Pharmacokinetic studies of amoxicillin,potassium clavulanate and their combination

Pharmacokinetic parameters after oral administration of 500 mg amoxicillin, 125 mg potassium clavulanate and 625 mg of their combination (augmentin) were determined in a randomized crossover study in ten healthy volunteers. The absolute bioavailability of amoxicillin (AUC_oral/AUC_i.v.) was 0.70±0.12. The mean maximum serum concentration of amoxicillin was 6.5±1.6 mg/l after administration alone and 6.5±1.4 mg/l after administration in combination. The respective values for potassium clavulanate were 3.4±1.4 mg/l and 2.8±1.1 mg/l. With both substances there was no significant difference between the pharmacokinetic parameters after administration alone and in combination. The AUC for amoxicillin was 19.5±5.4 h×mg/l after administration alone and 23.2±10.6 h×mg/l after administration in combination. The respective values for potassium clavulanate were 7.8±3.2 h×mg/l and 7.3±2.0 h×mg/l.     

Evaluation of safety and tolerance in clinical trials with antimicrobial agents

In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed. In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered. The different methods for registration of side-effects and their limitations are discussed. A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions. A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented.     

Epstein-Barr Virus (EBV) DNA in plasma is not encapsidated in patients with EBV-related malignancies.

Epstein-Barr Virus (EBV), a ubiquitous gamma herpes virus, infects more than 95% of the human population before adulthood. Life-long persistence, usually without adverse health consequences, relies on a balance between viral latency, viral replication, and host immune response. Patients with EBV-related disease often have high levels of EBV DNA in their plasma. This study addresses whether this circulating, cell-free EBV DNA is encapsidated in virions or exists as naked genomes. First, an assay was developed, combining DNase I and quantitative real-time PCR, to discriminate encapsidated from naked EBV DNA. EBV DNA was almost always naked in the plasma of AIDS-related lymphoma patients (n = 11) and immunosuppressed/posttransplantation patients (n = 8). In contrast, infectious mononucleosis patients (n = 30) often had a mixture of encapsidated and naked EBV DNA. These findings may be important in understanding how viral load relates to disease status and in predicting response to nucleoside analogs and other antiviral therapies.     

Rational antibiotic therapy and the position of ampicillin/sulbactam

In the current context of increasing antimicrobial resistance, it is important to use antibiotics rationally and to re-assess regularly the clinical usefulness of commonly used agents. This review focuses on the efficacy of the beta-lactam ampicillin co-administered with the beta-lactamase inhibitor sulbactam, either parenterally (ampicillin/sulbactam) or orally (sultamicillin), for the treatment of bacterial infections. Clinical findings from the past decade confirm the results of numerous older studies and together provide good evidence to support the continued use of ampicillin/sulbactam and sultamicillin in hospital- and community-acquired infections both in adults and children. This is also recognised in recent published national and international guidelines, many of which recommend ampicillin/sulbactam as first-line therapy for various respiratory and skin infections.     

Bridging Health Care and the Workplace: Formulation of a Return-to-Work Intervention for Breast Cancer Patients Using an Intervention Mapping Approach

Purpose An increasing number of breast cancer (BC) survivors of working age require return to work (RTW) support. Objective of this paper is to describe the development of a RTW intervention to be embedded in the care process bridging the gap between hospital and workplace. Method The Intervention Mapping (IM) approach was used and combined formative research results regarding RTW in BC patients with published insights on occupational therapy (OT) and RTW. Four development steps were taken, starting from needs assessment to the development of intervention components and materials. Results A five-phased RTW intervention guided by a hospital-based occupational therapist is proposed: (1) assessing the worker, the usual work and contextual factors which impacts on (re-)employment; (2) exploration of match/differences between the worker and the usual work; (3) establishing long term goals, broken down into short term goals; (4) setting up tailored actions by carefully implementing results of preceding phases; (5) step by step, the program as described in phase 4 will be executed. The occupational therapist monitors, measures and reviews goals and program-steps in the intervention to secure the tailor-made approach of each program-step of the intervention. Conclusion The use of IM resulted in a RTW oriented OT intervention. This unique intervention succeeds in matching individual BC patient needs, the input of stakeholders at the hospital and the workplace.