P.-M. Roger

Antibiotic misuse: a prospective clinical audit in a French university hospital

The aim of the study presented here was to prospectively audit antibiotic prescriptions given to patients attending L’Archet Hospital in Nice, France, with details of the initial medical examination included in the audit procedure. A total of 122 antibiotic treatments were evaluated, i.e. 31% of all antibiotic therapies initiated in the eight participating departments over the 9-week study period. Forty-two (34%) treatments were found to be unnecessary due to misdiagnosis, and 36 (30%) other treatments were inappropriate. Misdiagnosis, due to the misinterpretation or lack of clinical, microbiological and/or imaging data is thus a major cause of antibiotic misuse. Improvement in the diagnostic process should become part of antibiotic policy.

Overexpression of Fas/CD95 and Fas-induced apoptosis in a patient with idiopathic CD4+ T lymphocytopenia.

The mechanisms of apoptosis have become better understood, in part with the discovery of Fas/CD95. We report the case of a patient characterized by a decreased CD4+ T cell count and an overexpression of Fas/CD95 resulting in apoptosis. A 54-year-old man presented with disseminated Mycobacterium xenopi infection. Analysis showed CD4+ T lymphopenia. Tests for human immunodeficiency virus (HIV) types 1 and 2 were negative. We compared the patient with eight healthy controls and five HIV-infected patients in terms of the expression of Fas/CD95 and Fas-mediated apoptosis of peripheral T lymphocytes. The percent of CD95+ cells in lymphocytes was 98% for the patient, and the mean percent of CD95+ cells in lymphocytes +/- SD for HIV-infected patients and healthy controls was 75% +/- 16% and 36% +/- 26%, respectively. The patient had a high level of spontaneous apoptosis, and apoptotic cells were all identified as being CD4+ T cells. Monoclonal antibodies to CD95 dramatically increased apoptosis of CD4+ T cells exclusively. CD4+ T lymphopenia observed in our patient correlated with an overexpression of Fas together with spontaneous and Fas-induced apoptosis.

Antimicrobial lock therapy in central-line associated bloodstream infections: a systematic review

PurposeAntimicrobial lock therapy (ALT) seems a promising approach for treatment of central line associated bloodstream infections (CLABSI). The recent introduction of molecules such as daptomycin and tigecycline, alone or in combination with other molecules, improved chances of efficacy of ALT, due to their activity on the bacterial biofilm. Our aim was to review the literature concerning ALT for CLABSI, including data concerning novel molecules.MethodsWe included case-control studies evaluating two or more molecules as ALT in central venous catheter infections extracted from the Medline database. Among 221 available articles in Pubmed, 54 were selected for their particular interest concerning ALT.ResultsIncidence of CLABSI is high worldwide. Mechanisms of catheter infection include contamination by skin bacteria, hand contamination and hematogenous diffusion. Catheter-infection is associated with biofilm formation, which reduces the efficacy of ALT. The most promising situation for ALT to succeed in salvaging a catheter appears to be coagulase-negative Staphylococcus infection, which is the main causative agent of CLABSI. Daptomycin, Tigecycline, Ethanol and Taurolidine appear as the best options for treating CLABSI; data are mostly available for Daptomycin, which showed, alone or associated with Rifampin, good in vitro potency on biofilm, but few in vivo data exist on efficacy.ConclusionsThe introduction of novel molecules has increased chances of catheter salvage with ALT in case of CLABSI, but further in vivo studies are needed.

Gestion de services, tarification à l’activité, recherche clinique et évaluation des pratiques professionnelles : un même outil informatique

The current French hospital reform is based on the disease-related group (DRG) approach and the constitution of bigger units pooling several departments of different specialties. This reform needed an efficient assessment of various medical activities. We report our experience of a medical table of our hospital activities used for 27 months. This medical table was made with a basic software integrating 24 parameters. The original concept was the translation of the specific final diagnosis for DRG defined by the site of infection. To create this medical table, we first simplified the conclusions of the patients chart using a consensual and systematic plan. The number of patients per DRG and their evolution were therefore specifically determined. The medical table helped us in the daily management of our department, to identify the area of recruitment, the potential for heterogeneous care, allowing the implementation of protocols and their applications. Moreover, the table quantified morbidity and mortality, indicating our need for cooperation with other departments. All this data used medical-lexical terms, allowing other than economic analyses, even if this table identifies hospitalization-related costs, namely duration of hospital-stay, nosocomial infections and iatrogenic events. Finally, our table supports medical research and evaluation of practice. Our future goals are to introduce this table in several infectious-diseases units, and create specific tables for the main RDG, including economic parameters.

Fluoroquinolone prescriptions in a teaching hospital: a prospective audit.

The aim of this study was to identify prospectively the prevalence of unnecessary or inappropriate fluoroquinolone prescriptions in our teaching hospital and to identify the contributing factors. 55% of the 110 prescriptions evaluated were unnecessary or inappropriate. Ward and combination therapies were significantly associated with misuse.

Do viral load and CD8 cell count at initiation of tritherapy influence the increase of CD4 T-cell count?

