Survey on infectious disease telephone hotlines in primary care: General practitioners' satisfaction and compliance with advice.

OBJECTIVES: Infectious disease (ID) advice is a major part of antimicrobial stewardship programs. The objective of this study was to assess general practitioners' (GPs)' opinions and compliance with advice given by ID hotlines. PATIENTS AND METHODS: This multicenter survey was based on the 7-day assessment of initial advice requested by GPs to a hotline set up by volunteer hospital ID teams to record advice for 3 years. The primary endpoint was the GPs' satisfaction with the advice given by ID specialists. RESULTS: Ten ID teams participated in the study and recorded 4138 requests for advice, of which 1325 requests included a proposal for antibiotic therapy and justified a follow-up call at seven days. Only 398 follow-up calls (30%) were carried out because many GPs were not reachable. GPs were very satisfied with ID hotlines: 58% considered them indispensable and 38% very useful. The recommendations provided by ID specialists were followed by GPs in more than 80% of cases. The two main motivations for GPs to call the hotline were to get quick advice (86%) and to receive help in managing a patient (76%). CONCLUSIONS: The ID telephone consultations and advice systems for GPs are highly appreciated and are effective in terms of following the recommendations.

Epidemiology of candidemia in NICE area, France: A five-year study of antifungal susceptibility and mortality.

OBJECTIVES: The aim of this study was to investigate the epidemiology of candidemia, the fungal susceptibility, the first-line therapy and the morality rate over 5 years. Knowing the differences of the yeasts in the candidemia local epidemiology, is essential to obtain information on fungal epidemiology to adapt antifungal strategies. MATERIALS/METHODS: This retrospective study was conducted from January 2014 to December 2018. The susceptibility of the Candida strains were tested for amphotericin B, caspofungin, voriconazole and fluconazole. RESULTS: The 304 strains were isolated from 290 patients (40 patients in 2014, 65 in 2015, 72 in 2016, 62 in 2017 and 51 in 2018). The three most common Candida spp isolated from blood cultures were Candida albicans (44%), Candida glabrata (22%) and Candida parapsilosis (13%). The proportion of non-albicans Candida decreased from 68% in 2014 to 45% in 2018. C. albicans and C. parapsilosis were to the four antifungals tested. As first-line therapy, 60% of patients received caspofungin and 26% fluconazole. There was no significant difference in the mortality between the two arms of patients (, 27% and 21%, p = 0.47 at 30 days respectively). Thirty day all-cause mortality was 31% and it decreased from 2014 (46%) to 2018 (18%). CONCLUSIONS: We report that the absence of antifungal resistance of our C. albicans and C. parapsilosis candidemia suggests possible treatment after MALDI-TOF identification with fluconazole as first-line therapy in our hospital, as soon as possible and while continuing to perform the antifungal test.

A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project.

Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.

A 6-year antifungal stewardship programme in a teaching hospital.

PURPOSE: To describe the antifungal stewardship programme in our hospital and to assess its impact on total antifungal prescriptions and their cost, and on the process of care measures regarding the diagnostic and therapeutic management of invasive aspergillosis and candidaemia. METHODS: We conducted a prospective observational study describing the multifaceted antifungal stewardship programme in place at our French teaching tertiary-care hospital since 2005. Several actions were implemented successively, including the systematic evaluation of all costly antifungal prescriptions (echinocandins, lipid formulations of amphotericin B, posaconazole and voriconazole). RESULTS: A total of 636 antifungal prescriptions were discussed by the antifungal management team from 2005 to 2010 inclusive, mainly from the haematology department (72 %). In 344/636 cases (54 %), a piece of advice was fed back to the physician in charge of the patient, with an 88 % compliance rate. Optimal standard of care was achieved for galactomannan antigen testing, performance of chest computed tomography (CT) scan and voriconazole therapeutic drug monitoring for invasive aspergillosis, with no combination therapies used since 2008. Regarding candidaemia, optimal standard of care was achieved for the timing of antifungal therapy, recommended first-line therapy, duration of therapy and the removal of central venous catheters. Total antifungal prescriptions (in defined daily doses, DDD) and their cost were contained between 2003 and 2010. CONCLUSIONS: The implementation of an antifungal stewardship programme was feasible, sustainable and well accepted. We observed an improved quality of care for some process of care measures, and antifungal use and cost were contained in our hospital.

