Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

Prior Exposure to Angiotensin II Receptor Blockers in Patients With Septic Shock to Individualize Mean Arterial Pressure Target? A Post Hoc Analysis of the Sepsis and Mean Arterial Pressure (SEPSISPAM) Trial.

OBJECTIVES: Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The Sepsis and Mean Arterial Pressure (SEPSISPAM) trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target. DESIGN: Post hoc analysis of the SEPSISPAM trial. SETTING: The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90. PATIENTS: All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included. MEASUREMENTS AND MAIN RESULTS: We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09-0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival. CONCLUSIONS: Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

BACKGROUND: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. METHODS: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. RESULTS: A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. CONCLUSIONS: In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care-an analysis of the OUTCOMEREA database.

INTRODUCTION: Enterococcus species are associated with an increased morbidity in intraabdominal infections (IAI). However, their impact on mortality remains uncertain. Moreover, the influence on outcome of the appropriate or inappropriate status of initial antimicrobial therapy (IAT) is subjected to debate, except in septic shock. The aim of our study was to evaluate whether an IAT that did not cover Enterococcus spp. was associated with 30-day mortality in ICU patients presenting with IAI growing with Enterococcus spp. MATERIAL AND METHODS: Retrospective analysis of French database OutcomeRea from 1997 to 2016. We included all patients with IAI with a peritoneal sample growing with Enterococcus. Primary endpoint was 30-day mortality. RESULTS: Of the 1017 patients with IAI, 76 (8%) patients were included. Thirty-day mortality in patients with inadequate IAT against Enterococcus was higher (7/18 (39%) vs 10/58 (17%), p = 0.05); however, the incidence of postoperative complications was similar. Presence of Enterococcus spp. other than E. faecalis alone was associated with a significantly higher mortality, even greater when IAT was inadequate. Main risk factors for having an Enterococcus other than E. faecalis alone were as follows: SAPS score on day 0, ICU-acquired IAI, and antimicrobial therapy within 3 months prior to IAI especially with third-generation cephalosporins. Univariate analysis found a higher hazard ratio of death with an Enterococcus other than E. faecalis alone that had an inadequate IAT (HR = 4.4 [1.3-15.3], p = 0.019) versus an adequate IAT (HR = 3.1 [1.0-10.0], p = 0.053). However, after adjusting for confounders (i.e., SAPS II and septic shock at IAI diagnosis, ICU-acquired peritonitis, and adequacy of IAT for other germs), the impact of the adequacy of IAT was no longer significant in multivariate analysis. Septic shock at diagnosis and ICU-acquired IAI were prognostic factors. CONCLUSION: An IAT which does not cover Enterococcus is associated with an increased 30-day mortality in ICU patients presenting with an IAI growing with Enterococcus, especially when it is not an E. faecalis alone. It seems reasonable to use an IAT active against Enterococcus in severe postoperative ICU-acquired IAI, especially when a third-generation cephalosporin has been used within 3 months.

Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group.

PURPOSES: Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity. METHODS: Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay < 48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification. RESULTS: Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1-2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15-1.27, p < 0.001]; maximum lactate level day 1-2: (HR 1.07, 95% CI 1.02-1.12, p = 0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23-3.03, p = 0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15-0.50, p < 0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68-10.54, p = 0.003), in patients ≥ 65 years old (HR 2.59, 95% CI 1.56-4.28, < 0.001) and in those with body mass index (BMI) < 25 kg/m2 (HR 2.11, 95% CI 1.10-4.06, p = 0.025). CONCLUSIONS: Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged ≥ 65 years and with BMI < 25 kg/m2.

Endocarditis caused by Streptococcus canis: an emerging zoonosis?

We report a human case of infective endocarditis caused by Streptococcus canis. Identification was carried out from positive blood culture using mass spectrometry and SodA gene sequencing. S. canis related zoonotic invasive infections may have been previously underdiagnosed due to inadequate identification of group G Streptococcus species.

Ultrasonography for Screening and Follow-Up of Diaphragmatic Dysfunction in the ICU: A Pilot Study.

PURPOSE: Reversibility and impact of diaphragmatic dysfunction (DD) are unknown. The principal aim was to describe diaphragmatic function as assessed by ultrasonography during weaning trials. MATERIALS AND METHODS: The present study is a 6-month single-center prospective study. All patients under mechanical ventilation for more than 7 days and eligible for a spontaneous breathing trial (SBT) were enrolled prospectively. INTERVENTION: Two blinded ultrasonographers evaluated each hemidiaphragm during SBT. Prevalence of DD among weaning failure and death and interobserver reproducibility have been evaluated. RESULTS: The 34 included patients had a mean Simplified Acute Physiology Score version II of 55.7 ± 14 and a median intensive care unit (ICU) stay length of 17 days (13-30). Diaphragmatic dysfunction was found in 13 (38%) patients, on both sides in 8. Bilateral DD resolved before ICU discharge in 5 of the 7 reevaluated patients. No weaning failures were recorded. The ICU mortality was higher in patients with DD (37% vs 5%, P = .048). Mean interobserver agreement rate was 91%. Reproducibility was better with M-mode. CONCLUSION: The ICU-acquired DD usually improves before ICU discharge but might constitute a marker for greater disease severity. The present preliminary results require confirmation in a larger prospective multicenter study.

