Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

Management of severe imported malaria in adults.

Severe malaria accounts for approximately 10% of all cases of imported malaria in France; cases are mainly due to Plasmodium falciparum, while other Plasmodium species are possible but uncommon (P. vivax, P. knowlesi, P. malariae, and P. ovale). On the basis of WHO criteria for endemic areas, the French criteria defining severe imported malaria in adults have been progressively adapted to the European healthcare level. Management of severe imported malaria is a diagnostic and treatment emergency and must be initially conducted in the intensive care unit. Anti-infective treatment is now based on intravenous artesunate, which must be available in every hospital of the country likely to receive severe imported malaria patients. Intravenous quinine is thus used as a second-line treatment and is restricted to limited indications. Critical care management of organ failure is essential, particularly in patients presenting with very severe malaria. To date, no adjunctive therapy (including exchange transfusion) has demonstrated clear beneficial effects.

Management of oral antiretroviral administration in patients with swallowing disorders or with an enteral feeding tube.

HIV infection has evolved into a chronic disease with comorbidities since the combination antiretroviral therapy era. Complications still occur and patients may need to be admitted to an intensive care unit. Acute respiratory failure is the first cause of these admissions, questioning the administration of solid oral dosage formulations. This issue is also observed in geriatric units where the prevalence of dysphagia is high and underestimated. The problem of antiretroviral administration is critical: altered solid oral dosage formulations and/or administration via enteral feeding tubes are sometimes the only option. The aim is to help manage antiretroviral treatment in unconscious or intubated patients and those with swallowing disorders who are hospitalized in intensive care units or geriatric units. This review provides information on the main antiretroviral regimens and on practical and legal aspects of manipulating solid oral dosage formulations and administration via enteral feeding tubes. Alternatives to the solid formulation are available for most of the 27 oral antiretrovirals available, or manufacturers provide recommendations for patients who are unable to swallow. Manipulation of solid oral dosage formulations such as crushing tablets or opening capsules and administration via feeding tubes are frequently reported but should be the last option for safety and liability issues. Before any off-label administration of a drug, physicians should consider alternatives to the solid oral dosage formulation and check whether the drug can be altered. Therapeutic monitoring is important in this particular setting as the pharmacokinetic profile of drugs is difficult to predict.

Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016.

BACKGROUND: Patients with suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection should be hospitalized in isolation wards to avoid transmission. This suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than MERS-CoV. METHODS: We studied the characteristics and outcome of patients hospitalized for suspected MERS-CoV infection in the isolation wards of two referral infectious disease departments in the Paris area between January 2013 and December 2016. RESULTS: Of 93 adult patients (49 male (52.6%), median age 63.4 years) hospitalized, 82 out of 93 adult patients had returned from Saudi Arabia, and 74 of them were pilgrims (Hajj). Chest X-ray findings were abnormal in 72 (77%) patients. The 93 patients were negative for MERS-CoV RT-PCR, and 70 (75.2%) patients had documented infection, 47 (50.5%) viral, 22 (23.6%) bacterial and one Plasmodium falciparum malaria. Microbiological analysis identified Rhinovirus (27.9%), Influenza virus (26.8%), Legionella pneumophila (7.5%), Streptococcus pneumoniae (7.5%), and non-MERS-coronavirus (6.4%). Antibiotics were initiated in 81 (87%) cases, with two antibiotics in 63 patients (67.7%). The median duration of hospitalization and isolation was 3 days (1-33) and 24 h (8-92), respectively. Time of isolation decreased over time (P < 0.01). Two patients (2%) died. CONCLUSION: The management of patients with possible MERS-CoV infection requires medical facilities with trained personnel, and rapid access to virological results. Empirical treatment with neuraminidase inhibitors and an association of antibiotics effective against S. pneumoniae and L. pneumophila are the cornerstones of the management of patients hospitalized for suspected MERS-CoV infection.

Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia.

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3-101) and 97.4% (93.7-101), respectively) and amikacin (88.9% (81.7-96.1) and 96.4% (92.1-100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.

Clinical spectrum and outcomes of patients with encephalitis requiring intensive care.

BACKGROUND AND PURPOSE: Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis. METHODS: A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20-year period. Patients' characteristics and outcomes were compared between two 10-year periods: (i) 1991-2001 and (ii) 2002-2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4-6 (severe disability or death) 90 days after admission. RESULTS: A total of 279 patients were studied. Causes of encephalitis were infections (n = 149, 53%), immune-mediated causes (n = 41, 15%) and undetermined causes (n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune-mediated causes. At day 90, 208 (75%) patients had an mRS = 0-3 and 71 (25%) had an mRS = 4-6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06-17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47-11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53-0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17-2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01-1.07). CONCLUSIONS: Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.

Neurological complications of infective endocarditis: new breakthroughs in diagnosis and management.

Neurological complications are frequent in infective endocarditis (IE) and increase morbidity and mortality rates. A wide spectrum of neurological disorders may be observed, including stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left-sided abnormalities of native or prosthetic valves. Ischemic lesions account for 40% to 50% of IE central nervous system complications. Systematic brain MRI may reveal cerebral abnormalities in up to 80% of patients, including cerebral embolism in 50%, mostly asymptomatic. Neurological complications affect both medical and surgical treatment and should be managed by an experimented multidisciplinary team including cardiologists, neurologists, intensive care specialists, and cardiac surgeons. Oral anticoagulant therapy given to patients presenting with cerebral ischemic lesions should be replaced by unfractionated heparin for at least 2 weeks, with a close monitoring of coagulation tests. Recently published data suggest that after an ischemic stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Surgery should be postponed for 2 to 3 weeks for patients with intracranial hemorrhage. Endovascular treatment is recommended for cerebral mycotic aneurysms, if there is no severe mass effect. Recent data suggests that neurological failure, which is associated with the location and extension of brain injury, is a major determinant for short-term prognosis.

Infective endocarditis with symptomatic cerebral complications: contribution of cerebral magnetic resonance imaging.

BACKGROUND: Cerebral complications are well-identified causes of morbidity and mortality in patients with infective endocarditis (IE). Few studies have analysed the impact of brain magnetic resonance imaging (MRI) in IE patients with neurological manifestations. OBJECTIVES: The aims of this study were to assess the MRI contribution to the management of patients with IE neurological manifestations and to compare cerebral CT and MRI findings. MATERIAL AND METHODS: Patients with definite or probable IE and neurological manifestations were prospectively enrolled from 2005 to 2008, in a university hospital (Bichat Claude Bernard Hospital, Paris). Clinical and radiological characteristics and echocardiographic findings were systematically recorded. Brain MRI with angiography was performed and compared to available CT scans. The contribution of MRI results to cerebral involvement staging and to therapeutic plans was evaluated. RESULTS: Thirty patients, 37-89 years old, were included. Nineteen suffered from pre-existing heart disease. Blood cultures were positive in 29 cases and the main micro-organisms were streptococci (n = 14) and staphylococci (n = 13). The IE was mainly located on mitral (n = 15) and aortic valves (n = 13). Neurological events were strokes (n = 12), meningitis (n = 5), seizures (n = 1), impaired consciousness (n = 11) and severe headache (n = 1). MRI findings included ischaemic lesions (n = 25), haemorrhagic lesions (n = 2), subarachnoid haemorrhage (n = 5), brain abscess (n = 6), mycotic aneurysm (n = 7), vascular occlusion (n = 3) and cerebral microbleeds (n = 17). In 19/30 cases, neurological manifestations were observed before the diagnosis of IE. MRI was more sensitive than CT scan in detecting both clinically symptomatic cerebral lesions (100 and 81%, respectively) and additional asymptomatic lesions (50 and 23%, respectively). Therapeutic plans were modified according to MRI results in 27% of patients: antibiotherapy regimen modifications in 7% (switch for molecules with high cerebral diffusion) and surgical plan modifications in 20% (indication of valvular replacement due to the embolic nature of the vegetations revealed by MRI or postponement of surgery due to haemorrhagic lesions). None of the 16/30 (51%) operated-on patients experienced postoperative neurological worsening. In-hospital death occurred in 4 patients. CONCLUSION: In patients with IE neurological manifestations, MRI revealed a broader involvement of the brain (type and number of lesions) than indicated by clinical signs and/or CT scan. With a better disease staging of neurological manifestations, MRI brain imaging may help in patient management and the decision-making process especially for cardiac surgery indication and timing of valve replacement.

Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study.

PURPOSE: To determine whether procalcitonin (PCT) levels could help discriminate isolated viral from mixed (bacterial and viral) pneumonia in patients admitted to the intensive care unit (ICU) during the A/H1N1v2009 influenza pandemic. METHODS: A retrospective observational study was performed in 23 French ICUs during the 2009 H1N1 pandemic. Levels of PCT at admission were compared between patients with confirmed influenzae A pneumonia associated or not associated with a bacterial co-infection. RESULTS: Of 103 patients with confirmed A/H1N1 infection and not having received prior antibiotics, 48 (46.6%; 95% CI 37-56%) had a documented bacterial co-infection, mostly caused by Streptococcus pneumoniae (54%) or Staphylococcus aureus (31%). Fifty-two patients had PCT measured on admission, including 19 (37%) having bacterial co-infection. Median (range 25-75%) values of PCT were significantly higher in patients with bacterial co-infection: 29.5 (3.9-45.3) versus 0.5 (0.12-2) µg/l (P < 0.01). For a cut-off of 0.8 µg/l or more, the sensitivity and specificity of PCT for distinguishing isolated viral from mixed pneumonia were 91 and 68%, respectively. Alveolar condensation combined with a PCT level of 0.8 µg/l or more was strongly associated with bacterial co-infection (OR 12.9, 95% CI 3.2-51.5; P < 0.001). CONCLUSIONS: PCT may help discriminate viral from mixed pneumonia during the influenza season. Levels of PCT less than 0.8 µg/l combined with clinical judgment suggest that bacterial infection is unlikely.

Neurological complications of HIV infection in critically ill patients: clinical features and outcomes.

OBJECTIVE: We aimed to investigate the prognosis of HIV-infected patients with acute neurological complications at the highly active antiretroviral therapy (HAART) era. METHODS: We performed a retrospective study in HIV-infected patients admitted to a medical ICU with neurological complications between 2001 and 2008. RESULTS: Among the 210 studied patients (median [interquartile range] CD4-cell count: 80 [18-254]/µL; HIV viral load: 4.8 [2-5.3] log10/mL), 40 (19%) had unknown HIV status at admission. Neurological complications consisted in delirium (45%), coma (39%), seizures (32%) and/or intracranial hypertension (21%). Admission diagnoses were AIDS-defining CNS disease for 88 (42%) patients, non-AIDS-defining CNS disease for 45 (21%), and systemic disease with neurological signs for 77 (37%). Seizures (p=0.003), focal deficit (p<0.001) and intracranial hypertension (p<0.001) were more frequently observed in patients with AIDS-defining CNS disease. Factors independently associated with ICU mortality (29.5%) were intracranial hypertension [odds ratio (OR), 5.09; 95% confidence interval (95% CI), 2.17-11.91], vasopressor use [OR, 3.92; 95% CI, 1.78-8.60] and SAPS II score [per 10-point increment, OR, 1.59; 95% CI, 1.31-1.93]. CONCLUSIONS: Prognosis of HIV-infected patients with neurological complications depends rather on clinical presentation than on HIV-related parameters. Intracranial hypertension symptoms at admission have a major impact on outcome.

[Emergency antibiotherapy and adjuvant treatments for acute bacterial meningitis]. / Critères d'urgence de l'antibiothérapie : autres mesures associées.

The management of bacterial meningitis is based on the combination of several components. The objective of this review is to give an overview of the literature concerning both the arguments for urgent antibiotic treatment associated with a particular focus on the place of corticosteroids. Among other treatments, glycerol seems the best rated but symptomatic measures, which may not be achieved by randomized studies, should not be overlooked. Many animal studies explore other treatment options, but none can be translated into clinical practice. The neuroimaging has been little evaluated despite recent technological advances but remains important in monitoring of patients whose evolution is considered unfavorable.

Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia.

To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in patients requiring mechanical ventilation (MV), we performed a prospective cohort study that included 747 patients. Pneumonia was defined as a positive result for a protected quantitative distal sample. EOP was defined as pneumonia that occurred from day 3 to day 7 of MV. Eighty patients (10.7%) experienced EOP. Independent predictors of EOP were male sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.18-3.63), actual Glasgow Coma Scale value of 6-13 (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR, 1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28-7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26). Protection occurred with use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), beta -lactams and/or beta -lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation cephalosporins (OR, 0.33; 95% CI, 0.16-0.74). Sucralfate use and unplanned extubation are independent risk factors for EOP. Use of aminoglycosides, beta-lactams/ beta-lactamase inhibitors, or third-generation cephalosporins protects against EOP.