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Central venous catheter (CVC)-related infections (CRIs) are a key target for infection control in intensive care units (ICUs). The aim of this study was to describe temporal trends of CRI incidence in a network of volunteer ICUs in Northern France. During a 4 month surveillance period each year, all CVCs in place for more than 48h were prospectively followed until removal or patient discharge. Standard clinical and microbiological criteria were used to define colonization and CRI. The standardized incidence ratio (SIR) was estimated by dividing the number of observed CRIs by the number of expected CRIs, which was computed using a logistic regression model including risk factors for CRI. CRI incidence and SIR were fed back to ICUs as a benchmark at the end of each period. From 2001 to 2005, 135 ICUs participated for at least one surveillance period. Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR also decreased significantly from the first to the third surveillance period in these ICUs. These results suggest that surveillance programmes have a significant impact on CRI risk in ICUs and remain an important strategy for combating nosocomial infections in these settings.

Resume La prescription d'antibiotiques en reanimation est frequente, et fait souvent appel a des antibiotiques a large spectre ; sa qualite n'a jamais ete evaluee en reanimation pediatrique. Objectifs Relever les modalites de prescription des antibiotiques en reanimation pediatrique et les confronter aux recommandations de la litterature et aux donnees bacteriologiques. Methodes Analyse prospective, monocentrique, independante, de 52 prescriptions consecutives d'antibiotiques chez 45 enfants pour un total de 47 hospitalisations entre le 1 er janvier et le 31 mars 2005. Resultats Le diagnostic d'infection bacterienne etait retenu pour 50 des 52 prescriptions. L'infection etait communautaire dans 35 cas (70 %) et nosocomiale dans 15 cas. Dix malades sur 45 sont decedes en cours de traitement antibiotique (22 %), dont 5 a cause de l'infection. La monotherapie representait 56 % des prescriptions d'antibiotiques. L'antibiotherapie initiale etait empirique dans 42 cas sur 52 (81 %). Les prescriptions empiriques etaient secondairement documentees dans 48 % des cas. Un ou plusieurs micro-organismes etaient isoles pour 60 % des prescriptions initiales. Des erreurs de posologie (excessive [10 %] ou insuffisante [13 %]), du nombre d'administrations quotidiennes (4 %), du mode d'administration (6 %), de la voie d'administration (2 %), et/ou de la duree de traitement (excessive [4 %], insuffisante [8 %]) etaient constatees. Au total, 77 % des prescriptions semblaient adaptees aux germes identifies ou suspectes, mais seulement 63 % des prescriptions etaient en adequation avec les recommandations publiees. Conclusion Pres de 2 prescriptions antibiotiques sur 3 etaient en adequation avec les recommandations. La mise en place de protocoles standardises, specifiques devrait permettre d'optimiser ces prescriptions.

Position du probleme La surveillance epidemiologique des infections nosocomiales est l’un des axes importants de l’amelioration de la qualite des soins dans les etablissements de sante. Les services participant a un reseau ayant des methodes standardisees peuvent etre compares entre eux en utilisant des indices de risque ajustes. Au sein du reseau de surveillance des infections liees aux catheters veineux centraux (ILC) en reanimation (REACAT), nous proposons un indice de risque ajuste sur plusieurs facteurs de risque des ILC : le ratio standardise d’incidence (RSI). Methodes Tous les catheters veineux centraux (CVC) maintenus plus de 48h etaient surveilles en prospectif, 4 mois par an. Les ILC etaient definies sur des criteres cliniques et microbiologiques consensuels. Un modele de regression logistique, developpe sur les donnees regroupees des trois dernieres periodes de surveillance, a ete retenu comme modele predictif de l’ILC. Pour chaque service et annee, un nombre d’ILC attendu a ete calcule et a permis d’estimer le RSI. Resultats Entre 2000 et 2003, 108 services ont participe a au moins une des periodes de surveillance, incluant 6 414 CVC. Deux cent trente neuf ILC ont ete identifiees, soit une densite d’incidence (DI) de 3,6 ILC/1000 jours d’exposition aux CVC. Les facteurs associes a l’ILC etaient la duree de maintien (OR ajuste = 1,1 ; IC95 % [1,0-1,1]), le rang de pose (1,7 ; [1,1-2,2]), le site d’insertion (1,6 ; [1,2-2,1]), la perfusion d’antibiotique (0,5 [0,3-0,7]), l’existence d’au moins une defaillance viscerale (2,2 [1,5-3,2] ) et d’une infection a un autre site a l’ablation du CVC (1,9 [1,4-2,6]). Parmi les 14 services avec une DI superieure a 5,5 ILC/1 000 jours-CVC (correspondant au 75 e percentile), seulement 2 avaient un RSI significativement superieur a 1, dont un seul avait inclus plus de 20 CVC. Conclusion La surveillance REACAT a permis la construction d’un RSI, indice de risque global et robuste, permettant d’identifier des services ou le risque d’ILC est eleve et d’orienter les actions de prevention.

