José Garnacho-Montero

Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis.

ObjectivesOur 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. DesignProspective cohort study. SettingICU of a tertiary hospital. PatientsAll the patients meeting criteria for sepsis at admission to the ICU. InterventionsNone. Measurements and Main ResultsFour 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. ConclusionsIn 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.

A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization.

Objective:To obtain a score for deciding early antifungal treatment when candidal infection is suspected in nonneutropenic critically ill patients. Design:Analysis of data collected from the database of the EPCAN project, an ongoing prospective, cohort, observational, multicenter surveillance study of fungal infection and colonization in intensive care unit (ICU) patients. Setting:Seventy-three medical-surgical ICUs of 70 teaching hospitals in Spain. Patients:A total of 1,699 ICU patients aged 18 yrs and older admitted for at least 7 days between May 1998 and January 1999 were studied. Interventions:Surveillance cultures of urine, tracheal, and gastric samples were obtained weekly. Patients were grouped as follows: neither colonized nor infected (n = 719), unifocal or multifocal Candida colonization (n = 883), and proven candidal infection (n = 97). The odds ratio (OR) for each risk factor associated with colonization vs. proven candidal infection was estimated. A logistic regression model was performed to adjust for possible confounders. The “Candida score” was obtained according to the logit method. The discriminatory power was evaluated by the area under the receiver operating characteristics curve. Measurements and main results:In the logit model, surgery (OR = 2.71, 95% confidence interval [CI], 1.45–5.06); multifocal colonization (OR = 3.04, 95% CI, 1.45–6.39); total parenteral nutrition (OR = 2.48, 95% CI, 1.16–5.31); and severe sepsis (OR = 7.68, 95% CI, 4.14–14.22) were predictors of proven candidal infection. The “Candida score” for a cut-off value of 2.5 (sensitivity 81%, specificity 74%) was as follows: parenteral nutrition, +0.908; surgery, +0.997; multifocal colonization, +1.112; and severe sepsis, +2.038. Central venous catheters were not a significant risk factor for proven candidal infection (p = .292). Conclusions:In a large cohort of nonneutropenic critically ill patients in whom Candida colonization was prospectively assessed, a “Candida score” >2.5 accurately selected patients who would benefit from early antifungal treatment.

Treatment of Multidrug-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia (VAP) with Intravenous Colistin: A Comparison with Imipenem-Susceptible VAP

We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.

Acinetobacter baumannii ventilator-associated pneumonia : epidemiological and clinical findings

ObjectiveTo investigate prognostic factors and predictors of Acinetobacter baumannii isolation in ventilator-associated pneumonia (VAP). We specifically analyzed these issues for imipenem-resistant episodes.Design and settingAll episodes of VAP are prospectively included in a database. Information about risk factors was retrieved retrospectively.PatientsEighty-one patients exhibiting microbiologically documented VAP: 41 by A. baumannii (26 by imipenem-resistant) and 40 by other pathogens.Measurements and resultsThe following variables were noted: underlying diseases, severity of illness, duration of mechanical ventilation and of hospitalization before VAP, prior episode of sepsis, previous antibiotic, corticosteroid use, type of nutrition, renal replacement therapy, reintubation, transportation out of the ICU, micro-organisms involved in VAP, concomitant bacteremia, clinical presentation, Sequential Organ Failure Assessment (SOFA) scale on the day of diagnosis, and adequacy of empirical antibiotic therapy. Prior antibiotic use was found to be associated with development of VAP by A. baumannii (OR 14). Prior imipenem exposure was associated with the isolation of imipenem-resistant strains (OR 4). SOFA score on the day of diagnosis was the only predictor of in-hospital mortality (OR 1.22); adequacy of empirical antibiotic therapy was a protective factor (OR 0.067).ConclusionsOur results confirm that prior exposure to antimicrobials is an independent predictor for the development of A. baumannii VAP, the prognosis of which is similar to that of infections caused by other pathogens. This study highlights the importance of initial antibiotic choice in VAP or whatever cause.

Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome

IntroductionOur aims were to assess risk factors, clinical features, management and outcomes in critically ill patients in whom Aspergillus spp. were isolated from respiratory secretions, using a database from a study designed to assess fungal infections.MethodsA multicentre prospective study was conducted over a 9-month period in 73 intensive care units (ICUs) and included patients with an ICU stay longer than 7 days. Tracheal aspirate and urine samples, and oropharyngeal and gastric swabs were collected and cultured each week. On admission to the ICU and at the initiation of antifungal therapy, the severity of illness was evaluated using the Acute Physiology and Chronic Health Evaluation II score. Retrospectively, isolation of Aspergillus spp. was considered to reflect colonization if the patient did not fulfil criteria for pneumonia, and infection if the patient met criteria for pulmonary infection and if the clinician in charge considered the isolation to be clinically valuable. Risk factors, antifungal use and duration of therapy were noted.ResultsOut of a total of 1756 patients, Aspergillus spp. were recovered in 36. Treatment with steroids (odds ratio = 4.5) and chronic obstructive pulmonary disease (odds ratio = 2.9) were significantly associated with Aspergillus spp. isolation in multivariate analysis. In 14 patients isolation of Aspergillus spp. was interpreted as colonization, in 20 it was interpreted as invasive aspergillosis, and two cases were not classified. The mortality rates were 50% in the colonization group and 80% in the invasive infection group. Autopsy was performed in five patients with clinically suspected infection and confirmed the diagnosis in all of these cases.ConclusionIn critically ill patients, treatment should be considered if features of pulmonary infection are present and Aspergillus spp. are isolated from respiratory secretions.

Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy.

