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      Does nonadherence to local recommendations for empirical antibiotic therapy on admission to the intensive care unit have an impact on in-hospital mortality?

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          1/ To evaluate if empirical antibiotic prescription on admission to our intensive care unit (ICU) respects the local recommendations for antibiotic prescription and to identify predictors of nonadherence to these guidelines. 2/ To assess whether nonadherence to the guidelines is associated with increased in-hospital mortality due to the initial infection.

          Materials and methods

          This was a prospective six-month observational study performed in a 14-bed medical ICU. Patients were included if they received curative antibiotic therapy on admission. Respect of the local treatment recommendations was evaluated according to adherence to the local empirical guidelines defined in a 80-page booklet which is given in our hospital to every physician.


          Among 132 antibiotic prescriptions, 21 (16%) were unjustified (absence of infection), 17 (13%) were microbiologically documented at admission, and nine (7%) were given for infections from unknown origin. Among the 85 (64%) empirical prescriptions that could be evaluated for adherence to local recommendations, nine (11%) were inappropriate and 76 (89%) appropriate. In univariate analysis hospital-acquired infection was the sole predictor of inappropriate treatment (p = 0.0475). Independent predictors of in-hospital mortality due to the initial infection were inappropriate empirical treatment (odds ratio [OR] = 14.64, 95% confidence interval [CI]: 2.17–98.97; p = 0.006), prescription of fluoroquinolones (OR = 8.22, 95% CI: 1.88–35.95; p = 0.005) and a higher Simplified Acute Physiology Score II score (per one-point increment (OR = 1.04, 95% CI: 1.01–1.07; p = 0.02).


          Nonadherence to local empirical antibiotic therapy guidelines was associated with increased in-hospital mortality due to the initial infection.

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          Most cited references 10

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          Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study.

          To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources.
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            Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis.

            Our primary goal was to evaluate the impact on in-hospital mortality rate of adequate empirical antibiotic therapy, after controlling for confounding variables, in a cohort of patients admitted to the intensive care unit (ICU) with sepsis. The impact of adequate empirical antibiotic therapy on early (<3 days), 28-day, and 60-day mortality rates also was assessed. We determined the risk factors for inadequate empirical antibiotic therapy. DESIGN Prospective cohort study. ICU of a tertiary hospital. All the patients meeting criteria for sepsis at admission to the ICU. None. Four hundred and six patients were included. Microbiological documentation of sepsis was obtained in 67% of the patients. At ICU admission, sepsis was present in 105 patients (25.9%), severe sepsis in 116 (28.6%), and septic shock in 185 (45.6%). By multivariate analysis, predictors of in-hospital mortality were Sepsis-related Organ Failure Assessment (SOFA) score at ICU admission (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.19-1.40), the increase in SOFA score over the first 3 days in the ICU (OR, 1.40; 95% CI, 1.19-1.65), respiratory failure within the first 24 hrs in the ICU (OR, 3.12; 95% CI, 1.54-6.33), and inadequate empirical antimicrobial therapy in patients with "nonsurgical sepsis" (OR, 8.14; 95% CI, 1.98-33.5), whereas adequate empirical antimicrobial therapy in "surgical sepsis" (OR, 0.37; 95% CI, 0.18-0.77) and urologic sepsis (OR, 0.14; 95% CI, 0.05-0.41) was a protective factor. Regarding early mortality (<3 days), factors associated with fatality were immunosuppression (OR, 4.57; 95% CI, 1.69-13.87), chronic cardiac failure (OR, 9.83; 95% CI, 1.98-48.69) renal failure within the first 24 hrs in the unit (OR, 8.63; 95% CI, 3.31-22.46), and respiratory failure within the first 24 hrs in the ICU (OR, 12.35; 95% CI, 4.50-33.85). Fungal infection (OR, 47.32; 95% CI, 5.56-200.97) and previous antibiotic therapy within the last month (OR, 2.23; 95% CI, 1.1-5.45) were independent variables related to administration of inadequate antibiotic therapy. In patients admitted to the ICU for sepsis, the adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate was unaffected by the appropriateness of empirical antibiotic therapy.
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              Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.

              To define the impact of BAL data on the selection of antibiotics and the outcomes of patients with ventilator-associated pneumonia (VAP). Prospective observation and bronchoscopy with BAL, performed within 24 h of establishing a clinical diagnosis of a new episode of hospital-acquired VAP or progression of a prior episode of nosocomial pneumonia (NP). A 15-bed medical and surgical ICU. One hundred thirty-two patients hospitalized for more than 72 h, who were mechanically ventilated and had a new or progressive lung infiltrate plus at least two of the following three clinical criteria for VAP: abnormal temperature (> 38 degrees C or 10,000/mm3 or 10(4) cfu/mL), while 67 were BAL negative (BAL[-]). The BAL(+) patients had no differences in mortality, prior antibiotic use, and demographic features when compared with the BAL(-) patients. More of the BAL(+) patients (38/65) satisfied all three clinical criteria of VAP than did BAL(-) patients (24/67) (p < 0.05). A total of 50 BAL(+) patients received antibiotic therapy prior to bronchoscopy, and when this prior therapy was adequate (n = 16), as defined by the results of BAL, then mortality was 38%, while if prior therapy was inadequate (n = 34), mortality was 91% (p < 0.001), and if no therapy was given (n = 15), mortality was 60%. When therapy changes were made after bronchoscopy, more patients (n = 42) received adequate therapy, but mortality in this group was comparable to mortality among those who continued to receive inadequate therapy (n = 23). A total of 46 of the 65 BAL(+) patients died, with 23 of these deaths occurring during the 48 h after the bronchoscopy, before BAL results were known. When BAL data became available, 37 of the 42 surviving patients received adequate therapy, but their mortality was comparable to the patients who continued to receive inadequate therapy. Patients with a strong clinical suspicion of VAP have a high mortality rate, regardless of whether BAL cultures confirm the clinical diagnosis of VAP. When adequate antibiotic therapy is initiated very early (ie, before performing bronchoscopy), mortality rate is reduced if this empiric therapy is adequate, compared to when this therapy is inadequate or no therapy is given. If adequate therapy is delayed until bronchoscopy is performed or until BAL results are known, mortality is higher than if it had been given at the time of first establishing a clinical diagnosis of VAP. When patients were changed from inadequate antibiotic therapy to adequate therapy, based on the results of BAL, mortality was comparable to those who continued to receive inadequate therapy. Thus, even if bronchoscopy can accurately define the microbial etiology of VAP, this information becomes available too late to influence survival.

                Author and article information

                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                12 July 2009
                : 5
                : 491-498
                [1 ] Service de Réanimation Médicale
                [2 ] Service de Bactériologie-Virologie, Universite Pierre et Marie Curie, Paris, France
                [3 ] Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France
                Author notes
                Correspondence: Jean-Luc Baudel, Service de Réanimation Médicale, Hôpital Saint-Antoine, 184 rue du, Faubourg Saint-Antoine, 75 571, Paris Cedex 12, France, Tel +33 149 283 013, Fax +33 149 282 145, Email jean-luc.baudel@ 123456sat.aphp.fr
                © 2009 Baudel et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Original Research


                antimicrobial therapy, mortality, appropriateness, intensive care unit


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