mean fraction of response (LPIFR) was calculated based on the observed minimum inhibitory concentrations distribution in the hospital. A simple, tabular, model-informed dosing decision tool was developed for initial meropenem therapy. Dosing recommendations achieving PTA > 90% or LPIFR > 90% for patients with different creatinine clearances were integrated. Based on the experiences during the development process, a generalised workflow for the development of tabular dosing decision tools was derived. The proposed workflow can support the development of model-informed dosing tools for initial therapy of various drugs and hospital-specific conditions

The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces

Controlling mesenchymal stromal cell (MSC) shape is a novel method for investigating and directing MSC behaviour in vitro. it was hypothesized that specifigc MSC shapes can be generated by using stiffnessâ defined biomaterial surfaces and by applying cyclic tensile forces. Biomaterials used were thin and thick silicone sheets, fibronectin coating, and compacted collagen type I sheets. The MSC morphology was quantified by shape descriptors describing dimensions and membrane protrusions. Nanoscale stiffness was measured by atomic force microscopy and the expression of smooth muscle cell (SMC) marker genes (ACTA2, TAGLN, CNN1) by quantitative reverseâ transcription polymerase chain reaction. Cyclic stretch was applied with 2.5% or 5% amplitudes. Attachment to biomaterials with a higher stiffness yielded more elongated MSCs with fewer membrane protrusions compared with biomaterials with a lower stiffness. For cyclic stretch, compacted collagen sheets were selected, which were associated with the most elongated MSC shape across all investigated biomaterials. As expected, cyclic stretch elongated MSCs during stretch. One hour after cessation of stretch, however, MSC shape was rounder again, suggesting loss of stretchâ induced shape. Different shape descriptor values obtained by different stretch regimes correlated significantly with the expression levels of SMC marker genes. Values of approximately 0.4 for roundness and 3.4 for aspect ratio were critical for the highest expression levels of ACTA2 and CNN1. Thus, specific shape descriptor values, which can be generated using biomaterialâ associated stiffness and tensile forces, can serve as a template for the induction of specific gene expression levels in MSC. Copyright © 2017 John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141253/1/term2263.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141253/2/term2263_am.pd

Preparing for patients with high-consequence infectious diseases: Example of a high-level isolation unit

Introduction: Patients with high-consequence infectious diseases (HCID) are rare in Western Europe. However, high-level isolation units (HLIU) must always be prepared for patient admission. Case fatality rates of HCID can be reduced by providing optimal intensive care management. We here describe a single centre’s preparation, its embedding in the national context and the challenges we faced during the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Methods: Ten team leaders organize monthly whole day trainings for a team of doctors and nurses from the HLIU focusing on intensive care medicine. Impact and relevance of training are assessed by a questionnaire and a perception survey, respectively. Furthermore, yearly exercises with several partner institutions are performed to cover different real-life scenarios. Exercises are evaluated by internal and external observers. Both training sessions and exercises are accompanied by intense feedback. Results: From May 2017 monthly training sessions were held with a two-month and a seven-month break due to the first and second wave of the SARS-CoV-2 pandemic, respectively. Agreement with the statements of the questionnaire was higher after training compared to before training indicating a positive effect of training sessions on competence. Participants rated joint trainings for nurses and doctors at regular intervals as important. Numerous issues with potential for improvement were identified during post processing of exercises. Action plans for their improvement were drafted and as of now mostly implemented. The network of the permanent working group of competence and treatment centres for HCID (Ständiger Arbeitskreis der Kompetenz- und Behandlungszentren für Krankheiten durch hochpathogene Erreger (STAKOB)) at the Robert Koch-Institute (RKI) was strengthened throughout the SARS-CoV-2 pandemic. Discussion: Adequate preparation for the admission of patients with HCID is challenging. We show that joint regular trainings of doctors and nurses are appreciated and that training sessions may improve perceived skills. We also show that real-life scenario exercises may reveal additional deficits, which cannot be easily disclosed in training sessions. Although the SARS-CoV-2 pandemic interfered with our activities the enhanced cooperation among German HLIU during the pandemic ensured constant readiness for the admission of HCID patients to our or to collaborating HLIU. This is a single centre’s experience, which may not be generalized to other centres. However, we believe that our work may address aspects that should be considered when preparing a unit for the admission of patients with HCID. These may then be adapted to the local situations.Peer Reviewe