An antibiotic stewardship program in a French teaching hospital.

OBJECTIVES: An antibiotic stewardship program was implemented in our teaching hospital in 1999, and strengthened in 2005. We report its organization and impact on antibiotic use. METHODS: This observational study was conducted during a 10-year period (2002-2011). RESULTS: Many interventions were implemented: Infectious Diseases Specialists (IDS) led systematic ward rounds in several departments (1999); nominative antibiotic order form (2005); documentation of IDS advice in the patient's electronic medical record (2007); IDS advice triggered by the pharmacist (formulary restriction, 2007) or because of positive blood cultures (2009); automated weekly extraction of advice given into a database (2011). Seven thousand two hundred and five pieces of advice were recorded between 2007 and 2011: 63% following physician request, 26% triggered by the pharmacist and 9% because of positive blood cultures. Advice was provided by IDS in 95% of cases (63% by phone). The number of antibiotic prescriptions remained stable since 2005 at around 400 defined daily doses (DDD)/1000 patient-days. Documenting, sharing, and choice of action were improved due to the database. CONCLUSIONS: Our antibiotic stewardship program is well accepted by physicians and allows controlling antibiotic use in our hospital.

Possible pandemic HIN1 influenza complicated by Pneumocystis jirovecii pneumonia in an HIV-infected patient.

Immune response to a pandemic influenza A 2009 (H1N1) virus infection can influence the way a second unrelated pathogen is handled by the host. We report here a case of pandemic flu with marked CD4 T-cell lymphopenia complicated by a possible Pneumocystis jirovecii pneumonia in an HIV-infected patient.

Increased time exposure to tenofovir is associated with a greater decrease in estimated glomerular filtration rate in HIV patients with kidney function of less than 60 ml/min/1.73 m2.

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, -0.07 ± 0.08 and -0.87 ± 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

Cutaneous infections, good use of antibiotics and diagnostic accuracy.

UNLABELLED: The medical dashboard (DB) recording our clinical practices indicated on one hand the use of two different diagnosis terms, acute dermohypodermitis (ADH) or cellulitis, and on the other hand, an important antibiotic prescription heterogeneity. Our aim was to define these two diagnosis groups and to document compliance to our antibiotic therapy protocol. METHOD: ADH and cellulitis were selected in our medical DB that records all patient data. Our local antibiotic therapy protocol was designed in April 2009; the prescription of recommended antibiotic agents defined the compliance to recommendations. The patient files indicating non-consensual therapy were analyzed to determine the reasons for inappropriate prescription. RESULTS: Three hundred and four cases of ADH and 82 of cellulitis were diagnosed over 6.5years. ADH was associated with older age (P=0.007), a higher frequency of venous insufficiency (P=0.015), a lower frequency of cancer (P=0.007), and was more often located on lower limbs (P<0.001), compared to cellulitis. The diagnosis of ADH was associated with higher compliance to our antibiotic therapy protocol, compared to cellulitis: 68% versus (vs.) 24%, P<0.001, and after April 2009: 53% vs. 64%, P=0.033. Among the 162 inappropriate antibiotic prescriptions (42%), 75 were deemed justified after analyzing the patient file, but less frequently for ADH compared to cellulitis: 49% vs. 11,5%, P<0.001. CONCLUSION: ADH presents different clinical characteristics compared to cellulitis. The antibiotic therapy protocol for ADH cannot be applied to cellulitis.

Adverse effects of parenteral antimicrobial therapy for chronic bone infections.