Resume L'aspergillose invasive est une complication grave de l'immunodepression. L'arrivee de nouveaux antifongiques a amene le CHRU de Lille a rediger des recommandations, multidisciplinaires, et reactualisees regulierement. Ces recommandations sont d'ordre diagnostique et therapeutique. Le diagnostic repose principalement sur la realisation precoce d'un scanner thoracique ainsi que sur le dosage du galactomannane sanguin et dans le liquide de lavage bronchoalveolaire. Le texte differencie prophylaxie, traitement probabiliste et traitement documente. Seules de rares situations (greffe pulmonaire, allogreffe de moelle si GVH et corticotherapie) justifient d'une prophylaxie primaire. Le traitement probabiliste de premiere intention doit etre une des formes commercialisees d'amphotericine B choisie selon le terrain. La caspofungine est une alternative. Le traitement documente est, selon le tableau ou la localisation, une monotherapie mais peut aussi etre une association antifongique. Le traitement de premier choix en cas de monotherapie est le voriconazole intraveineux. Les derives lipidiques de l'amphotericine B sont une alternative. Une association est licite d'emblee en cas de lesions multiples, ou, secondairement, en cas d'evolution malgre une monotherapie. Elle comporte de la caspofungine, associee avec de l'amphotericine B liposomale ou du voriconazole. Une cooperation medicochirurgicale precoce est recommandee.

Resume L’analyse de la litterature a permis d’identifier un certain nombre d’actions dont l’impact clinique, pharmacologique, ecologique et economique a pu etre evalue, et de les hierarchiser en fonction de leur utilite, de la simplicite de leur mise en œuvre, et de leur cout. A l’echelle de l’etablissement, l'element pivot des strategies gagnantes de la politique d’utilisation des antibiotiques est le couple pharmacien–infectiologue, associant maitrise de la dispensation et expertise clinique, au sein d’une equipe multidisciplinaire. En ne retenant que les mesures utiles, et dans un compromis entre priorite et faisabilite, les actions a mettre en place dans les etablissements de soins peuvent etre hierarchisees de la facon suivante : 1) creation sans delai d’une commission des antibiotiques ; 2) et mise en place d’une equipe pluridisciplinaire operationnelle en infectiologie composee de temps de pharmacien, de bacteriologiste, et de clinicien referent ; 3) redaction des referentiels de prescriptions (antibioprophylaxie, antibiotherapie curative pour 80 % des situations) ; 4) puis mise en place des ordonnances specifiques nominatives justifiees, uniquement si les referentiels existent, et du controle de prescription cible pour les situations difficiles ; 5) informatisation progressive de la prescription, dont l’absence initiale ne doit pas freiner la mise en place des premieres mesures de controle ; 6) a tout moment utilisation de l’outil d’audit pour evaluer les situations existantes et l’impact des mesures prises ; 7) information et formation des prescripteurs.

Resume Cas cliniques – Nous rapportons deux observations de bacteriemie a M. bovis , apres instillation endovesicale du BCG pour carcinome vesical. Un sondage traumatique a precede la BCG-therapie dans les deux cas. Cas n°1 : Un homme de 64 ans a ete hospitalise pour choc septique apres la deuxieme instillation endovesicale. Le traitement initial par ciprofloxacine a ete un echec. Le diagnostic de BCGite a ete affirme par la ponction biopsie hepatique. L'evolution a ete favorable sous traitement antituberculeux et corticoides. Cas n°2 : Un homme de 70 ans a ete hospitalise, dans les memes conditions, quelques heures apres la troisieme instillation endovesicale. Une hemoculture a ete positive a M. bovis variant BCG Connaught (souche vaccinale). Le traitement antituberculeux triple et corticoides a permis une amelioration franche. Commentaires – Les deux observations plaident pour l'utilisation systematique de corticosteroides dans les formes graves de BCGites en association avec une tri therapie antituberculeuse.

Resume Objectif – Evaluer les moyens consacres a la lutte contre l'infection nosocomiale, et les politiques de maitrise de la diffusion des bacteries multiresistantes. Materiel et methodes – Des recommandations pour la maitrise de la diffusion des bacteries multi-resistantes ont ete elaborees. En les utilisant comme referentiel, une enquete multicentrique dans la region Nord–Pas-de-Calais a ete realisee. 62 etablissements (21 631 lits), ont ete inclus dans l'etude. Resultats – Six Unites d'Hygiene ont ete identifiees; 17 etablissements (27%) beneficiaient des prestations d'une unite operationnelle en hygiene directement ou par convention. Il a ete denombre 1 equivalent temps plein (ETP) medecin / 4 081 lits de court sejour, 1 ETP d'infirmiere hygieniste / 600 lits de court sejour. Un seul etablissement avait le ratio recommande de praticien hygieniste, et 12 celui d'infirmiere hygieniste. Le deficit etait de 21,7 ETP (medecins) et de 19 ETP (infirmieres hygienistes). 81% des etablissements declaraient l'existence de referents en hygiene. La proportion de chambres seules etait de 58%, celle des points d'eau equipes pour le lavage des mains au savon doux de 45% et de 38% pour le lavage anti-septique. La signalisation des patients porteurs de bacteries multiresistantes etait utilisee correctement dans 12,5%. Dans 55% des etablissements, aucune unite n'avait la totalite du materiel necessaire pour un isolement technique. 77% d'entre elles disaient modifier l'organisation des soins en presence de patients porteurs de bacteries multiresistantes. Des protocoles ecrits (lavage des mains, procedures d'isolement) etaient accessibles dans 71% des unites.

