Management of end-stage heart failure patients with or without ventricular assist device: an observational comparison of clinical and economic outcomes.

OBJECTIVES: Heart transplantation (HT) and ventricular assist devices (VAD) for the management of end-stage heart failure have not been directly compared. We compare the outcomes and use of resources with these 2 strategies in 2 European countries with different allocation systems. METHODS: We studied 83 patients managed by VAD as the first option in Bad Oeynhausen, Germany (Group I) and 141 managed with either HT or medical therapy, as the first option, in Paris, France (Group II). The primary end-point was 2-year survival. Kaplan-Meier analyses were performed after the application of propensity score weights to mitigate the effects of non-random group assignment. The secondary end-points were resource utilization and costs. Subgroup analyses were performed for patients undergoing HT and patients treated with inotropes at the enrolment time. RESULTS: The Group I patients were more severely ill and haemodynamically compromised, and 28% subsequently underwent HT vs 55% primary HT in Group II, P < 0.001. The adjusted probability of survival was 44% in Group I vs 70% in Group II, P <0.0001. The mean cumulated 2-year costs were €281 361 ± 156 223 in Group I and €47 638 ± 35 061 in Group II, P < 0.0001. Among patients who underwent HT, the adjusted probability of survival in Group I (n = 23) versus Group II (n = 78) was 76% versus 68%, respectively (0.09), though it differed in the inotrope-treated subgroups (77% in Group I vs 67% in Group II, P = 0.04). CONCLUSIONS: HT should remain the first option for end-stage heart failure patients, associated with improved outcomes and better cost-effectiveness profile. VAD devices represent an option when transplant is not possible or when patient presentation is not optimal.

Outcomes in elderly patients admitted to the intensive care unit with solid tumors.

BACKGROUND: As the population ages and cancer therapies improve, there is an increased call for elderly cancer patients to be admitted to the intensive care unit (ICU). This study aimed to assess short-term survival and prognostic factors in critically ill patients with solid tumors aged ≥65 years. METHODS: We conducted a retrospective study. The primary endpoint was ICU mortality. Resumption of anticancer therapy in patients who survived the ICU stay and 90-day mortality were secondary endpoints. All patients aged ≥65 years admitted to the ICU of Georges Pompidou Hospital (Paris, France) between 2009 and 2014 were eligible. RESULTS: Of 2327 eligible elderly patients (EP), 262 (75.0 ± 6.7 years) with solid tumors were analyzed. These patients were extremely critically ill (SAPS 2 61.9 ± 22.5), and 60.3% had metastatic disease. Gastrointestinal, lung and genitourinary cancers were the most common types of tumors. Mechanical ventilation was required in 51.5% of patients, inotropes in 48.1% and dialysis in 12.6%. Most patients (66.7%) were admitted for reasons unrelated to cancer, including sepsis (30.5%), acute respiratory failure (28.2%) and neurological problems (8.0%). ICU mortality in patients with cancer was 33.6 versus 32.6% among patients without cancer (p = 0.75). Among the cancer EP, the 90-day mortality was 51.9% (n = 136). In multivariate analysis, increased SAPS 2 score and primary tumor site were associated with 90-day death, whereas previous anticancer therapies and poor performance status were not. Among survivor patients from ICU with anti-tumoral treatment indication, 77 (52.7%) had resumption of anticancer treatment. CONCLUSIONS: Elderly solid tumor patients admitted to the ICU had a mortality rate similar to EP without cancer. Prognostic factors for 90-day mortality were more related to severity of clinical status at admission than the presence or stage of cancer, suggesting that early admission of EP with cancer to the ICU is appropriate.

Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Biosimilars: from Technical to Pharmacoeconomic Considerations.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Medico-economic evaluation of healthcare products. Methodology for defining a significant impact on French health insurance costs and selection of benchmarks for interpreting results.

Decree No. 2012-1116 of 2 October 2012 on medico-economic assignments of the French National Authority for Health (Haute autorité de santé, HAS) significantly alters the conditions for accessing the health products market in France. This paper presents a theoretical framework for interpreting the results of the economic evaluation of health technologies and summarises the facts available in France for developing benchmarks that will be used to interpret incremental cost-effectiveness ratios. This literature review shows that it is difficult to determine a threshold value but it is also difficult to interpret then incremental cost effectiveness ratio (ICER) results without a threshold value. In this context, round table participants favour a pragmatic approach based on "benchmarks" as opposed to a threshold value, based on an interpretative and normative perspective, i.e. benchmarks that can change over time based on feedback.

Severe excessive dynamic airway collapse in a patient with primary Sjögren's syndrome.

Airway and cystic lung diseases can be observed in patients with Sjögren's syndrome. We report a case of such a patient suffering from respiratory failure due to recurrent episodes of right pneumothorax, requiring invasive mechanical ventilation. Despite thoracic drainage and adequate pneumothorax management, the patient could not be weaned from the ventilator. Fiberoptic bronchoscopy revealed severe central excessive dynamic airway collapse of the lower part of the trachea and proximal bronchi. The severity of airway collapse was maximal at the intermediate bronchus level, with a near-complete obstruction during expiration. Inspiratory and expiratory computed tomography studies confirmed the fiberoptic findings and suggested a possible expiratory posterior compression of the intermediate bronchus by parenchymal lung cysts. Stenting was considered, but the patient died from ventilator-associated pneumonia before the procedure could be performed. This case is the first description of severe central excessive dynamic airway collapse in a patient with primary Sjögren's syndrome complicated by diffuse airway and cystic lung disease.

Impact of organizational culture on preventability assessment of selected adverse events in the ICU: evaluation of morbidity and mortality conferences.

PURPOSE: To determine whether organizational culture is associated with preventability assessment of reported adverse events (AE) in intensive care units (ICU). DESIGN: Blind review of time randomly distributed case notes written in the form of structured abstracts by the nurses who participated in recently implemented morbidity and mortality conferences from December 2006 to June 2010 in a 18-bed ICU in France. Ninety-five abstracts summarizing the discussions of 95 AE involving 95 patients were reviewed by two external blinded pairs (each comprised of one senior intensivist and one psychologist). METHODS: A score for each organizational culture style was determined, with the highest scorer being considered the dominant style present in the abstract. RESULTS: Reliability of the classification and quantification of culture traits between pairs was very good or good for 13 dimensions and moderate for two others. The two pairs deemed 32/95 and 43/95 of AE preventable (κ = 0.59). Concordance was very good (κ = 0.85) between the external pairs for evaluation of the dominant culture style. The Cochran-Armitage trend test indicated an increasing trend for change of the dominant organizational culture style over time: the team-satisfaction-oriented culture took a leading role (p = 0.02), while the people-security-oriented culture decreased dramatically (p < 0.001). The task-security-oriented culture was significantly associated with a preventable judgment, while the people-security-oriented culture was significantly associated with an unpreventable judgment (p < 0.001). CONCLUSIONS: This study demonstrated a strong relationship between preventability assessment of AE reported by caregivers and their organizational culture in the ICU.

Impact of morbidity and mortality conferences on analysis of mortality and critical events in intensive care practice.

BACKGROUND: Morbidity and mortality conferences are a tool for evaluating care management, but they lack a precise format for practice in intensive care units. OBJECTIVES: To evaluate the feasibility and usefulness of regular morbidity and mortality conferences specific to intensive care units for improving quality of care and patient safety. METHODS: For 1 year, a prospective study was conducted in an 18-bed intensive care unit. Events analyzed included deaths in the unit and 4 adverse events (unexpected cardiac arrest, unplanned extubation, reintubation within 24-48 hours after planned extubation, and readmission to the unit within 48 hours after discharge) considered potentially preventable in optimal intensive care practice. During conferences, events were collectively analyzed with the help of an external auditor to determine their severity, causality, and preventability. RESULTS: During the study period, 260 deaths and 100 adverse events involving 300 patients were analyzed. The adverse events rate was 16.6 per 1000 patient-days. Adverse events occurred more often between noon and 4 pm (P = .001).The conference consensus was that 6.1% of deaths and 36% of adverse events were preventable. Preventable deaths were associated with iatrogenesis (P = .008), human errors (P < .001), and failure of unit management factors or communication (P = .003). Three major recommendations were made concerning standardization of care or prescription and organizational management, and no similar incidents have recurred. CONCLUSION: In addition to their educational value, regular morbidity and mortality conferences formatted for intensive care units are useful for assessing quality of care and patient safety.

Partitioning of exhaled NO in ventilated patients undergoing cardiac surgery.