Group A Escherichia coli-related purpura fulminans: an unusual manifestation due to an unusual strain?

We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence.

Predictors of functional outcome after intraoperative cardiac arrest.

BACKGROUND: Few outcome data are available about intraoperative cardiac arrest (IOCA). The authors studied 90-day functional outcomes and their determinants in patients admitted to the intensive care unit after IOCA. METHODS: Patients admitted to 11 intensive care units in a period of 2000-2013 were studied retrospectively. The main outcome measure was a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 140 patients (61 women and 79 men; median age, 60 yr [interquartile range, 46 to 70]), 131 patients (93.6%) had general anesthesia, 80 patients (57.1%) had emergent surgery, and 73 patients (52.1%) had IOCA during surgery. First recorded rhythms were asystole in 73 patients (52.1%), pulseless electrical activity in 44 patients (31.4%), and ventricular fibrillation/ventricular tachycardia in 23 patients (16.4%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation were 0 min (0 to 0) and 10 min (5 to 20), respectively. Postcardiac arrest shock was identified in 114 patients (81.4%). Main causes of IOCA were preoperative complications (n = 46, 32.9%), complications of anesthesia (n = 39, 27.9%), and complications of surgical procedures (n = 36, 25.7%). On day 90, 63 patients (45.3%) were alive with Cerebral Performance Category score 1/2. Independent predictors of day-90 Cerebral Performance Category score 1/2 were day-1 Logistic Organ Dysfunction score (odds ratio, 0.78 per point; 95% CI, 0.71 to 0.87; P = 0.0001), ventricular fibrillation/tachycardia as first recorded rhythm (odds ratio, 4.78; 95% CI, 1.38 to 16.53; P = 0.013), and no epinephrine therapy during postcardiac arrest syndrome (odds ratio, 3.14; 95% CI, 1.29 to 7.65; P = 0.012). CONCLUSIONS: By day 90, 45% of IOCA survivors had good functional outcomes. The main outcome predictors were directly related to IOCA occurrence and postcardiac arrest syndrome; they suggest that the intensive care unit management of postcardiac arrest syndrome may be amenable to improvement.

Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure.

RATIONALE: The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain. OBJECTIVES: To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP. METHODS: From the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence. MEASUREMENTS AND MAIN RESULTS: A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048). CONCLUSIONS: Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Artery of Percheron infarction as an unusual cause of coma: three cases and literature review.

OBJECTIVE: Stroke due to occlusion of the artery of Percheron (AOP), an uncommon anatomic variant supplying the bilateral medial thalami, may raise diagnostic challenges and cause life-threatening symptoms. Our objective here was to detail the features and outcomes in three patients who required intensive care unit (ICU) admission and to review the relevant literature. METHODS: Description of three cases and literature review based on a 1973-2013 PubMed search. RESULTS: Three patients were admitted to our ICU with sudden-onset coma and respiratory and cardiovascular dysfunctions requiring endotracheal mechanical ventilation. Focal neurological deficits, ophthalmological signs (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities were variably combined. Initial CT scan was normal. Cerebral MRI demonstrated bilateral paramedian thalamic infarction, with extension to the cerebral peduncles in two patients. Consciousness improved rapidly and time to extubation was 1-4 days. All three patients were discharged alive from the hospital and two had good 1-year functional outcomes. Similar clinical features and outcomes were recorded in the 117 patients identified in the literature, of whom ten required ICU admission. CONCLUSIONS: Bilateral paramedian thalamic stroke due to AOP occlusion can be life threatening. The early diagnosis relies on MRI with magnetic resonance angiography. Recovery of consciousness is usually rapid and mortality is low, warranting full-code ICU management.

Real-life use of ceftobiprole for severe infections in a French intensive care unit.

Ceftobiprole (CBP) is an anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin with a wide spectrum of activity. We aimed to describe our experience of real-life use of CBP for the treatment of severe infections of critically ill patients with multiple infected sites and related trough CBP concentrations. We performed a retrospective, observational, monocentric study in our intensive care unit (ICU) that included all patients treated with CBP for documented infections between January 2016 and December 2021. We collected demographic, clinical, and microbiological data. When available, we report the CBP trough concentrations. The primary endpoint was clinical cure at the end of treatment. The secondary endpoints were in-hospital mortality and documentation of the carriage of multidrug-resistant (MDR) bacteria not present before CBP treatment. Between January 2016 and December 2021, 47 patients were treated in the ICU with CBP. The main indication for treatment was pneumonia (51%) and most patients presented with associated bacteremia (72%). All infections were polymicrobial. A clinical cure was achieved for nearly 80% of the patients. Only five patients presented new carriage of MDR bacteria. In-hospital mortality was 32%. Out of 21 strains of Enterobacterales for which the MIC was available, 33% were considered to be resistant to CBP according to the EUCAST 2023 clinical breakpoint. Trough CBP concentrations were reported for 16 patients. In our real-life experience, treatment of ICU patients with CBP for polymicrobial severe infections resulted in most cases in a clinical cure. Monitoring of trough concentrations is critical, especially in cases of high MIC.

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study.

INTRODUCTION: Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections. However, little is known on the clinical features and outcomes of ICU patients with pneumococcal pneumonia. The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP. METHODS: We performed a retrospective review of two prospectively-acquired multicentre ICU databases (2001-2008). Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae. Patients with bronchitis, aspiration pneumonia or with non-pulmonary pneumococcal infections were excluded. RESULTS: Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 [36-64]. Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission. Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%). Bacteraemia was diagnosed in 101 patients. The prevalence of S. pneumoniae strains with decreased susceptibility to penicillin was 39.7%. Although antibiotherapy was adequate in 92.3% of cases, hospital mortality reached 28.8%. In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)). Co-morbidities, macrolide administration, concomitant bacteremia or penicillin susceptibility did not influence outcome. CONCLUSIONS: In ICU, mortality of pneumococcal CAP remains high despite adequate antimicrobial treatment. Baseline demographic data and renal replacement therapy have a major impact on adverse outcome.

Cerebrospinal fluid features in comatose survivors of cardiac arrest: A pilot study.

INTRODUCTION: Lumbar puncture is among the investigations used to identify various neurological conditions, including some that can cause cardiac arrest (CA). However, CA per se may alter cerebrospinal fluid (CSF) characteristics. Few studies have investigated CSF findings after CA. In this descriptive work, we assessed the frequency and risk factors of abnormal CSF findings after CA and the contribution of CSF analysis to the etiological diagnosis. MATERIALS AND METHODS: We retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007-2016 with sustained return of spontaneous circulation (ROSC) after CA and who underwent lumbar puncture as an etiological investigation. RESULTS: Of 1984 patients with sustained ROSC, 55 (2.7%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of CA in 2/55 (3.6%) patients. Nonspecific CSF abnormalities were noted in 37/53 (69.8%) patients. By multivariate analysis, postresuscitation shock was positively associated with CSF abnormalities (OR, 6.92; 95% confidence interval [95%CI], 1.62-37.26; P = 0.013). A no-flow time above 6 minutes (OR, 0.19; 95%CI, 0.03-1.11; P = 0.076) and a respiratory cause of CA (OR, 2.91; 95%CI, 0.53-23.15; P = 0.24) were not statistically associated with CSF abnormalities. Nonspecific CSF abnormalities were not significantly associated with poor outcomes (Cerebral Performance Category ≥3; P = 0.06). CONCLUSIONS: Lumbar puncture, although infrequently performed, may contribute to the etiological diagnosis of CA, albeit rarely. Nonspecific CSF abnormalities seem common after CA, notably with postresuscitation shock, and may be related to blood-brain barrier disruption. These findings may help to interpret CSF findings after CA. Further studies are warranted to assess our results.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial.

BACKGROUND: In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. METHODS: The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling. RESULTS: We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. CONCLUSION: Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality.

Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units.

INTRODUCTION: Few studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients. METHODS: In a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection. RESULTS: A total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18). CONCLUSIONS: More than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT.

Invasive Aspergillosis associated with Covid-19: A word of caution.

INTRODUCTION: Invasive pulmonary aspergillosis is a well-known complication of acute respiratory distress syndrome, the most serious manifestation of COVID-19. Four recent studies have reported its incidence among ICU COVID-19 patients. However, they do not share the same case definition, and have provided conflicting results. In this paper we have aimed at reported the incidence of invasive pulmonary aspergillosis for COVID-19 patients in our ICU, and at comparing the different definitions in order to assess their respective relevance. METHODS: Retrospective cohort study of critically ill patients with severe COVID-19 requiring ICU management between 1st March and 30th April 2020. RESULTS: Our results showed significantly lower incidence of invasive pulmonary aspergillosis (1.8%;1/53), compared to three out of four previous studies, and wide variation in the numbers of cases with regard to the different definitions. CONCLUSION: Large-scale studies are needed for a better definition and a more accurate estimation of invasive pulmonary aspergillosis coinfection during COVID-19.