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.
To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis.
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.
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.
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.
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).
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.
clinicaltrials.gov Identifier: NCT00774631.
In inflammatory states, particularly in response to infectious stimuli, local procalcitonin (PCT) production rises, and because these tissues cannot further process PCT into calcitonin, serum levels ...increase. In the critical care setting, PCT should be considered a useful tool to help physicians in some specific, although frequent, situations. Serial measurements of PCT levels may indicate the effectiveness of medical decisions such as the appropriateness of antibiotic therapy, the detection of new infections, and the exclusion of a diagnosis of sepsis. PCT-guided algorithms may also help to decrease the duration of antimicrobial therapy. However, the role of PCT as a prognostic marker in critically ill patients is controversial. In a study by Karlsson and colleagues, PCT concentrations did not differ between hospital survivors and nonsurvivors, but the outcome was better in patients whose PCT concentrations decreased more than 50%. The study of PCT kinetics thus could offer an individual risk assessment in patients with severe sepsis.
We report the case of a man who underwent a left-lung transplantation for pulmonary fibrosis and who developed deterioration of his respiratory condition at Day 16 post-operatively, with marked ...hypoxemia not explained by the usual early respiratory complications of lung transplantation. Contrast-enhanced transthoracic echocardiography identified a patent foramen ovale with massive spontaneous right-to-left shunting. As for the pathogenesis of this right-to-left shunting, we found no evidence supporting an elevation of right-side pressures, with the redirection of the inferior vena cava flow toward the patent foramen ovale being the suspected mechanism. We conclude that delayed reopening of the patent foramen ovale leading to massive right-to-left shunting is a possible complication after lung transplantation.
Candidemia is the fourth most frequent health care-associated bloodstream infection, and the most frequent severe fungal infection developing in critically ill patients in intensive care units ...(ICUs). Diagnosis of candidemia in ICU patients is a complex task made of both early and late assessments involving both conventional diagnostic methods and novel rapid tests. Management strategies to optimize treatment of candidemia can be challenging and include starting early adequate therapy, use of an adequate dose and duration of therapy, de-escalating treatment whenever possible, and early discontinuation of useless antifungals in those with no definitive diagnosis of fungal infection. Herein, we will discuss recent epidemiological data on candidemia in ICUs and current diagnostic techniques before concentrating on antifungal treatments.
Anti-staphylococcal penicillins (ASPs) are recommended as first-line agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Concerns about their safety profile have contributed ...to the increased use of cefazolin. The comparative clinical effectiveness and safety profile of cefazolin versus ASPs for such infections remain unclear. Furthermore, uncertainty persists concerning the use of cefazolin due to controversies over its efficacy in deep MSSA infections and its possible negative ecological impact.
The aim of this narrative review was to gather and balance available data on the efficacy and safety of cefazolin versus ASPs in the treatment of MSSA bacteraemia and to discuss the potential negative ecological impact of cefazolin.
PubMed and EMBASE electronic databases were searched up to May 2017 to retrieve available studies on the topic.
Although described in vitro and in experimental studies, the clinical relevance of the inoculum effect during cefazolin treatment of deep MSSA infections remains unclear. It appears that there is no significant difference in rate of relapse or mortality between ASPs and cefazolin for the treatment of MSSA bacteraemia but these results should be cautiously interpreted because of the several limitations of the available studies. Compared with cefazolin, there is more frequent discontinuation for adverse effects with ASP use, especially because of cutaneous and renal events. No study has evidenced any change in the gut microbiota after the use of cefazolin.
Based on currently available studies, there are no data that enable a choice to be made of one antibiotic over the other except in patients with allergy or renal impairment. This review points out the need for future prospective studies and randomized controlled trials to better address these questions.
A prospective study was initiated in an intensive care unit (ICU) where extended-spectrum β-lactamase- producing enterobacteriaceae (ESBLPE) were endemic. From July 1990 to July 1991, patients ...hospitalized for ⩾5 days were screened for ESBLPE acquisition by means of weekly rectal sampling and clinical cultures. Baseline characteristics and various ICU procedures in 62 cases of ESBLPE were compared with those for 205 patients without ESBLPE, with use of Cox's model. Risk for acquiring ESBLPE (Klebsiella pneumoniae in most cases) increased during the ICU stay, from 4.2% in the first week to 24% in the fourth week. Baseline characteristics were not different between the two groups. Urinary catheterization (P = .04) and arterial catheterization (P = .03) were independent risk factors for acquiring ESBLPE and probably reflected frequency of health care manipulations. The first site of ESBLPE acquisition was the digestive tract in 58 of the 62 patients; 28 infections developed in 22 patients, and these followed or occurred simultaneously with rectal colonization in 18 of those 22. DNA macrorestriction analysis suggested that the same strain was responsible for most cases. In conclusion, ESBLPE acquisition depends on length of stay in the ICU and the use of invasive procedures. Colonization is a prerequisite for infection.
Purpose
Amikacin requires pharmacodynamic targets of peak serum concentration (
C
max
) of 8–10 times the minimal inhibitory concentration, corresponding to a target
C
max
of 60–80 mg/L for the less ...susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30 % of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient
C
max
in a population of critically ill patients.
Methods
Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of
C
max
< 60 mg/L were identified by mixed model multivariate analysis.
Results
Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 41–68) were included. At inclusion, the SOFA score was 8 6–12, 119 (66 %) episodes required vasopressors, 150 (83 %) mechanical ventilation, and 81 (45 %) renal replacement therapy. The amikacin
C
max
was 69 54.9–84.4 mg/L. Overall, 60 (33 %) episodes had a
C
max
< 60 mg/L. The risk of
C
max
< 60 mg/L associated with BMI < 25 kg/m
2
varied across quarters of inclusion. Independent risk factors for
C
max
< 60 mg/L were a BMI < 25 kg/m
2
over the first quarter (odds ratio (OR) 15.95, 95 % confidence interval (CI) 3.68–69.20,
p
< 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95 % CI 1.01–1.11,
p
= 0.018).
Conclusions
Despite an amikacin dose of 25 mg/kg of total body weight, 33 % of patients still had an amikacin
C
max
< 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of
C
max
< 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.
Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome.
To ...determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28.
Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs.
Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129).
The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia.
Among 260 patients (mean age 63 years; 91 35% women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio HR, 1.35 95% CI, 0.87-2.08). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 95% CI, 0.85-2.33). Day-28 IFI-free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 95% CI, 0.96-2.94). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients 12%) (P = .008).
Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
clinicaltrials.gov Idenitfier: NCT01773876.
Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of ...PCT-guided antibiotic management in patients with bacteremia.
We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days.
Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days 95% confidence interval CI, -4.88 to -.84; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections.
This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.
Although frequent, little is known about early-onset pneumonia that occurs in the postresuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, ...its influence on the occurrence of early-onset pneumonia is not well defined.
To describe the incidence, risk factors, causative agents, and impact on outcome of early-onset pneumonia occurring within 3 days after out-of-hospital cardiac arrest (OHCA).
Retrospective analysis of a large cohort study of all patients successfully resuscitated after OHCA and admitted from July 2002 to March 2008 in two medical intensive care units (ICUs). Patients who presented accidental hypothermia or a known pneumonia before OHCA, or patients who died within the first 24 hours, were excluded.
During this 6-year period, 845 patients were admitted after OHCA, and 641 consecutive patients were included. A total of 500 patients (78%) were treated with therapeutic hypothermia. In the first 3 days, 419 (65%) presented early-onset pneumonia. Multivariate analysis disclosed therapeutic hypothermia as the single independent risk factor of early-onset pneumonia (odds ratio, 1.90; 95% confidence interval, 1.28-2.80; P = 0.001). Early-onset pneumonia increased length of mechanical ventilation (5.7 ± 5.9 vs. 4.7 ± 6.2 d; P = 0.001) and ICU stay (7.9 ± 7.2 versus 6.7 ± 7.6 d; P = 0.001), but did not influence incidence of ventilator-associated pneumonia (P = 0.25), favorable neurologic outcome (P = 0.35), or ICU mortality (P = 0.26).
After OHCA, therapeutic hypothermia is associated with an increased risk of early-onset pneumonia. This complication was associated with prolonged respiratory support and ICU stay, but did not significantly influence ICU mortality.
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