Thiago Lisboa

Severity of Pneumococcal Pneumonia Associated with Genomic Bacterial Load

BACKGROUND There is a clinical need for more objective methods of identifying patients at risk for septic shock and poorer outcomes among those with community-acquired pneumonia (CAP). As viral load is useful in viral infections, we hypothesized that bacterial load may be associated with outcomes in patients with pneumococcal pneumonia. METHODS Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) was prospectively conducted on whole-blood samples from a cohort of 353 patients who were displaying CAP symptoms upon their admission to the ED. RESULTS CAP caused by S pneumoniae was documented in 93 patients (36.5% with positive blood culture findings). A positive S pneumoniae rt-PCR assay finding was associated with a statistically significant higher mortality (odds ratio [OR], 7.08), risk for shock (OR, 6.29), and the need for mechanical ventilation (MV) [OR, 7.96]. Logistic regression, adjusted for age, sex, comorbidities, and pneumonia severity index class, revealed bacterial load as independently associated with septic shock (adjusted odds ratio [aOR], 2.42; 95% CI, 1.10 to 5.80) and the need for MV (aOR, 2.71; 95% CI, 1.17 to 6.27). An S pneumoniae bacterial load of >or= 10(3) copies per milliliter occurred in 29.0% of patients (27 of 93 patients; 95% CI, 20.8 to 38.9%) being associated with a statistically significant higher risk for septic shock (OR, 8.00), the need for MV (OR, 10.50), and hospital mortality (OR, 5.43). CONCLUSION In patients with pneumococcal pneumonia, bacterial load is associated with the likelihood of death, the risk of septic shock, and the need for MV. High genomic bacterial load for S pneumoniae may be a useful tool for severity assessment.

Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units.

Objectives:Information on clinical practice regarding the diagnosis of pneumonia in European intensive care units is limited. The aim of this study was to describe the spectrum of actual diagnostic practices in a large sample of European intensive care units. Design:Prospective, observational, multicenter study. Setting:Twenty-seven intensive care units of nine European countries. Patients:Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or receiving mechanical ventilation for >48 hrs irrespective of admission diagnosis. Interventions:None. Measurements and Main Results:A total of 2,436 patients were evaluated; 827 were admitted with or developed nosocomial pneumonia (hospital-acquired pneumonia [HAP], 27.1%; ventilator-associated pneumonia [VAP], 56.2%; very early onset VAP, 16.7%). Mean age was 59.4 ± 18.1 yrs, 65.0% were men, and mean admission Simplified Acute Physiology Score II was 46.7 ± 17.1. Worsening oxygenation (76.8%), purulent/changing respiratory secretions (72.1%), and new temperature elevation (69.2%) were the most frequent clinical signs of nosocomial pneumonia. Etiological diagnosis was based on noninvasive respiratory specimens in 74.8% of episodes. Bronchoscopy was performed in 23.3% of episodes. Bronchoscopy performance, after adjustment by severity of illness, age, and type of hospital, were predicted by worsening oxygenation (odds ratio 2.03; 95% confidence interval, 1.27–3.24) and male sex (odds ratio 1.77; 95% confidence interval, 1.19–2.65). Definite cause was documented in 69.5% of nosocomial pneumonia cases. The most common isolates were Staphylococcus aureus (16.3% methicillin-sensitive S. aureus and 16.0% methicillin-resistant S. aureus), Pseudomonas aeruginosa (23.1%), and Acinetobacter baumannii (19.1%). Presence of nosocomial pneumonia significantly prolonged mean length of mechanical ventilation (10.3 days, p < .05) and mean intensive care unit length of stay (12.2 days, p < .05) in intensive care unit survivors. Mortality rate was 37.7% for nosocomial pneumonia vs. 31.6% for patients without pneumonia (p < .05). Conclusions:Etiological diagnosis of nosocomial pneumonia in a large sample of European intensive care units was based mainly on noninvasive techniques. However, there was high variability in bronchoscopy use between the participating intensive care units.

Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia

IntroductionThis study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated.MethodsThis prospective observational cohort study was conducted in a teaching hospital. The subjects were 75 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before the 28th day were non-survivors. There were no interventions.ResultsPCT, CRP and SOFA score were determined on day 0 and day 4. Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, decreasing ΔSOFA, decreasing ΔPCT and decreasing ΔCRP. Survival was directly related to decreasing ΔPCT with odds ratio (OR) = 5.67 (95% confidence interval 1.78 to 18.03), decreasing ΔCRP with OR = 3.78 (1.24 to 11.50), decreasing ΔSOFA with OR = 3.08 (1.02 to 9.26) and APACHE II score with OR = 0.92 (0.86 to 0.99). In a multivariable logistic regression model for survival, only decreasing ΔPCT with OR = 4.43 (1.08 to 18.18) and decreasing ΔCRP with OR = 7.40 (1.58 to 34.73) remained significant. Decreasing ΔCPIS was not related to survival (p = 0.59). There was a trend to correlate adequacy to survival. Fifty percent of the 20 patients treated with inadequate antibiotics and 65.5% of the 55 patients on adequate antibiotics survived (p = 0.29).ConclusionMeasurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients. A decrease in either one of these marker values predicts survival.

Pseudomonas aeruginosa Virulence and Therapy: Evolving Translational Strategies

Objective:Although most reviews of Pseudomonas aeruginosa therapeutics focus on antibiotics currently in use or in the pipeline, we review evolving translational strategies aimed at using virulence factor antagonists as adjunctive therapies. Data Source:Current literature regarding P. aeruginosa virulence determinants and approaches that target them, with an emphasis on type III secretion, quorum-sensing, biofilms, and flagella. Data Extraction and Synthesis:P. aeruginosa remains one of the most important pathogens in nosocomial infections, with high associated morbidity and mortality. Its predilection to develop resistance to antibiotics and expression of multiple virulence factors contributes to the frequent ineffectiveness of current therapies. Among the many P. aeruginosa virulence determinants that impact infections, type III secretion, quorum sensing, biofilm formation, and flagella have been the focus on much recent investigation. Here we review how increased understanding of these important bacterial structures and processes has enabled the development of novel approaches to inhibit each. These promising translational strategies may lead to the development of adjunctive therapies capable of improving outcomes. Conclusions:Adjuvant therapies directed against virulence factors have the potential to improve outcomes in P. aeruginosa infections.

PIRO score for community-acquired pneumonia: a new prediction rule for assessment of severity in intensive care unit patients with community-acquired pneumonia.

Objective:To develop a severity assessment tool to predict mortality in community-acquired pneumonia (CAP) patients in intensive care unit (ICU), comparing its performance with Acute Physiology and Chronic Health Evaluation (APACHE) II score and American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) criteria as a prognostic index in CAP patients requiring ICU admission. Design:Secondary analysis of prospective observational cohort study. Setting:Thirty-three ICUs. Patients:Five hundred and twenty-nine adult patients with CAP requiring ICU admission. Measurements and Main Results:A severity assessment score was developed based on the PIRO (predisposition, insult, response, and organ dysfunction) concept including the presence of the following variables: Comorbidities (chronic obstructive pulmonary disease, immunocompromise); age >70 years; multilobar opacities in chest radiograph; shock, severe hypoxemia; acute renal failure; bacteremia and acute respiratory distress syndrome. PIRO score was obtained at ICU within 24 hours from admission, and one point was given for each present feature (range, 0–8 points). The mean PIRO score was significantly higher in nonsurvivors than in survivors (4.6 ± 1.2 vs. 2.3 ± 1.4). Considering the observed mortality for each PIRO score, the patients were stratified in four levels of risk: a) Low, 0–2 points; b) Mild, 3 points; c) high, 4 points; and d) Very high, 5–8 points. Mild-risk (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.1–2.9; p < 0.05), high-risk (HR 3.1; 95% CI = 2.0–4.7; p < 0.001), and very high risk levels (HR 6.3; 95% CI = 4.2–9.4; p < 0.001) were significantly associated with higher risk of death in Cox proportional hazards regression analysis. Furthermore, analysis of variance showed that higher levels of PIRO score were significantly associated with higher mortality (p < 0.001), prolonged length of stay in the ICU (p < 0.001), and days of mechanical ventilation (p < 0.001). Receiver operating characteristic curves showed that PIRO score (area under the curve [AUC] = 0.88) performed better than APACHE II (AUC = 0.75, p < 0.001) and ATS/IDSA criteria (AUC = 0.80, p < 0.001) to predict 28-day mortality. Conclusions:The PIRO score performed well as 28-day mortality prediction tool in CAP patients requiring ICU admission with a better performance than APACHE II and ATS/IDSA criteria in this subset of patients. Furthermore, PIRO score also is associated with increased healthcare resource utilization in CAP patients admitted in the ICU.

