OBJECTIVES Healthcare-associated infections due to third-generation cephalosporin-resistant Enterobacteriaceae (CRE) have become a major public health threat, especially in intensive care units (ICUs). We assessed and compared β-lactam use, the prevalence of colonization with CRE at admission and the incidence of CRE acquisition across ICUs. PATIENTS AND METHODS A cohort study was conducted in 10 ICUs of the Paris (France) metropolitan area between November 2005 and February 2006. Antibiotic use was recorded prospectively in all patients admitted during the study period. Rectal swabs were collected at admission, twice weekly thereafter, before β-lactam prescription and before discharge. RESULTS A total of 893 patients provided 3453 rectal swabs; 793 of the patients were newly admitted, mostly for medical reasons (80.7%). On admission, 74 patients (9.6%) were colonized with CRE, including 32 with an extended-spectrum β-lactamase (ESBL)-producing strain. Among the remaining 694 naive patients, 94 acquired CRE during their follow-up, including 31 with an ESBL-producing strain. Incidence rates of colonization ranged from 8.8 to 21.0/1000 patient-days for all CRE, and from 1.4 to 10.9/1000 patient-days for ESBL producers. A majority of patients (68.3%) were prescribed β-lactams during their ICU stay, with defined daily doses ranging from 428 to 985/1000 patient-days. Across ICUs, prescriptions of all antibiotics, β-lactams and carbapenems were significantly correlated to incidence rates of colonization with ESBL-producing CRE. CONCLUSIONS The standardized and systematic follow-up of patients in 10 ICUs revealed great heterogeneity in the rates of colonization with ESBL- and non-ESBL-producing CRE, as well as in antimicrobial prescription practices.

Les critères de choix bithérapie vs monothétapie dans la LC demeurent controversés. Le but de cette étude est l'analyse descriptive des pts traités par L ou L + M pour LC. Comparaison (Test exact de Fisher) des données démographiques, cliniques et biologiques, facteurs de risques, scores de gravité et évolution recueillis prospectivement de mars 2006 à juin 2007 chez les pts traités par L (103) ou L + M (76), soit 45 paramètres. Les seules différences observées concernent la température > 38,5 ° [82 (81,2 %) vs 70 (95,9 %), p = 0,005], la confusion [26 (25,2 %) vs 35 (46,1 %), p = 0,004], un séjour en réanimation [18 (17,5 %) vs 28 (36,8 %), p = 0,005], le recours à la ventilation mécanique [6 (5,8 %) vs 12 (15,8 %), p = 0,042], une valeur moyenne de CRP plus élevée [285 vs 348, p = 0,008], une PaO2 < 60 mmHg [23 (33,8 %) vs 36 (58,1 %), p = 008], la survenue d'une insuffisance rénale [5 (4,9 %) vs 12 (15,8 %), p = 0,019], significativement supérieure dans le groupe L + M. La comparaison des paramètres d'évolution (durée de traitement, guérison, décès, complications.) n'objective pas de différence statistiquement significative entre les deux groupes. Le recours à L + M semble être associé au séjour en réanimation et aux facteurs associés confondants. L'analyse des paramètres évolutifs ne retrouve pas d'argument en faveur de la bithérapie L + M vs L dans cette étude.

Objective. - Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines.Study design. - Prospective, observational, French multicenter study (October 2005-May 2006).Patients and methods. - Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis.Results. - One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida.Conclusion. - The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines. (C) 2008 Elsevier Masson SAS. Tous droits reserves.

Las neumonías agudas comunitarias son causa frecuente de hospitalización y mortalidad. El reconocimiento inmediato de las formas graves según criterios simples, clínicos, radiológicos y de laboratorio, es una etapa esencial para un tratamiento rápido en el servicio de reanimación con el fin de controlar los fallos orgánicos. La obtención de muestras apropiadas para realizar estudios microbiológicos precede al tratamiento antibiótico, que se debe instaurar con rapidez después de diagnosticar la neumonía. Pese a las técnicas de identificación, sólo la mitad de las neumonías se documentan adecuadamente. El tratamiento antibiótico, en principio empírico, integra los gérmenes patógenos, tanto extracelulares como intracelulares, que producen neumonías con mayor frecuencia; siempre debe ser activo contra el neumococo, la bacteria implicada más a menudo. La asociación de un betalactámico y un macrólido o una fluoroquinolona es la que mejor responde a este objetivo. En las recomendaciones más comunes, las fluoroquinolonas activas contra los neumococos sustituyen a los fármacos precedentes. En el caso excepcional de los pacientes con factores de riesgo especiales, el tratamiento empírico debe tener en cuenta Pseudomonas aeruginosa. La gravedad de parte de las neumonías comunitarias justifica el que se recurra a tratamientos complementarios. Se debe evaluar de nuevo el tratamiento antibiótico en las 72 horas siguientes a su instauración, a fin de valorar su eficacia, adaptar el tratamiento en caso necesario y simplificarlo. El mantenimiento de antibióticos de amplio espectro expone al paciente a efectos secundarios y contribuye a producir resistencias bacterianas. En cuanto a las neumonías neumocócicas, las fluoroquinolonas activas contra el neumococo podrían representar una alternativa en caso de que el neumococo desarrolle resistencia a los betalactámicos. La mortalidad persistente de las neumonías sigue siendo notable. Esto debe fomentar la mejora del tratamiento inicial y la búsqueda de nuevas opciones terapéuticas.

PURPOSE: This study was done to better understand treatment risks and benefits of drotrecogin alfa (activated) (DrotAA).

Objective:To investigate community-acquired pneumonia (CAP) as a cause of severe sepsis in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial and to evaluate the effect of drotrecogin alfa (activated) (DrotAA) in this subgroup. Design:Retrospective analysis of the severe CAP subgroup in the PROWESS trial. Setting:Tertiary care institutions in 11 countries. Interventions:DrotAA (n = 850), 24 &mgr;g·kg−1·hr−1 for 96 hrs, or placebo (n = 840). Participants:The 1,690 patients with severe sepsis enrolled in the PROWESS trial. Measurements and Main Results:Patients were classified as having CAP if lung was the primary site of infection and if they were enrolled directly from home (private residence) with ≤4 days in the hospital before receipt of study drug in the PROWESS trial. Survival at 28 days, hospital discharge, and 90 days was compared in DrotAA and placebo groups in the CAP subgroup of PROWESS and CAP subgroups based on disease severity. Of the 1,690 PROWESS patients, 35.6% (DrotAA, n = 324; placebo, n = 278) were classified as severe CAP. Of these severe CAP patients, 26.1% had Streptococcus pneumoniae infections. Within CAP, 79.1% were enrolled by the end of the second calendar day in the hospital, and approximately 90% of CAP patients were at high risk of death according to the Pneumonia Severity Index category. Based on their dependence on vasopressors, 59% of CAP patients were judged at high risk of death. Biomarkers of coagulation and inflammation were markedly abnormal in severe CAP patients. In severe CAP patients treated with DrotAA, a relative risk reduction in mortality of 28% was observed at 28 days, with a relative risk reduction in mortality of 14% observed at 90 days from the start of study drug infusion. The survival benefit was most pronounced in severe CAP patients with S. pneumoniae and in severe CAP patients at high risk of death as indicated by Acute Physiology and Chronic Health Evaluation II score of ≥25, Pneumonia Severity Index score of ≥4, or CURB-65 (confusion, urea, respiratory rate, blood pressure, age) score of ≥3. Conclusions:CAP associated with a high Pneumonia Severity Index score, bacteremia, or an intense coagulation and inflammatory response requiring intensive care unit care were indicators of a high risk of death from severe sepsis. In patients with severe sepsis resulting from CAP, a readily identifiable disease, DrotAA, improved survival compared with placebo.

Les pneumonies aiguës communautaires sont des causes fréquentes d'hospitalisation et de mortalité. La reconnaissance immédiate des formes sévères sur des critères simples, cliniques, radiologiques et biologiques, est une étape importante pour une prise en charge rapide en réanimation afin de contrôler les défaillances d'organes. Les prélèvements appropriés microbiologiques précèdent l'antibiothérapie qui doit être instituée très rapidement après le diagnostic de pneumonie. Malgré les techniques d'identification, la moitié seulement des pneumonies sont documentées. Cette antibiothérapie, initialement probabiliste, intègre les germes pathogènes les plus souvent responsables, extra- et intracellulaires ; elle doit toujours être active sur le pneumocoque, bactérie la plus fréquente. L'association d'une β-lactamine et d'un macrolide ou d'une fluoroquinolone répond le mieux à cet objectif. Les fluoroquinolones actives sur le pneumocoque se sont substituées aux précédentes dans les plus récentes recommandations. Dans le cas exceptionnel des patients ayant des facteurs de risque particuliers, le traitement probabiliste doit prendre en compte Pseudomonas aeruginosa. La gravité d'une partie des pneumonies communautaires justifie le recours à des traitements adjuvants. L'antibiothérapie doit être réévaluée dans les 72 heures dans le but d'apprécier son efficacité, de l'adapter éventuellement et de la simplifier. La poursuite des antibiotiques à large spectre expose le patient à des effets indésirables et contribue aux résistances bactériennes. Pour les pneumonies dues au pneumocoque, les fluoroquinolones actives sur le pneumocoque pourront constituer une alternative en cas d'évolution importante des résistances du pneumocoque aux β-lactamines. La mortalité persistante des pneumonies reste sévère. Ceci doit stimuler l'amélioration de la prise en charge initiale et faire rechercher de nouvelles thérapeutiques.