Background:Tritherapies including protease inhibitors improve clinical status and usually increase CD4 T cell count. However, the dissociation between the marked decreases in viral load and the incomplete restoration of CD4 cell counts with a three-drug combination has been reported. We assessed this potential difference among our patients. Methods:Patients were enrolled when a protease inhibitor was prescribed to them for the first time. Using a computerized medical record (ADDIS®), we retrospectively assessed a potential relationship between the increase in CD4 T cells (δCD4) at M3, M6 and variables including sex, age, CDC staging, protease inhibitor, prior antiviral therapy, CD8 and viral load at baseline. We used Epi-Info 6.4 and BMDP software. Results:Data were analyzed on 154 patients. The median CD4 T cell count was 157 at baseline, 215 at month 3 and 202 at month 6. The median viral load was 52 000 copies at baseline, 530 at month 3 and 500 at month 6. In a univariate analysis, a significant relationship was found between δCD4 and CD8 at baseline. A statistically significant negative correlation appeared between the CD8 cell count at baseline and δCD4 at M6 (r = −0.28, Pearson). Moreover, we found that there also was a relationship between δCD4 and viral load at baseline. There was a correlation between δCD4 at M6 and the viral load at MO (r = 0.37, Pearson). In a multiple regression model, after CD8 count at baseline had been accounted for, we found a significant correlation between δCD4 and viral load at baseline (multiple r = 0.33 at M3, and 0.40 at M6). Conclusions:Patients with a low viral load do not benefit from as great an increase in CD4 T cell count as others when they receive a tritherapy including protease inhibitors. These results suggest that another mechanism rather than direct viral pathogenicity leads to CD4 T cell destruction. This mechanism may not be efficiently stopped by antiviral therapy, especially protease inhibitors.

Early CD4+ T Cell Recovery in Human Immunodeficiency Virus-Infected Patients Receiving Effective Therapy Is Related to a Down-Regulation of Apoptosis and Not to Proliferation

This prospective study investigated the contributions of apoptosis and proliferation of CD4(+) T cells obtained by the introduction of a new antiretroviral treatment for human immunodeficiency virus infection. Virus load; T cell counts; apoptosis of T cell subsets, including naive cells; and proliferation were determined from treatment initiation to the third month in a cohort of patients. An increase in CD4(+) T cell count > or = 100 cells/microL over baseline was considered to be a satisfactory immune reconstitution. Sixty-nine patients completed the protocol, 22 of whom met our definition of a satisfactory immune reconstitution, showing a significantly more pronounced reduction in spontaneous CD4(+) T cell apoptosis at month 1 as well as month 3, compared with the other patients. In contrast, neither Fas-induced apoptosis down-regulation nor Fas-induced increased proliferation capacity was associated with a satisfactory immune reconstitution. Down-regulation of CD4(+) T cell apoptosis by antiretroviral treatment is the main mechanism associated with early CD4(+) T cell increase.

Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway

T-cell apoptosis during septic shock (SS) has been associated with deleterious outcome, but the mechanisms of apoptosis are not well understood. As T-cells are not infected in bacterial infection, our hypothesis was that deleterious interactions between lymphocytes and monocytes could be involved. This is a cross-sectional study of 27 patients presenting with community-acquired SS, 23 infected patients without SS and 18 controls. Cytofluorometric techniques were used to study apoptosis, the costimulatory pathway and cytokine synthesis. Apoptosis was increased in SS compared to infected patients without SS and controls: the median values were 18, 2 and 3%, respectively, for CD4+ T-cells (P < 0.001), and 12, 5 and 2%, respectively, for CD8+ T-cells (P < 0.001). Patients with SS exhibited significant CD152 over-expression on T-cells, while CD86 expression was decreased on monocytes (P = 0.004). The synthesis of interleukin-2 was decreased in patients with SS compared to the other groups, while secretions of interferon-gamma and TNF-alpha were not altered. Ten surviving patients with SS showed a trend towards the normalisation of these parameters on day 7. In SS, T-cell apoptosis is related, at least in part, to the alteration of the costimulatory pathway, which, in turn, leads to significant modification of the cytokine network.

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 patients 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.

Syndrome de Lemierre : à propos de 6 cas

Resume Propos. – Le syndrome de Lemierre est une pathologie rare mais grave qui associe fievre, douleur cervicale et symptomatologie pulmonaire dans les suites d’une infection oropharyngee, le plus souvent une angine. La large utilisation des antibiotiques dans les infections oropharyngees n’a pas permis une disparition de cette infection. Nous avons voulu, a travers ces 6 observations originales faire partager notre experience. Methodes. – Il s’agit d’une etude descriptive retrospective menee entre 1995 et 2000 dans deux services (maladies infectieuses et tropicales et reanimation medicale) du centre hospitalier universitaire de Nice. Resultats. – Nous presentons une serie de 6 cas de ce syndrome, tous de sexe feminin et âges de 27 ans en moyenne. Il s’agissait de sujets anterieurement sains et la symptomatologie oropharyngee initiale etait une angine. Ces patientes presentaient dans la majorite des cas des signes de sepsis severe et une patiente est decedee des suites d’un choc septique. Dans les autres cas, l’evolution a ete favorable sous traitement. Le delai entre l’angine et l’apparition du syndrome infectieux etait de 7 jours en moyenne. Le traitement a consiste en une association betalactamine et metronidazole dans 4 cas, amoxicilline–acide clavulanique pour les autres cas. Une anticoagulation a ete systematiquement debutee en cas de thrombose jugulaire interne documentee. Conclusions. – Le diagnostic peut etre fortement suspecte sur la clinique et confirme secondairement par les examens complementaires. Le pronostic depend etroitement de la rapidite et de la qualite de la prise en charge. Nous avons donc souhaite familiariser nos confreres avec cette pathologie en rapportant notre experience personnelle.