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients

Purpose: Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. Methods: We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charite Universitatsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. Results: Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112-8.697) and SAPS (OR 1.063, CI95 1.028-1.098) to be independent risk factors for CAPA. Conclusion: In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA

Antiplatelet agents for the treatment of adults with COVID-19

Background Severe coronavirus disease 2019 (COVID‐19) can cause thrombotic events that lead to severe complications or death. Antiplatelet agents, such as acetylsalicylic acid, have been shown to effectively reduce thrombotic events in other diseases: they could influence the course of COVID‐19 in general. Objectives To assess the efficacy and safety of antiplatelets given with standard care compared to no treatment or standard care (with/without placebo) for adults with COVID‐19. Search methods We searched the Cochrane COVID‐19 Study Register (which comprises MEDLINE (PubMed), Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science, WHO COVID‐19 Global literature on coronavirus disease and the Epistemonikos COVID‐19 L*OVE Platform to identify completed and ongoing studies without language restrictions to December 2022. Selection criteria We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating antiplatelet agents for the treatment of COVID‐19 in adults with COVID‐19, irrespective of disease severity, gender or ethnicity. Data collection and analysis We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (RoB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes. Main results Antiplatelets plus standard care versus standard care (with/without placebo) Adults with a confirmed diagnosis of moderate to severe COVID‐19 We included four studies (17,541 participants) that recruited hospitalised people with a confirmed diagnosis of moderate to severe COVID‐19. A total of 8964 participants were analysed in the antiplatelet arm (either with cyclooxygenase inhibitors or P2Y12 inhibitors) and 8577 participants in the control arm. Most people were older than 50 years and had comorbidities such as hypertension, lung disease or diabetes. The studies were conducted in high‐ to lower middle‐income countries prior to wide‐scale vaccination programmes. Antiplatelets compared to standard care: – probably result in little to no difference in 28‐day mortality (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.85 to 1.05; 3 studies, 17,249 participants; moderate‐certainty evidence). In absolute terms, this means that for every 177 deaths per 1000 people not receiving antiplatelets, there were 168 deaths per 1000 people who did receive the intervention (95% CI 151 to 186 per 1000 people); – probably result in little to no difference in worsening (new need for invasive mechanical ventilation or death up to day 28) (RR 0.95, 95% CI 0.90 to 1.01; 2 studies, 15,266 participants; moderate‐certainty evidence); – probably result in little to no difference in improvement (participants discharged alive up to day 28) (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 15,454 participants; moderate‐certainty evidence); – probably result in a slight reduction of thrombotic events at longest follow‐up (RR 0.90, 95% CI 0.80 to 1.02; 4 studies, 17,518 participants; moderate‐certainty evidence); – may result in a slight increase in serious adverse events at longest follow‐up (Peto odds ratio (OR) 1.57, 95% CI 0.48 to 5.14; 1 study, 1815 participants; low‐certainty evidence), but non‐serious adverse events during study treatment were not reported; – probably increase the occurrence of major bleeding events at longest follow‐up (Peto OR 1.68, 95% CI 1.29 to 2.19; 4 studies, 17,527 participants; moderate‐certainty evidence). Adults with a confirmed diagnosis of asymptomatic SARS‐CoV‐2 infection or mild COVID‐19 We included two RCTs allocating participants, of whom 4209 had confirmed mild COVID‐19 and were not hospitalised. A total of 2109 participants were analysed in the antiplatelet arm (treated with acetylsalicylic acid) and 2100 participants in the control arm. No study included people with asymptomatic SARS‐CoV‐2 infection. Antiplatelets compared to standard care: – may result in little to no difference in all‐cause mortality at day 45 (Peto OR 1.00, 95% CI 0.45 to 2.22; 2 studies, 4209 participants; low‐certainty evidence); – may slightly decrease the incidence of new thrombotic events up to day 45 (Peto OR 0.37, 95% CI 0.09 to 1.46; 2 studies, 4209 participants; low‐certainty evidence); – may make little or no difference to the incidence of serious adverse events up to day 45 (Peto OR 1.00, 95% CI 0.60 to 1.64; 1 study, 3881 participants; low‐certainty evidence), but non‐serious adverse events were not reported. The evidence is very uncertain about the effect of antiplatelets on the following outcomes (compared to standard care plus placebo): – admission to hospital or death up to day 45 (Peto OR 0.79, 95% CI 0.57 to 1.10; 2 studies, 4209 participants; very low‐certainty evidence); – major bleeding events up to longest follow‐up (no event occurred in 328 participants; very low‐certainty evidence). Quality of life and adverse events during study treatment were not reported. Authors' conclusions In people with confirmed or suspected COVID‐19 and moderate to severe disease, we found moderate‐certainty evidence that antiplatelets probably result in little to no difference in 28‐day mortality, clinical worsening or improvement, but probably result in a slight reduction in thrombotic events. They probably increase the occurrence of major bleeding events. Low‐certainty evidence suggests that antiplatelets may result in a slight increase in serious adverse events. In people with confirmed COVID‐19 and mild symptoms, we found low‐certainty evidence that antiplatelets may result in little to no difference in 45‐day mortality and serious adverse events, and may slightly reduce thrombotic events. The effects on the combined outcome admission to hospital or death up to day 45 and major bleeding events are very uncertain. Quality of life was not reported. Included studies were conducted in high‐ to lower middle‐income settings using antiplatelets prior to vaccination roll‐outs. We identified a lack of evidence concerning quality of life assessments, adverse events and people with asymptomatic infection. The 14 ongoing and three completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review

Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

Ivermectin for preventing and treating COVID‐19

Background Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS‐CoV‐2 infection and COVID‐19 treatment is conflicting. Objectives To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID‐19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS‐CoV‐2 (postexposure prophylaxis). Search methods We searched the Cochrane COVID‐19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021. Selection criteria We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID‐19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS‐CoV‐2 infection. Co‐interventions had to be the same in both study arms. We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy. Data collection and analysis We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate‐to‐severe COVID‐19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID‐19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS‐CoV‐2 infection: SARS‐CoV‐2 infection, development of COVID‐19 symptoms, adverse events, mortality, admission to hospital, and quality of life. Main results We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID‐19 in inpatient settings and four treating mild COVID‐19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS‐CoV‐2 infection. Eight studies had an open‐label design, six were double‐blind and placebo‐controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias. Ivermectin doses and treatment duration varied among included studies. We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies. Ivermectin compared to placebo or standard of care for inpatient COVID‐19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low‐certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low‐certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low‐certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low‐certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low‐certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low‐certainty evidence) and duration of hospitalization (mean difference (MD) −0.10 days, 95% CI −2.43 to 2.23; 1 study; 45 participants; low‐certainty evidence). No study reported quality of life up to 28 days. Ivermectin compared to placebo or standard of care for outpatient COVID‐19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low‐certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low‐certainty evidence) or non‐IMV or high flow oxygen requirement (0 participants required non‐IMV or high flow; 1 study, 398 participants; very low‐certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low‐certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low‐certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low‐certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days. Ivermectin compared to no treatment for prevention of SARS‐CoV‐2 infection We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low‐certainty evidence). The study reported results for development of COVID‐19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS‐CoV‐2 infection, hospital admission, and quality of life up to 14 days. Authors' conclusions Based on the current very low‐ to low‐certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID‐19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID‐19 outside of well‐designed randomized trials