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Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.

The SARS-CoV-2 pandemic caused an increase in intensive care unit (ICU) hospitalizations with a rise in morbidity and mortality; nevertheless, there is still little evidence on the impact of the pandemic on antibiotic resistance in ICUs. This is a retrospective, monocentric epidemiological study. The aim of the study was to describe and analyze the impact of the SARS-CoV-2 pandemic on ICU bacterial resistance patterns. All bacteria isolated from all patients admitted to the E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. A total of 1021 microorganisms were identified, of which 221 (12.47%) had a resistance pattern (resistant organisms; ROs). In this time, there were 1679 patients with a total of 12,030 hospitalization days. The majority of microorganisms were Gram-negative (79.66% in 2018, 77.29% in 2019, 61.83% in 2020, 62.56% in 2021, and 60.75% in 2022), but an increase in Gram-positive microorganisms was observed (20.34 to 39.25% between 2018 and 2022). The prevalence of AR was 19.44% in 2018, 11.54% in 2019, 38.04% in 2020, 34.15% in 2021, and 39.29% in 2022 for Gram-positive microorganisms and 19.86% in 2018, 13.56% in 2019, 18.12% in 2020, 12.41% in 2021, and 12.31% in 2012 for Gram-negative microorganisms. The incidence of ROs showed a COVID-19-related increase in 2020–2021, followed by a lowering trend since 2021, and a new increase in 2022. Possible explanations are antibiotic overtreatment and a decrease in containment measures. An interesting finding was the cumulative lowering trend of carbapenem-resistant K. pneumoniae and P. aeruginosa, probably due to different patient features.

The fixed-dose combination (FDC) elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/c/FTC/TDF) is a once-daily, single-tablet regimen containing an integrase strand transfer inhibitor and a pharmacoenhancer (cobicistat) associated with two nucleos(t)ide reverse transcriptase inhibitors. It is approved as the preferred regimen and as the first-line combined antiretroviral therapy in treatment-naïve patients with HIV infection. Two large trials, 102-Study and 103-Study, demonstrated that EVG/c/FTC/TDF was not inferior to efavirenz/FTC/TDF and ritonavir-boosted atazanavir in association with FTC/TDF, in terms of virological suppression and immunological reconstitution through week 144. Also, simplification arms containing EVG/c/FTC/TDF reached noninferiority in comparison with a nonnucleoside reverse transcriptase inhibitor, or a protease inhibitor, or a raltegravir-based regimen. Furthermore, EVG/c/FTC/TDF exhibited an excellent tolerability profile, with a safer lipid profile, and despite the indication of its use in subjects with an estimated creatinine clearance >70 mL/min, recent data demonstrated that EVG/c/FTC/TDF determined a reduction in estimated glomerular filtration rate (GFR) but not a reduction of actual GFR. Moreover, in a cohort of naïve patients with pretreatment mild-to-moderate renal impairment, GFR decrease was noted as early at week 2, after which it generally stabilized and was nonprogressive through week 48. The FDC's efficacy and good tolerability enable EVG/c/FTC/TDF to meet the patients' needs, improving adherence and quality of life, which are among the most important factors affecting the therapeutic efficacy of an antiretroviral regimen. This paper describes the evidence making EVG/c/FTC/TDF a new therapeutic opportunity for different HIV-infected patients.

Introduction HIV/HCV coinfection is a risk factor for hepatic injury in patients receiving HAART and previous studies support a favourable effect of antiretroviral regimens including maraviroc (MVC) on the course of coinfection compared with other antiretroviral drugs. There are few observations about MVC use in simplified treatment of coinfected patients.Objective: To evaluate the efficacy and the safety of simplification to darunavir (DRV)/ritonavir (r)/maraviroc (MVC) in virologically HIV‐suppressed patients and to explore the effect of simplified treatment on coinfected patients. Material and Methods GUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC with standard HAART with three drugs. The study enrols patients with HIV‐1 RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to analyze factors associated to time‐to a single viral load (VL) over 50cp/mL and FIB‐4>1.45. Results We included 62 patients with at least the 24 week follow‐up for FIB‐4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3 years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells 659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline (BL) FIB‐4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two arms, except for platelets (−34.96 109/L, in the study arm, p=0.028) and CD4 at nadir (−70cell/µL, p0.051). After 24 weeks a significant reduction in total bilirubin (TB) (−0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (−12.96 UI/L, p=0.002) was observed in the study group. A statistically significant difference in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week between control and study group was observed. No grade 3/4 transaminase elevation was observed for any patient even if HIV/HCV coinfected and receiving MVC. A single HCV negative patient in the control arm had grade 3 bilirubin increase. Including all patients with at least one follow‐up HCV status was not associated with an increased risk of detectable VL (n=114, 4072 person‐week‐follow‐up [IQR12;51.6]), nor with FIB‐4>1.45 (n=98, 3513 person‐week‐follow‐up [IQR11.4;50.9]). Conclusions The initial results from GUSTA study show that ART‐regimen including MVC did not increase the incidence of adverse events or severe laboratory liver abnormalities in HIV‐1‐infected patients with or without HCV coinfection. Coinfected patients did not show an increased risk of failure on simplification treatment with MVC/DRV/r.

Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

In several settings, the COVID-19 pandemic determined a negative impact on the occurrence of healthcare-associated infection, particularly for on central lines associated bloodstream infections (CLABSI). In our setting, we observed a significant increase in CLABSI in our intensive care unit (ICU) during 2020 and 2021 vs. 2018 to 2019. A refresher training activity on central venous catheter (CVC) management bundles was carried out in September–October 2021 for the ICU health staff. We assessed the impact of bundle implementation by means of standardized indicators, such as the Device Utilization Ratio (DUR), in this case, the Central Line Utilization Ratio, the Standardized Utilization Ratio (SUR), and the device Standardized Infection Ratio (dSIR). Standardized ratios for device use and infection ratio were computed using data from 2018 and 2019 as expectation data. After bundle implementation, we observed a significant reduction of dSIR (p < 0.001), which dropped from 3.23 and 2.99 in the 2020–2021 biennium to 1.11 in 2022 (CLABSI in the first quarter only); no more CLABSI were observed afterwards. Standardized ratios proved helpful in identify increasing trends of CLABSI in the ICU and monitoring the impact of a simple effective tool, i.e., training on and implementation of a bundle for CVC management.

In several settings, the COVID-19 pandemic determined a negative impact on the occurrence of healthcare-associated infection, particularly for on central lines associated bloodstream infections (CLABSI). In our setting, we observed a significant increase in CLABSI in our intensive care unit (ICU) during 2020 and 2021 vs. 2018 to 2019. A refresher training activity on central venous catheter (CVC) management bundles was carried out in September–October 2021 for the ICU health staff. We assessed the impact of bundle implementation by means of standardized indicators, such as the Device Utilization Ratio (DUR), in this case, the Central Line Utilization Ratio, the Standardized Utilization Ratio (SUR), and the device Standardized Infection Ratio (dSIR). Standardized ratios for device use and infection ratio were computed using data from 2018 and 2019 as expectation data. After bundle implementation, we observed a significant reduction of dSIR (p < 0.001), which dropped from 3.23 and 2.99 in the 2020–2021 biennium to 1.11 in 2022 (CLABSI in the first quarter only); no more CLABSI were observed afterwards. Standardized ratios proved helpful in identify increasing trends of CLABSI in the ICU and monitoring the impact of a simple effective tool, i.e., training on and implementation of a bundle for CVC management.

Vertical transmission of human immunodeficiency virus (HIV) represents an important worldwide health problem and rapid decline in viral load is essential for HIV pregnant women to prevent mother to child transmission. Specific issues such as late presentation of pregnant HIV-infected women remain a clinical challenge. We present a case of an HIV-infected woman who presented to our hospital at 35 weeks of pregnancy, who was successfully treated with raltegravir-based first-line combined antiretroviral regimen. Even though there is limited information about safety and tolerability of the use of raltegravir in pregnancy, in our case this drug resulted in a rapid decline in HIV-RNA viral load, without side effects. The aim of the present study and literature review was to demonstrate that raltegravir can be a good treatment choice for very late presenting pregnant women. [PUBLICATION ABSTRACT]

Introduction The aim of this study was to analyze the likelihood and the predictors of discontinuation of first‐line regimen in the late HAART era. Methodology An observational multi‐center analysis of HIV‐positive patients enrolled in ICONA. Patients eligible were those starting a first‐line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co‐morbidity, years since starting HAART, immuno‐virological status, third drug and backbone of the first regimen. Kaplan Meier (KM) analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time. Results Data of 1759 patients who started first HAART and had at least one month of clinical follow‐up were analyzed. The overall discontinuation risk was 33% over a median follow‐up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25–29) and 41% by two years (95% CI 38–44). Main reason for stopping at least one drug in regimen was simplification (10%), followed by intolerance (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93–1.00; p=0.039), regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42–5.76; p=0.003 vs TDF/FTC) and an NNRTI‐based regimen (HR 2.47; 95% CI 0.91–6.72; p=0.07 vs regimens not NNRTI‐based). Conclusions In a previously reported analysis of the ICONA data [1], the overall risk of discontinuation of first‐line HAART was 36% with 21% due to intolerance/toxicity. In this updated analysis, the main reason for stopping is simplification (accounting for 32% of stops), reflecting the recent changes in recommendations aimed to minimize drug toxicity, enhancing adherence and quality of life.