Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m(2 )AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF

Comparison of the Fully Automated FilmArray BCID Assay to a 4-Hour Culture Test Coupled to Mass Spectrometry for Day 0 Identification of Microorganisms in Positive Blood Cultures

Rapid bacterial identification of positive blood culture is important for adapting the antimicrobial therapy in patients with blood stream infection. The aim of this study was to evaluate the performance of the multiplex FilmArray Blood Culture Identification (BCID) assay by comparison to an in-house protocol based on MALDI-TOF MS identification of microcolonies after a 4-hour culture, for identifying on the same day the microorganisms present in positive blood culture bottles. One hundred and fifty-three positive bottles from 123 patients were tested prospectively by the 3 techniques of bacterial identification: 11 bottles yielding negative results by the 3 tests were considered false positive (7.2%). The reference MALDI-TOF MS technique identified 134 monomicrobial (87.6%) and 8 double infections (5.2%), which resulted in a total of 150 microorganisms. Globally, 137 (91.3%) of these 150 pathogens were correctly identified by the fully automated multiplex FilmArray BCID system at the species or genus level on day of growth detection, versus 117 (78.8%) by MALDI-TOF MS identification on nascent microcolonies after a 4-hour culture (P < 0.01). By combining the two approaches, 140 (93.5%) of the positive bottles were identified successfully at day 0. These results confirm the excellent sensitivity of the FilmArray BCID assay, notably in case of multimicrobial infection. Due to the limited number of targets included into the test, it must be coupled to another identification strategy, as that presented in this study relying on MALDI-TOF MS identification of microcolonies obtained after a very short culture period

Performance of the Chromogenic Medium CHROMagar Staph Aureus and the Staphychrom Coagulase Test in the Detection and Identification of Staphylococcus aureus in Clinical Specimens

CHROMagar Staph aureus (CSAM) (CHROMagar Microbiology, Paris, France) is a new chromogenic medium designed to enable detection of colonies of Staphylococcus aureus by their pink color. A total of 775 specimens were cultured in parallel on CHROMagar Staph aureus and conventional media. Among the 267 S. aureus strains recovered on at least one medium, 263 were isolated on CSAM medium (sensitivity, 98.5%), and 245 (sensitivity, 91.8%) were isolated on conventional media. The specificity of presumptive identification of S. aureus on the basis of pink colony color on CSAM medium was 97% (493 of 508). This specificity increased to 100% when coagulase detection with the Staphychrom coagulase test was added and to 98.8% when S. aureus surface components were detected by agglutination in the Pastorex Staph Plus test. Susceptibility testing of 67 S. aureus strains, performed in parallel on pink CSAM colonies and on colonies grown on blood agar, gave similar results. Thus, rapid and accurate recognition and identification of S. aureus isolates were achieved with CSAM as the primary isolation medium, followed by the staphylocoagulase Staphychrom test. Antimicrobial susceptibility testing (disk-diffusion method or ATB STAPH System) can be performed directly on pink CSAM colonies

Specific Identification of Staphylococcus aureus by Staphychrom II, a Rapid Chromogenic Staphylocoagulase Test

We compared the performance of Staphychrom II (International Microbio, Signes, France), a rapid (2-h) chromogenic staphylocoagulase test that uses human prothrombin and protease inhibitors, with those of the reference tube coagulase test (TCT) and the latex agglutination test (LAT) Slidex Staph Plus for the rapid identification of S. aureus. Prospective evaluation with 293 fresh clinical isolates yielded sensitivities, specificities, and predictive and negative predictive values of 98.1, 100, 100, and 95.1%, respectively, for the Staphychrom II test; 98.6, 98.7, 99.6, and 96.3%, respectively, for LAT; and 97.6, 98.7, 99.5, and 93.9%, respectively, for TCT. The perfect specificity of the Staphychrom II test was confirmed by testing 193 collection strains selected because of their potential testing pitfalls. The Staphychrom II test was positive for 90% of the 215 S. aureus strains tested after only 1 h of incubation. The Staphychrom II test was as sensitive as the reference TCT and was 100% specific

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease

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Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life

International audienceBackground: Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life.Methods: In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed.Results: Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches.Conclusion: Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration