Determinants of worse liver-related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort.

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

An Improvement in the Antimicrobial Resistance Patterns of Urinary Isolates in the Out-Of-Hospital Setting following Decreased Community Use of Antibiotics during the COVID-19 Pandemic.

After the onset of COVID-19 pandemic, a decrease in antibiotic consumption in the out-of-hospital setting was observed. However, data about the impact of this reduction on antimicrobial resistance are lacking. The aim of this study was to assess antibiotic consumption and antibiotic resistance at the community level in an Italian province before and after the beginning of the COVID-19 pandemic. We carried out an observational study, comparing antibiotic consumption in the community during 2019 and 2020 and the antibiotic resistance patterns of Enterobacterales cultured from urine samples from the out-of-hospital setting during the first semester of 2020 and 2021. Overall, antibiotic consumption decreased by 28% from 2019 to 2020 (from 13.9 to 9.97 DDD/1000 inhabitants/day). The main reductions involved penicillins (ATC J01C, from 6.9 to 4.8 DDD/1000 inhabitants/day, −31%), particularly amoxicillin/clavulanate (ATC J01CR02, −30%) and amoxicillin (J01CA04, −35.2%). Overall, 6445 strains of Enterobacterales were analyzed; in 2020, the susceptibility rate of amoxicillin/clavulanate increased from 57.5% to 87% among isolates from the primary care setting (p < 0.001) and from 39% to 72% (p < 0.001) among isolates from LTCF. The reduction in the community use of antibiotics observed in 2020 was followed by a change in the antimicrobial resistance patterns of urinary isolates.

Treatment duration for central line-associated infection caused by Enterococcus spp.: a retrospective evaluation of a multicenter cohort.

Objective of this study was to assess the appropriate treatment duration for enterococcal central line-associated bloodstream infections (CLABSIs). This observational, retrospective, multicenter study conducted between 2011 and 2019 enrolled all hospitalized patients with monomicrobial enterococcal CLABSI. Those with infective endocarditis and non-survivors at least 7 days from index blood culture (BC) were excluded. Primary endpoint was 30-day mortality. We enrolled 113 patients, of whom 59% were male, median age was 64 (SD ± 15) and median Charlson's index score 5 (IQR 3-8). Enterococcus faecalis and Enterococcus faecium were found in 51% and 44% of cases, respectively. Median treatment duration was 11 days (IQR 6-17), and 32% of patients (n = 36) received ≤ 7 days. Characteristics of patients receiving more or less than 7 days of treatment were similar. Central line was removed in 82% (n = 93) of cases within a median of 3 days (1-8). At both uni- and multivariate analysis, duration of antibiotic treatment > 7 days was not associated with 30-day mortality [HR 0.41 (95% CI, 0.13-1.24), p = 0.12] even after adjustment with propensity score [HR 0.47 (95% CI 0.17-1.26), p = 0.13]. A 7-day treatment course appears to be safe in non-complicated enterococcal CLABSIs.

Risk factors for persistent enterococcal bacteraemia: a multicentre retrospective study.

OBJECTIVES: Conditions favouring persistent enterococcal bacteraemia (p-EB) have not been fully investigated yet. The aim of our study is to analyse risk factors for p-EB and its impact on mortality. METHODS: International two-centre retrospective study of all hospitalised adults with enterococcal bacteraemia managed with follow-up blood cultures (BCs) during the period 2011-2019. Exclusion criteria were: (1) death within 72 hours from index BCs and (2) polymicrobial bacteraemia. Primary endpoint was p-EB, defined as further isolation of the same species of Enterococcus spp. from BCs after at least 72 hours of appropriate antibiotic therapy. Multivariable logistic regression model was performed to assess risk factors for p-EB. The impact of p-EB on 30-day mortality was assessed by Kaplan-Meier survival curve and Cox regression multivariable model. RESULTS: During the study period, 244 enterococcal bacteraemia were diagnosed. P-EB were 13.5% (33/244). At multivariable analysis, factors independently associated with p-EB were hematologic malignancy (OR 4.60 [95% CI 1.32-16.00], P = 0.01), infective endocarditis (OR 7.99 [95% CI 2.20-28.9], P = 0.002), and use of daptomycin as initial treatment (OR 4.50 [95% CI 1.29-15.61], P = 0.018). Mortality rate was higher in the p-EB group (32% vs. 18%). Kaplan-Meier survival curve showed that patients with p-EB were less likely to survive at 30 days from index BCs (log-rank P = 0.002). Using a Cox regression model, independent predictors of 30-day mortality were hematologic malignancy (HR 2.30 [95% CI 1.02-4.11], P = 0.043), p-EB (HR 1.93 [95% CI 0.92-4.04], P = 0.08), and septic shock (HR 5.92 [95% CI 2.17-16.30], P = 0.001). CONCLUSION: P-EB was diagnosed mainly in very fragile patients and in those receiving daptomycin as frontline therapy. P-EB may have an impact on mortality.

Out-of-Hospital Treatment of Hepatitis C Increases Retention in Care among People Who Inject Drugs and Homeless Persons: An Observational Study.