Objective:To evaluate whether one antibiotic achieves equal outcomes compared with combination antibiotic therapy in patients with Pseudomonas aeruginosa ventilator-associated pneumonia. Design:A retrospective, multicenter, observational, cohort study. Setting:Five intensive care units in Spanish university hospitals. Patients:Adult patients identified to have monomicrobial episodes of ventilator-associated pneumonia with significant quantitative respiratory cultures for P. aeruginosa. Interventions:None. Measurement and Main Results:A total of 183 episodes of monomicrobial P. aeruginosa ventilator-associated pneumonia were analyzed. Monotherapy alone was used empirically in 67 episodes, being significantly associated with inappropriate therapy (56.7% vs. 90.5%, p < .001). Hospital mortality was significantly higher in the 40 patients with inappropriate therapy compared with those at least on antibiotic with activity in vitro (72.5% vs. 23.1%, p < .05). Excess mortality associated with monotherapy was estimated to be 13.6% (95% confidence interval −2.6 to 29.9). The use of monotherapy or combination therapy in the definitive regimen did not influence mortality, length of stay, development of resistance to the definitive treatment, or appearance of recurrences. Inappropriate empirical therapy was associated with increased mortality (adjusted hazard ratio 1.85; 95% confidence interval 1.07–3.10; p = .02) in a Cox proportional hazard regression analysis, after adjustment for disease severity, but not effective monotherapy (adjusted hazard ratio 0.90; 95% confidence interval 0.50–1.63; p = .73) compared with effective combination therapy (adjusted hazard ratio 1). The other two variables also independently associated with mortality were age (adjusted hazard ratio 1.02; 95% confidence interval 1.01–1.04; p = .005) and chronic cardiac insufficiency (adjusted hazard ratio 1.90; 95% confidence interval 1.04–3.47; p = .035). Conclusions:Initial use of combination therapy significantly reduces the likelihood of inappropriate therapy, which is associated with higher risk of death. However, administration of only one effective antimicrobial or combination therapy provides similar outcomes, suggesting that switching to monotherapy once the susceptibility is documented is feasible and safe.

Pneumonia caused by oxacillin-resistant staphylococcus aureus treated with glycopeptides*

Objective:To determine whether ventilator-associated pneumonia caused by oxacillin-resistant Staphylococcus aureus (VAP-ORSA) treated with glycopeptides is associated with an increased mortality rate. Design:Retrospective matched cohort study. Setting:Four intensive care units in teaching hospitals. Patients:Seventy-five patients were matched to 75 controls. Interventions:None. Measurements and Main Results:All adult intensive care unit patients with microbiologically documented VAP-ORSA were matched to intubated controls who did not develop VAP-ORSA, based on disease severity (Acute Physiology and Chronic Health Evaluation II score) at admission (±3 points), diagnostic category, and length of stay before pneumonia onset. Population characteristics and intensive care unit mortality rates of patients with VAP-ORSA and their controls without pneumonia were compared. Attributable mortality was determined by subtracting the crude mortality rate of controls from the crude mortality rate of VAP-ORSA patients. Thirty-six of the 75 matched VAP-ORSA patients died, representing a crude mortality rate of 48%, whereas 19 of the 75 controls died, a crude mortality rate of 25.3% (p < .01). Excess mortality was estimated to be 22.7% (95% confidence interval, 2.4–42.9%). Median length of intensive care unit stay in the surviving pairs was 33 days (interquartile range, 25–75%: 25-45 days) for VAP-ORSA patients and 21 days (interquartile range, 25–75%: 15–34.75 days) days for controls (p = .054). Conclusions:Despite appropriate glycopeptide therapy, there is an increased attributable mortality for pneumonia by ORSA, after careful adjustment for disease severity and diagnostic category.

Implications of COPD in patients admitted to the intensive care unit by community- acquired pneumonia

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included <20% of critically ill patients. The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP. In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01–1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63–4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged ≥70 yrs, smokers and who had chronic heart disease or Pseudomonas aeruginosa were higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19–12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18–4.53) and shock (OR 3.53; 95% CI 1.31–9.71). In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.

Multiresistant acinetobacter baumannii infections: epidemiology and management

Purpose of review We present recent data about epidemiology of Acinetobacter baumannii in the hospital setting, major resistance mechanisms, and therapeutic options for infections caused by multidrug-resistant strains. Recent findings A. baumannii has emerged as a major cause of healthcare-associated infections. It commonly presents resistance to multiple antimicrobial agents, including carbapenems. These strains are now ussually resistant to the rest of antipseudomonal β-lactams and sulbactam, a β-lactamase inhibitor with bactericide activity against A. baumannii. Rifampicin has demonstrated its effectiveness in animal models but can never be used in monotherapy because of the rapid development of resistance. Colistin, an old antibiotic, has re-emerged as a valid alternative given its excellent in-vitro activity. Numerous studies have confirmed its efficacy in serious infections, including ventilator-associated pneumonia and nosocomial meningitis, with an acceptable safety profile. Tigecycline appears as a promising therapeutic option for multidrug resistant A. baumannii, althogh more clinical data about its efficacy especially in pulmonary infections are required. The role of combination therapy or the use or colistin in alternative routes (nebulized or intrathecally) has not been established. Summary The optimal treatment for multidrug-resistant A. baumannii nosocomial infections has not been established. Carbapenems are the mainstay of treatment in susceptible isolates. Colistin and tigecycline retain good in-vitro activity and in many cases represent the only therapeutic options.

Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis.

IntroductionGenetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients.MethodThe inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-α 308 promoter polymorphism; the polymorphism in the first intron of the TNF-β gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission.ResultsA group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy.ConclusionThis study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.