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.

A Randomized Trial of Dental Brushing for Preventing Ventilator-Associated Pneumonia

BACKGROUND Poor oral hygiene is associated with respiratory pathogen colonization and secondary lung infection. The impact of adding electric toothbrushing to oral care in order to reduce ventilator-associated pneumonia (VAP) incidence is unknown. METHODS The study design was a prospective, simple-blind, randomized trial of adult patients intubated for > 48 h. Controlling for exposure to antibiotic treatment, patients were randomized to oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group). VAP was documented by quantitative respiratory cultures. Mechanical ventilation (MV) duration, hospital ICU length of stay (LOS), antibiotic use, and hospital ICU mortality were secondary end points. RESULTS The study was terminated after randomizing 147 patients (74 toothbrush group) in a scheduled interim analysis. The two groups were comparable at baseline. The toothbrush group and standard group had similar rates of suspected VAP (20.3% vs 24.7%; p = 0.55). After adjustment for severity of illness and admission diagnosis, the incidence of microbiologically documented VAP was also similar in the two groups (hazard ratio, 0.84; 95% confidence interval, 0.41 to 1.73). The groups did not differ significantly in mortality, antibiotic-free days, duration of MV, or hospital ICU LOS. CONCLUSIONS Our findings suggest that the addition of electric toothbrushing to standard oral care with 0.12% chlorhexidine digluconate is not effective for the prevention of VAP. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00842478.

The Ventilator-Associated Pneumonia PIRO Score: A Tool for Predicting ICU Mortality and Health-Care Resources Use in Ventilator-Associated Pneumonia

BACKGROUND No score is available to assess severity and stratify mortality risk in ventilator-associated pneumonia (VAP). Our objective was to develop a severity assessment tool for VAP patients. METHODS A prospective, observational, cohort study was performed including 441 patients with VAP in three multidisciplinary ICUs. Multivariate logistic regression was performed to identify variables independently associated with ICU mortality. Results were converted into a four-variable score based on the PIRO (predisposition, insult, response, organ dysfunction) concept for ICU mortality risk stratification in VAP patients. RESULTS Comorbidities (COPD, immunocompromise, heart failure, cirrhosis, or chronic renal failure); bacteremia; systolic BP < 90 mm Hg; and ARDS. A simple, four-variable VAP PIRO score was obtained at VAP onset. Mortality varied significantly according to VAP PIRO score (p < 0.001). On the basis of observed mortality for each VAP PIRO score, patients were stratified into three levels of risk: (1) mild, 0 to 1 points; (2) high, 2 points; (3) very high, 3 to 4 points. VAP PIRO score was associated with higher risk of death in Cox regression analysis in the high-risk group (hazard ratio, 2.14; 95% confidence interval [CI], 1.19 to 3.86) and the very-high-risk group (hazard ratio, 4.63; 95% confidence interval, 2.68 to 7.99). Moreover, medical resource use after VAP diagnosis was higher in high-risk and very-high-risk levels compared to patients at mild risk, evaluated using length of ICU stay (mean +/- SD, 22.0 +/- 10.6 d vs 18.7 +/- 12.8 d, p < 0.05) and duration of mechanical ventilation (18.3 +/- 10.1 d vs 15.1 +/- 11.5 d, p < 0.05). CONCLUSIONS VAP PIRO score is a simple, practical clinical tool for predicting ICU mortality and health-care resources use that is likely to assist clinicians in determining VAP severity.