Resume La pertinence et les indications eventuelles des traitements adjuvants d'une forme grave de paludisme a Plasmodium falciparum ont ete objectivement evaluees au travers de la revue de la litterature. Malgre la publication de pres de 120 cas d'exsanguinotransfusion, il est encore difficile aujourd'hui de se prononcer sur son interet reel. De ce fait, ses indications devraient etre limitees aux formes les plus graves. L'utilisation des antibiotiques ne doit pas etre negligee dans le traitement des infections bacteriennes associees, notamment en presence d'un etat de choc a l'admission ou en cours d'evolution, ou du developpement d'un syndrome de detresse respiratoire aigue. L'heparine et les corticoides n'ont pas d'indications, car inutiles, voire deleteres. Les convulsions doivent etre traitees rapidement avec une benzodiazepine, et leur prevention par l'utilisation de phenobarbital semble possible. La restauration d'une volemie efficace est necessaire, mais elle doit etre realisee de facon prudente, compte tenu des risques de developpement d'un œdeme pulmonaire lesionnel dans le cadre d'une agression pulmonaire aigue ou d'un syndrome de detresse respiratoire aigue. En cas d'insuffisance renale aigue, le recours a l'hemodialyse doit etre precoce, meme si l'etat clinique ne semble pas alarmant. L'hemofiltration veinoveineuse continue n'est actuellement pas recommandee en l'absence d'insuffisance renale aigue.

Resume Objectif Nous avons voulu apprecier l'influence des ordonnances nominatives a duree limitee sur la prescription des antibiotiques dans un CHU. Methodes Nous avons instaure, en janvier 1998, des ordonnances nominatives a duree limitee (quatre jours pour les traitements probabilistes et sept jours pour les traitements documentes). Les formes intraveineuses des molecules suivantes etaient concernees: amikacine, cefepime, sulbactam, ciprofloxacine, ceftazidime, fosfomycine, acide fusidique, ofloxacine, piperacilline, teicoplanine, tazocilline, imipeneme, fluconazole et vancomycine. Elles n'etaient delivrees que sur presentation d'une ordonnance specifique. Les quantites consommees ont ete suivies mensuellement depuis 1997 et exprimees en doses definies journalieres pour 100 jours d'hospitalisation. Les antibiotiques non restreints etaient evalues annuellement. Resultats L'activite de l'etablissement a legerement augmente (journees d'hospitalisation: + 1,9 %, admissions: + 5,1 %) de 1997 a 1998. Une diminution de 17,7 % de la consommation des antibiotiques restreints et une augmentation de 3 % des autres a ete observee. La baisse des molecules restreintes etait compensee par une hausse des molecules non restreintes de meme classe. Cependant, une diminution globale de 1,6 % des doses consommees a ete observee. Cela s'est traduit par une baisse de 7,4 % du budget antibiotique et de 11,7 % du ≪ cout antibiotique ≫ par patient. Commentaires La qualite des soins ne semble pas avoir ete modifiee (stabilite de la duree de sejour et du taux de mortalite). Le suivi est trop court pour voir un effet sur les isolements de bacteries multiresistantes. Cette etude suggere que des methodes faiblement coercitives peuvent reduire l'utilisation des antibiotiques a l'hopital.

A population approach was used to determine isepamicin pharmacokinetics in 196 intensive care unit patients treated for nosocomial pneumonia with isepamicin and a broad-spectrum beta-lactam. Patients were randomized in four groups with respect to the following isepamicin dosing regimens: (i) 15 mg/kg od for 5 days or (ii) 10 days, (iii) 25 mg/kg on the first day followed by 15 mg/kg od for 4 days or (iv) 9 days. A total of 1489 serum isepamicin concentrations were measured (median, eight per patient; range, 1-18). Mean +/- S.D. 1 h-peak levels at day 1 were 76 +/- 32 mg/L after the 25 mg/kg dose (n = 85) and 43 +/- 15 mg/L after the 15 mg/kg dose (n = 99). A bicompartmental model was fitted to the data by a mixed-effect modelling approach. Isepamicin clearance was related to age, bodyweight and serum creatinine level. Central volume of distribution was related to bodyweight. Pharmacokinetic parameters were independent of the dosage in the range 15-25 mg/kg and were not different in the patients treated for 5 or 10 days. Bayesian estimates of individual pharmacokinetic parameters were used to calculate various surrogate markers of isepamicin exposure to be tentatively correlated with clinical outcome and nephrotoxicity. No correlation was found between peak, AUC or their ratio with MIC and clinical efficacy. A weak correlation was found between the increase of serum creatinine level (day 1 versus day 5) and isepamicin 24 h trough level at day 1 (R2 = 0.10). These data do not favour a systematic therapeutic monitoring of isepamicin in intensive care unit patients, at least with the doses and antibiotic combinations used in this study.

Resume Une etude d'incidence de Pseudomonas aeruginosa a ete menee en 1996 par 25 centres hospitaliers (13913 lits) de la region Nord-Pas-de-Calais. L'enquete s'est deroulee sur deux periodes trimestrielles durant lesquelles ces etablissements ont realise 230 018 entrees. L'incidence des patients infectes ou colonises par P. aeruginosa s'etablit a 9,4/1 000 admissions et rapportee a l'annee a 31,2/100 lits. Les incidences d'isolement calculees par discipline montrent des taux eleves pour les services de reanimation : 425,8 P. aeruginosa par an et pour 100 lits. Trois serotypes (O 11 , O 6 , O 4 ) representent plus de 40 % du recrutement. Les pourcentages de sensibilite aux antibiotiques (3 056 souches) sont de 66,5 % pour la ticarcilline, 84,7 % pour la ceftazidime, 82,2 % pour l'imipeneme, 73,3 % pour l'amikacine et 61,2 % pour la ciprofloxacine. Cette enquete confirme l'importance de P. aeruginosa dans les hopitaux de la region mais montre de tres grandes differences quant a la situation locale de chaque etablissement tant en termes d'incidence qu'en termes de niveau de resistance.

Resume Objectif: L'etude Phare (pneumonies hospitalieres axepime [cefepime] en reanimation) avait pour objectif de comparer les associations cefepime (2 fois 2 g·j −1 ) + amikacine (2 fois 7,5 mg·kg −1 ·j −1 ) (= cefe—ami) et ceftazidine (2 fois 3 g·j −1 ) + amikacine (2 fois 7,5 mg·kg −1 ·j −1 ) (= cefta—ami) chez des patients en ventilation mecanique et atteints de pneumonie nosocomiale. Type d'etude: Etude multicentrique ouverte, comparative, randomisee. Patients: L'etude a porte sur 275 patients de reanimation inclus soit dans le groupe cefe-ami ( n = 141), soit dans le groupe cefta-ami ( n = 134). Methode: Les dossiers ont ete revus en insu par le comite de pilotage. Resultats: L'examen bacteriologique etait positif chez 74 % des patients du groupe cefe-ami et chez 63 % de ceux du groupe cefta-ami; 319 souches bacteriennes presumees responsables ont ete isolees. La duree moyenne de traitement etait de 12 jours pour la cefepime, de 11 jours pour la ceftazidine et de 8 jours pour l'amikacine. En intention de traiter, les taux de guerison clinique etaient de 48,2 % dans le groupe cefe—ami et de 44,8 % dans le groupe cefta—ami. Pour la population avec une pneumonie documentee, le taux de guerison sous cefe—ami etait de 53,3 %, significativement superieur au taux enregistre sous cefta-ami (39,3 %) ( P = 0,05). En per-protocole, ces taux etaient respectivement de 67,7 et 68,2 % dans les groupes cefe—ami et cefta—ami. L'eradication bacterienne a ete obtenue dans 86,5 % des cas documentes bacteriologiquement du groupe cefe—ami et 89,3 % de ceux du groupe cefta—ami. Conclusion: L'association cefepime—amikacine a une efficacite comparable a l'association de reference dans le traitement des pneumonies nosocomiales chez les sujets sous ventilation mecanique, mais s'est revelee significativement superieure chez ceux ayant une pneumonie documentee bacteriologiquement.

Resume Un questionnaire a ete distribue aux participants a la reunion annuelle organisee le 26.5.97 parl'ARECLIN (association regionale des comites de lutte contre l'infection nosocomiale) consacree aux accidents d'exposition au sang. L'ARECLIN regroupe une trentaine d'hopitaux du Nord-Pas de Calais. Sur 529 questionnaires distribues, 446 ont ete recus dont 445 evaluables (84%). La plupart des repondants etaient infirmiers (63%), eleves infirmiers (10%), cadres infirmiers (6%) ou medecins (5%). 63% avaient termine leur formation initiale depuis plus de 10 ans, 60% exercaient en CHG, 22% en CHU et 8% en clinique privee. 47,2% (180/381) des repondants a une question specifique declaraient avoir eu au moins un accident d'exposition au sang. Le taux etait maximum chez les infirmieres (58%), mais present dans toutes les categories professionnelles: puericultrices et sages-femmes (55%), cadres infirmiers (35%), eleves infirmieres (32%), personnel de laboratoire (27%) medecins (25%), aides-soignantes (17%) et personnel medico-technique (12%). La declaration systematique de tout accident d'exposition au sang etait reconnue par 97% des repondants; cette declaration se faisant preferentiellement au medecin du travail (81%) ou a la surveillante du service (75%). Sur l'ensemble des repondants, 34% declaraient dans l'heure suivant l'accident d'exposition au sang, invoquant la prophylaxie anti-VIH et 41% declaraient dans les 24 h. La conduite pratique comportait nettoyage au savon pour 68% et desinfection par eau de Javel pour 83%. 71% connaissaient le concept de precautions universelles. Sur 10 mesures, seules 3 etaient connues par moins de 80% des personnes: non desadaptation des aiguilles a la main (73%), panser et couvrir les plaies des soignants (77%) et decontamination des surfaces souillees par eau de Javel (66%). La moyenne globale etant de 8,6 bonnes reponses sur 10. Bien que le theme de la reunion ait probablement selectionne des personnes motivees par le risque d'accident d'exposition au sang, les resultats sont encourageants et montrent une bonne connaissance des accidents d'exposition au sang et des precautions universelles dans le personnel soignant.

Summary “Once a day” dose concept in aminoglycoside utilisation is based upon bactericidal quickness and important post-antibiotic effect, both highly concentration-dependent, as upon hypothesis of a better tolerance. Blaser and Konig, in a meta-analysis about twenty-four clinical series, assign to “once a day” dose versus conventional doses a significantly upper clinical and bacteriological efficacy (p et al. , in an other meta-analysis about twenty clinical series, observe better clinical efficacy (p = 0.027) and tolerance trend. Adaptative resistance phenomenon or first exposure effect, which is a transitory reduction ( Antibiotic associations to aminoglycosides must privilege very long half-life antibiotics and adapted use to get best synergic effects. Loading dose and reduction of treatment time are also ends to be researched in aminoglycosides management.

Vancomycin penetration in epithelium lining fluid was studied in ten mechanically ventilated patients with methicillin-resistant Staphylococcus 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 micrograms/ml). Concordance between high plasma concentrations (20 micrograms/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 micrograms/ml. Further studies are required to determine the clinical relevance of these observations.

