Brucellar Endocarditis of the Tricuspid Valve: A Case Report and Review of the Literature.

Brucellar endocarditis is a rare entity commonly described as a severe disease associated with high mortality and generally requiring valve surgery for cure. Right-sided endocarditis, a very uncommon presentation of brucellosis, may be associated with a better prognosis. We describe the case of a 72-year-old woman admitted to our institution with a persistent fever and multiple pulmonary infiltrates. Transthoracic echocardiography and serologic tests led to the diagnosis of brucellar tricuspid endocarditis. The patient responded favorably to antibiotic treatment alone and did not need surgery. Prolonged antibiotic therapy with a combination of drugs active on intracellular microorganisms in the absence of surgical treatment could be effective in brucellar tricuspid endocarditis when the valve is not severely damaged.

Streptococcus intermedius Brain Abscess with Lung Abscess and Aortic Valve Endocarditis: A Case Report and Literature Review.

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscesses due to this agent with infective endocarditis. We describe the case of a 40-year-old man complaining of cough, fever, and headache who was diagnosed with a brain abscess due to S. intermedius, a concomitant lung abscess, and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis.

BACKGROUND: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors. METHODS: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL. RESULTS: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS. CONCLUSIONS: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission.

INTRODUCTION: The use of steroid therapy in patients within the context of SARS-CoV-2 infection is still a matter of debate. This study aimed to evaluate if potential steroid benefits could be predicted by the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) (P/F) in COVID-19 patients at admission. MATERIALS AND METHODS: Medical records were retrospectively collected from all adult patients admitted because of COVID-19 from 29 January to 31 July 2020. The association of steroid therapy with 28-day all-cause mortality outcome was analysed in a multivariable logistic regression model adjusted for confounding factors. RESULTS: Overall, 511 patients were analysed, of which 39.1% underwent steroid therapy. Steroid treated patients were mostly male, older, and more frequently treated with antiviral drugs and aminoquinolines; the most common comorbidities were hypertension, followed by cardiovascular disease. Overall, 51 patients died within 28-days, and overall 28-days mortality was 19.5% in the cohort of patients exposed to steroids versus 3.9% mortality in unexposed patients (p < 0.001). Steroid therapy on patients with P/F ratio of 235 mmHg or higher at admission can be considered as detrimental, with an 8% increased probability of death. CONCLUSIONS: Steroid therapy is associated with increased 28-day mortality in COVID-19 in patients with mild or no ARDS.

Salmonella Hessarek Gastroenteritis with Bacteremia: A Case Report and Literature Review.

Salmonella enterica subspecies enterica serotype Hessarek (Salmonella Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of S. Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array® GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for Salmonella. The culture of the feces was negative, but the blood culture was positive for Salmonella spp., which was identified as Salmonella Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Salmonella Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of S. Hessarek disease in humans.

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial.

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.

Persistent detection of dengue virus RNA in vaginal secretion of a woman returning from Sri Lanka to Italy, April 2017.

We describe the dynamics of dengue virus (DENV) infection in a woman in her mid-30s who developed fever after returning from Sri Lanka to Italy in April 2017. Laboratory testing demonstrated detectable DENV-RNA in plasma, urine, saliva, vaginal secretion. Persistent shedding of DENV-RNA was demonstrated in vaginal secretion, and DENV-RNA was detectable in the pelleted fraction up to 18 days from symptom onset. These findings give new insights into DENV vaginal shedding and vertical transmission.

Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M).

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients.

Pharmacological treatment of HIV-associated pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a rare but severe disease that results from chronic obstruction of small pulmonary arteries, leading to right ventricular failure and, ultimately, death. One established risk factor for the development of PAH is HIV infection. The presence of PAH is an independent risk factor for mortality in HIV-infected patients. This article will focus on HIV-associated PAH (HIV-PAH) with special considerations to the available treatments. With the approval of the soluble guanylate cyclase stimulator riociguat, a new drug class has become available in addition to the already existing prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Guidelines for the treatment of idiopathic PAH and guidelines for antiretroviral therapy should be followed for the treatment of HIV-PAH.

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort.

PURPOSE: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. METHODS: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. RESULTS: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168). CONCLUSIONS: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE.

Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus- infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor.

Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH) in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI). We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI.

Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI).

BACKGROUND: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. METHODS: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). RESULTS: There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001). CONCLUSIONS: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery.

Extra-cerebral severe infections associated with haemorrhagic hereditary telangiectasia (Rendu-Osler-Weber Disease): five cases and a review of the literature.

Hereditary haemorrhagic telangiectasia (HHT) is one of the most common autosomal dominant disorders and is characterized by genetically determined abnormalities of vascular structure. People affected by HHT are predisposed to severe infections such as cerebral abscesses, typical of patients with pulmonary arteriovenous malformations, and extra-cerebral infections such as bacteraemia, septic arthritis, osteomyelitis, hepatic abscesses, skin infections and infective endocarditis. We present a retrospective series of severe bacterial extra-cerebral infections in five patients affected by HHT, admitted to our Institute from January 2007 to June 2013. We also reviewed the literature of the last five years concerning infectious complications in people affected by HHT. Our study shows that HHT patients with infectious complications exclusively localized in extra-cerebral sites are usually fragile, old and affected by comorbidities. Moreover, we recognized a trend of Staphylococcus aureus (SA) severe infection recurrence in such patients, both in our series and in the literature. In our opinion these results suggest the need to evaluate the possible benefits of SA nasal colonization screening and decolonization in such patients.

QTc interval prolongation in HIV-infected patients: a case-control study by 24-hour Holter ECG recording.

BACKGROUND: Aim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated. METHODS: A case-control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec) QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording. RESULTS: Duration of HIV disease was significantly longer among cases than among controls (p=0.04). Waist/hip ratio was also higher among cases than among controls (p=0.05). Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF) in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007). CONCLUSIONS: In our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

Sildenafil plasma concentrations in two HIV patients with pulmonary hypertension treated with ritonavir-boosted protease inhibitors.

Sildenafil is increasingly used for the therapy of pulmonary arterial hypertension (PAH) in HIV infected patients. However, concerns exist about pharmacokinetic interactions between sildenafil and protease inhibitors (PI); in particular, ritonavir has been shown to increase sildenafil AUC and Cmax by several folds. The aim of our study was to determine the plasma levels of sildenafil and PI in two HIV patients with PAH treated with antiretroviral therapy including ritonavir-boosted PI. Our patients both experienced sildenafil Cmax above 500 ng/mL; however, they did not report any significant adverse reactions to sildenafil during the follow-up period. Therapeutic drug monitoring of sildenafil should be taken in consideration during treatment in order to avoid overdosage.