Responsible pathogens of chronic bone infections (CBI) are frequently resistant, requiring parenteral antimicrobial therapy. Therefore, adverse effects may be observed. We have determined the rate of adverse effects of antimicrobial therapy for CBI in a retrospective study of all patients receiving parenteral drugs via an implantable port. Patients from one medical ward (n = 89) and from one surgical ward (n = 40) between January 1995 and December 2005 were included in this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint infections (34%). The main group of pathogens was gram positive cocci (n = 144; 65%). The total duration of antibiotic treatment was 205 +/- 200 days, including 133 +/- 100 days for parenteral therapy. Thirty-three catheter-related complications were observed in 27 patients (21%). All complications led to hospitalization but none led to death. Twenty-one antibiotic-related complications occurred in 18 patients (16%), and one allergic reaction led to death. The mean duration of follow-up was 290 days. Remission was observed in 84 patients (65%). In multivariate analysis, adverse effects were mostly observed in the medical department. Adverse effects affect at least one third of the patients treated for CBI with parenteral antimicrobial therapy and are related to both the implantable port and the antibiotic compounds.

[The computer-assisted management programs for antibiotic therapies in connection with an application in geriatrics]. / Les systèmes informatiques d'aide à la décision en antibiothérapie à propos d'une application en gériatrie.

OBJECTIVES: Improve antibiotic therapies in a geriatrics hospital by enhancing guidelines impact. Historical background. - Study of the uses of the data-processing tool: detection of adverse drug events and inappropriate therapies; diffusion of the probable bacteria and their sensitivities to antibiotics following the infected site; creating decisional algorithms leading to suggested antibiotic therapy concept. METHOD: Referring to the conferences of consensus: drafting of local protocols of antibiotic therapies by using data processing if possible. Description of computer-systems implemented in Salt Lake City (USA) and Tubingen (Germany). With the assistance of an expert infectiologist, design of a database containing clinical details of the different situations in the pulmonary and urinary infections: once the clinical data are entered, a suggested antibiotic therapy appears on the screen, followed by a suggested prescription adapted to patient's specifications. During five years, survey of Defined Daily Dose per 1000 occupied bed-days; survey of sensitivities to antibiotics of urinary tract bacteria. RESULTS: Decrease of overall antibiotic consumption; decrease of broad-spectrum agents; modifications of E. coli sensitivities lead to variations of suggested antibiotic therapy. DISCUSSION: Seizure of the clinical determinants imposes a reducing effect; but it is necessary to apply to antibiotic therapies a hierarchicalbasis on account of bacterial resistances process and on account of "tonnage" of antibiotic prescriptions. CONCLUSION: Computer-assisted decision in antibiotic therapy can draw prescribers' attention to guidelines. The adhesion of the physicians to the computerized decision-making system is consolidated by their direct participation in the design of this system.

[Assessment of the habits of physicians involved in the management of HIV-infected patients. A clinical audit on the biological follow-up]. / Pratiques professionnelles de médecins suivant des patients infectés par le VIH. Un audit clinique sur le suive biologique.

BACKGROUND: The aim of this study was to assess the habits of hospital and community-based physicians involved in the management of HIV-infected patients and to measure the gap between their practice and follow-up guidelines. METHOD: The guidelines considered as reference were the 1998 Dormont report. Data were prospectively collected from the medical files of the first 10 HIV-infected patients who presented for an out-patient visit (laboratory tests at initial consultation, type and frequency of follow-up during the previous year, relation between biological data and treatment strategy). RESULTS: 22 physicians (14 hospital-based physicians (HP) and 8 community-based general practitioners (GP) participated in the survey. Initial biological data were available for 211 patients; 45% had tests strictly conforming to the recommendations (HP: 57%, GP 23%; p<0.001). Among patients followed by a GP, the initial biological assessment was adequate in 7% of cases when an opiate substitute was prescribed versus 33% in the absence of opiate substitute prescription (p=0.05). For all patients, syphilis serology was the test most frequently lacking (38%). Among 78 patients with HIV-RNA levels>5,000 copies/ml, 18% did not benefit from a change in treatment. Among the patients treated by a GP, 15% had a three-fold increase in HIV-RNA, compared to their initial measurement. Of these, 3/4 were redirected to a hospital out-patient unit. CONCLUSION: This study highlights the discrepancy between initial laboratory testing and expert recommendations, particularly concerning patients attended by a GP. Improvement in data collection is essential. However, recommendations concerning patients' biological follow-up are applied, with the exception of the delay between the initial prescription or treatment modification and HIV-RNA measurement, which should be shortened.