The change in exhaled NO after cardio-pulmonary bypass remains controversial. The aims were to determine whether exhaled NO sources (alveolar or bronchial) are modified after bypass, and whether mechanical ventilation (MV) settings during bypass modify exhaled NO changes. Thirty-two patients were divided into three groups: without MV during bypass and positive end-expiratory pressure (PEEP) (n=12), dead space MV without PEEP (n=10) and dead space MV with PEEP (n=10). Alveolar NO concentration and bronchial NO flux were calculated before and 1h after surgery using a two-compartment model of NO exchange developed in spontaneous breathing patients. Whereas a significant decrease in bronchial NO was found after bypass in the two groups without PEEP during bypass, this decrease was not observed in patients with dead space ventilation with PEEP. Alveolar NO was not significantly modified whatever the ventilation settings. In conclusion, the impairment of bronchial NO seemed related to airway closure since dead space mechanical ventilation with PEEP prevented its decrease.

Prediction of nosocomial infection acquisition in ventilated patients by nasal nitric oxide: proof-of-concept study.

The development of biomarkers able to predict the occurrence of nosocomial infection could help manage preventive strategies, especially in medical patients whose degree of acquired immunosuppression may be variable. We hypothesized that the NO fraction present in the airways (upper and lower) of critically ill patients under mechanical ventilation could constitute such a biomarker. We conducted an observational proof-of-concept study in a medical intensive care unit of a teaching hospital. Forty-five patients (26 men; 72 [25th-75th percentiles] years [56-82]; Simplified Acute Physiology Score II, 63 [50-81], 14 infected) under mechanical ventilation (>3 days) underwent on day 1 and day 3 of their stay: nasal and exhaled (partitioned in bronchial and alveolar sources) bedside NO measurements, determination of urine NO end products and plasma cytokine (IL-6, IL-10) concentrations, and Sequential Organ Failure Assessment score calculation. Nosocomial infection incidence was recorded during the 15 subsequent days. Fifteen patients (33%) acquired a nosocomial infection (16 infections, 15 ventilator-associated pneumonia and 1 bacteremia). Nasal NO was the only marker significantly different between patients with and without subsequent infection (day 1, 52 ppb [20-142] vs. 134 [84-203], P = 0.038; day 3, 98 ppb [22-140] vs. 225 [89-288], P = 0.006, respectively). Nasal NO fraction 148 ppb or less at day 3 had an 80% sensitivity, a 70% specificity, and an odds ratio of 2.7 (95% confidence interval, 1.9-3.8) to predict acquisition of nosocomial infection. Nonsurvivors had a higher IL-6 concentration on day 3 (P = 0.014), whereas their nasal NO fractions were not significantly different. Nasal NO seems to be a relatively sensitive and specific biomarker of subsequent nosocomial infection acquisition (at least for ventilator-associated pneumonia), which warrants confirmation in a multicenter trial.

Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration.

PURPOSE: Septic shock is one of the leading causes of acute kidney injury. The mechanisms of this injury remain mostly unknown notably because of the lack of data on renal histological lesions in humans. METHODS: Kidney biopsy was performed immediately post-mortem in consecutive patients who died of septic shock. Comparisons were made with specimens from eight patients who died of trauma on scene and nine ICU patients that died of non-septic causes. RESULTS: Nineteen septic patients were included, 11 were male, and age was 72 +/- 12 years. Anuria occurred in all patients 2.2 +/- 1.4 days before death. Seven patients had disseminated intravascular coagulation. In all patients we observed (1) acute tubular lesions whose intensity correlated with blood lactate concentration; (2) intense infiltration by leukocytes, mainly monocytic, in glomeruli and interstitial capillaries as compared to controls; (3) presence of tubular cell apoptosis proved by the presence of apoptotic bodies (2.9% of tubular cells) significantly more frequently than in controls and confirmed by TUNEL and activated caspase-3 staining. Arteriolar/arterial thromboses were observed in only 4 of 19 patients, without any association with presence of disseminated intravascular coagulation. CONCLUSIONS: Kidney lesions in septic shock go beyond those associated with simple acute tubular injury, notably capillary leukocytic infiltration and apoptosis. Vascular thrombosis, however, did not appear to play a major role in the majority of patients. The extent to which these lesions are specific to sepsis or are common to all multi-organ failure independent of its cause is yet to be elucidated. Electronic supplementary material The online version of this article (doi:10.1007/s00134-009-1723-x) contains supplementary material, which is available to authorized users.

Ultrasonographic diagnostic criterion for severe diaphragmatic dysfunction after cardiac surgery.

BACKGROUND: Severe diaphragmatic dysfunction can prolong mechanical ventilation after cardiac surgery. An ultrasonographic criterion for diagnosing severe diaphragmatic dysfunction defined by a reference technique such as transdiaphragmatic pressure measurements has never been determined. METHODS: Twenty-eight patients requiring mechanical ventilation > 7 days postoperatively were studied. Esophageal and gastric pressures were measured to calculate transdiaphragmatic pressure during maximal inspiratory effort and the Gilbert index, which evaluates the diaphragm contribution to respiratory pressure swings during quiet ventilation. Ultrasonography allowed measuring right and left hemidiaphragmatic excursions during maximal inspiratory effort. Best E is the greatest positive value from either hemidiaphragm. Twenty cardiac surgery patients with uncomplicated postoperative course were also evaluated with ultrasonography preoperatively and postoperatively. Measurements were performed in semirecumbent position. RESULTS: Transdiaphragmatic pressure during maximal inspiratory effort was below normal value in 27 of the 28 patients receiving prolonged mechanical ventilation (median, 39 cm H(2)O; interquartile range [IQR] 28 cm H(2)O). Eight patients had Gilbert indexes 0 (30 mm; IQR, 10 mm; vs 19 mm; IQR, 7 mm, respectively; p = 0.001). Best E < 25 mm had a positive likelihood ratio of 6.7 (95% confidence interval [CI], 2.4 to 19) and a negative likelihood ratio of 0 (95% CI, 0 to 1.1) for having a Gilbert index

Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

BACKGROUND: The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial. STUDY OBJECTIVE, DESIGN, AND PATIENTS: We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15 days of antibiotics. RESULTS: Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P = 0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status. CONCLUSIONS: For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.

Phosphodiesterase 4 inhibitors modulate beta2-adrenoceptor agonist-induced human airway hyperresponsiveness.

Chronic exposure of human isolated bronchi to beta2-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. 5'-Cyclic adenosine monophosphate (cAMP) pathways are involved in fenoterol-induced hyperresponsiveness. The present study investigated whether chronic elevation of intracellular cAMP by other pathways than beta2-adrenoceptor stimulation provokes bronchial hyperresponsiveness. Samples from eighteen human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C), or, under similar conditions, were incubated with a selective type-3 phosphodiesterase inhibitor (1 microM siguazodan), two selective type-4 phosphodiesterase inhibitors (0.1 microM rolipram and 0.1 microM cilomilast), a combination of fenoterol and rolipram (0.1 microM each) or of fenoterol and cilomilast (0.1 microM each). Rolipram and cilomilast, but not siguazodan, induced hyperresponsiveness (p < 0.01 and p < 0.05 vs. paired controls, respectively) similar to the fenoterol effect. Fenoterol-induced bronchial hyperresponsiveness was significantly enhanced by coincubation with cilomilast (p < 0.05 vs. fenoterol alone) but not with rolipram. Our results suggest that prolonged activation of intracellular cAMP through phosphodiesterase 4 inhibition induces hyperresponsiveness to ET-1 in human isolated bronchi. However, differences in subcellular localization of phosphodiesterase 4 may provoke divergent responsiveness patterns when human bronchi are continuously exposed to selective phosphodiesterase inhibitors with or without beta2-adrenergic agonists.

Diagnosis and treatment of ventilator-associated pneumonia: fiberoptic bronchoscopy with bronchoalveolar lavage is essential.

The management of patients suspected of having ventilator-associated pneumonia (VAP) requires a strategy for diagnosis and treatment that is designated to: (1) identify patients with true lung bacterial infection; (2) determine the pathogen(s) responsible for pneumonia; (3) permit early selection of appropriate antimicrobial therapy; and (4) avoid indiscriminate administration of antibiotics. The use of bronchoscopic techniques to obtain bronchoalveolar lavage (BAL) specimens from the affected area in the lung allows definition of a strategy superior to that based exclusively on clinical evaluation. When BAL is performed before introduction of new antibiotics, it enables physicians to identify patients who need immediate treatment and help to select initial antibiotic therapy (with the results of direct examination of BAL liquid) and to withhold, deescalate, and/or optimize treatment (when the results of quantitative cultures are available), in a manner that is safe and well tolerated by patients. This strategy, based on clinical and bacteriological evaluation, prevents resorting to broad-spectrum drug coverage in all patients who develop signs and symptoms suggestive of pneumonia, thus minimizing the emergence of resistant flora, and redirects the search for another infection site.

