SARS-CoV-2 Vaccination in Solid-Organ Transplant Recipients

The coronavirus disease 2019 (COVID-19) pandemic has posed significant global challenges for solid organ transplant (SOT) recipients. Mortality rates of COVID-19 in this patient population remain high, despite new available therapeutic options and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination. Priority access to SARS-CoV-2 vaccination for waitlisted candidates and for SOT patients and their family members is recommended since the advantage from vaccination reduces the risk of COVID-19-related complications. However, immunogenicity and efficacy of COVID-19 vaccines are lower in waitlisted candidates and SOT recipients than in the general population. Routine systematic assessment of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, although highly recommended for investigation and improvement of knowledge. SOT recipients should continue to adhere to preventive protective measures despite vaccination and may undergo passive antibody prophylaxis. This article seeks to provide an update on SARS-CoV-2 vaccination and preventive measures in SOT recipients based on existing literature and international guidelines

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii

Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature

BackgroundMalaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids.MethodsA systematic research of current literature related to PMNS was performed.Results151 cases of PMNS were included, the majority of which occurred after severe P. falciparum infections. Four main clinical pattern were identified: 37% of the cases presented as "classical" PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms.ConclusionsPMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management

Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis

Diagnòstic; Malalties fúngiques invasores; PneumocystisDiagnóstico; Enfermedades fúngicas invasivas; PneumocystisDiagnosis; Invasive fungal diseases; PneumocystisThe Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.The present project did not require additional funding from routine research activities. Costs for open-access publications were covered by research funds of the main authors

Treatment of Infections Due to MDR Gram-Negative Bacteria

The treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in critically ill patients presents many challenges. Since an effective treatment should be administered as soon as possible, resistance to many antimicrobial classes almost invariably reduces the probability of adequate empirical coverage, with possible unfavorable consequences. In this light, readily available patient's medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and firmly guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. Rapid diagnostics and efficient laboratory workflows are also of paramount importance both for anticipating diagnosis and for rapidly narrowing the antimicrobial spectrum, with de-escalation purposes and in line with antimicrobial stewardship principles. Carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii are being reported with increasing frequencies worldwide, although with important variability across regions, hospitals and even single wards. In the past few years, new treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, plazomicin, and eravacycline have become available, and others will become soon, which have provided some much-awaited resources for effectively counteracting severe infections due to these organisms. However, their optimal use should be guaranteed in the long term, for delaying as much as possible the emergence and diffusion of resistance to novel agents. Despite important progresses, pharmacokinetic/pharmacodynamic optimization of dosages and treatment duration in critically ill patients has still some areas of uncertainty requiring further study, that should take into account also resistance selection as a major endpoint. Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB

One Word to Describe My Experience as a COVID-19 Survivor Six Months after Its Onset: Findings of a Qualitative Study

The COVID-19 pandemic emotionally affected the lives of patients cared for in different settings. However, a comprehensive view of the whole experience as lived by survived patients, from the onset of the disease and over time, is substantially unknown to date. A descriptive qualitative design was implemented according to the Standards for Reporting Qualitative Research. Adult patients (=1067) cared for during the first wave (March/April 2020) capable of answering an interview and willing to participate were interviewed (=397) by phone with an interview guide including open- and closed-ended questions. In this context, they were asked to summarise with a metaphor their entire COVID-19 experience at six months. Then, the emotional orientation (positive, neutral, or negative) of the metaphors expressed was identified. The participants were mainly female (206; 51.9%), with an average age of 52.6 years (CI 95% 50.4-53.6), reporting a mild severity of COVID-19 disease at the onset (261; 65.7%) and the perception of being completely healed (294; 70%) at six months. The patients summarised their experiences mainly using negative-oriented (248; 62.5%) metaphors; only 54 (13.6%) reported positive-oriented metaphors and a quarter (95; 23.95) neutral-oriented metaphors. Nearly all positive-oriented metaphors were reported by patients with symptoms at the onset (53; 98.1%), a significantly higher proportion compared to those reporting negative- (219; 88.3%) and neutral-oriented (78; 82.1%) metaphors (p = 0.014). While no other clinical features of the disease were associated, among females, significantly more negative-oriented metaphors emerged. Moreover, neutral-oriented metaphors were reported by younger patients (49.5 years, CI 95% 64.11-52.92) as compared to those negative and positive that were reported by more mature patients (53.9; CI 95% 52.04-55.93 and 54.8; CI 95% 50.53-59.24, respectively) (p = 0.044). Nurses and healthcare services require data to predict the long-term needs of patients. Our findings suggest that, for many patients, the COVID-19 lived experience was negative over time

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge

Background COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known.Objective To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness.Methods With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness.Results Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness.Conclusions In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.[GRAPHICS]

Is first-line antimicrobial therapy still adequate to treat MRSA in the ICU? A report from a highly endemic country

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Vaccine Hesitancy among Italian Patients Recovered from COVID-19 Infection towards Influenza and Sars-Cov-2 Vaccination

We aimed to assess the attitude towards influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations among coronavirus disease 2019 (COVID-19) recovered patients. We performed a cross-sectional study consisting of a standardized telephone interview carried out between September and November 2020 targeting a cohort of adult in- and out-patients that had recovered from COVID-19 after the first wave (March-May 2020) at Udine Hospital (Italy). Overall, 599 people participated (320 female, median age 53 years) and most had experienced an acute COVID-19 with mild illness (409, 68.3%). The majority were hesitant or undecided towards influenza (327, 54.6%) and SARS-CoV-2 (353, 59.2%) vaccines. Older age, public work exposure, and previous 2019 flu shots were the main factors associated with a positive attitude toward both vaccinations (p < 0.05). Being hospitalized during the acute COVID-19 phase was associated with the willingness to get a flu shot (94/272, 34.5%) but not SARS-CoV-2 vaccine (70/244, 28.7%). Vaccine hesitancy is diffuse and multifactorial also among COVID-19 recovered

Evaluation of qualitative and semi-quantitative cut offs for rapid diagnostic lateral flow test in relation to serology for the detection of SARS-CoV-2 antibodies: findings of a prospective study

There is limited information to compare the qualitative and semi-quantitative performance of rapid diagnostic tests (RDT) and serology for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the objective of the study was (a) to compare the efficacy of SARS-CoV-2 antibody detection between RDT and laboratory serology, trying to identify appropriate semi-quantitative cut-offs for RDT in relation with quantitative serology values and to (b) evaluate diagnostic accuracy of RDT compared to the NAAT gold standard in an unselected adult population