BACKGROUND: People who inject drugs (PWID) and homeless people represent now a large reservoir of Hepatitis C virus (HCV) infection. However, Hepatis C elimination programs can barely reach these subgroups of patients. We aimed to evaluate and compare the retention in care among these difficult-to-treat patients when managed for HCV in hospital or in an out-of-hospital setting. METHODS: In our retrospective study, we categorized the included patients (PWID and homeless persons) into two groups according to whether anti-HCV treatment was offered and provided in a hospital or an out-of-hospital setting. We run logistic regressions to evaluate factors associated with retention in care (defined as the completion of direct antiviral agents (DAAs) therapy). RESULTS: We included 56 patients in our study: 27 were in the out-of-hospital group. Overall, 33 patients completed DAAs therapy. A higher rate of retention in care was observed in the out-of-hospital group rather than in-hospital group (p = 0.001). At the univariate analysis, retention in care was associated with the out-of-hospital management (p = 0.002) and with a shorter time between the first visit and the scheduled start of DAAs (p = 0.003). CONCLUSIONS: The choice of treatment models that can better adapt to difficult-to-treat populations, such as an out-of-hospital approach, will be important for achieving the eradication of HCV infection.

Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus.

OBJECTIVES: Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN: We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS: We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS: During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/µl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. CONCLUSION: Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.

How do I manage a patient with enterococcal bacteraemia?

BACKGROUND: Enterococcal bacteraemia (EB) is common, particularly in the nosocomial setting, and its management poses a challenge for clinicians and microbiologists. OBJECTIVES: The aim was to summarize the more relevant features of EB and to provide a practical state-of-the-art on the topics that more directly affect its management. SOURCES: Pubmed articles from inception to 31 May 2020. CONTENT: The following topics are covered: epidemiological, clinical and microbiological characteristics and factors associated with prognosis of EB; diagnosis and work-up, including the use of echocardiography to rule out endocarditis; antibiotic management with special focus on antimicrobial resistance and complicated EB; and the role of infectious disease consultation and the use of bundles in EB. In addition, three clinical vignettes are presented to illustrate the practical application of the guidance provided, and major gaps in the current evidence supporting EB management are discussed. IMPLICATIONS: EB is associated with large burdens of morbidity and mortality, particularly among fragile and immunosuppressed patients presenting complicated bacteraemia due to multidrug-resistant enterococci. Most cases of EB are caused by Enterococcus faecalis, followed by E. faecium. EB often presents as polymicrobial bacteraemia. Rapidly identifying patients at risk of EB is crucial for timely application of diagnostic techniques and empiric therapy. Early alert systems and rapid diagnostic techniques, such as matrix-assisted desorption ionization-time of flight mass spectrometry, especially if used together with infectious disease consultation within bundles, appear to improve management and prognosis of EB. Echocardiography is also key in the work-up of EB and should probably be more extensively used, although its exact indications in EB are still debated. Multidisciplinary approaches are warranted due to the complexity and severity of EB.

SARS-CoV-2 related pneumonia in an adult with cystic fibrosis: natural favourable clinical course or effective therapy?

We report the case of a man affected by cystic fibrosis who developed a severe SARS-CoV-2 related pneumonia in March 2020. In addition to lopinavir/ritonavir and hydroxychloroquine, he was treated with two doses of tocilizumab, displaying a significant clinical improvement. This is the first case described in the literature of an adult patient affected by cystic fibrosis who received tocilizumab for COVID-19, with documented total recovery, also assessed by a spirometry.

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.

Impact on Mortality of a Bundle for the Management of Enterococcal Bloodstream Infection.

OBJECTIVE: In this study, we evaluated the effectiveness of a management bundle for Enterococcus spp bloodstream infection (E-BSI). METHOD: This was a single-center, quasi-experimental (pre/post) study. In the prephase (January 2014 to December 2015), patients with monomicrobial E-BSI were retrospectively enrolled. During the post- or intervention phase (January 2016 to December 2017), all patients with incident E-BSI were prospectively enrolled in a nonmandatory intervention arm comprising infectious disease consultation, echocardiography, follow-up blood cultures, and early targeted antibiotic treatment. Patients were followed up to 1 year after E-BSI. The primary outcome was 30-day mortality. RESULTS: Overall, 368 patients were enrolled, with 173 in the prephase and 195 in the postphase. The entire bundle was applied in 15% and 61% patients during the pre- and postphase, respectively (P < .001). Patients enrolled in the postphase had a significant lower 30-day mortality rate (20% vs 32%, P = .0042). At multivariate analysis, factors independently associated to mortality were age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00-1.05), intensive care unit admission (HR, 2.51; 95% CI, 1.18-3.89), and healthcare-associated (HR, 2.32; 95% CI, 1.05-5.16) and hospital-acquired infection (HR, 2.85; 95% CI, 1.34-4.76), whereas being enrolled in the postphase period (HR, 0.49; 95% CI, 0.32-0.75) was associated with improved survival. Results were consistent also in the subgroups with severe sepsis (HR, 0.37; 95% CI, 0.16-0.90) or healthcare-associated infections (HR, 0.53; 95% CI, 0.31-0.93). A significantly lower 1-year mortality was observed in patients enrolled in the postphase period (50% vs 68%, P < .001). CONCLUSIONS: The introduction of a bundle for the management of E-BSI was associated with improved 30-day and 1-year survival.

Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.

Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.

Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment.

BACKGROUND: The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies. METHODS: The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. RESULTS: The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS. CONCLUSIONS: The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.