Nous rapportons les resultats d'une etude prospective portant sur le profil des patients atteints d'infection nosocomiale a staphylocoque resistant a la meticilline et se trouvant, pour quelque raison que ce soit, en situation de difficulte therapeutique. Cette etude, baptisee PROPHYL , a ete menee au cours d'une periode de quatre mois aupres d'un vaste echantillon representatif des services de reanimation francais. La frequence des difficultes therapeutiques constatees etait de 23 % lors du traitement par des glycopeptides des 581 cas d'infections nosocomiales (60 % de Staphylococcus aureus et 40 % de staphylocoque a coagulase negative). Les echecs cliniques etaient predominants, suivis de l'insuffisance renale preexistante ou apparue en cours de traitement, et d'une diminution de la sensibilite aux glycopeptides. Compte tenu de la diversite de ces difficultes, des recommandations de prise en charge paraissent necessaires.

Methicillin-resistant staphylococcal infections (MRSI) are still common in an intensive care setting. Their management is mainly based on glycopeptides, combined with other antibiotics when this is possible, and also on treatment of the portal of entry (removal of foreign bodies, surgery...). Implementation of this antibiotic therapy may meet with difficulties linked to the micro-organism (existence of strains with diminished sensitivity to glycopeptides), to the toxicity of glycopeptides or to the unfavourable course of the infection. A survey of practices was performed on a representative sample of 240 intensive care units in France. Glycopeptides, and particularly vancomycin, were the most frequently employed and prescribed in combination with other compounds. Therapeutic problems were considered as occasional, their incidence ranging from 0 to 50%. The problems reported were mainly linked to adverse effects: most frequently renal toxicity and, to a lesser extent, immunological and allergic complications. Diminished sensitivity to glycopeptides was only reported by a third of physicians, and this sporadically. Such a survey of practices is an essential preliminary to an epidemiological study of the incidence of MRSI and related therapeutic problems.

Les infections à staphylocoques résistants à la méticilline (SRM) restent fréquentes en réanimation. La prise en charge de ces infections repose essentiellement sur les glycopeptides, associés à d’autres antibiotiques quand cette association est possible, mais aussi sur le traitement de la porte d’entrée (ablation d’un matériel étranger, intervention chirurgicale…). La conduite de cette antibiothérapie peut se heurter à des difficultés liées soit à la bactérie avec l’existence de souches de sensibilité diminuée aux glycopeptides, soit à la toxicité des glycopeptides, soit à l’évolution défavorable de l’infection. Une enquête de pratique a été effectuée sur un échantillon représentatif de 240 services de réanimation en France. Les glycopeptides, surtout la vancomycine, sont le plus souvent utilisés et prescrits en association. Les difficultés thérapeutiques sont considérées comme occasionnelles, avec une dispersion dans la fréquence estimée de 0 à 50 %. Ces difficultés rapportées sont surtout liées aux effets indésirables, plus particulièrement à la toxicité rénale et à une moindre fréquence des effets immuno-allergiques. La diminution de la sensibilité aux glycopeptides n’est signalée que par le tiers des médecins et de manière occasionnelle. Cette enquête de pratique est l’étape préalable à une étude épidémiologique sur la fréquence des infections à SRM et des difficultés thérapeutiques.

Background: Traditional approaches to mechanical ventilation use tidal volumes of 10–15 ml/kg body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml/kg predicted body weight and an airway pressure measured after a 0.5 s pause at the end of inspiration (plateau pressure) of 50 cm H2O or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml/kg predicted body weight and a plateau pressure of 30 cm H2O or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0% vs 39.8%, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean (SD) 12 (11) vs 10 (11); P=0.007). The mean tidal volumes on days 1–3 were 6.2 (0.8) and 11.8 (0.8) ml/kg predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25 (6) and 33 (8) cm H2O (P<0.001), respectively. Conclusions: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. (N Engl J Med 2000;342:1301–8)