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S Schalkowsky

Publications and source records attributed to S Schalkowsky.

6 recordsLinked to original sources
PubMed1995

Assessment of therapeutic potential by means of a probability model of antimicrobial action.

The probability model of antimicrobial action is based on the definition of bactericidal activity as the probability, q, that any cell in the population will be killed during a division interval. Bacteriostatic activity is defined as a change in the division intervals (generation times) of the cells. A simplified, homogeneous model is used which assumes that, at a constant concentration of the drug, all cells have the same kill probability and the same generation times. Birth-death analysis techniques require that the combined bacteriostatic and bactericidal effects of the drug (they are not mutually exclusive) are accounted for. Moreover, to suitably reflect the combined effect, the rate of change of the viable population, i.e. the slope of a kill curve (activity), needs to be expressed not in terms of exposure time, but in units of drug-free generations (DFGs), obtained by dividing exposure time by a measured DFG time interval (growth rate). A Discrete MIC (DMIC) is defined as the zero slope kill curve, coinciding with the horizontal axis and dividing population change into a restrained (subinhibitory) growth region, below the DMIC, and population reduction above it. At the DMIC, the probability of a cell being killed is 0.5, resulting in no change from the initial inoculum concentration, since half the cells are killed but the remaining cells double. The DMIC is found to be a measure of bactericidal activity only, even though bacteriostatic activity may also be present. An antibiotic-organism activity profile includes measurement of the DMIC, rate of change of activity at the DMIC and normalized activity at a number of clinically relevant drug concentrations. An overall, quantitative efficacy value over a dosing interval can be obtained from the activity profile and expressed as the number of DFGs which are needed to achieve a 99.9% reduction of the viable population at the site of infection. These reference efficacy values can be used to derive interpretive standards (break-points) based upon a quantitative relationship between laboratory measurements and population reduction at the site of infection. Model-derived measures of efficacy also provide a basis for assessing drug combination activity, including quantitative criteria of synergy and antagonism.

Anti-Bacterial Agents↗
PubMed1989

Development and validation of the spiral Salmonella assay: an automated approach to bacterial mutagenicity testing.

Since its development by Dr. Bruce Ames and his colleagues more than a decade ago, the Salmonella/mammalian microsome mutagenicity assay has become a widely accepted tool to assist in the identification of chemicals with mutagenic and carcinogenic potential. Several automated approaches to Salmonella testing have been proposed in recent years but have failed to gain acceptance in the scientific community due to poor performance or lack of demonstrated usefulness. In this paper we report on an automated system that successfully generates dose-response data and, moreover, reduces the labor, materials, and sample mass required to obtain such information. In the standard plate-incorporation assay, dose-response relationships are defined by testing discrete doses of the test agent on a series of agar plates. In contrast, the spiral Salmonella assay generates dose-response data from a continuous concentration gradient on a single agar plate. Upon analysis, each spiral plate yields a dose-response curve consisting of 13 data points that span a concentration range of about 15:1, which is equivalent to 5 two-fold serial dilutions. The performance of the spiral Salmonella assay was compared to that of the conventional plate-incorporation assay using 13 mutagens and 7 nonmutagens selected from a variety of chemical classes. Concordant qualitative responses were obtained for all compounds tested, and comparable dose-response relationships were generated by all mutagens with the exception of sodium azide and cyclophosphamide, which are highly water-soluble and, thus, are unable to maintain a well-defined concentration gradient on a spiral plate due to rapid diffusion. In general, toxicity was expressed at a lower dose in the spiral assay, and the mutagenic potencies (slopes of the dose-response curves) were greater in the spiral assay relative to the plate-incorporation assay. These differences will be discussed, as will the applicability of the spiral plating technique to routine screening and its relevancy to future mutagenesis testing.

4-Nitroquinoline-1-oxide↗
PubMedDate not supplied

Development and evaluation of the spiral gradient endpoint method for susceptibility testing of anaerobic gram-negative bacilli.

The spiral gradient endpoint (SGE) method for antimicrobial susceptibility testing was evaluated as an alternative agar-dilution procedure that would require less time and materials than the reference standard agar-dilution (SAD) susceptibility test for anaerobic bacteria. For the SGE test a spiral plater produces a drug concentration gradient equivalent to up to eight twofold dilutions in a single agar plate. Bacteria are streaked in radial lines across this gradient, and the drug concentration at the endpoint location where growth ceases can be calculated. Early results demonstrated the need to develop a standardized procedure, various technical improvements, and revised SGE formulas that correct for drug diffusion in calculating endpoint concentrations for tests on aerobes and anaerobes. The revised SGE method demonstrated an overall 90.7% agreement (within +/- 1 twofold dilution) of the minimal inhibitory concentrations with those determined by the SAD method tested in parallel for 161 strains of a wide variety of anaerobic gram-negative bacilli and eight antimicrobial agents. The reproducibility, sensitivity, and significantly increased efficiency warrant further evaluation of the revised SGE method.

Gram-Negative Anaerobic Bacteria↗