Severe Escherichia coli infections in critical adult patients: two case reports and genomic analysis.

Pathogenic Escherichia coli strains can infect a variety of body sites due to the expression of virulence factors necessary to overcome the host defenses. Here, we present two cases of E. coli infection in adults and discuss the associated genomic features. Whole-genome sequencing was performed using both Illumina iSeq 100 and Oxford Nanopore MinION systems. Assembly was carried out with Unicycler using a hybrid approach. The genomes were annotated with RASTtk and scanned for genes involved in antimicrobial resistance, virulence and stress response with AMRFinderPlus. Sequence analysis was conducted using tools from the Center for Genomic Epidemiology (CGE) website. The two strains, named SO80 and SO81, carried a genome of 5,229,956 and 5,437,935 base pairs, respectively. SO80 belonged to ST70 and carried 13 virulence factors, 6 of which were located on a 170 Kb plasmid, while SO81 belonged to ST69 and carried 29 virulence factors, 5 of which were located on a 113 Kb plasmid. Our work highlights key factors which may have contributed to the complicated clinical status of these patients, and provides new in-depth data on E. coli infections with few precedents in the literature.

How important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised COVID-19 patients? Results from a single Italian centre.

OBJECTIVE: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. RESEARCH DESIGN AND METHODS: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. RESULTS: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31-4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53-9.74, P < 0.001). A significantly higher risk of death was observed in patients with a BMI ≥ 35 kg/m2 (OR: 12.1; 95% CI: 3.25-45.1, P < 0.001). CONCLUSIONS: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

Background: The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods: A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results: Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion: Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

[Non-AIDS-associated cancer disorders. A novel scenario after over thirty years from HIV discovery? Clinical experience and literature appraisal]. / Patologie tumorali non correlate ad AIDS. Un nuovo scenario a oltre trent'anni di distanza dalla scoperta del virus HIV? Esperienza clinica e revisione della letteratura.

INTRODUCTION: Both natural history and epidemiological trend of HIV infection have been deeply modified by the introduction of highly active antiretroviral therapy (HAART), around twenty years ago. METHODS: However, despite a rapid drop of the incidence of the large majority of opportunistic infections, a slow, but continued increase of malignancies occurred, with particular evidence focused on cancers which are not strictly related to the definition of full blown AIDS (the so called non-AIDS-defining malignancies). RESULTS: The unique clinical occurrence of HIV infection complicated by even four non-AIDS-defining cancers prompted us to re-discuss the epidemiology and the possible pathogenesis, the clinical presentation, and the differential diagnosis of this pathologic presentation. CONCLUSIONS: On the ground of our experience in this field, and the available literature evidences, we discuss how this clinical occurrence is acting on HIV infection presentation during the HAART era of the third millennium. These changes need broad scale studies, and promise relevant consequences on etiopathogenetic, prevention, therapeutic, and management aspects of HIV disease in the next future.

A prospective evaluation of maraviroc administration in patients with advanced HIV disease and multiple comorbidities: focus on efficacy and tolerability issues.

In our HIV outpatient centre where over 1,200 patients are followed, maraviroc as an entry inhibitor was introduced in 2010. We aimed to assess the background, the therapeutic challenges and the prospective monitoring of all patients treated with a combination antiretroviral therapy (cART) including maraviroc. Sixty-six patients started a maraviroc-containing cART with a history of HIV infection lasting 13.9±10.7 years. This interim analysis presents patients who had at least 12 (mean 16.9±12.8) months of follow-up. One to 17 previous cART changes prompted the introduction of maraviroc in rescue regimens in the great majority of patients considered (53 of 66); in 13 cases, maraviroc was given to patients with advanced HIV disease and no immune recovery after 2-3 years of a virologically-effective cART. The most frequent companion antiretroviral agents were: darunavir/ritonavir (51 cases), raltegravir (49 subjects), and etravirine (36 cases). The most common underlying conditions were: AIDS (41 cases), liver cirrhosis (21), AIDS-related or other malignancies (20 cases), major cardiovascular events (18 cases), osteonecrosis and haemodialysis-treated kidney failure (3 cases each). A chronic HCV and HBV hepatitis were of concern in 25 and 13 patients. The addition of maraviroc added favourably to clinical-laboratory markers of HIV disease progression, and those of comorbid conditions. HIV viraemia became (or remained) undetectable in 55 patients of 66 (83.3%). An improvement in CD4+ count was observed in all 66 patients, based on a mean 24.9±19.2% increase versus baseline, paralleled by an improvement in mean absolute CD4+ count of 134.7±121.1 cells/µL. A tendency towards an increased mean and peak CD4+ count was observed in the subgroup receiving a maraviroc-raltegravir-based cART. As no clinical-laboratory adverse events attributable to maraviroc occurred, nobody discontinued the study drug. Only mild-transient gastrointestinal disturbances, fatigue and anorexia, were reported during maraviroc administration, but their relationship with the study drug was difficult to assess because of the multiple comorbidities and polypharmacy. Our preliminary experience with maraviroc, even considering the limits of the proportionally reduced sample, the patients' salvage stage of advanced disease and the related-unrelated morbidities, underlines its excellent efficacy and safety profile.

Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome.

We describe a case of chronic fatigue syndrome (CFS) associated to Parvovirus B19 infection where administration of intravenous immunoglobulins (IVIG), previously reported as effective, induced a paradoxical clinical response and increased viral replication. The indication of IVIG administration in the treatment of Parvovirus B19-associated CFS should be carefully reconsidered.

Tenofovir/emtricitabine/efavirenz plus rosuvastatin decrease serum levels of inflammatory markers more than antiretroviral drugs alone in antiretroviral therapy-naive HIV-infected patients.

OBJECTIVES: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. DESIGN: To assess the anti-inflammatory effects of statins in HIV-infected patients, because very limited data are available today. METHODS: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. RESULTS: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P < .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. CONCLUSIONS: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.

Prevalence of renal disease within an urban HIV-infected cohort in northern Italy.

BACKGROUND: Renal disease is an increasingly recognized noninfectious comorbidity associated with human immunodeficiency virus (HIV) infection. METHODS: Our retrospective, cross-sectional study evaluated prevalence of nephropathy among HIV-infected patients followed up in our outpatient clinic during the year 2011. Renal dysfunction and chronic kidney disease (CKD) were defined as estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m(2) and as renal damage or eGFR <60 ml/min per 1.73 m(2) over a 3-month or greater period, respectively. RESULTS: We enrolled 894 HIV-infected patients with a mean age of 44.2 years and a mean current CD4 lymphocyte count of 508 cells/mm(3). The prevalence of renal dysfunction and CKD was 27.4 and 21.3 %, respectively. Older age, male gender, hypertension, diabetes, proteinuria, hypertriglyceridemia, lower nadir CD4 cell count, current use of tenofovir or tenofovir plus a ritonavir-boosted protease inhibitor were independently associated with renal dysfunction. CONCLUSION: Renal dysfunction is a frequent comorbidity among HIV-infected persons and requires a careful clinical and laboratory monitoring of renal function.

Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy: sample population, virological-immunological activity, and tolerability profile.

Raltegravir, as the first HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a combination antiretroviral therapy (cART) including raltegravir, for at least 12 months. In all, 109 pretreated patients started a raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion antiretroviral agents were: darunavir/ritonavir (75 cases), maraviroc (47 subjects), and etravirine (38 cases). The most common underlying conditions were: AIDS (46 patients), liver cirrhosis (31 cases), AIDS-related or other malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of raltegravir favourably affected all clinical-laboratory markers of HIV disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to raltegravir, such that no patients discontinued raltegravir during the observation period. Only three AIDS-defining conditions became apparent during raltegravir-based cART; chemotherapy and/or radiotherapy cycles were performed as scheduled in patients suffering from cancer; chronic hepatitis B and C progressed to liver cirrhosis and/or hepatocarcinoma in only 2 and 6 patients. Otherwise, treatment with pegylated interferon-ribavirin became feasible in 25 patients of 48 with chronic HCV. During raltegravir-containing cART, neither autoimmune disorders nor novel malignancies were diagnosed. Only mild-transient gastrointestinal disorders, fatigue, dizziness, insomnia and cutaneous rash were reported, although their relationship with the study drug was difficult to assess due to multiple comorbidities and polypharmacy. Abnormal liver function testings were observed in 57 patients (52.3%), all suffering from concurrent hepato-biliary disorders. Significant increases in serum lipids and/or lipase levels versus baseline values were never registered: serum lipid levels significantly improved after raltegravir introduction. Our experience with raltegravir underlines its excellent efficacy and safety profile, which exploits a novel mechanism of action, and displays no cross-resistance with any other antiretroviral. A progressively extended prescription in naive patients and early cART lines will allow the therapeutic potential of raltegravir to be exploited.

Amiodarone-related pneumonitis and peripheral neuropathy in an elderly patient.

Amiodarone, which has been used since 1967 as an antiarrhythmic drug, gives rise to a variety of cardiac and extracardiac adverse side-effects. Among these, pulmonary toxicity is considered the most frequent and serious extracardiac side-effect, since it may occur in various atypical forms and often limits the drug's clinical use. We encountered a 67-year-old white male patient with suspected amiodarone pneumonitis characterized by multiple lung nodules associated with pleural and pericardial effusion and peripheral neuropathy. Because differential diagnosis with pulmonary infectious diseases may be extremely difficult, the attending physician should therefore bear in mind the possibility of amiodarone pneumonitis whenever the drug is given.