Francisco Álvarez-Lerma

Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit

ObjectiveTo assess the frequency of and the reasons for changing empiric antibiotics during the treatment of pnnumonia acquired in the intensive care unit (ICU).DesignA prospective multicenter study of 1 years duration.SettingMedical and surgical ICUs in 30 hospitals all over Spain.PatientsOf a total of 16872 patients initially enrolled into the study, 530 patients developed 565 episodes of pneumonia after admission to the ICU.ResultsEmpiric antibiotics were administered in 490 (86.7%) of the 565 episodes of pneumonia. The antimicrobials most frequently used were amikacin in 120 case, tobramycin in 110, ceftazidime in 96, and cefotaxime in 96. Monotherapy was indicated in 135 (27.6%) of the 490 episodes, a combination of two antibiotics in 306 episodes (62.4%), and a combination of three antibiotics in 49 episodes (10%). The empiric antibiotic treatment was modified in 214 (43.7%) cases because of isolation of a microorganism not covered by treatment in 133 (62.1%) cases, lack of clinical response in 77 (36%), and development of resistance in 14 (6.6%). Individual factors associated with modification of empiric treatment identified in the multivariate analysis were microorganism not covered (relative risk (RR)) 22.02; 95% confidence interval (CI) 11.54 to 42.60;p<0.0001), administration of more than one antimicrobial (RR 1.29; 95% CI 1.02 to 1.65;p=0.0018) attributable mortability was 16.2%.

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.

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain

IntroductionPatients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain.MethodsWe used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay.ResultsIllness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 ± 3.3).ConclusionsOver a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.

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.

A clinical trial on the prevention of catheter-related sepsis using a new hub model.

BACKGROUND Catheter hub contamination is being increasingly recognized as a source of catheter-related sepsis. The authors have investigated the efficacy of a new hub design in preventing endoluminal catheter contamination and catheter-related sepsis arising at the hub. METHODS Adult surgical and intensive care patients requiring a subclavian catheter for at least 1 week were randomly assigned to receive catheters with standard connectors (control group, n=73) or equipped with a new hub model (new hub group, n=78). Skin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or because of suspicion of sepsis, in which case peripheral blood cultures were taken. RESULTS Of the 151 patients included, 15 (10%) developed catheter-related sepsis. Catheters were more often withdrawn because suspicion of infection in the control group (42 vs. 19%, p<0.005). Catheter sepsis rate was higher in the control group (16 vs. 4%, p<0.01) because of the low rate of catheter sepsis arising at the hub observed in the new hub group (1 vs. 11%, p<0.01). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (18 vs. 5%, P<0.03). CONCLUSIONS A new catheter hub has proved to be useful in preventing endoluminal bacterial colonization and catheter-related sepsis in subclavian lines inserted for a mean of 2 weeks.

Economic Impact of Candida Colonization and Candida Infection in the Critically Ill Patient

The objective of the study presented here was to assess the economic impact of Candida colonization and Candida infection in critically ill patients admitted to intensive care units (ICUs). For this purpose, a prospective, cohort, observational, and multicenter study was designed. A total of 1,765 patients over the age of 18 years who were admitted for at least 7 days to 73 medical-surgical ICUs in 70 Spanish hospitals between May 1998 and January 1999 were studied. From day 7 of ICU admission to ICU discharge, samples of tracheal aspirates, pharyngeal exudates, gastric aspirates and urine were collected every week for culture. Prolonged length of stay was associated with severity of illness, Candida colonization or infection, infection by other fungi, antifungal therapy, treatment with more than one antifungal agent, and toxicity associated with this therapy. Compared to non-colonized, non-infected patients (n=720), patients with Candida colonization (n=880) had an extended ICU stay of 6.2 days (OR, 1.69; 95%CI, 1.53–1.87; P<0.001) and an extended hospital stay of 8.6 days (OR, 1.27; 95%CI, 1.16–1.40; P<0.001). The corresponding figures for patients with Candida infection (n=105) were 12.7 days for ICU stay (OR, 2.13; 95%CI, 1.72–2.64; P<0.001) and 15.5 days for hospital stay (OR, 1.23; 95%CI, 0.99–1.52; P=0.060). Candida colonization resulted in an additional 8,000 EUR in direct costs and Candida infection almost 16,000 EUR. Both Candida colonization and Candida infection had an important economic impact in terms of cost increases due to longer stays in both the ICU and in the hospital.

Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study

IntroductionAntibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance.MethodsTo assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem ± aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7–9 days post therapy.ResultsMicrobial identification – based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4% – was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization.ConclusionThis study mainly highlights the current practice of a specific algorithm of de-escalation solely based on the available microbiological data, and highlights the barriers to using it more widely. In this setting, de-escalation was less likely to occur in the presence of potentially multiresistant pathogens. Prior antibiotic administration and the low use of bronchoscopic techniques may have influenced negatively the implementation of de-escalation. Optimization of de-escalation strategies for NP should rely on a correct choice of empiric antibiotics, on appropriate microbiological investigations, and on a balanced interpretation of microbiological and clinical data.

Impact of a national multimodal intervention to prevent catheter-related bloodstream infection in the ICU: The Spanish experience

Objective:Prevention of catheter-related bloodstream infection is a basic objective to optimize patient safety in the ICU. Building on the early success of a patient safety unit-based comprehensive intervention (the Keystone ICU project in Michigan), the Bacteremia Zero project aimed to assess its effectiveness after contextual adaptation at large-scale implementation in Spanish ICUs. Design:Prospective time series. Setting:A total of 192 ICUs throughout Spain. Patients:All patients admitted to the participating ICUs during the study period (baseline April 1 to June 30, 2008; intervention period from January 1, 2009, to June 30, 2010). Intervention:Engagement, education, execution, and evaluation were key program features. Main components of the intervention included a bundle of evidence-based clinical practices during insertion and maintenance of catheters and a unit-based safety program (including patient safety training and identification and analysis of errors through patient safety rounds) to improve the safety culture. Measurements and Main Results:The number of catheter-related bloodstream infections was expressed as median and interquartile range. Poisson distribution was used to calculate incidence rates and risk estimates. The participating ICUs accounted for 68% of all ICUs in Spain. Catheter-related bloodstream infection was reduced after 16–18 months of participation (median 3.07 vs 1.12 episodes per 1,000 catheter-days, p < 0.001). The adjusted incidence rate of bacteremia showed a 50% risk reduction (95% CI, 0.39–0.63) at the end of the follow-up period compared with baseline. The reduction was independent of hospital size and type. Conclusions:Results of the Bacteremia Zero project confirmed that the intervention significantly reduced catheter-related bloodstream infection after large-scale implementation in Spanish ICUs. This study suggests that the intervention can also be effective in different socioeconomic contexts even with decentralized health systems.

Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study

BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

Risk factors for candidaemia in critically ill patients : a prospective surveillance study

Candidaemia is frequently a life‐threatening complication in patients admitted to the intensive care unit (ICU). To assess the risk factors for candidaemia in critically ill patients with prolonged ICU stay, a total of 1765 adult patients admitted for at least 7 days to 73 medical–surgical ICUs of 70 tertiary care hospitals in Spain participated in a prospective cohort study. Candidaemia was defined as recovery of Candida spp. from blood culture. Sixty‐eight episodes of candidaemia occurred in 63 patients, representing 35.7 episodes per 1000 ICU patients admitted, with an incidence rate of 1.5 episodes per 1000 days of ICU stay. Causative fungi were C. albicans in 57.1% of cases and non‐albicansCandida spp. in 42.9%. In the multivariate analysis, independent factors significantly associated with candidaemia were Candida colonisation (OR = 4.12, 95% CI: 1.82–9.33), total parenteral nutrition (OR = 3.89, 95% CI: 1.73–8.78), elective surgery (OR = 2.75, 95% CI: 1.17–6.45) and haemofiltration procedures (OR = 1.96, 95% CI: 1.06–3.62). In the ICU setting in Spain and in patients who have stayed in units for >7 days, more than half of cases of candidaemia were caused by C. albicans. Risk factors for candidaemia identified included Candida colonisation, elective surgery, total parenteral nutrition and haemodialysis.