Resume Decouvertes dans les annees 80, les beta-lactamases “a spectre etendu” conferent aux enterobacteries qui en sont secretrices une resistance a l'encontre des penicillines, des cephalosporines et des monobactams. L'incidence de ces souches multiresistantes atteint un tel niveau dans certains centres hospitaliers francais qu'une lutte contre leur diffusion devient imperative. Celle-ci est basee sur la connaissance des mecanismes physiopathologiques sous-jacents : selection, colonisation, transmission. L'emploi raisonne des antibiotiques a large spectre represente l'element determinant de la lutte contre la selection. La colonisation, essentiellement digestive, est combattue par les techniques de decontamination intestinale. Enfin la transmission, majoritairement manuportee, impose pour sa prevention le respect strict d'une hygiene de soins absolue. Ce n'est qu'a ce prix que la diffusion des enterobacteries secretrices de beta-lactamases a spectre etendu pourra etre stoppee. La surveillance de leur prevalence sera le marqueur privilegie de la qualite des soins et de la strategie de prevention.

Resume La mortalite des acces pernicieux graves reste elevee (de 10 a 40 p. 100 selon les etudes) malgre un traitement medicamenteux actuellement bien codifie. L'exsanguino-transfusion (EST) a ete proposee en 1974 comme traitement adjuvant au traitement conventionnel. Developpee par de nombreuses equipes depuis 1980, celle-ci reste l'objet de controverses. Nous rapportons l'etude retrospective de 28 patients consecutifs hospitalises en reanimation de 1986 a 1992 pour paludisme grave (selon les criteres de l'OMS). Dans cette population, 24 patients ont ete traites conventionnellement. Neuf d'entre eux (37,5 p. 100) presentaient une parasitemie superieure a 10 p. 100 et la mortalite globale etait de 16,7 p. 100. Quatre patients (âge moyen 52,3 ans [34–65], IGS moyen 15 [11–20], parasitemie moyenne 24,5 p. 100 [16–40]) ont beneficie d'une EST en raison de criteres de gravite initiaux ou de l'absence d'amelioration sous traitement conventionnel. Ces 4 patients ont gueri sans sequelles. La revue de la litterature ne revele pas de complications graves que l'on puisse attribuer uniquement a l'EST. Si pour la plupart des auteurs, le but therapeutique a atteindre est clair (diminuer la parasitemie en dessous de 5 p. 100 aussi rapidement que possible), les modalites techniques et les volumes devant etre echanges ne font pas l'objet d'une unanimite. Les resultats sont encourageants chez ce type de patients dont le pronostic vital peut-etre engage, meme si l'absence d'etudes controlees et randomisees ne permet pas de conclure de facon definitive. L'EST parait etre un traitement adjuvant interessant chez ces patients en cas d'aggravation initiale sous traitement. De nouveaux traitements chimiotherapiques ou immunologiques conduiront peut-etre a reviser cette position.

Resume Le pronostic a court et moyen terme des insuffisants respiratoires chroniques presentant une decompensation aigue reste encore imprecis. Ceci nous a incite a etudier, entre janvier 1990 et decembre 1991, le devenir de 154 patients (sexe ratio M/F = 2,85), porteurs d'une insuffisance respiratoire chronique (IRC), presentant une decompensation aigue admis pour ventilation assistee, dans trois services de reanimation. Ces insuffisances respiratoires chroniques (PaO2 de base = 61,4 ± 9,2 mmHg, PaCO2 de base = 45,1 ± 7,5 mmHg), comprenaient 74 insuffisances respiratoires de type obstructif, 33 de type restrictif, 29 de type mixte et 18 silicoses. L'âge moyen etait de 67,4 ± 10,4 ans. A l'admission en reanimation, l'IGS moyen etait de 13,5 ± 4. Le facteur principal de decompensation etait represente par les infections respiratoires (n = 101 ; 39 pneumonies et 62 surinfections bronchiques). La duree moyenne de ventilation etait de 13,7 ± 14,3 jours. Quarante-six patients sont decedes en reanimation. Les facteurs de mauvais pronostic etaient : le sexe masculin (p

Resume Les donnees in vitro et experimentales ont demontre une meilleure efficacite et une moindre toxicite cochleovestibulaire et renale de l'administration des aminosides en dose unique journaliere. Chez les patients presentant une infection a bacilles a Gram negatif prouvee ou fortement suspectee, l'administration en dose unique journaliere merite d'etre serieusement consideree. Les etudes ont suggere une efficacite et une tolerance, au moins equivalentes a l'administration conventionnelle.

Resume Si le recours aux aminosides demeure la regle dans le traitement des infections severes a bacilles a Gram negatif, leur administration conventionnelle en deux voire trois doses journalieres est remise en cause au profit de la dose uniquotidienne. Les arguments bacteriologiques, experimentaux et cliniques sont assez convaincants pour etendre ce rythme d'administration aux patients de reanimation. Ceci a ete evalue sur le plan clinique, pharmacocinetique et de la tolerance dans trois etudes qui sont largement analysees et discutees dans cet article.

Resume Les infections pulmonaires a bacille a Gram negatif sont un probleme quotidien en reanimation. Ces infections necessitent une association d'antibiotiques incluant un aminoglycoside. Recemment, un nouveau mode d'administration a ete propose. L'administration en une dose quotidienne pourrait entrainer moins de toxicite et une efficacite au moins egale voire superieure aux modes classiques. Nous avons etudie les concentrations bronchiques d'amikacine chez des patients traites en une ou deux doses quotidiennes. Chez les patients recevant l'amikacine en deux doses quotidiennes, les concentrations bronchiques se situent entre 3 et 4 μg/ml, ce qui est similaire aux resultats precedemment publies. Les pics bronchiques surviennent entre trois et quatre heures apres le debut de la perfusion. Chez les patients recevant l'amikacine en une dose quotidienne, les concentrations bronchiques sont plus de deux fois plus elevees, superieures a 6 μg/ml pendant plus de 12 heures. Les pics bronchiques moyens surviennent egalement entre 3 et 4 heures apres le debut de la perfusion. Ces concentrations sont superieures aux CMI des bacteries a Gram negatif les moins sensibles, telles Acinetobacter sp et Pseudomonas aeruginosa . Ces resultats representent un argument en faveur de l'administration en une dose quotidienne des aminosides dans le traitement des pneumopathies a bacille a Gram negatif.

