CSF penetration of vancomycin in critical care patients with proven or suspected ventriculitis: a prospective observational study.

BACKGROUND: Vancomycin is recommended for ventriculitis. However, penetration into the CNS is relatively poor. OBJECTIVES: To investigate the population pharmacokinetics of vancomycin in serum and CSF in critical care patients with proven or suspected CNS infections from neurosurgical procedures. PATIENTS AND METHODS: This was an observational pharmacokinetic study in critical care patients with proven or suspected CNS infections receiving intravenous vancomycin. Multiple blood and intraventricular CSF samples were collected. Population pharmacokinetic analysis and simulation were undertaken with ADAPT5 and Pmetrics. RESULTS: A total of 187 blood and CSF samples were collected from 21 patients. The median (range) Cmax and Cmin concentrations in serum were 25.67 (10.60-50.78) and 9.60 (4.46-23.56) mg/L, respectively, with a median daily dose of 2500 (500-4000) mg. The corresponding median concentrations in CSF were 0.65 (<0.24-3.83) mg/L and 0.58 (<0.24-3.95) mg/L, respectively. The median AUC0-24 in serum and CSF was 455.09 and 14.10 mg·h/L, respectively. A three-compartment linear population pharmacokinetic model best fitted the observed data. Vancomycin demonstrated poor penetration into CSF, with a median CSF/serum ratio of 3% and high intersubject pharmacokinetic variability of its penetration. CONCLUSIONS: Therapeutic drug monitoring in both serum and CSF and higher daily doses may be an option to ensure adequate trough levels and to optimize patient therapy. Novel dosing strategies designed to reduce renal toxicity, such as administration by continuous infusion, should be investigated in further clinical studies to avoid antibiotic underexposure in CSF.

Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study.

BACKGROUND: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. METHODS: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics. RESULTS: In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60.7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability. CONCLUSIONS: Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis.

Decreased Linezolid Serum Concentrations in Three Critically Ill Patients: Clinical Case Studies of a Potential Drug Interaction between Linezolid and Rifampicin.

Linezolid is a valuable treatment option for treating infections caused by multi-resistant gram-positive pathogens. Lack of effective linezolid levels due to the co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this potential drug interaction (DI) for critically ill patients is still unclear. This was a retrospective analysis of 3 critically ill patients with the combination therapy of linezolid and rifampicin or rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority of observed linezolid trough concentrations in all 3 patients were below 2 mg/l. Furthermore, linezolid trough concentrations remained below 2 mg/l after discontinuation of rifampicin. This potential DI between linezolid and rifampicin could lead to treatment failure. Therefore, we strongly recommend that linezolid serum concentrations be monitored in patients with rifampicin co-administration or rifampicin pretreatment.

Effects of pharmaceutical counselling on antimicrobial use in surgical wards: intervention study with historical control group.

PURPOSE: The objective of this study was to assess the impact of pharmaceutical consulting on the quality of antimicrobial use in a surgical hospital department in a prospective controlled intervention study. METHODS: Patients receiving pharmaceutical intervention (intervention group, IG, n = 317) were compared with a historical control group (control group, CG, n = 321). During the control period, antimicrobial use was monitored without intervention. During the subsequent intervention period, a clinical pharmacist reviewed the prescriptions and gave advice on medication. RESULTS: Intervention reduced the length of antimicrobial courses (IG = 10 days, CG = 11 days, incidence rate ratio for i.v. versus o.p. = 0.88, 95% confidence interval 0.84 to 0.93) and shortened i.v. administration (IG = 8 days, CG = 10 days, hazard rate = 1.76 in favour of switch from i.v. to p.o., 95% confidence interval 1.23 to 2.52). Intervention also helped to avoid useless combination therapy and reduced total costs for antimicrobials. CONCLUSIONS: A clinical pharmacist who reviews prescriptions can promote an increase in efficiency, for example, by shortening the course of treatment. Counselling by ward-based clinical pharmacists was shown to be effective to streamline antimicrobial therapy in surgical units and to increase drug safety.

Is there a need for a hospital pharmacy common training framework? Review of the literature on the impact of educational interventions on health outcome.

BACKGROUND: With the update of the directive 2005/36/EU on the recognition of professional qualifications (2013/55/EU), the European Union (EU) legislation opened also to pharmacists the possibility to define specialisations via a common training framework (CTF). OBJECTIVE: The aim of this study was to review, synthesise and present published evidence on the impact of health educational interventions targeting healthcare professionals on patients' health outcomes that support a hospital pharmacy CTF in EU. METHOD: The search was carried out in Medline and Cumulative Index to Nursing & Allied Health Literature and was limited to English language full review articles or primary research published since 2000. Data were extracted independently and compared by three of the researchers. RESULTS: Ten papers (9 primary research studies and one literature review) were identified. Almost one-third of the studies (30%, n=3) targeted pharmacists in their research. The majority of studies (80%, n=8) have shown that higher education levels among healthcare professionals improved patient outcomes. No study discussed the importance of a CTF. CONCLUSION: The review of the literature has demonstrated the need for education and training of health personnel to improve patient outcome. Controlled studies about pharmacist education and training in European countries showed that the benefit of a CTF is lacking.