Serge Alfandari

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres

Objective:To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. Design:Multicentric, observational, retrospective cohort study. Setting:Ten AIDS reference centres in France. Patients:All patients followed in each centre from September 1995 through October 1996. Main outcome measures:AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. Results:Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US

Liposomal Amphotericin B in Combination With Caspofungin for Invasive Aspergillosis in Patients With Hematologic Malignancies : A Randomized Pilot Study (Combistrat Trial)

12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US

Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial

248 852 (i.e., by US

Pulmonary disposition of vancomycin in critically ill patients

101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US

Computer tomography in pulmonary invasive aspergillosis in hematological patients with neutropenia: an useful tool for diagnosis and assessment of outcome in clinical trials.

113 578 (i.e., by US

Specific control measures for antibiotic prescription are related to lower consumption in hospitals: results from a French multicentre pilot study

38 per patient per month). Conclusions:This study supports the extensive use of HAART in HIV-infected patients.

Salvage treatment of methicillin-resistant staphylococcal endocarditis with ceftaroline: a multicentre observational study

Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds.

Jugular versus Femoral Short-Term Catheterization and Risk of Infection in Intensive Care Unit Patients. Causal Analysis of Two Randomized Trials

BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. METHODS In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) or 5% povidone iodine-69% ethanol (povidone iodine-alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. FINDINGS Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine-alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine-alcohol (580 patients with scrubbing, 588 without). Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol; hazard ratio 0·15, 95% CI 0·05-0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol (27 [3%] patients vs seven [1%] with povidone iodine-alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. INTERPRETATION For skin antisepsis, chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. FUNDING University Hospital of Poitiers, CareFusion.

Community-Acquired Pneumonia in the Intensive Care Unit: Epidemiological and Prognosis Data in Older People

Vancomycin penetration in epithelium lining fluid was studied in ten mechanically ventilated patients with methicillin-resistantStaphylococcus aureus pneumonia 24 hours after the onset of treatment. Vancomycin was given intravenously at a daily dose of 30 mg/kg. Vancomycin levels were detectable in four patients (range, 1–2.77 μg/ml). Concordance between high plasma concentrations (> 20 μg/ml) and detectable vancomycin levels in epithelium lining fluid was noted. These results suggest that the pulmonary disposition of vancomycin remains low for most patients 24 h after the onset of treatment compared with the minimum inhibitory concentrations for most gram-positive organisms. One therapeutic goal of vancomycin treatment could be to obtain through plasma levels of 20 μg/ml. Further studies are required to determine the clinical relevance of these observations.

Tolerance, compliance and psychological consequences of post-exposure prophylaxis in health-care workers

BACKGROUND AND OBJECTIVE The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial. DESIGN AND METHODS Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n=26) or proven (n=4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT). RESULTS For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p=0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p=0.003 for D14 vs. D7, but with p=0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p<0.001) but it was not significantly different when compared to D0 (p=0.11). CONCLUSIONS The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials.