The present article \"is a progress report rather than a review and in large part summarizes studies from a single laboratory\" on the minimal essential medium for cultivation of mammalian cells in either monolayer or suspension. Every cell culture examined, whether human or animal in origin, required at least 13 amino acids for survival and growth. All the cultured human cells examined were found to contain large amounts of glutathione, taurine, glutamine, ammonia, and glutamic acid. [The SCI® indicates that this paper was cited 2,255 times in the period 1961-1975.]

https://science.sciencemag.org/content/sci/130/3373/432.full.pdf

Amino Acid Metabolism in Mammalian Cell Cultures

Antimicrobial pharmacodynamics is the discipline that integrates microbiology and pharmacology, with the aim of linking a measure of drug exposure, relative to a measure of drug potency for the pathogen in question, to the microbiological or clinical effect achieved. The delineation of such relationships allows the drug dose to be chosen in a rational manner, so that the desired effect (for example, the maximal bactericidal effect) can be achieved in a large proportion of the intended patient population. Ultimately, the goal of any anti-infective therapy is to administer a dose of drug that has an acceptably high probability of achieving the desired therapeutic effect balanced with an acceptably low probability of toxicity. Appropriate use of the latest pharmacodynamic modelling approaches can minimize the emergence of resistance and optimize the outcome for patients.

Antimicrobial pharmacodynamics: critical interactions of 'bug and drug'

Current antimicrobial dosing regimens are designed to maintain active drug levels for most of the dosing interval and are based on 40-y-old observations. With use of numerous multiple-dosing regimens in an animal model, this study is the first to successfully minimize the interdependence between pharmacokinetic parameters and thereby determine, by stepwise multivariate regression analysis, that the time that serum levels exceeded the minimum inhibitory concentration (MIC) was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides. Optimal dosing intervals were no greater than the time that serum levels exceeded the MIC plus the duration of the postantibiotic effect. Careful application of these concepts should allow other investigators to use more optimally dosed regimens than those previously used in preclinical trials and to design studies to improve on current dosing regimens for humans.

Correlation of Antimicrobial Pharmacokinetic Parameters with Therapeutic Efficacy in an Animal Model

Silver first gained regulatory approval for use as an antimicrobial agent in the early 20th century, but its usage diminished with the introduction of antibiotics in the 1940s. Recently, however, topical silver has gained popularity once again, principally in the management of open wounds. This has been largely due to the spread of methicillin-resistant Staphylococcus aureus and the resultant reduction in first-line antibiotic prescribing. The increase in the use of topical silver has raised issues concerning silver resistance, together with questions about the standardization of antimicrobial testing methods for silver. Issues related to silver product testing include a failure to establish standard procedures for determining MIC values, an absence of recognized breakpoints, a lack of conformity in the way different products release silver and variations in the effects of microbiological media on silver release and the measurement of inhibitory activity. The clinical incidence of silver resistance remains low, and emergence of resistance can be minimized if the level of silver ions released from products is high and the bactericidal activity rapid.

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The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern?

Since the advent of the modern era of antimicrobial chemotherapy in the 1930s, animal infection models have allowed for the in vivo evaluation of antimicrobial agents for the treatment of experimentally induced infection. Today, animal pharmacokinetic-pharmacodynamic (PK-PD) infection models serve as a cornerstone of the preclinical assessment process for antibacterial agents and dose and dosing interval selection, as decision support for setting in vitro susceptibility breakpoints, and, finally, for the evaluation of the meaning of in vitro resistance. Over the past 15 years, considerable PK-PD data have been derived from infected patients for many classes of antimicrobial agents. These data provide the opportunity to confirm knowledge gained from animal PK-PD infection models.

Pharmacokinetics-Pharmacodynamics of Antimicrobial Therapy: It's Not Just for Mice Anymore

THERE is a considerable body of experimental evidence that the therapeutic action of penicillin rests in large part on its direct bactericidal action, and that the factor that primarily determines its therapeutic efficacy is the total time for which the drug remains at effective levels at the focus of infection.1 2 3 4 Thus, the number of streptococci or pneumococci surviving in an intramuscular focus in mice after an injection of aqueous sodium penicillin G was found to decrease rapidly only so long as the penicillin remained at effective levels.3 , 4 Extremely large doses, providing concentrations greatly in excess of the effective level, were . . .

"Continuous" vs. "discontinuous" therapy with penicillin; the effect of the interval between injections on therapeutic efficacy.

Effect of schedule of administration on the therapeutic efficacy of penicillin: Importance of the aggregate time penicillin remains at effectively bactericidal levels

http://www.jbc.org/content/234/3/592.full.pdf

Protein Turnover in Mammalian Cell Cultures

Excerpt Although penicillin is known to be actively bactericidal, there is reason to believe that its therapeutic activity is not determined solely by that direct bactericidal action, and that othe...

The bactericidal action of penicillin in vivo: the participation of the host, and the slow recovery of the surviving organisms.

/pdf/clinical-uses-of-2-2-dimercaptopropanol-bal-the-systemic-4dp3d6gdnm.pdf

Clinical uses of 2,2-dimercaptopropanol (BAL); the systemic treatment of experimental arsenic poisoning (mapharsen, lewisite, phenyl arsenoxide) with BAL.

Ralph Fleischman

Papers

"Continuous" vs. "discontinuous" therapy with penicillin; the effect of the interval between injections on therapeutic efficacy.

Effect of schedule of administration on the therapeutic efficacy of penicillin: Importance of the aggregate time penicillin remains at effectively bactericidal levels

Protein Turnover in Mammalian Cell Cultures

The bactericidal action of penicillin in vivo: the participation of the host, and the slow recovery of the surviving organisms.

Clinical uses of 2,2-dimercaptopropanol (BAL); the systemic treatment of experimental arsenic poisoning (mapharsen, lewisite, phenyl arsenoxide) with BAL.