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

Clinical and magnetic resonance study of a case of subacute sclerosing panencephalitis treated with ketogenic diet

Background Subacute sclerosing panencephalitis is a progressive neurodegenerative disorder caused by a latent and mutant measles virus which is extremely rare in developed countries. The lack of effective treatments leads to the research of other anti-inflammatory and neuroprotective treatments. Case Here we present a case of a 17-year-old patient affected by subacute sclerosing panencephalitis who manifest a dramatic improvement in neurological and general clinical conditions, as well as an arrest in the progression of demyelinating process in the central nervous system, after the beginning of a high ratio ketogenic diet. Conclusions Given its anti-inflammatory, antioxidant and metabolic effects, we believe that ketogenic diet utilisation could be a rational approach, can be considered a safe add-on therapy, carrying on with only a minimal risk of adverse effects or interactions

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Antibiotic-resistant Pseudomonas aeruginosa: Focus on care in patients receiving assisted ventilation

This article discusses ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Ventilator-associated pneumonia caused by P. aeruginosa is one of the leading causes of morbidity and mortality in the intensive care unit, and nowadays it represents a major concern due to the increasing resistance rate of the pathogen to different classes of antibiotics. Here, the choice between a combination therapy and a monotherapy in the empirical setting is analyzed and discussed, by focusing on the recommendations of different published guidelines. Pros and cons of the different possible associations are analyzed and suggestions are given in light of the emergence of multidrug-resistant strains. Route of administration is also discussed, with an emphasis on the use of nebulized antibiotics. Optimal duration of treatment is an additional point of discussion, and explanations are provided for the suggested longer course compared with that of other etiologies

Multidrug-resistant Gram-negative bacteria-resistant infections: epidemiology, clinical issues and therapeutic options

In the last decade, we have witnessed a dramatic increase in the number of multidrug resistant Gram-negative (MDRGN) bacterial pathogens, both in Italy and worldwide, with Enterobacteriacae (mostly Klebsiella pneumoniae), Pseudomonas aeruginosa and Acinetobacter baumannii being the major threats in clinical practice. Inadequate empirical antimicrobial therapy of severe infections caused by MDR Enterobacteriacae has been associated with an increased morbidity and mortality. However, a careful selection of patients who may receive empirical treatment covering MDR Enterobacteriacae is important to avoid the overuse of broad-spectrum antibiotics. The aim of this review is to describe the mechanism of resistance, epidemiology, risk factors, clinical issues, and therapeutic options for MDRGN pathogens

The management of multidrug-resistant enterobacteriaceae

Purpose of review Multidrug-resistant (MDR) Enterobacteriaceae are often related to the production of extended-spectrum blactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CRE), and represent an increasing global threat. Recommendations for the therapeutic management of MDR-related infections, however, are mainly derived from retrospective and nonrandomized prospective studies. The aim of this review is to discuss the challenges in the treatment of patients with infections because of MDR Enterobacteriaceae and provide an expert opinion while awaiting for more definitive data. Recent findings To avoid the selection of carbapenemase-producing Enterobacteriaceae, carbapenem-sparing strategies should be considered. B-lactams/b-lactamase inhibitors, mainly piperacillin-tazobactam, minimum inhibitory concentration (MIC) 16/4mg/ml or less represents the best alternative to carbapenems for the treatment of ESBL-producing strains. Overall, combination therapy may be preferred over monotherapy for CRE. The combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside can be administered at high-dose prolonged infusion with therapeutic drug monitoring for the treatment of CRE with MIC for meropenem 8-16 mg/l or less. For MIC higher than 8-16 mg/l, the use of meropenem should be avoided and various combination therapies based on the in-vitro susceptibility of antimicrobials (e.g., colistin, high-dose tigecycline, fosfomycin, and aminoglycosides) should be selected. Summary Carbapenem-sparing strategies should be used, when feasible, for ESBL infections. The majority of available nonrandomized studies highlight that combination for CRE seem to offer some therapeutic advantage over monotherapy. Strict infection control measures toward MDR Gram-negative pathogens remain necessary while awaiting for new treatment option

Delafloxacin: An improved fluoroquinolone developed through advanced molecular engineering

The emergence of antimicrobial resistance threatens current clinical practice across a range of infection types. Delafloxacin, a non-zwitterionic fluoroquinolone recently approved by the US FDA for the treatment of acute bacterial skin and skin structure infections, has been developed to address some of these challenges. Uniquely delafloxacin has increased intracellular penetration and enhanced antibacterial activity under acidic conditions, an environment seen in many infection sites including abscesses. Delafloxacin is active against a wide range of Gram-positive and-negative species including methicillin-resistant Staphylococcus aureus and many fluoroquinolone-resistant strains. Additionally, according to preclinical and clinical trial data, well-known adverse events related to fluoroquinolone class do not appear to occur with this new molecule. Delafloxacin has been studied in acute bacterial skin and skin structure infections with >1400 patients exposed to both intravenous and oral formulation for up to 14 days and has shown noninteriority to vancomycin with or without aztreonam. For its interesting microbiological and pharmacokinetic/pharmacodynamics characteristics and for its safety profile, delafloxacin represents a very promising option for the treatment of infections caused by multidrug-resistant pathogens