Pierre Roger

The early phase of human sepsis is characterized by a combination of apoptosis and proliferation of T cells

PURPOSE T cell activation as well as unresponsiveness has been described in separate studies in sepsis. Our aim was to establish the coexistence of both T cell fate in human sepsis. PATIENTS AND METHODS This is a cross-sectional study of 48 patients presenting with severe sepsis or septic shock and 15 healthy controls. Cytofluorometric techniques were used to quantify T cell activation, apoptosis, proliferation, expression of costimulatory molecules, and cytokine secretion. RESULTS Patients with sepsis were characterized by a significant increase in the percentage of activated T cell subsets, as measured using CD69 marker, compared with healthy controls (P<.05). T cell proliferation as measured through Ki67 expression was obvious in infected patients for both CD4 and CD8 T cell subsets compared with controls (P ≤.006). T cell subset apoptosis as measured using Hoechst dye was also increased in infected patients compared with controls (P ≤.002). CD4 T cell proliferation was correlated with interleukin 2 secretion (R(2)=0.84, P<.001), whereas up-regulation of CD4 T cell apoptosis was correlated with CTLA-4 expression (R(2)=0.24, P=.001). No such similar relationship was observed for CD8(+) T cells. CONCLUSIONS Concomitant T cell proliferation and T cell apoptosis are observed in human sepsis, being related to a different pathway.

Factors associated with effective reassessment of antibiotic therapy on day 3

UNLABELLED Reassessment of antibiotic therapy (RA) after 3 days is constitutive of French antibiotic stewardship. This delay is required because of the need for clinical reappraisal and for obtaining microbiological data. Our aim was to determine the factors associated with an effective RA. PATIENTS AND METHOD A prospective study was made in a 350-bed general hospital in which all prescriptions are computerized and validated daily by prescribers. All curative antibiotic therapies were reassessed during 4 weeks. RA was defined as effective if the initial antibiotic treatment was modified. All clinical, biological, and radiological data having contributed to the initial prescription and to RA were recorded during bedside visit with the prescribers, two hospital physicians and one infectious diseases specialist. RESULTS In one month, 148 antibiotic treatments were reassessed. Pulmonary, digestive, and urinary infections accounted for two thirds of the cases. An effective RA was recorded in 28 cases (19%) and associated with hospitalization in the ICU (P=0.001), imaging supporting the diagnosis (P=0.016), and persistence or aggravation of clinical signs (P=0.007). Microbiological findings were not contributive to an effective RA. CONCLUSION RA was associated to hospitalization in the ICU, to an inflammatory syndrome, and to the clinical outcome after 3 days. These results should help to improve the implementation of infectious diseases advice.

J-09 Évaluation prospective des associations d’antibiotiques par l’infectiologue référent d’un centre hospitalier

Nous avons rapporte un taux d’antibiotherapies (ATB) inadequates superieur a 30 % au sein d’un hopital presentant une organisation optimale (protocoles ecrits, prescriptions informatisees, commission des antibiotiques active). Cette mesure a permis l’institution d’une consultation d’un infectiologue referent (IR). Nous rapportons ici une evaluation prospective des bitherapies antibiotiques par l’IR. Patients et methodes La consultation de l’IR avait lieu une demi-journee par semaine. Les ATB comprenant au moins deux molecules etaient repertoriees par la pharmacie grâce aux prescriptions informatisees, de meme que la duree d’administration avant la consultation de l’IR. Une discussion contradictoire avec le clinicien en charge du patient etait systematique, evaluant la pertinence des prescriptions en termes diagnostique et therapeutique. Resultats Durant 12 semaines, 207 patients beneficiaient d’une ATB comprenant au moins deux molecules : 58 etaient evalues par l’IR (28 %). Trois des 12 services hospitaliers (reanimation, pneumologie, medecine interne) representaient la moitie des prescriptions. L’evaluation indiquait une concordance diagnostique pour 37 patients (64 %), le diagnostic etant incertain 14 fois (24 %) et inadequate 7 fois. L’antibiotherapie etait 21 fois documentees (36 %), 28 fois probabilistes (48 %) et 9 fois empiriques. La discussion contradictoire mettait en evidence 29 ATB inutiles (50 %), 15 utiles (26 %) et 14 d’interet discutable. Les infections respiratoires constituaient le motif essentiel des bitherapies inutiles ou d’interet discutable, soit 26 des 58 evaluations (45 %). La duree totale d’ATB inutile etait de 114 jours. Conclusion La discussion diagnostique, independante de la qualite d’organisation hospitaliere, est un element central du bon usage des antibiotiques. L’informatisation des prescriptions permet l’evaluation de l’antibiotherapie par l’IR malgre une duree de passage limitee.

Infections respiratoires des sujets âgés : intérêt d’une structure spécialisée

Resume Objectifs L’afflux important durant l’hiver 1999 de patients âges presentant une affection cardiorespiratoire febrile a justifie l’ouverture d’une unite specialisee temporaire au sein de notre institution. Cette structure appelee « Medecine d’Hiver » a ete l’occasion d’experimenter une nouvelle methodologie de travail basee sur un objectif : « un bilan infectiologique rapide » sur une periode determinee permettant de combiner une prise en charge a la fois ambulatoire et hospitaliere. Materiel et methodes Une unite d’hospitalisation de 24 lits etait ouverte a l’hopital Pasteur du CHU de Nice. L’equipe medicale etait composee de deux praticiens detaches du service des maladies infectieuses et l’equipe paramedicale etait recrutee sur la base du volontariat. Le medecin du service etait le seul habilite a accepter les patients dans l’unite quelle que soit l’heure, via le service d’accueil des urgences (SAU). Un bilan clinique, microbiologique et iconographique, focalise sur la pathologie cardiorespiratoire febrile du sujet âge, etait realise a l’entree du patient. La sortie etait effectuee en temps reel via un courrier etabli le jour de la sortie et communique au patient et aux partenaires medicaux et paramedicaux de ville. Resultats Une infection respiratoire etait diagnostiquee chez 330 des 1 015 patients hospitalises (32 %) durant les six periodes d’ouverture du service de Medecine d’Hiver. Deux cent vingt-trois patients (68 %) venaient de leur domicile et 107 d’une maison de retraite ou d’une institution ; 87 % de ces patients avaient au moins une co-morbidite. Les motifs d’admission a partir du SAU etaient une bronchite dans 81 cas (24 %), une pneumonie dans 140 cas (42 %), une fievre dans 58 cas (18 %) ou un autre motif dans 51 cas (16 %). Les diagnostics en fin d’hospitalisation etaient une bronchite dans 151 cas (45 %), une exacerbation de BPCO dans 25 cas (8 %) et une pneumonie dans 154 cas (47 %). Les deux agents pathogenes les plus frequents etaient le pneumocoque, isole 51 fois, et le virus grippal, 67 fois. Durant l’hospitalisation 177 patients (54 %) ont beneficie d’un traitement, de maniere probabiliste dans 60 cas (34 %), et donc d’emblee documentee dans 117 cas (66 %). Il s’agissait d’une bitherapie dans 30/177 cas (18 %), la duree moyenne de traitement hospitalier etant de 4 ± 10 jours. Trente-sept patients decedaient (11 %). Conclusion Meme si l’ouverture de cette structure s’est faite dans l’urgence, le fonctionnement de celle-ci s’est rapidement organise autour de la pathologie cardiorespiratoire febrile du patient âge. Une nouvelle methodologie de travail, un engagement important du personnel soignant et une collaboration etroite des partenaires medicaux et paramedicaux de ville ont permis une prise en charge specialisee, a la fois hospitaliere et ambulatoire, de ce type de pathologie.

Improved quality of care for patients infected or colonised with ESBL-producing Enterobacteriaceae in a French teaching hospital: impact of an interventional prospective study and development of specific tools

The increasing incidence of ESBL-producing Enterobacteriaceae (ESBL-E) in France prompted the publication of national recommendations in 2010. Based on these, we developed a toolkit and a warning system to optimise management of ESBL-E infected or colonised patients in both community and hospital settings. The impact of this initiative on quality of care was assessed in a teaching hospital. The ESBL toolkit was developed in 2011 during multidisciplinary meetings involving a regional network of hospital, private clinic and laboratory staff in Southeastern France. It includes antibiotic treatment protocols, a check list, mail templates and a patient information sheet focusing on infection control. Upon identification of ESBL-E, the warning system involves alerting the attending physician and the infectious disease (ID) advisor, with immediate, advice-based implementation of the toolkit. The procedure and toolkit were tested in our teaching hospital. Patient management was compared before and after implementation of the toolkit over two 3-month periods (July–October 2010 and 2012). Implementation of the ESBL-E warning system and ESBL-E toolkit was tested for 87 patients in 2010 and 92 patients in 2012, resulting in improved patient management: expert advice sought and followed (16 vs 97%), information provided to the patient’s general practitioner (18 vs 63%) and coding of the condition in the patient’s medical file (17 vs 59%), respectively. Our multidisciplinary strategy improved quality of care for in-patients infected or colonised with ESBL-E, increasing compliance with national recommendations.

Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection

AIM To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients in a real life setting. METHODS Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin (PegIFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database (Nadis(®)). Liver fibrosis was measured by elastometry (Fibroscan(®)) with the following cut-off values: F0-F1: < 7.1 kPa, F2: 7.1-9.5 kPa, F3: 9.5-14.5 kPa, F4: ≥ 14.5 kPa. The proportion of patients with sustained virological response (SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS Forty-one patients were included: 13 (31.7%) patients were HCV-treatment naïve, 22 (53.7%) had advanced liver fibrosis or cirrhosis (Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them (83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia (88%) and rash (25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION Telaprevir and boceprevir retain their place among potential treatment strategies in HIV-HCV coinfected patients including those with advanced compensated liver disease and who failed previous PegIFN/RBV therapy.

T-08 Réévaluation de l’antibiothérapie à 48-72 heures (R-ATB) à l’échelle d’un Centre Hospitalier Régional

Introduction et objectifs La R-ATB est une etape majeure du bon usage des antibiotiques. Sa realisation peut s’averer difficile, les facteurs limitants etant nombreux. Nous rapportons ici une R-ATB menee a l’echelle d’un centre hospitalier. Materiels et methodes Il s’agissait d’une etude prospective visant a inciter la R-ATB, menee par 2 medecins cliniciens et un infectiologue dans tous les services d’un hopital regional, a l’exception du SAU. Les prescriptions etant informatisees, toutes les antibiotherapies etaient repertoriees par la pharmacie. Dans un premier temps etait proposee aux prescripteurs une feuille repertoriant les arguments diagnostiques conduisant a l’antibiotherapie. Puis a 48-72 heures, une nouvelle feuille d’evaluation visait a caracteriser les motifs de cette R-ATB. Resultats Cette enquete etait menee du 1 er au 15 juin 2008 : 108 antibiotherapies curatives etaient prescrites, dont 105 effectivement reevaluees. Il s’agissait de 89 % d’infections communautaires, dont 38 % de pneumopathies, 19 % d’infections urinaires et 13 % d’infections digestives. A l’initiation therapeutique, plus de 2 signes cliniques en faveur du diagnostic etaient rapportes dans 41 % des cas, tandis qu’aucune donnee clinique n’etait enoncee dans 29 % des cas. Le syndrome inflammatoire etait l’unique motif de la prescription dans 12 % des cas. Il s’agissait de 26 bitherapies et 79 monotherapies, documentee d’emblee dans 19 % des cas et probabiliste dans 72 % des cas. La R-ATB amenait a la modification de 14/105 antibiotherapies (13 %), 2 traitements etant stoppes. Les antibiotherapies modifiees etaient caracterisees par une plus grande documentation clinique. Conclusion La R-ATB est une demarche difficile a instaurer. Les motifs de prescription etant restreints, les raisons d’en changer a court terme sont quasi-inexistantes en l’absence de discussion contradictoire.

Péritonite à Candida après gastrostomie percutanée. Echec du traitement par fluconazole ; existence d'une lymphopénie CD4 non liée au virus de l'immunodéficience humaine

Summary We report a case of peritoneal candidiosis following percutaneous gastrostomy. Specific antibodies were detected in peritoneal fluid. A severe but transient CD4 lymphopenia was found in this patient non-infected by HIV. Despite adequate fluconazole concentrations in ascitis, treatment failed. Combination of amphotericin B with flucytosine resultes in successful outcome.