Bruno Mourvillier

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

Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis.

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.

Linezolid for the Treatment of Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

TO THE EDITOR—We read with interest the article by Wunderink et al [1] that showed better efficacy of linezolid compared with vancomycin for the treatment of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). The authors should be congratulated for the high quality of this study. In the discussion, it is stated that linezolid superiority was obtained despite vancomycin dose optimization. That statement could be challenged if the vancomycin trough levels are considered. Serum vancomycin levels were not available for 21% of the patients, and day-3 trough levels for the remaining 138 patients were <12.3 μg/mL for 72 (52%). These concentrations are below the 15–20 μg/mL vancomycin serum levels recently recommended by the Infectious Disease Society of America to treat severe MRSA infections such as pneumonia [2]. In a recent study including 320 patients with MRSA bacteremia, initial trough levels <15 mg/L were independently associated with an increased risk of therapeutic failure [3]. As in most previous clinical trials, patients received vancomycin (15 mg/kg every 12 hours) without a loading dose. This standard dosing approach is unlikely to achieve optimal pharmacodynamic targets (ie, a 0–24-hour vancomycin area under the concentration-time curve to minimum inhibitory concentration ratio >400 [4]). In addition, appropriate dosing is crucial during the early stage of the infection, when the bacterial load is the highest. Through a modeling approach, Roberts et al recently showed that higher-than-recommended vancomycin loading (35 mg/kg) and daily (35 mg/kg continuously infused) doses seem to be necessary to rapidly achieve therapeutic serum concentrations in critically ill patients with normal renal function [5]. In the present trial, clinical success rates were strictly identical in the 2 arms in the subgroup of patients with glomerular filtration rates <50 mL/min. A possible explanation could be the higher serum vancomycin levels obtained in those patients with impaired renal function. Vancomycin will probably remain the comparator in future trials on serious gram-positive infections. In our opinion, the design of these trials should take into account all data recently accumulated on pharmacodynamic parameters predictive of vancomycin efficacy.

Update on ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is the most frequent life-threatening nosocomial infection in intensive care units. The diagnostic is difficult because radiological and clinical signs are inaccurate and could be associated with various respiratory diseases. The concept of infection-related ventilator-associated complication has been proposed as a surrogate of VAP to be used as a benchmark indicator of quality of care. Indeed, bundles of prevention measures are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory secretions must be collected for bacteriological secretions before any new antimicrobials. Quantitative distal bacteriological exams may be preferable for a more reliable diagnosis and therefore a more appropriate use antimicrobials. To improve the prognosis, the treatment should be adequate as soon as possible but should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic selection pressure. For empiric treatments, the selection of antimicrobials should consider the local prevalence of microorganisms along with their associated susceptibility profiles. Critically ill patients require high dosages of antimicrobials and more specifically continuous or prolonged infusions for beta-lactams. After patient stabilization, antimicrobials should be maintained for 7–8 days. The evaluation of VAP treatment based on 28-day mortality is being challenged by regulatory agencies, which are working on alternative surrogate endpoints and on trial design optimization.