Pharmacodynamics of Antibiotics-Consequences for Dosing: Proceedings of a Symposium Held in Stockholm, June 7–9, 1990

Cars, Otto; Craig, William A.

doi:10.3109/inf.1990.22.suppl-74.01

Cited by 5 publications

References 508 publications

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Single‐Dose Antibiotic Therapy: What Has the Past Taught Us?

Carbon

1992

The Journal of Clinical Pharma

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The proper dosage schedule of antibiotics has generally been determined empirically, due to the difficulty of clinical trials. Initially, the dosage was chosen to allow high sustained levels greater than MIC in the blood. Antibiotics (beta lactams, tetracyclins, macrolides) were given at high doses three to six times daily, whatever their kinetic properties. The data obtained by Eagle3 with beta lactams in animal models of streptococcal and treponemal infections outlined the importance of interval between doses on the in vivo efficacy. They also showed that increasing the dose of penicillin had a positive effect on the bactericidal activity only through the persistence of effective levels (greater than MIC) at the site of infection. Further illustrations were given through experimental and clinical studies with beta lactams or other compounds on different types of infections: LRTIs, UTIs, meningitis, and endocarditis. The importance of both dynamic (i.e., pattern of bactericidal effect) and kinetic (elimination half-life) parameters was thus further identified. Information on toxicity with some compounds with a narrow therapeutic index, such as aminoglycosides, indicated that increasing the dose to enhance efficacy had some limitations. This led to numerous studies on the relations between concentration and toxicity, stating that nephro- or ototoxicity were not directly related to peak level in serum. Experimental studies showed that OD administration of aminoglycosides was both more efficient and less toxic than the multiple-dose regimen of the same daily amount. Economic considerations progressively justified attempts to both reduce the dose and the work load related to multiple administrations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Single‐Dose Antibiotic Therapy: What Has the Past Taught Us?

Carbon

1992

The Journal of Clinical Pharma

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Antibiotic Adjuvants

Melander

2017

Topics in Medicinal Chemistry

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Physiological study of pulmonary involvement in adults with cystic fibrosis through simulated modeling of different clinical scenarios

Sousa

Fernández

Miller

et al. 2018

Med Biol Eng Comput

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Cystic fibrosis is an inherited disorder of the cystic fibrosis transmembrane conductance regulator gene (CFTR) that affects the respiratory system. Current treatment is palliative, but there is a gene therapy under investigation which involves inserting a functional CFTR gene into affected cells. Given the clinical variety of the disease, it is necessary to characterize key indicators in its evolution (e.g., the number of functional alveolar sacs and its relationship with a healthy lung function), to anticipate its advancement. A dynamic model was used to evaluate the evolution of cystic fibrosis over time. We considered the application of conventional medical treatments and evaluated the benefits of the application of an experimental gene therapy that would reverse lung damage. Without treatment the life expectancy of the patient is low, but it is increased with the application of conventional treatments, being the progressive loss of the lung function inevitable. Simulating the application of a gene therapy, the life expectancy of patients would not be limited, given the recovery of all altered cellular processes. With this model we can make predictions that demonstrate the need for a curative treatment, in addition to presenting the evolution of pathology in a specific clinical setting. Graphical abstract Graphic representation of the analysis performed in the present work on simulation of different clinical situations regarding patients with cystic fibrosis of pulmonary involvement.

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Pharmacodynamics of Antibiotics-Consequences for Dosing: Proceedings of a Symposium Held in Stockholm, June 7–9, 1990

Cited by 5 publications

References 508 publications

Single‐Dose Antibiotic Therapy: What Has the Past Taught Us?

Single‐Dose Antibiotic Therapy: What Has the Past Taught Us?

Antibiotic Adjuvants

Physiological study of pulmonary involvement in adults with cystic fibrosis through simulated modeling of different clinical scenarios

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