Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study.

BACKGROUND: The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. METHODS: This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. RESULTS: Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. CONCLUSION: Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.

Host-pathogen interactions and prognosis of critically ill immunocompetent patients with pneumococcal pneumonia: the nationwide prospective observational STREPTOGENE study.

PURPOSE: To assess the relative importance of host and bacterial factors associated with hospital mortality in patients admitted to the intensive care unit (ICU) for pneumococcal community-acquired pneumonia (PCAP). METHODS: Immunocompetent Caucasian ICU patients with PCAP documented by cultures and/or pneumococcal urinary antigen (UAg Sp) test were included in this multicenter prospective study between 2008 and 2012. All pneumococcal strains were serotyped. Logistic regression analyses were performed to identify risk factors for hospital mortality. RESULTS: Of the 614 patients, 278 (45%) had septic shock, 270 (44%) had bacteremia, 307 (50%) required mechanical ventilation at admission, and 161 (26%) had a diagnosis based only on the UAg Sp test. No strains were penicillin-resistant, but 23% had decreased susceptibility. Of the 36 serotypes identified, 7 accounted for 72% of the isolates, with different distributions according to age. Although antibiotics were consistently appropriate and were started within 6 h after admission in 454 (74%) patients, 116 (18.9%) patients died. Independent predictors of hospital mortality in the adjusted analysis were platelets ≤ 100 × 109/L (OR, 7.7; 95% CI, 2.8-21.1), McCabe score ≥ 2 (4.58; 1.61-13), age > 65 years (2.92; 1.49-5.74), lactates > 4 mmol/L (2.41; 1.27-4.56), male gender and septic shock (2.23; 1.30-3.83 for each), invasive mechanical ventilation (1.78; 1-3.19), and bilateral pneumonia (1.59; 1.02-2.47). Women with platelets ≤ 100 × 109/L had the highest mortality risk (adjusted OR, 7.7; 2.8-21). CONCLUSIONS: In critically ill patients with PCAP, age, gender, and organ failures at ICU admission were more strongly associated with hospital mortality than were comorbidities. Neither pneumococcal serotype nor antibiotic regimen was associated with hospital mortality.

Respiratory changes of the inferior vena cava diameter predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmias.

BACKGROUND: Whether the respiratory changes of the inferior vena cava diameter during a deep standardized inspiration can reliably predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmia is unknown. METHODS: This prospective two-center study included nonventilated arrhythmic patients with infection-induced acute circulatory failure. Hemodynamic status was assessed at baseline and after a volume expansion of 500 mL 4% gelatin. The inferior vena cava diameters were measured with transthoracic echocardiography using the bi-dimensional mode on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. The collapsibility index of the inferior vena cava was calculated as [(expiratory-inspiratory)/expiratory] diameters. RESULTS: Among the 55 patients included in the study, 29 (53%) were responders to volume expansion. The areas under the ROC curve for the collapsibility index and inspiratory diameter of the inferior vena cava were both of 0.93 [95% CI 0.86; 1]. A collapsibility index ≥ 39% predicted fluid responsiveness with a sensitivity of 93% and a specificity of 88%. An inspiratory diameter < 11 mm predicted fluid responsiveness with a sensitivity of 83% and a specificity of 88%. A correlation between the inspiratory effort and the inferior vena cava collapsibility was found in responders but was absent in nonresponder patients. CONCLUSIONS: In spontaneously breathing patients with cardiac arrhythmias, the collapsibility index and inspiratory diameter of the inferior vena cava assessed during a deep inspiration may be noninvasive bedside tools to predict fluid responsiveness in acute circulatory failure related to infection. These results, obtained in a small and selected population, need to be confirmed in a larger-scale study before considering any clinical application.

Diagnostic Accuracy of the Inferior Vena Cava Collapsibility to Predict Fluid Responsiveness in Spontaneously Breathing Patients With Sepsis and Acute Circulatory Failure.