Intracellular concentration of protease inhibitors in HIV-1-infected patients: correlation with MDR-1 gene expression and low dose of ritonavir.

BACKGROUND: Protease inhibitors (PIs) are substrates for the P-glycoprotein (P-gp/170) encoded by the multi-drug resistance gene (MDR-1). HIV infection is associated with increased expression of P-gp. The role of MDR gene overexpression in clinical pharmacokinetics is not known. METHOD: We determined by HPLC, at trough and peak levels, the current PI concentrations in plasma (P) and in peripheral blood mononuclear cells (PBMCs) (intracellular concentration [IC]) from 49 HIV-infected patients receiving different treatment combinations: nelfinavir ([NFV] n = 12); indinavir ([IDV] n = 10); amprenavir ([APV] n = 5); ritonavir (RTV) 100 bid/IDV 800 mg bid (n = 6); RTV 400 bid/IDV 400 mg bid (n = 3); RTV 100 bid/saquinavir (SQV) 600 mg tid (n = 9); APV 600 bid/RTV 100 mg bid (n = 4). We determined the mean ratio of intracellular/plasma PI concentration for each treatment group. The MDR-1 gene expression was determined by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). HIV viral load was simultaneously measured. RESULTS: 49 patients (mean age 41 +/- 8.7 years; mean CD4 cell count 418 [57-972]; mean HIV RNA 2.1 +/- 0.8 log(10)) were included in the study. Patients who overexpressed the MDR-1 gene had significantly lower trough intracellular PI levels (p =.02) or lower intracellular accumulation of PI (p =.042). Patients treated with low-dose RTV in combined regimens with detectable RTV intracellular concentration showed lack of MDR-1 gene expression (p =.01). Patients with HIV RNA < 40 copies/mL had significantly higher RTV intracellular accumulation (p =.029). CONCLUSION: In HIV-infected patients, IC of PI is inversely correlated with MDR-1 gene overexpression. Undetectable viral load was associated with the use of low-dose RTV, probably linked to better intracellular accumulation of the drug. Nevertheless, further investigation is needed to confirm these results.

Iatrogenic Cushing's syndrome in an HIV-infected patient treated with inhaled corticosteroids (fluticasone propionate) and low dose ritonavir enhanced PI containing regimen.

In HIV-infected patients, ritonavir, a potent cytochrome P450 inhibitor, is increasingly used to improve the pharmacokinetic profile of the associated protease inhibitor. HIV physicians are often faced with potential drug-drug interaction while treating associated diseases. We report the case of an HIV-infected patient with clinical features of Cushing's syndrome due to the interaction of low dose ritonavir with inhaled fluticasone propionate (FP). Safety of life-long CYP450 inhibition has still to be demonstrated.

[Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice. A prospective study]. / Motifs de prescriptions des antibiotiques dans le service des urgences du centre hospitalier universitaire de Nice. Enquête prospective.

OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice. Unjustified antiobiotherapy is often initiated. We therefore conducted a survey to study the motives and validity of antibiotic prescriptions. METHOD: This prospective study was conducted in two phases. The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed. In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed. The experts only had access to the clinical and para-clinical data available. Moreover, their therapeutic judgement was based on previously published consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays could not be interpreted in 11% of cases. In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation. In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117). In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified. Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection. The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy.

Persistent viral load in patients on HAART is associated with a higher level of activation-induced apoptosis of CD4(+) T cells.

Apoptosis is one of the mechanisms involved in the persistent CD4(+) T cell lymphopenia occurring in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART). The aim of this study was to look at the relationship between the level of T cell apoptosis in patients on HAART and their HIV viral load measurement. Forty-five patients receiving HAART for a median time of 5 months were included: 13 had an undetectable viral load and 32 had a viral load > or = 200 copies/mL. No relationship was observed between the level of spontaneous T cell apoptosis and the viral load measurement. Patients with a viral load > or = 200 copies/mL exhibited a significantly higher level of CD4-induced apoptosis of CD4(+) T cells, compared with patients with undetectable viraemia (38 versus 15%, respectively, P = 0.03). Activation-induced apoptosis may be involved in the paucity of the immune reconstitution observed in HIV-infected patients treated with HAART.

Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata.