Assessment of a Multiplex LAMP Assay (Eazyplex® CSF Direct M) for Rapid Molecular Diagnosis of Bacterial Meningitis: Accuracy and Pitfalls.

Background: Automated molecular panels are attractive tools for improving early meningitis diagnosis. This study assessed the Eazyplex® CSF direct M panel (EP), a multiplex real-time Loop-Mediated Isothermal Amplification assay. Methods: From December 2016 to December 2019, cerebrospinal fluid (CSF) samples were routinely tested with the EP V1.0. CSF parameters and microbiological and clinical data were retrospectively collected. Results: Out of 230 CSF samples, the EP yielded positive, negative, and invalid results for 32 (13.9%) (16 N. meningitidis, nine S. pneumoniae, two S. agalactiae, two E. coli, two H. influenzae, one L. monocytogenes), 182 (79.1%), and 16 (7%) samples, respectively. Among the positive samples, 14 (44%) remained negative in culture (antibiotic therapy before lumbar puncture (n = 11), meningococcal meningitis (n = 3)). High CSF protein concentrations and cellularity were associated with LAMP inhibition, counteracted by centrifugation. The automated software yielded 13 false positive and five false negative results. Amplification curve analysis was necessary and enabled the attainment of positive (PPA) and negative percentage agreement and positive and negative predictive values of 91.4%, 100%, 100%, and 98.3%. Three false negative results remained (two E. coli and one N. meningitidis). E. coli presented the poorest PPA (50%). Conclusion: This work confirms the strong performance of the EP, of particular interest in cases of antibiotic therapy before lumbar puncture.

High-Dose Ceftriaxone for Bacterial Meningitis and Optimization of Administration Scheme Based on Nomogram.

High dosages of ceftriaxone are used to treat central nervous system (CNS) infections. Dosage adaptation according to the glomerular filtration rate is currently not recommended. Ceftriaxone pharmacokinetics (PK) was investigated by a population approach in patients enrolled in a French multicenter prospective cohort study who received high-dose ceftriaxone for CNS infection as recommended by French guidelines (75 to 100 mg/kg of body weight/day without an upper limit). Only those with suspected bacterial meningitis were included in the PK analysis. A population model was developed using Pmetrics. Based on this model, a dosing nomogram was developed, using the estimated glomerular filtration rate (eGFR) and total body weight as covariates to determine the optimal dosage allowing achievement of targeted plasma trough concentrations. Efficacy and toxicity endpoints were based on previous reports, as follows: total plasma ceftriaxone concentrations of ≥20 mg/liter in >90% of patients for efficacy and ≤100 mg/liter in >90% of patients for toxicity. Based on 153 included patients, a two-compartment model including eGFR and total body weight as covariates was developed. The median value of the unbound fraction was 7.57%, and the median value of the cerebral spinal fluid (CSF)/plasma ratio was 14.39%. A nomogram was developed according to a twice-daily regimen. High-dose ceftriaxone administration schemes, used to treat meningitis, should be adapted to the eGFR and weight, especially to avoid underdosing using current guidelines. (This study has been registered at ClinicalTrials.gov under identifier NCT01745679.).

Risk-benefit Assessment of Systematic Thoracoabdominal-pelvic Computed Tomography in Infective Endocarditis.

BACKGROUND: In the management of infective endocarditis (IE), the presence of extracardiac complications has an influence on both diagnosis and treatment. Current guidelines suggest that systematic thoracoabdominal-pelvic computed tomography (TAP-CT) may be helpful. Our objective was to describe how systematic TAP-CT affects the diagnosis and the management of IE. METHODS: In this multicenter cohort study, between January 2013 and July 2016 we included consecutive patients who had definite or possible IE according to the Duke modified criteria, validated by endocarditis teams. We analyzed whether the Duke classification and therapeutic management were modified regarding the presence or the absence of IE-related lesion on CT and investigated the tolerance of this examination. RESULTS: Of the 522 patients included in this study, 217 (41.6%) had 1 or more IE-related lesions. On the basis of CT results in asymptomatic patients, diagnostic classification was upgraded from possible endocarditis to definite endocarditis for only 4 cases (0.8%). The presence of IE-related lesions on CT did not modify the duration of antibiotic treatment (P = .55), nor the decision of surgical treatment (P = .39). Specific treatment of the lesion was necessary in 42 patients (8.0%), but only 9 of these lesions (1.9%) were asymptomatic and diagnosed only on the TAP-CT. Acute kidney injury (AKI) within 5 days of CT was observed in 78 patients (14.9%). CONCLUSIONS: The TAP-CT findings slightly affected diagnosis and treatment of IE in a very small proportion of asymptomatic patients. Furthermore, contrast media should be used with caution because of the high risk of AKI.