To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD).Prospective exploratory, open-labelled study.Critical Care Unit in a University Medical Centre.3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study.Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection. Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion.Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23). The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion. The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5). The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively. Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min. The mean volume of distribution was 47.4 +/- 6.4 l.CVVHD is effective for vancomycin elimination. In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.

Resume Les essais therapeutiques dans les pneumonies communautaires sont rares et peu performants, car de methodologie tres variee. En effet, les conditions requises pour un essai clinique sont strictes. L'etude doit etre comparative, prospective et randomisee, sur un echantillon de taille justifiee, a partir d'une stratification primaire. La pneumonie communautaire sera definie cliniquement et radiologiquement, l'antibiotique de reference choisi en fonction des bacteries cibles a traiter. L'efficacite ne sera jugee qu'en terme de guerison ou d'echec. Cette methodologie rigoureuse est tres difficile a appliquer dans la realite.

Resume Les endocardites aigues a staphylocoque dore depassent largement le cadre strictement cardiologique, et doivent etre considerees en raison de la virulence particuliere de l'agent causal comme des septico-pyohemies dont le bilan lesionnel infectieux s'impose. Il n'est pas rare d'etre confronte aux cas d'endocardites aigues necessitant un geste de remplacement valvulaire precoce en raison d'une insuffisance cardiaque grave qui ne peut etre operee a priori en raison d'une complication neurologique centrale a type d'abces ou de ramollissement. Les auteurs montrent qu'en pareille situation, la mortalite est constante et proposent l'intervention chirurgicale precoce pour remplacement valvulaire.

In a multicentre non-randomized open prospective study, 124 patients hospitalized in medical infectious disease or intensive care units, with severe community and hospital-acquired bacterial infections were treated with 15 mg/kg body weight amikacin in a once-daily dose given as a 30 min iv infusion, combined with other antibiotics. Infections were bacteriologically proven in 101 patients. The clinical responses showed 83.1% primary success and 83.9% definitive cure predominantly in intensive care patients with hospital-acquired infections and pneumonia. Bacteriological eradication was achieved in 67.3%. Bacteria associated with true failures and colonizations were predominantly Pseudomonas, Acinetobacter and Staphylococcus spp. The risk of nephrotoxicity may be decreased with such a regimen of amikacin, but no conclusions could be drawn with regard to ototoxicity. In summary, a once-daily dosing regimen of amikacin 15 mg/kg is practical and probably efficacious and safe in severely infected patients.

The antibiotic prescription in intensive care units is frequent using often broad-spectrum antibiotics; its quality has never been evaluated in paediatric intensive care units.To describe the modalities of antibiotic prescriptions in a paediatric intensive care unit and confront them to the literature guidelines and bacteriological data.From January 1st to March 31st 2005, 52 consecutive prescriptions regarding 45 children, with a total of 47 hospitalisations were prospectively analysed.Confirmed diagnosis of bacterial infection was retained for 50 of the 52 patients: community acquired infection in 35 cases (70%) and a nosocomial infection in 15 cases. Ten children died during the antibiotic treatment (22%), with 5 deaths related to the infection (11%). Monotherapy represented 56% of the prescriptions of antibiotics. The initial antibiotic treatment was empirical in 42 of 52 cases (81%). The empirical prescriptions were documented afterward in 48% of cases. One or more microorganisms were isolated for 60% of the initial prescriptions. Misuses in antibiotic doses (in excess [10%] or by insufficiency [13%]), number of daily administration (4%), and way of administration and/or length of treatment were observed. Seventy-seven percent of the initial prescriptions seemed to be adapted to the identified or suspected bacteria, but only 63% adequate to recommendations.Almost 2/3rd of the antibiotic prescriptions were adequate to the recommendations. The implementation of standardized and specific protocols should contribute to improve the quality of these prescriptions.

The effect of three stabilized peracetic acid (PAA) preparations (Bioxal M), with or without surfactants, on an Escherichia coli biofilm model was studied. The biofilm was prepared in glass tubes, and was evaluated indirectly using spectrophotometry. The ability of the products to fix or remove the biofilm was determined by their detergent activity (DA). None of the preparations tested fixed the biofilm. The effect of Bioxal M-1 on the biofilm was equivalent to the control (sterile water). Bioxal M-2 and Bioxal M-3 displayed slightly positive DAs. Non-ionic surfactant improved the DA of the products. Regardless of disinfectant activity, PAA agents display different DAs depending on their formulation. This criterion could be used to select the weakest biofilm-fixing agents. Users should therefore be concerned about the efficiency of the cleaning stage of medical devices. When choosing PAA products, non-fixing ability should be considered in addition to antimicrobial activity.