C-reactive protein correlates with bacterial load and appropriate antibiotic therapy in suspected ventilator-associated pneumonia

Objective:Appropriateness of antibiotic therapy is associated with reduction of bacterial load in ventilator-associated pneumonia. C-reactive protein is a valid biochemical surrogate. The objective was to determine the correlation of bacterial load, measured by quantitative tracheal aspirate (QTA), with serum C-reactive protein as an indicator of inflammatory response in episodes of ventilator-associated pneumonia and association of its variation with antibiotic appropriateness. Design:Prospective, observational cohort study. Setting:Two medical-surgical intensive care units at large urban hospitals affiliated with teaching institutions. Patients:Sixty-eight intubated patients with monomicrobial ventilator-associated pneumonia. Interventions:None. Measurements and Main Results:QTA and serum C-reactive protein were measured in patients with suspected ventilator-associated pneumonia on diagnosis (baseline) and 96 hrs afterward (follow-up). Its logarithm value (logQTA) was calculated. LogQTA correlated positively with serum C-reactive protein (&rgr; = 0.46, p < .05), temperature (&rgr; = 0.20, p = .05), and white blood cell count (&rgr; = 0.22, p < .05). LogQTA decreased significantly more from baseline to follow-up in patients receiving appropriate empirical antibiotic therapy compared with those with inappropriate treatment (logQTA ratio 0.77 ± 0.22 vs. 1.02 ± 0.27, p < .05). Mean serum C-reactive protein levels showed a similar pattern, decreasing from baseline to follow-up in patients receiving appropriate empirical antibiotic treatment but not in episodes with inappropriate treatment (C-reactive protein ratio 0.58 ± 0.32 vs. 1.36 ± 1.11, p < .05). There was a positive correlation between serum C-reactive protein and logQTA variations (r2 = .59, p < .05). Adjusted mean serum C-reactive protein levels by analysis of covariance on follow-up were significantly lower in patients with appropriate antibiotic treatment than in those with inappropriate empirical treatment (103 ± 10 mg/L vs. 192 ± 14 mg/L, p < .05). A C-reactive protein ratio of 0.8 at 96 hrs was a useful indicator of appropriateness of antibiotic therapy (sensitivity 77%; specificity 87%; area under the receiver operating characteristic curve 0.86 [0.75–0.96]). Conclusions:C-reactive protein is a useful biochemical surrogate of bacterial burden in patients with ventilator-associated pneumonia. Follow-up measurements of serum C-reactive protein anticipate the appropriateness of antibiotic therapy.

Why Mortality Is Increased in Health-Care-Associated Pneumonia: Lessons From Pneumococcal Bacteremic Pneumonia

BACKGROUND A cohort of patients with bacteremic Streptococcus pneumoniae pneumonia was reviewed to assess why mortality is higher in health-care-associated pneumonia (HCAP) than in community-acquired pneumonia (CAP). METHODS A prospective cohort of all adult patients with bacteremic pneumococcal pneumonia attended at the ED was used. RESULTS One hundred eighty-four cases were classified as CAP and 44 (19%) as HCAP. Fifty-two (23%) were admitted to the ICU. Three (1.5%) isolates were resistant to beta-lactams, and only two patients received inappropriate therapy. The CAP cohort was significantly younger (median age 68 years, interquartile range [IQR] 42-78 vs 77 years, IQR 67-82, P < .001). The HCAP cohort presented a higher Charlson index (2.81 +/- 1.9 vs 1.23 +/- 1.42, P < .001) and had higher severity of illness at admission (altered mental status, respiratory rate > 30/min, Pao(2)/Fio(2) < 250, and multilobar involvement). HCAP patients had a lower rate of ICU admission (11.3% vs 25.5%, P < .05), and a trend toward lower mechanical ventilation (9% vs 19%, P = .17) and vasopressor use (9% vs 18.4%, P = .17) were documented. More patients in the HCAP cohort presented with a pneumonia severity index score > 90 (class IV-V, 95% vs 65%, P < .001), and 30-day mortality was significantly higher (29.5% vs 7.6%, P < .001). A multivariable regression logistic analysis adjusting for underlying conditions and variables related to severity of illness confirmed that HCAP is an independent variable associated with increased mortality (odds ratio = 5.56; 95% CI, 1.86-16.5). CONCLUSIONS Pneumococcal HCAP presents excess mortality, which is independent of bacterial susceptibility. Differences in outcomes were probably due to differences in age, comorbidities, and criteria for ICU admission rather than to therapeutic decisions.