Pieter Depuydt

Clinical and Economic Outcomes in Critically Ill Patients with Nosocomial Catheter-Related Bloodstream Infections

BACKGROUND Central venous catheters are universally used during the treatment of critically ill patients. Their use, however, is associated with a substantial infection risk, potentially leading to increased mortality and costs. We evaluate clinical and economic outcomes associated with nosocomial central venous catheter-related bloodstream infection (CR-BSI) in intensive care unit (ICU) patients. METHODS A retrospective (1992-2002), pairwise-matched (ratio of case patients to control subjects, 1:2 or 1:1), risk-adjusted cohort study was performed at a 54-bed general ICU at a university hospital. ICU patients with microbiologically documented CR-BSI (n = 176) were matched with control subjects (n = 315) on the basis of disease severity, diagnostic category, and length of ICU stay (equivalent or longer) before the onset of CR-BSI in the index case patient. Clinical outcome was principally evaluated by in-hospital mortality. Economic outcome was evaluated on the basis of duration of mechanical ventilation, length of ICU and hospital stays, and total hospital costs, as derived from the patients hospital invoices. RESULTS The attributable mortality rate for CR-BSI was estimated to be 1.8% (95% confidence interval, -6.4% to 10.0%); in-hospital mortality rates for patients with CR-BSI and matched control subjects were 27.8% and 26.0%, respectively. CR-BSI was associated with significant excesses in duration of mechanical ventilation, duration of ICU and hospital stays, and a significant increase in total hospital cost. Linear regression analysis with adjustment for duration of hospitalization and clinical covariates, revealed that CR-BSI is independently associated with higher costs. CONCLUSIONS In ICU patients, CR-BSI does not result in increased mortality. It is, however, associated with a significant economic burden, emphasizing the importance of continuous efforts in prevention.

Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis.

RATIONALE Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. OBJECTIVES We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. METHODS Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. MEASUREMENTS AND MAIN RESULTS Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. CONCLUSIONS Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients

IntroductionThe diagnosis of invasive pulmonary aspergillosis, according to the criteria as defined by the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), is difficult to establish in critically ill patients. The aim of this study is to address the clinical significance of isolation of Aspergillus spp. from lower respiratory tract samples in critically ill patients on the basis of medical and radiological files using an adapted diagnostic algorithm to discriminate proven and probable invasive pulmonary aspergillosis from Aspergillus colonisation.MethodsUsing a historical cohort (January 1997 to December 2003), all critically ill patients with respiratory tract samples positive for Aspergillus were studied. In comparison to the EORTC/MSG criteria, a different appreciation was given to radiological features and microbiological data, including semiquantitative cultures and direct microscopic examination of broncho-alveolar lavage samples.ResultsOver a 7 year period, 172 patients were identified with a positive culture. Of these, 83 patients were classified as invasive aspergillosis. In 50 of these patients (60%), no high risk predisposing conditions (neutropenia, hematologic cancer and stem cell or bone marrow transplantation) were found. Typical radiological imaging (halo and air-crescent sign) occurred in only 5% of patients. In 26 patients, histological examination either by ante-mortem lung biopsy (n = 10) or necropsy (n = 16) was performed, allowing a rough estimation of the predictive value of the diagnostic algorithm. In all patients with histology, all cases of clinical probable pulmonary aspergillosis were confirmed (n = 17). Conversely, all cases classified as colonisation had negative histology (n = 9).ConclusionA respiratory tract sample positive for Aspergillus spp. in the critically ill should always prompt further diagnostic assessment, even in the absence of the typical hematological and immunological host risk factors. In a minority of patients, the value of the clinical diagnostic algorithm was confirmed by histological findings, supporting its predictive value. The proposed diagnostic algorithm needs prospective validation.

Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: a pilot study.

OBJECTIVE Patients receiving mechanical ventilation through an endotracheal tube are at increased risk for pneumonia. Because microaspiration of contaminated supraglottic secretions past the endotracheal tube cuff is considered to be central in the pathogenesis of ventilator-associated and postoperative pneumonia, better sealing of the upper trachea by the endotracheal tube cuff could possibly reduce this risk. We therefore postulated that use of a polyurethane cuffed tube would prevent early postoperative pneumonia through this mechanism in a population of cardiac surgical patients. METHODS In a prospective, single-blind, randomized study, patients scheduled for cardiac surgery were allocated to intubation with a polyurethane cuffed endotracheal tube or the routinely used polyvinyl chloride cuffed endotracheal tube. Patients were scheduled for routine or emergency cardiac surgery and admitted to an 8-bed cardiac surgical intensive care unit of a tertiary care hospital. RESULTS A total of 134 patients were available for analysis (67 in each group). Whereas mortality was not different between the groups, the incidence of early postoperative pneumonia and empirical prescription of antibiotic therapy were significantly lower in the polyurethane group than in the polyvinyl chloride group (23% vs 42%, P < .03). Intensive care unit and hospital stays were not significantly different between the two study subsets (3 +/- 5 days vs 3 +/- 4 days and 16 +/- 9 vs 17+/-11 days, respectively). In a multivariate regression analysis, preoperative serum creatinine levels (odds ratio 1.85, confidence interval 1.02-3.37, P = .04) and perioperative transfusion (odds ratio 1.50, confidence interval 1.08-3.37, P = .015) were independently associated with increased risk of early postoperative pneumonia, whereas use of a polyurethane endotracheal tube was protective (odds ratio 0.31, confidence interval 0.13-0.77, P = .01). CONCLUSION Polyurethane cuffed endotracheal tubes can reduce the frequency of early postoperative pneumonia in cardiac surgical patients.

Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?

BackgroundCorrect antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.MethodsThis was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.ResultsWe obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% f T>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% f T>MIC.ConclusionsIn this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.

Bacteremia in patients with ventilator-associated pneumonia is associated with increased mortality: A study comparing bacteremic vs. nonbacteremic ventilator-associated pneumonia*

Objective:To assess whether bacteremic ventilator-associated pneumonia (B-VAP) differs in terms of risk factors, organisms, and outcomes from nonbacteremic VAP (NB-VAP). Design:A retrospective, single-center, observational, cohort study. Setting:Multidisciplinary teaching intensive care unit. Patients:Adult patients requiring mechanical ventilation, identified as having VAP in a 44-month prospective surveillance database. Interventions:Each B-VAP patient was matched with two controls with VAP and negative blood cultures based on the microbial etiology responsible for VAP, Acute Physiology and Chronic Health Evaluation II score on admission (±3 points), diagnostic category, and length of stay before pneumonia onset. Measurements and Main Results:B-VAP was documented in 35 (17.6%) of 199 microbiologically confirmed VAP episodes. B-VAP developed later (median 8 vs. 5 days, p = .03) and was more frequent in previously hospitalized patients (34.3% vs. 11.0%, p < .01) and in older patients (57.4 ± 15.2 vs. 49.5 ± 19.3 yrs, p = .02). B-VAP was more often caused by methicillin-resistant Staphylococcus aureus (12 [20.7%] vs. 13 [5.1%] episodes, p < .01), whereas Haemophilus influenzae was associated with NB-VAP (52 [20.4%] vs. 0, p < .01). Multivariate analysis confirmed an association between B-VAP and both methicillin-resistant S. aureus (odds ratio 3.18; 95% confidence interval 1.15–8.76, p < .01) and prior hospitalization (odds ratio 2.56; 95% confidence interval 1.01–6.54, p = .05). After adjustment for potential confounders, B-VAP (hazard ratio for death 2.55; 95% confidence interval 1.25–5.23, p = .01) and vasopressor use (hazard ratio 2.43; 95% confidence interval 1.23–4.82, p = .01) remained associated with mortality. The estimated relative risk of death for bacteremic cases was 2.86 (95% confidence interval 1.09–7.51), since mortality for cases and matched NB-VAP controls was 40.6% (13 of 32) and 19.3% (11 of 57), respectively. Conclusions:B-VAP occurs later during intensive care unit stay, is more frequent in previously hospitalized patients, is more often caused by methicillin-resistant S. aureus, and is independently associated with increased intensive care unit mortality.

Colonization status and appropriate antibiotic therapy for nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in an intensive care unit.

OBJECTIVE Timely initiation of antibiotic therapy is crucial for severe infection. Appropriate antibiotic therapy is often delayed for nosocomial infections caused by antibiotic-resistant bacteria. The relationship between knowledge of colonization caused by antibiotic-resistant gram-negative bacteria (ABR-GNB) and rate of appropriate initial antibiotic therapy for subsequent bacteremia was evaluated. DESIGN Retrospective cohort study. SETTING Fifty-four-bed intensive care unit (ICU) of a university hospital. In this unit, colonization surveillance is performed through routine site-specific surveillance cultures (urine, mouth, trachea, and anus). Additional cultures are performed when presumed clinically relevant. PATIENTS ICU patients with nosocomial bacteremia caused by ABR-GNB. RESULTS Infectious and microbiological characteristics and rates of appropriate antibiotic therapy were compared between patients with and without colonization prior to bacteremia. Prior colonization was defined as the presence (detected > or = 2 days before the onset of bacteremia) of the same ABR-GNB in colonization and subsequent blood cultures. During the study period, 157 episodes of bacteremia caused by ABR-GNB were suitable for evaluation. One hundred seventeen episodes of bacteremia (74.5%) were preceded by colonization. Appropriate empiric antibiotic therapy (started within 24 hours) was administered for 74.4% of these episodes versus 55.0% of the episodes that occurred without prior colonization. Appropriate therapy was administered within 48 hours for all episodes preceded by colonization versus 90.0% of episodes without prior colonization. CONCLUSION Knowledge of colonization status prior to infection is associated with higher rates of appropriate therapy for patients with bacteremia caused by ABR-GNB.

Measuring the impact of multidrug resistance in nosocomial infection.

Purpose of review The review examines potential confounders hampering measurement of the impact of multidrug resistance in nosocomial infections. Methodological techniques dealing with the problem of confounding are discussed and current findings in how multidrug resistance affects outcome in patients with nosocomial infection are highlighted. Recent findings Outcome comparisons between patients infected with multidrug-resistant pathogens and patients infected with susceptible microorganisms are hampered by confounders such as differences in disease severity, prolonged hospitalization prior to onset of infection (exposure time), the causative pathogen, the type of infection, and the rate of appropriate empirical antimicrobial therapy. The confounding effect can be countered by means of either multivariable regression techniques or matched cohort studies, or a combination of both. Recent literature on the impact of multidrug resistance (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum β-lactamase producing Enterobacteriaceae, etc) is conflicting and highly dependable on the way disturbing variables are accounted for. Summary Recent data underscore that the impact of multidrug resistance on the outcome of nosocomial infection might differ depending on the study population, type of infection, type of pathogen and appropriateness of therapy, and hence, that any conclusion drawn prior to accurate accounting for imbalanced confounders is premature and potentially false.

Antimicrobial resistance in nosocomial bloodstream infection associated with pneumonia and the value of systematic surveillance cultures in an adult intensive care unit.

Objective:To study the occurrence of multiple-drug-resistant pathogens in nosocomial bloodstream infection associated with pneumonia. To evaluate prediction of multiple drug resistance by systematic surveillance cultures. Design:A retrospective study of a prospectively gathered cohort. Setting:Fifty-four-bed adult medical-surgical intensive care unit of a tertiary hospital. Patients:One hundred twelve intensive care unit patients with nosocomial bloodstream infection associated with pneumonia from 1992 through 2001. Interventions:None. Measurements and Main Results:Concordance of blood cultures with prior surveillance culture was assessed. Surveillance cultures were taken routinely as thrice weekly urinary cultures and oral swabs, once weekly anal swabs, and thrice weekly tracheal aspirates in intubated patients. Tracheal surveillance cultures from 48 to 96 hrs before bloodstream infection and surveillance cultures from any site during the same intensive care unit episode but ≥48 hrs before bloodstream infection were evaluated separately. Forty-four bloodstream infections (39%) were caused by a multiple-drug-resistant pathogen. Multiple-drug-resistant pathogens were predicted by tracheal surveillance culture in 70% (concordant); in 15%, tracheal surveillance culture grew a multiple-drug-resistant pathogen not found in blood cultures (discordant). Multiple-drug-resistant pathogens were predicted by any surveillance culture in 88%, but these surveillance cultures grew additional multiple-drug-resistant pathogens not causing bloodstream infection in up to 46% of patients. In 86% of bloodstream infections, early (i.e., within 48 hrs) antibiotic therapy was appropriate. Patients were divided into four risk categories for multiple-drug-resistant bloodstream infection based on length of prior intensive care unit stay and prior antibiotic exposure. In patients with two risk factors, knowledge of surveillance cultures increased appropriateness of early antibiotic therapy from 75–79% to 90% (p < .05) while limiting use of broad-spectrum antibiotics such as antipseudomonal betalactams, fluoroquinolones, and carbapenems. Conclusions:In our intensive care unit, tracheal surveillance culture predicted multiple-drug-resistant etiology of bloodstream infection associated with pneumonia in 70% of patients but yielded discordant resistant pathogens in 15%. In the subgroup of patients with two risk factors for multiple-drug-resistant infection, incorporating results of surveillance cultures moderately contributed to adequacy of early antibiotic therapy while limiting antibiotic consumption.

Daily cost of antimicrobial therapy in patients with Intensive Care Unit-acquired, laboratory-confirmed bloodstream infection

This study analysed daily antimicrobial costs of Intensive Care Unit (ICU)-acquired, laboratory-confirmed bloodstream infection (BSI) per patient admitted to the ICU of a university hospital, based on prospectively collected data over a 4-year period (2003-2006). Costs were calculated based on the price of the agent(s) initiated on the first day of appropriate treatment and according to: (i) focus of infection; (ii) pathogen; and (iii) antimicrobial agent. The study included 310 adult patients who developed 446 BSI episodes. Mean overall daily antimicrobial cost was euro114.25. Daily antimicrobial cost was most expensive for BSIs with unknown focus (euro137.70), followed by catheter-related (euro122.73), pulmonary (euro112.80), abdominal (euro98.00), wound (euro89.21), urinary (euro87.85) and other inciting focuses (euro81.59). Coagulase-negative staphylococci were the most prevalent pathogens isolated. Treatment of BSIs caused by Candida spp. was the most costly. The daily antimicrobial costs per infected patient with multidrug-resistant BSI was ca. 50% higher compared with those without (euro165.09 vs. euro82.67; P<0.001). Among the total of 852 prescriptions, beta-lactam antibiotics accounted for approximately one-third of the overall daily cost of antimicrobial agents. The antibiotic cost associated with ICU-acquired, laboratory-confirmed BSI is significant and should be reduced by implementing infection control measures and preventive strategies.