Invasive aspergillosis is a severe complication in immunocompromised patients. The arrival of new antifungal agents motivated the redaction of guidelines, regularly updated, by a Lille University hospital multidisciplinary task force. These guidelines assess diagnostic and therapeutic issues. The main recommended diagnosis tool is the chest CT scan, ordered at the smallest suspicion and, also, measure of the blood and broncho alveolar lavage fluid galactomannan. Treatment guidelines assess prophylaxis, empirical and documented therapy. Primary prophylaxis is warranted in only two cases, pulmonary graft or stem cell transplant in patients with chronic GVH and receiving corticosteroids. Empirical therapy should use one of the available amphotericin B formulations, chosen according to the patient history. Caspofungin is another choice. Documented therapy, depending on presentation, can be a single drug or a combination. First line therapy for single drug is i.v. voriconazole. Lipid formulations of amphotericin B are another choice. A combination therapy can be used as a first line treatment, for multiple lesions, or as salvage therapy. It must include caspofungin, associated with liposomal amphotericin B or voriconazole. A tight cooperation with thoracic surgeons is recommended.

Aminoglycosides presently constitute ¢rst-line antibacterial therapy, particularly in high-risk patients with serious and life-threatening aerobic Gram-negative infections. However, aminoglycosides continue to manifest undesirable side-eiects such as nephrotoxicity, complicating 5^35% of therapeutic courses. The incidence of these side-eiects can be reduced when appropriate attention is paid to the dose of the drug, the durationof therapy, the avoidance ofdehydrationand hypokalemia, and the speci¢c aminoglycoside selected for therapy. Actually, there is continuing debate over the most appropriate administration regimen for these drugs. Aminoglycosides have been administered in twice- or thrice-daily dosing regimens since their introduction to clinical use four decades ago. Recently, increasing numbers of experimental and clinical studies have demonstrated that a once-daily dosing regimen may be at least as eiective as, and possibly less toxic than multiple dosing. It seems essential to achieve high peak concentrations, since the bactericidal activity of the aminoglycosides is concentration-dependent and the ratio of the peak concentration to the MIC correlates closely with therapeutic outcome

To compare the associations of cefepime (2 g x 2/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefe-ami) and ceftazidime (2 g x 3/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefta-ami) in patients under mechanical ventilation suffering from a nosocomial pneumonia.Multi-centre, open, comparative, randomised study.The study included 275 ICU patients enrolled either in the cefe-ami group (n = 141) or in the cefta-ami group (n = 134).All cases were reviewed in a blinded fashion by the steering committee.Microbiology laboratory tests were positive in 74% of patients of the cefe-ami group and in 63% of the cefta-ami group respectively; 319 presumed causative strains of bacteria were isolated. The mean duration of treatment was 12 days for cefepime, 11 days for ceftazidime and 8 days for amikacin. In intention to treat, the clinical recovery rate was 48.2% in the cefe-ami group and 44.8% in the cefta-ami group respectively. In the population with a documented pneumonia, the clinical recovery was significantly better in the cefe-ami group (53.3%), than in the cefta-ami group (39.3%) (P = 0.05). In per protocol analysis, these rates reached 67.7% in the cefe-ami group and 68.2% in the cefta-ami group respectively. In the bacteriologically documented cases the eradication rates were 86.5% and 89.3% respectively.The efficacy rates of cefe-ami and cefta-ami combinations were similar in ICU patients under mechanical ventilation with a nosocomial pneumonia. However the cefe-ami association was significantly more efficient in the population with a bacteriologically documented pneumonia.

Objective: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome. Design: Retrospective (1987–1992) and prospective (1993–1995) study. Setting: Three participating ICUs from primary care hospitals. Patients: Five hundred and five patients (mean age: 63 ± 17 years) with severe community-acquired pneumonia (CAP). Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3). Measurements and results: Admission data and data on the disease's course were recorded. The mean Simplified Acute Physiologic Score (SAPS) was 12.5 ± 5.4. On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis was established for 309 (61.2 %) patients. S. pneumoniae was isolated in 137 (27.1 %) patients. Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall mortality rate was 27.5 % (29.2 % in group 1). In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis. Conclusions: Few features facilitate the identification of pneumococcal CAP on ICU admission. The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome. Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay.

A 59 year-old-man had ataxia and hemiparesis of progressive onset which resolved in a few weeks. CT scan and magnetic resonance imaging showed white matter multiple lesions. The cerebrospinal fluid was consistent with an inflammatory disease. The diagnosis of multiple sclerosis was evoked. However, the patient had chronic brucellosis and serological rates increased and decreased according to the clinical and radiological signs. Thus, encephalitis caused by brucellosis was evoked. The mechanism is assumed to be a demyelinating process caused by a deep focus reactivation.

Aims In infective endocarditis, the true incidence of embolic events and metastatic infections remains unknown probably because a large number of events are asymptomatic. The consequences of the prognosis of such events have never been evaluated by a prospective follow-up. This study aimed to assess the incidence of symptomatic or asymptomatic embolic events and metastatic infections in definite infective endocarditis and to determine whether these events carry a risk of mortality. Methods and results From January 1991 to December 1993, 102 patients with suspected or known infective endocarditis were referred to our institution. Among them, we selected 68 patients (50 males, 18 females, mean age = 52.7 years) exhibiting definite infective endocarditis according to the Duke University criteria. Blood cultures were positive in 49 cases (72%). Echocardiography revealed valvular vegetations in 55 cases (81%). Irrespective of the clinical presentation, patients were examined radiologically by cerebral computed tomography scanning (n = 60), magnetic resonance imaging (n = 3), abdominal computed tomography scanning (n = 32) or abdominal echocardiography (n = 20). Depending on the symptoms, thoracic computed tomography scanning (n = 22), pulmonary angiography (n = 2), ventilation-perfusion scintigraphy (n = 4), or gallium citrate radionuclide scanning (n = 7) were also performed. All patients were prospectively followed-up for a mean period of 21.4 +/- 17.5 months. In 35 patients (51%), 51 embolic or metastatic events were revealed, involving the central nervous system (n = 23), spleen (n = 7), kidney (n = 5), lung (n = 5), liver (n = 4), bone and joint (n = 4), iliac (n = 2) or mesenteric (n = 1) arteries. During the hospital stay, the mortality rate was higher in patients exhibiting embolic or metastatic events (20 vs 12%), but the difference did not reach statistical significance. Kaplan-Meier analysis demonstrated no difference in long-term follow-up. Conclusion Our data suggest that embolic or metastatic events had a high incidence (51%) during infective endocarditis, but were not associated with significant attributable mortality.

Isepamicin is a new aminoglycoside antibiotic which possesses greater stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides. In this prospective, randomised, open trial, the safety and efficacy of intravenous administration of isepamicin was compared with that of intravenous amikacin in seriously ill adults with nosocomial pneumonia or septicaemia. Each study aminoglycoside was administered concurrently with ceftazidime or imipenem. Patients were randomised to receive isepamicin 15 mg/kg once daily, isepamicin 7.5 mg/kg twice daily or amikacin 7.5 mg/kg twice daily. For patients with nosocomial pneumonia, the proportions of patients in the intent-to-treat population (n = 130) who were clinically cured at the end of treatment were similar in each treatment group: 18/44 (41%) isepamicin once daily; 19/45 (42%) isepamicin twice daily; and 17/41 (42%) amikacin. Corresponding results for the efficacy population (n = 58) were: 12/20 (60%) isepamicin once daily; 14/21 (67%) isepamicin twice daily; 9/17 (53%) amikacin. In patients with septicaemia, clinical cure was achieved in 8/10 (80%) patients treated with isepamicin once daily, compared with 8/13 (62%) patients who received isepamicin twice daily, and 7/12 (58%) patients treated with amikacin. For both diagnoses, there were no statistically significant differences between the treatment groups in clinical cure rate. The most commonly isolated target pathogen was Pseudomonas aeruginosa. For both nosocomial pneumonia and septicaemia, the proportion of patients in the intent-to-treat population whose pretreatment valid target pathogens were eliminated was similar in each treatment group. In total, 51 patients (30%) died during study, mostly due to disease progression or complications, or concurrent illness. All three treatment regimens were well tolerated. The proportion of patients experiencing at least one adverse event was 11%, 25% and 9% for isepamicin once daily, isepamicin twice daily and amikacin, respectively. The incidence of ototoxicity and nephrotoxicity was relatively low in both treatment groups.

Aminoglycosides remain a mainstay of antimicrobial therapy, especially for treatment of serious Gram-negative infections. Aminoglycosides represent cornerstone of antibiotic combination therapy and, despite their well-documented toxicity, continue to be used because of their excellent bactericidal efficacy and their limited tendency towards the development of resistance during therapy. Various factors, particularly their concentration-dependent bactericidal activity and prolonged post-antibiotic effect, indicate that aminoglycosides can be given effectively in a once-daily dosing regimen. Once-daily dosing has also been shown to reduce toxicity in animal studies. Although once-daily administration of amino-glycosides also has a number of practical advantages, questions remain concerning the indications that should be treated, the optimal peak and trough serum concentrations that should be attained, and the requirement for an initial loading dose. The present article examines the role of aminoglycosides in the treatment of serious infections and reviews the evidence presently available to answer questions on their appropriate clinical use.

A clinical isolate of Pseudomonas aeruginosa resistant to pefloxacin (Pef) but susceptible to ciprofloxacin (Cip) was studied to compare the in vitro and in vivo activities of Pef, ofloxacin (Ofl), and Cip. The time-kill curve method showed no bactericidal activity for Pef and Ofl, but a reduction of 4 log10 CFU/ml was achieved with Cip at 1 h. A model of experimental P. aeruginosa pneumonia was used to evaluate in vivo the relevance of the difference in susceptibility observed in vitro. At 36 h, a 100% cumulative survival rate was observed in Cip-treated rats, which was far higher than the survival rate obtained with Pef (53%) or Ofl (46%) (P < 0.001). At 4 h, no bacteremia was observed in Cip-treated rats, whereas 93% of the Pef-treated rats and 80% of the Ofl-treated rats were bacteremic (P < 0.001). The best pulmonary bacterial clearance was observed with Cip. Interestingly, Pef and Ofl, to which the strain was resistant in vitro, showed a fairly good in vivo activity despite sub-MIC concentrations. Cip was more effective than Pef and Ofl in terms of pulmonary and systemic bactericidal activity and provided the best survival rate in animals. We conclude that differences between the different quinolones in terms of the organism's sensitivity assessed in vitro may be relevant and that it might be useful to reconsider the use of a quinolone to which P. aeruginosa shows resistance if the organism shows sensitivity to no other agent.

Exchange transfusion (ET) is a controversial ancillary treatment of severe falciparum malaria.We conducted a retrospective analysis of severe malaria treated in our institution. Nine cases of ET were identified between 1991 and 1998 and compared to 12 controls with similar parasitemia.Groups were similar at admission except for an increased age in the ET group (p0.02). All patients received iv quinine. Outcome was similar in both groups (two deaths in the ET group, three in the control group). However, in patients with parasitemia30%, the death rate was significantly lower in ET patients than in controls (0/4 vs 3/3, p0.029).Despite definitive data from controlled trials, we suggest that ET should be considered in severe malaria cases with very high parasitemia and severity criteria or worsening clinical condition despite adequate chemotherapy.