Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

OBJECTIVES: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. METHODS: All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. RESULTS: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. CONCLUSIONS: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

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.

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.

Evaluation of trace calls by Xpert MTB/RIF ultra for clinical management in low TB burden settings.

BACKGROUND: Clinical interpretation of trace results by Xpert MTB/RIF Ultra assay (Ultra) used as an initial diagnostic test for tuberculosis (TB) may be challenging. The aim of the study was to evaluate the frequency and epidemiology of trace readouts in routine clinical practice in a low TB prevalence setting and to propose guidance on how to manage patients with trace calls considering the data available (clinical, radiological, bacteriological etc.). MATERIALS AND METHODS: A retrospective, observational, monocentric study was conducted at IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy between November 2017-December 2020. Presumptive TB patients with at least one Ultra trace result during diagnostic workup before treatment were included in the study. Patients with ongoing anti-TB treatment at the time of the trace call result or with no clinical data available were excluded from the study. RESULTS: Fifty-nine presumptive TB patients with Ultra trace readouts were included in the study (mean age 37.0 years, 61% males). Four patients had a history of TB in the last 2 years. Twenty-five (42.4%) of the 59 samples with trace results were respiratory material. 57/59 (96.6%) patients started anti-TB treatment soon after obtaining trace results, based on clinical, radiological or other information available, while for two patients with a recent history of TB the trace result did not lead to anti-TB treatment. Culture was positive for M. tuberculosis for 31/59 (52.5%) samples with trace calls: 13/25 (52.0%) were respiratory samples and 18/33 (54.5%) non-respiratory samples. The clinical and/or radiological findings of 47/57 (82.4%) patients given anti-TB therapy improved during treatment. CONCLUSION: In low TB incidence settings, Ultra trace calls in presumptive TB patients should be considered as true-positive and treatment should be started promptly, except in cases of recent history of TB, where careful evaluation of other diagnostic criteria is necessary before starting anti-TB treatment. A decisional algorithm for clinical management is proposed.

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.

Short Communication: No Significant Increase in Body Fat Mass in Naive HIV-Infected Patients Starting Raltegravir Plus Tenofovir Disoproxil Fumarate/Emtricitabine.

A significant weight gain has been reported in HIV-infected patients starting combination antiretroviral therapy (cART) including integrase strand transfer inhibitors, but clinical data about changes in body fat mass are still lacking. An observational retrospective analysis was made to evaluate changes in body fat mass and weight in 39 cART-naive patients initiating a first antiretroviral treatment, including tenofovir disoproxil fumarate/emtricitabine plus raltegravir (RAL) or darunavir/ritonavir (DRV/r), and who had a follow-up of at least 12 months and a whole-body dual-energy X-ray absorptiometry performed at baseline and after 12 months. After 12 months, changes in weight and total fat mass were comparable and statistically not significant in both groups. The median increase [interquartile range (IQR)] in weight was +2.02 kg (+1.19, +2.95; p = .378) in RAL group, and +1.71 kg (+0.89, +2.54; p = .449) in DRV/r group. The median increase in body fat mass (IQR) was +1.27 kg (+1.09, +1.43; p = .278) in RAL group, and +1.04 kg (+0.89, +1.22; p = .781) in DRV/r group. In conclusion, in our study, an initial regimen including RAL plus tenofovir/emtricitabine after 12 months led to a small and nonsignificant increase in weight and body fat mass, and changes were comparable with a DRV/r-based initial regimen.