OBJECTIVE: To investigate whether the collapsibility index of the inferior vena cava recorded during a deep standardized inspiration predicts fluid responsiveness in nonintubated patients. DESIGN: Prospective, nonrandomized study. SETTING: ICUs at a general and a university hospital. PATIENTS: Nonintubated patients without mechanical ventilation (n = 90) presenting with sepsis-induced acute circulatory failure and considered for volume expansion. INTERVENTIONS: We assessed hemodynamic status at baseline and after a volume expansion induced by a 30-minute infusion of 500-mL gelatin 4%. MEASUREMENTS AND MAIN RESULTS: We measured stroke volume index and collapsibility index of the inferior vena cava under a deep standardized inspiration using transthoracic echocardiography. Vena cava pertinent diameters were measured 15-20 mm caudal to the hepatic vein junction and recorded by bidimensional imaging on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep standardized inspiration followed by passive exhalation. The collapsibility index expressed in percentage equaled the ratio of the difference between end-expiratory and minimum-inspiratory diameter over the end-expiratory diameter. After volume expansion, a relevant (≥ 10%) stroke volume index increase was recorded in 56% patients. In receiver operating characteristic analysis, the area under curve for that collapsibility index was 0.89 (95% CI, 0.82-0.97). When such index is superior or equal to 48%, fluid responsiveness is predicted with a sensitivity of 84% and a specificity of 90%. CONCLUSIONS: The collapsibility index of the inferior vena cava during a deep standardized inspiration is a simple, noninvasive bedside predictor of fluid responsiveness in nonintubated patients with sepsis-related acute circulatory failure.

The use of static and dynamic haemodynamic parameters before volume expansion: A prospective observational study in six French intensive care units.

OBJECTIVE: The aim of the present study was to determine the use of static and dynamic haemodynamic parameters for predicting fluid responsiveness prior to volume expansion (VE) in intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS). METHODS: We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. ICU physicians were audited concerning their use of static and dynamic haemodynamic parameters before each VE performed in patients with SIRS for 6 consecutive weeks. RESULTS: The median volume of the 566 VEs administered to patients with SIRS was 1000mL [500-1000mL]. Although at least one static or dynamic haemodynamic parameter was measurable before 99% (95% CI, 99%-100%) of VEs, at least one them was used in only 38% (95% CI, 34%-42%) of cases: static parameters in 11% of cases (95% CI, 10%-12%) and dynamic parameters in 32% (95% CI, 30%-34%). Static parameters were never used when uninterpretable. For 15% of VEs (95% CI, 12%-18%), a dynamic parameter was measured in the presence of contraindications. Among dynamic parameters, respiratory variations in arterial pulse pressure (PPV) and passive leg raising (PLR) were measurable and interpretable before 17% and 90% of VEs, respectively. CONCLUSIONS: Haemodynamic parameters are underused for predicting fluid responsiveness in current practice. In contrast to static parameters, dynamic parameters are often incorrectly used in the presence of contraindications. PLR is more frequently valid than PPV for predicting fluid responsiveness in ICU patients.

Accuracy of alpha amylase in diagnosing microaspiration in intubated critically-ill patients.

OBJECTIVES: Amylase concentration in respiratory secretions was reported to be a potentially useful marker for aspiration and pneumonia. The aim of this study was to determine accuracy of α-amylase in diagnosing microaspiration in critically ill patients. METHODS: Retrospective analysis of prospectively collected data collected in a medical ICU. All patients requiring mechanical ventilation for at least 48 h, and included in a previous randomized controlled trial were eligible for this study, provided that at least one tracheal aspirate was available for α-amylase measurement. As part of the initial trial, pepsin was quantitatively measured in all tracheal aspirates during a 48-h period. All tracheal aspirates were frozen, allowing subsequent measurement of α-amylase for the purpose of the current study. Microaspiration was defined as the presence of at least one positive tracheal aspirate for pepsin (>200 ng.mL-1). Abundant microaspiration was defined as the presence of pepsin at significant level in >74% of tracheal aspirates. RESULTS: Amylase was measured in 1055 tracheal aspirates, collected from 109 patients. Using mean α-amylase level per patient, accuracy of α-amylase in diagnosing microaspiration was moderate (area under the receiver operator curve 0.72±0.05 [95%CI 0.61-0.83], for an α-amylase value of 1685 UI.L-1). However, when α-amylase levels, coming from all samples, were taken into account, area under the receiver operator curve was 0.56±0.05 [0.53-0.60]. Mean α-amylase level, and percentage of tracheal aspirates positive for α-amylase were significantly higher in patients with microaspiration, and in patients with abundant microaspiration compared with those with no microaspiration; and similar in patients with microaspiration compared with those with abundant microaspiration. α-amylase and pepsin were significantly correlated (r2 = 0.305, p = 0.001). CONCLUSION: Accuracy of mean α-amylase in diagnosing microaspiration is moderate. Further, when all α-amylase levels were taken into account, α-amylase was inaccurate in diagnosing microaspiration, compared with pepsin.

Hemodynamic changes during a deep inspiration maneuver predict fluid responsiveness in spontaneously breathing patients.

OBJECTIVE: We hypothesized that the hemodynamic response to a deep inspiration maneuver (DIM) indicates fluid responsiveness in spontaneously breathing (SB) patients. DESIGN: Prospective study. SETTING: ICU of a general hospital. PATIENTS: Consecutive nonintubated patients without mechanical ventilation, considered for volume expansion (VE). INTERVENTION: We assessed hemodynamic status at baseline and after VE. MEASUREMENTS AND MAIN RESULTS: We measured radial pulse pressure (PP) using an arterial catheter and peak velocity of femoral artery flow (VF) using continuous Doppler. Changes in PP and VF induced by a DIM (ΔPPdim and ΔVFdim) were calculated in 23 patients. ΔPPdim and ΔVFdim ≥12% predicted responders to VE with sensitivity of 90% and specificity of 100%. CONCLUSIONS: In a restricted population of SB patients with severe sepsis or acute pancreatitis, ΔPPdim and ΔVFdim are accurate indices for predicting fluid responsiveness. These results should be confirmed in a larger population before validating their use in current practice.

Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis.

OBJECTIVE: Rapid fluid loading is standard treatment for hypovolemia. Because volume expansion does not always improve hemodynamic status, predictive parameters of fluid responsiveness are needed. Passive leg raising is a reversible maneuver that mimics rapid volume expansion. Passive leg raising-induced changes in stroke volume and its surrogates are reliable predictive indices of volume expansion responsiveness for mechanically ventilated patients. We hypothesized that the hemodynamic response to passive leg raising indicates fluid responsiveness in nonintubated patients without mechanical ventilation. DESIGN: Prospective study. SETTING: Intensive care unit of a general hospital. PATIENTS: We investigated consecutive nonintubated patients, without mechanical ventilation, considered for volume expansion. INTERVENTIONS: We assessed hemodynamic status at baseline, after passive leg raising, and after volume expansion (500 mL 6% hydroxyethyl starch infusion over 30 mins). MEASUREMENTS AND MAIN RESULTS: We measured stroke volume using transthoracic echocardiography, radial pulse pressure using an arterial catheter, and peak velocity of femoral artery flow using continuous Doppler. We calculated changes in stroke volume, pulse pressure, and velocity of femoral artery flow induced by passive leg raising (respectively, Deltastroke volume, Deltapulse pressure, and Deltavelocity of femoral artery flow). Among 34 patients included in this study, 14 had a stroke volume increase of >or=15% after volume expansion (responders). All patients included in the study had severe sepsis (n = 28; 82%) or acute pancreatitis (n = 6; 18%). The Deltastroke volume >or=10% predicted fluid responsiveness with sensitivity of 86% and specificity of 90%. The Deltapulse pressure >or=9% predicted fluid responsiveness with sensitivity of 79% and specificity of 85%. The Deltavelocity of femoral artery flow >or=8% predicted fluid responsiveness with sensitivity of 86% and specificity of 80%. CONCLUSIONS: Changes in stroke volume, radial pulse pressure, and peak velocity of femoral artery flow induced by passive leg raising are accurate and interchangeable indices for predicting fluid responsiveness in nonintubated patients with severe sepsis or acute pancreatitis.

Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study.

INTRODUCTION: Ventilator-associated tracheobronchitis (VAT) is associated with increased duration of mechanical ventilation. We hypothesized that, in patients with VAT, antibiotic treatment would be associated with reduced duration of mechanical ventilation. METHODS: We conducted a prospective, randomized, controlled, unblinded, multicenter study. Patients were randomly assigned (1:1) to receive or not receive intravenous antibiotics for 8 days. Patients with ventilator-associated pneumonia (VAP) prior to VAT and those with severe immunosuppression were not eligible. The trial was stopped early because a planned interim analysis found a significant difference in intensive care unit (ICU) mortality. RESULTS: Fifty-eight patients were randomly assigned. Patient characteristics were similar in the antibiotic (n = 22) and no antibiotic (n = 36) groups. Pseudomonas aeruginosa was identified in 32% of VAT episodes. Although no difference was found in mechanical ventilation duration and length of ICU stay, mechanical ventilation-free days were significantly higher (median [interquartile range], 12 [8 to 24] versus 2 [0 to 6] days, P < 0.001) in the antibiotic group than in the no antibiotic group. In addition, subsequent VAP (13% versus 47%, P = 0.011, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04 to 0.70) and ICU mortality (18% versus 47%, P = 0.047, OR 0.24, 95% CI 0.07 to 0.88) rates were significantly lower in the antibiotic group than in the no antibiotic group. Similar results were found after exclusion of patients with do-not-resuscitate orders and those randomly assigned to the no antibiotic group but who received antibiotics for infections other than VAT or subsequent VAP. CONCLUSION: In patients with VAT, antimicrobial treatment is associated with a greater number of days free of mechanical ventilation and lower rates of VAP and ICU mortality. However, antibiotic treatment has no significant impact on total duration of mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00122057.

Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study.

OBJECTIVE: A pathogenic interaction between Candida albicans and Pseudomonas aeruginosa has recently been demonstrated. In addition, experimental and clinical studies identified Candida spp. tracheobronchial colonization as a risk factor for P. aeruginosa pneumonia. The aim of this study was to determine the impact of antifungal treatment on ventilator-associated pneumonia (VAP) or tracheobronchial colonization due to P. aeruginosa. DESIGN AND SETTING: Retrospective observational case-control study conducted in a 30-bed ICU during a 1-year period. PATIENTS AND METHODS: One hundred and two patients intubated and ventilated for longer than 48 h with tracheobronchial colonization by Candida spp. Routine screening for Candida spp. and P. aeruginosa was performed at ICU admission and weekly. Antifungal treatment was based on medical staff decisions. Patients with P. aeruginosa VAP or tracheobronchial colonization were matched (1:2) with patients without P. aeruginosa VAP or tracheobronchial colonization. In case and control patients, risk factors for P. aeruginosa VAP or tracheobronchial colonization were determined using univariate and multivariate analyses. RESULTS: Thirty-six patients (35%) received antifungal treatment. Nineteen patients (18%) developed a P. aeruginosa VAP or tracheobronchial colonization, and all were successfully matched. Antifungal treatment [31% vs 60%; p=0.037, OR (95% CI)=0.67 (0.45-0.90)], and duration of antifungal treatment (7+/-11 vs 14+/-14 days; p=0.045, in case and control patients respectively) were significantly associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization. Antifungal treatment was the only variable independently associated with P. aeruginosa VAP or tracheobronchial colonization (OR=0.68, 95% CI=0.49-0.90, p=0.046). CONCLUSION: In patients with Candida spp. tracheobronchial colonization, antifungal treatment may be associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization.

Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk factors, and outcome.

INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 +/- 16 versus 7 +/- 11 days, p < 0.001), and duration of ICU stay (29 +/- 21 versus 15 +/- 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality.