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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., (© 2021. The Author(s).)

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 × 10 9 /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 × 10 9 /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.

Importance: Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia., Objective: To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis., Design, Setting, and Patients: An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized., Interventions: Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care., Main Outcomes and Measures: Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients., Results: After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977)., Conclusions and Relevance: Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke., Trial Registration: clinicaltrials.gov Identifier: NCT00774631.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use. [ABSTRACT FROM AUTHOR]

Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction and 2) test the safety and efficacy of a novel extracorporeal blood filter to remove proinflammatory molecules and improve organ function. After a dose-finding pilot study, 12 animals were inoculated with Streptococcus pneumoniae [5 × 109 colony-forming units (CFU)], given ceftriaxone at 24 h after inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate (n = 6) or sham treatment (n = 6) for 4 h at 30 h after inoculation. For safety analysis, four uninfected animals also underwent purification. At 48 h, necropsy was performed. Inoculated animals developed severe pneumonia and septic shock. Compared with sham-treated animals, septic animals treated with purification displayed significantly less kidney injury, metabolic acidosis, hypoglycemia, and shock (P < 0.05). Purification blocked the rise in peripheral blood S. pneumoniae DNA, attenuated bronchoalveolar lavage (BAL) CCL4, CCL2, and IL-18 levels, and reduced renal oxidative injury and classical NLRP3 inflammasome activation. Purification was safe in both uninfected and infected animals and produced no adverse effects. We demonstrate that heparin-based blood purification significantly attenuates levels of circulating S. pneumoniae DNA and BAL cytokines and is renal protective in baboons with severe pneumococcal pneumonia and septic shock. Purification was associated with less severe acute kidney injury, metabolic derangements, and shock. These results support future clinical studies in critically ill septic patients. [ABSTRACT FROM AUTHOR]

A recent individual patient data meta-analysis reported that I more i active fever management did not increase survival compared with I less i active fever management in an all-comers population of critically ill adults [[3]]. However, for patients with fever and suspected infection, the common practice of administering paracetamol to treat fever does not appear to either improve or worsen patient outcomes [[6]]. Although further research evaluating temperature management in out-of-hospital cardiac arrest patients is underway, current guidelines recommend avoidance of fever in this group of patients [[16]]. [Extracted from the article]

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The article offers information on potential benefits and risks associated with fever in the intensive care unit (ICU). It mentions that in the absence of infection, low-grade fever appears to be independently associated with reduced mortality risk compared with normothermia. It presents information on fever management in patients with traumatic brain injury, ischaemic stroke, and hemorrhage.

The article focuses on impact of bacterial meningitis on patients which lead to admission in intensive care unit (ICU). Topics discussed include performance of cranial imaging for patients with symptoms of bacterial meningitis before lumbar puncture, reduction in hearing loss by using corticosteroids whose effects have been shown only in high income countries and improvement in mental health of patients by using therapy of intracranial pressure (ICP).

Purpose: We previously showed that external cooling decreases day 14 mortality in febrile septic shock. Because cooling may participate in heart rate control, we studied the respective impact of heart rate and temperature lowering on mortality.Methods: Post hoc analysis of the Sepsiscool randomized controlled trial database (NCT00527007). Cooling was applied to maintain normothermia (36.5-37 °C) during 48 h. We assessed the time spent below different thresholds of temperature and heart rate on day 14 mortality. The best threshold was selected by AUC-ROC and tested as a potential mediator of mortality reduction. Mediation analysis was adjusted for severity and treatments influencing temperature and heart rate evolution. Sensitivity analysis was done using only patients with appropriate antimicrobial therapy.Results: A total of 197/200 patients with adequate heart rate and temperature monitoring were analyzed. The best threshold differentiating survivors and nonsurvivors was 38.4 °C for temperature and 95 b/min for heart rate. During the 48 h of intervention, cooling significantly increased the time spent with a temperature below 38.4 °C, p = 0.001, and with a heart rate below 95 b/min, p < 0.01. The longer was the time spent with a temperature below 38.4 °C, the lower was the mortality [adjOR 0.17 (0.06-0.49), p = 0.001]. The time spent with a heart rate below 95 b/min was similar in survivors and nonsurvivors [adjOR 0.68 (0.27-1.72), p = 0.42]. Mediation analysis showed that the time spent with a temperature below 38.4 °C was a significant mediator of mortality.Conclusion: The time spent with a temperature below 38.4 °C was independently associated with patient's outcome and explained 73% of the effect of the randomization on the day 14 mortality. Heart rate lowering was not a mediator of mortality. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia is commonly used to improve neurological outcomes in patients after cardiac arrest. However, therapeutic hypothermia increases sepsis risk and unintentional hypothermia in surgical patients increases infectious complications. Nonetheless, the molecular mechanisms by which hypothermia dysregulates innate immunity are incompletely understood. We found that exposure of human monocytes to cold (32°C) potentiated LPS-induced production of TNF and IL-6, while blunting IL-10 production. This dysregulation was associated with increased expression of microRNA-155 (miR-155), which potentiates Toll-like receptor (TLR) signaling by negatively regulating Ship1 and Socs1. Indeed, Ship1 and Socs1 were suppressed at 32°C and miR-155 antagomirs increased Ship1 and Socs1 and reversed the alterations in cytokine production in cold-exposed monocytes. In contrast, miR-155 mimics phenocopied the effects of cold exposure, reducing Ship1 and Socs1 and altering TNF and IL-10 production. In a murine model of LPS-induced peritonitis, cold exposure potentiated hypothermia and decreased survival (10 vs. 50%; P < 0.05), effects that were associated with increased miR-155, suppression of Ship1 and Socs1, and alterations in TNF and IL-10. Importantly, miR-155-deficiency reduced hypothermia and improved survival (78 vs. 32%, P < 0.05), which was associated with increased Ship1, Socs1, and IL-10. These results establish a causal role of miR-155 in the dysregulation of the inflammatory response to hypothermia. [ABSTRACT FROM AUTHOR]

The article discusses several studies about the potential role of fever control in critically ill patients. Topics discussed include a relationship observed between early fever and a decrease in mortality assessed at 28 days or hospital discharge, a study investigating the effect of temperature reduction in febrile critically ill patients that both exclude patients with acute neurological presentations, and the effect of induced hypothermia for patients with sepsis due to bacterial meningitis.

An index of the authors for the January 2011 issue of the journal "Réanimation," is presented.