Innovative Approaches to Monitor Central Line Associated Bloodstream Infections (CLABSIs) Bundle Efficacy in Intensive Care Unit (ICU): Role of Device Standardized Infection Rate (dSIR) and Standardized Utilization Ratio (SUR)-An Italian Experience.

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.

The Clinical Efficacy of Multidose Oritavancin: A Systematic Review.

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.

Impact of the COVID-19 Pandemic on Epidemiology of Antibiotic Resistance in an Intensive Care Unit (ICU): The Experience of a North-West Italian Center.

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.

Predictors of retention in care in HIV-infected patients in a large hospital cohort in Italy.

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.

Discontinuation of Initial Antiretroviral Therapy in Clinical Practice: Moving Toward Individualized Therapy.

BACKGROUND: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. METHODS: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥ 1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. RESULTS: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4 cell (P = 0.011), and higher lymphocyte T CD8 cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). CONCLUSIONS: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity.

Genetic polymorphisms of IL28b gene as predictors of response to dual therapy in genotypes 1 and 4-HCV and HIV/HCV-infected patients.

We describe the genotypes and allele distribution of interleukin 28B (IL28B) rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in hepatitis C virus (HCV) G1-4 infected patients, to assess predictive ability and to determine whether the combined determination of two IL28B SNPs might improve sustained virologic response (SVR) prediction of both in HCV mono- and HIV/HCV co-infected patients. IL28B SNPs were genotyped in 269 patients, 181 mono- and 88 co-infected, treated with pegylated interferon and ribavirin. Data stratified by HCV mono- and HCV/HIV co-infected patients showed that 58% and 31% of the rs12979860CC carriers and 49% and 21% of the rs8099917TT carriers had SVR. IL28B SNPs, HCV mono-infection and HCV RNA load were associated with SVR as independent predictors in the two study groups as a whole. ROC curve analyses in the two populations separately, based on gender, age, baseline HCV RNA load and rs12979860/rs8099917 revealed similar receiver operating characteristics (ROC) areas under the curve values. Combining the determination of IL28B SNPs, rs8099917 genotyping improved the response prediction in rs12979860CT carriers only in mono-infected patients. In the era of direct-acting antiviral agents, adopting SVR baseline predictors to orientate naïve-patient management represents an important issue. A model involving IL28B SNPs appears able to predict SVR in both populations.

May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

Efficacy, safety, and patient acceptability of elvitegravir/cobicistat/emtricitabine/tenofovir in the treatment of HIV/AIDS.

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.

Increased CD38 expression on T lymphocytes as a marker of HIV dissemination into the central nervous system.

Cross-sectional analysis on 20 HIV-1 patients with neurological symptoms admitted to two infectious disease units. Cut-off of HIV-RNA (VL) was 20 copies/ml for plasma and cerebral spinal fluid (CSF). Flow cytometry was used to analyze the phenotype of circulating and CSF T lymphocytes. CD38 mean fluorescence intensity (MFI) was higher on circulating CD4+T lymphocytes from patients with VL>20 copies/ml in plasma (P=0.001) or CSF (P=0.001). The frequency of circulating CD8+CD38+T cells and CD38 MFI on these cells were higher in patients with VL>20 copies/ml than in those with undetectable plasma VL (P=0.030 and P=0.023). The frequency of CSF CD4+CD38+T, as well as their CD38 and CD95 MFI, were increased in patients with detectable than non-detectable plasma VL (P=0.01, P=0.03, and P=0.05). The % CD38+CD8+T in CSF correlated with time of virological suppression (ρ=-0.462, P=0.040) and the CNS penetration-effectiveness (CPE) score (ρ=-0.467, P=0.038). In conclusion, (a) the expression of CD38+ on both CD4+, CD8+T lymphocytes from peripheral blood and CSF discriminated between viremic and non-viremic patients and (b) T cell activation/apoptosis markers inversely correlated with CPE to remark the importance for therapy to restore immunological functions.

Transitioning HIV-infected children and adolescents into adult care: an Italian real-life experience.

As young people living with HIV age, transition to adult care is increasingly required. The aim of our study was to describe how a care transition program was developed in an HIV adult clinic in Genoa, Italy. This is a descriptive study including 45 HIV-infected patients who participated in the transition process from a pediatric unit to an adult Infectious Diseases Unit, which started in 2000. A dedicated day, patient-customized environment, psychological support, and all health services in one site were provided. In 2014, a survey form was created to investigate the efficacy of the transition. At survey compilation time, 38 patients (84.4%) were retained in care, 2 were lost to follow-up, 2 were transferred to another adult clinic, and 3 had died. We highlight the importance of planning the transition process and the role of the interprofessional team to guarantee a successful transition for HIV-infected children and adolescents.

Role of HCV-RNA decay and IP-10 levels after 48 hours of standard HCV therapy as predictors of rapid virological response.

BACKGROUND AND OBJECTIVES: Rapid virological response (RVR) is a critical end-point in the era of the new direct-acting antiviral agents (DAA). The aim of this study was to evaluate the predictive value in achieving RVR of HCV-RNA load and IP10 after 48 hours of standard anti HCV therapy. METHODS: HCV mono-infected and HIV/HCV co-infected patients naives to interferon were included. Demographic data, immune-virological HIV-related condition and HCV disease status were recorded before starting treatment. HCV-RNA and IP10 concentrations were also measured 48 hours after first interferon dose. Univariate model, logistic regression and ROC curve were performed for statistical analysis. RESULTS: Thirty-two patients were enrolled (mean age 49.2 ± 5.6 years): all were treated with pegylated-interferon and ribavirin. Nineteen (59.3%) were HIV/HCV co-infected patients. RVR was reached in 10 patients (31.2%). A decline of more than two log of HCV-RNA after 48 hours of therapy was associated with RVR (P=0.004). A trend was observed between increased IP10 levels at 48 hours and RVR (P=0.08). In a multivariable model only HCV-RNA at 48 hours was associated with RVR (P=0.011). ROC curve analysis for both HCV-RNA at 48 hours and IP-10 at 48 hours showed an area under the curve of 0.87 (95%CI: 0.74-1; P=0.001) with specificity of 72.2% and sensibility of 90%. CONCLUSION: In HCV treatment-naïve patients HCV-RNA and IP10 determination after 48 hours of interferon and ribavirin may be a worthwhile endpoint to predict RVR and select patients that may not require DAA addition.

Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in HIV/HCV coinfected patients: initial results from GUSTA study.

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.

Treatment discontinuation in HIV-1-infected individuals starting their first-line HAART after 2008: data from the ICONA Foundation Study Cohort.

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.

Which patients have greatest need for elvitegravir/cobicistat/ emtricitabine/tenofovirDF-based therapy?

Elvitegravir/cobicistat/emtricitabine/tenofovirDF (EVG/COBI/FTC/TDF) is the new single-tablet, fixed-dose formulation containing an integrase strand transfer inhibitor recently approved as antiretroviral treatment. In this paper we analysed its use and advantages in naïve and experienced HIV-infected patients and we focused on special populations in which EVG/COBI/FTC/TDF could be a suitable option. Furthermore the manuscript reports the recent patent of EVG which may have an influence on the management of HIV-infected patients in the next future.

Genotypic determination of HIV tropism in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy.

The aim of this study was to determine the coreceptor tropism by performing genotypic HIV-1 tropism testing in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy. Genotypic coreceptor tropism was determined in patients with HIV-1 RNA<100 copies/mL using PBMC samples by gp120 V3 sequencing followed by geno2pheno interpretation (set at a false positive rate [FPR] of 20%) and in patients with ≯100 copies/mL using plasma samples (set at a FPR of 20%), according to European guidelines. Out of 55 patients, 50 had an HIV-1 subtype B strain, and mean (SD) age was 18.2 (4.6) years. The median duration of antiretroviral therapy was 13 years (range, 3-23). Thirty-three (60%) patients harbored the R5 virus. At the time of the testing, the median CD4+ T lymphocyte cell count and percentage were 705 cells/mm3 (474-905) and 32.5% in group R5 and 626 cells/mm3 (450-755) and 31.7% in group X4/D-M, respectively. The nadir of CD4+ T-cell count in groups R5 and X4/D-M were 322 cells/mm3 (230-427) and 340 cells/mm3 (242-356), respectively. These differences were not statistically significant. Fifteen patients had HIV-1 RNA ≯50 copies/mL. The median HIV-1 RNA and HIV-1 DNA were comparable in both groups without a statistical difference. The study provides an overview of the prevalence of coreceptor tropism in a cohort of patients who were vertically infected with HIV-1. The high prevalence of X4/D-M-tropic strains may simply reflect the long-term exposure to HIV.

Aspergillus osteomyelitis: epidemiology, clinical manifestations, management, and outcome.

BACKGROUND: The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood. METHODS: Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome. RESULTS: Among 180 evaluable patients, 127 (71%) were males. Possible predisposing medical conditions in 103 (57%) included pharmacological immunosuppression, primary immunodeficiency, and neutropenia. Seventy-three others (41%) had prior open fracture, trauma or surgery. Eighty (44%) followed a hematogenous mechanism, 58 (32%) contiguous infections, and 42 (23%) direct inoculation. Aspergillus osteomyelitis was the first manifestation of aspergillosis in 77%. Pain and tenderness were present in 80%. The most frequently infected sites were vertebrae (46%), cranium (23%), ribs (16%), and long bones (13%). Patients with vertebral Aspergillus osteomyelitis had more previous orthopedic surgery (19% vs 0%; P = 0.02), while those with cranial osteomyelitis had more diabetes mellitus (32% vs 8%; P = 0.002) and prior head/neck surgery (12% vs 0%; P = 0.02). Radiologic findings included osteolysis, soft-tissue extension, and uptake on T2-weighted images. Vertebral body Aspergillus osteomyelitis was complicated by spinal-cord compression in 47% and neurological deficits in 41%. Forty-four patients (24%) received only antifungal therapy, while 121 (67%) were managed with surgery and antifungal therapy. Overall mortality was 25%. Median duration of therapy was 90 days (range, 10-772 days). There were fewer relapses in patients managed with surgery plus antifungal therapy in comparison to those managed with antifungal therapy alone (8% vs 30%; P = 0.006). CONCLUSIONS: Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. The most common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response.

Pharmacokinetics of lopinavir determined with an ELISA test in youths with perinatally acquired HIV.

OBJECTIVE: To investigate the plasma levels of lopinavir by enzyme-linked immunosorbent assay (ELISA) in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV). METHODS: Plasma levels of lopinavir (Cmin) were determined by ELISA test in patients treated with lopinavir/ritonavir-based combined antiretroviral therapy who had achieved virological response after 4 wk of therapy. Reference lopinavir concentrations were Cmin 1-8 µg/mL. Correlation between lopinavir plasma concentration and continuous variables was evaluated by mean of Pearson correlation coefficient. Differences in lopinavir (LPV) concentration for binary categorical variables were assessed by Mann-Whitney test, while for variables with more than two categories Kruskal-Wallis test was used. RESULTS: Thirty-four patients were enrolled; median age was 133 mo (15-265). The median lopinavir dose tested was 383.5 mg/kg (IQR: 266.6-400 mg/kg), with a median plasma concentration of 8.8 µg/mL (IQR: 5-14 µg/mL). Lopinavir Cmin was <1 µg/mL in only one sample (2.9 %), while 14 samples had Cmin between 1 and 8 µg/mL (41.2 %) and 19 (55.9 %) > 8 µg/mL. No significant correlations were found between plasma concentrations of lopinavir and the continuous variables considered in the study. A negative but, not completely significant, correlation was found between plasma drug concentration and body mass index (r = -0.29; p = 0.09). CONCLUSIONS: The use of a simple and relatively cost-effective methodology might render therapeutic drug monitoring (TDM) appeal in the daily clinical practice.

Phalangeal quantitative ultrasound: cheaper methods for screening and follow-up of bone pathologies in HIV-infected women?

This study estimated the prevalence of bone pathologies in a cohort of HIV-infected women in comparison with a cohort of HIV-negative women. Bone mineral density was measured by phalangeal quantitative ultrasound (AD-SoS: amplitude- dependent speed of sound; UBPI: ultrasound bone profile index). Risk of fracture, expressed by UBPI, was considered for value <0.39. Comparisons between groups and multivariate analyses were carried out using an ANOVA model. Correlations were evaluated using the Pearson correlation coefficient. Osteopenia and osteoporosis were present in 34.4% and 2% of patients, respectively. UBPI was pathologic in 5.7%. In a multivariate linear regression model significant correlations were found between AD-SoS z-score, duration of HIV-infection and BMI value. We also compared our cohort with 499 HIV-negative women as a historical control group of healthy subjects. AdSoS (2100 versus 2070 m/s) and UBPI (0.89 versus 0.74) were lower in HIV-infected women (p<0.001). Significant differences were also found in T-score values (p = 0.0013). These data show a high prevalence of bone diseases in women with HIV infection, correlated with duration of HIV-infection and BMI values. This non-invasive technique opens up new interesting perspectives, suggesting a possible use for bone mass screening in HIV-infected women.