A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia.

RATIONALE: Iseganan, an antimicrobial peptide, is active against aerobic and anaerobic gram-positive and gram-negative bacteria as well as fungi and yeasts. The drug has shown little resistance in vitro and to be safe and well tolerated in 800 patients with cancer treated for up to 6 wk. OBJECTIVES: To determine the efficacy of iseganan for the prevention of ventilator-associated pneumonia (VAP). METHODS: Mechanically ventilated patients in the United States and Europe were randomized to oral topical iseganan or placebo (1:1) and treated six times per day while intubated for up to 14 d. Patients were eligible if randomized within 24 h of intubation and estimated to survive and remain mechanically ventilated for 48 h or more. The primary efficacy endpoint of the study was VAP measured among survivors at Day 14. MEASUREMENTS AND MAIN RESULTS: A total of 709 patients were randomized and received at least one dose of study drug. The two groups were comparable at baseline except iseganan-treated patients were, on average, 3 yr older. The rate of VAP among survivors at Day 14 was 16% (45/282) in patients treated with iseganan and 20% (57/284) in those treated with placebo (p = 0.145). Mortality at Day 14 was 22.1% (80/362) in the iseganan group compared with 18.2% (63/347) in the placebo group (p = 0.206). No pattern of excess adverse events in the iseganan group compared with placebo was observed. CONCLUSIONS: Iseganan is not effective in improving outcome in patients on prolonged mechanical ventilation.

Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia.

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.

[Nosocomial pneumonia]. / Pneumopathies infectieuses nosocomiales.

Nosocomial pneumonia complicates the course of a large number of hospitalized patients, associated with a higher risk of death, prolonged length of stay and over-costs. Rates of pneumonia are considerably higher in the ICU, in the post-operative period, particularly in patients treated with mechanical ventilation. Microorganisms responsible for nosocomial pneumonia are frequently multiresistant, particularly in case of late-onset pneumonia and in patients receiving prior antimicrobial therapy. Management of patients suspected of having nosocomial pneumonia aims to identify patients with true lung infection and not only colonization of the lower respiratory tract, to identify responsible pathogen(s) and to optimize the choice of antimicrobial therapy. To do that, bronchoscopic techniques with the use of bronchoalveolar lavage or protected specimen brush have the best sensitivity and specificity. Appropriate antimicrobial treatment must be initiated without delay. The potential interest of combination therapy, nebulized antibiotics needs to be clearly demonstrated by further investigations; similarly the optimal duration of treatment ensuring efficacy and avoiding the emergence and development of infections due to multiresistant pathogens remains to be more precisely evaluated.

Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia.

OBJECTIVE: To evaluate the potential ability of an algorithm based on the clinical pulmonary infection score (CPIS) to identify and treat patients with bacterial ventilator-associated pneumonia (VAP) compared to a strategy based on quantitative cultures of bronchoscopic specimens. DESIGN: Retrospective cohort study. SETTING: Thirty-one critical care units across France. PATIENTS: Two hundred and one patients clinically suspected of having VAP who had been included in the "invasive strategy" group of the French multicenter randomized trial and for whose quantitative cultures bronchoscopic specimens were obtained. CPIS was determined retrospectively, based on data that had been collected for the initial study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical pulmonary infection score was determined on days 1 and 3, and compared in patients identified as having developed VAP or not, as defined by bronchoscopic specimen culture results. On day 3 138 of the 201 patients (69%) had a CPIS of more than 6 that would have required prolonged antimicrobial therapy based on the algorithm. In contrast, based on bronchoscopy, only 88 (44%) patients were considered to have VAP (kappa coefficient for concordance between the two strategies, 0.33). While the sensitivity of CPIS more than 6 on day 3 for identifying VAP was 89%, its specificity was only 47%, leading to potentially unnecessary treatment of 60 (53%) of the 113 patients without VAP as diagnosed by bronchoscopy. CONCLUSION: A strategy based on the CPIS to decide which patients with suspected VAP should receive prolonged administration of antibiotics would appear to over-prescribe these agents, as compared to a strategy based on bronchoscopy.