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Biomedical subjects

C W Hanson

Publications and source records attributed to C W Hanson.

At least 55 records · Page 3Linked to original sources

The frequency of in-vitro resistance development to fluoroquinolones and the use of a murine pyelonephritis model to demonstrate selection of resistance in vivo.

The frequency of development of resistance to the fluoroquinolones in vitro was generally low with Escherichia coli (in the order of 10(-7) to less than 10(-9) and high with Pseudomonas aeruginosa (in the order of 10(-5) to 10(-7)). Susceptibility to the fluoroquinolones also decreased after serial transfer in increasing concentrations of the drug. Although the MICs for the resistant E. coli variants were higher than that of the parent organism, they were still susceptible to achievable serum concentrations of all the quinolones except nalidixic acid. On the other hand some of the P. aeruginosa variants selected for resistance were resistant to achievable serum concentrations of all the quinolones. When E. coli pyelonephritis in mice was treated with the fluoroquinolones, difloxacin, A-56620, and ciprofloxacin were more effective than norfloxacin and nalidixic acid in lowering viable bacterial counts in the kidneys. The susceptibility of E. coli isolated from kidneys of mice treated with the quinolones was the same as that of the parent strain. When P. aeruginosa pyelonephritis in mice was treated with the fluoroquinolones an initial reduction in the cell count was seen, followed by an increase in the number of resistant variants. The resistant variants differed in their colony morphology and cell envelope proteins. The levels of resistance for the P. aeruginosa variants ranged from a two- to a 64-fold increase in the MIC.

Animals↗

Comparative antibacterial activities of temafloxacin hydrochloride (A-62254) and two reference fluoroquinolones.

The in vitro and in vivo properties of a new 1-difluorophenyl-6-fluoroquinolone, temafloxacin hydrochloride (A-62254), were compared with those of difloxacin and ciprofloxacin. Temafloxacin hydrochloride was as active as ciprofloxacin and difloxacin against staphylococci and as active as ciprofloxacin and 2 twofold dilutions more active than difloxacin against streptococci. Against gram-negative enteric bacteria and Pseudomonas aeruginosa, temafloxacin hydrochloride was 2 twofold dilutions more active than difloxacin but 2 to 4 twofold dilutions less active than ciprofloxacin. The MICs of temafloxacin hydrochloride and difloxacin were increased by 2 to 5 twofold dilutions in urine at pH 6.5 compared with 4 to 5 twofold-dilution increases in the MICs of ciprofloxacin. The MICs of temafloxacin hydrochloride, difloxacin, and ciprofloxacin were increased by 1 to 3 twofold dilutions in serum. The MICs of temafloxacin hydrochloride, difloxacin, and ciprofloxacin were the same or within 1 to 2 twofold dilutions at pHs 6.5, 7.2, and 8.0. When administered orally in mouse protection tests, temafloxacin hydrochloride was as active as difloxacin and 5 to 10 times more active than ciprofloxacin against infections with Staphylococcus aureus and streptococci. Against infections with gram-negative enteric bacteria and P. aeruginosa, temafloxacin hydrochloride was as active as difloxacin and ciprofloxacin. Temafloxacin hydrochloride was three times less active than difloxacin but was five times more active than ciprofloxacin against infections with Salmonella typhimurium. Temafloxacin hydrochloride was as active as difloxacin and ciprofloxacin against P. aeruginosa and Proteus mirabilis pyelonephritis in mice. The peak serum concentration and serum half-life of temafloxacin hydrochloride in mice were approximately one-half and one-sixth, respectively, that of difloxacin after oral administration. The peak serum concentration of temafloxacin hydrochloride in mice after oral administration was six times higher than that of ciprofloxacin, and the serum half-life was equal to that of ciprofloxacin.

Animals↗

Regression analysis, proposed interpretative zone size standards, and quality control guidelines for a new macrolide antimicrobial agent, A-56268 (TE-031).

A-56268 is a 6-O-methyl derivative of erythromycin A which has a spectrum of activity similar to that of erythromycin and is 1 log2 dilution more potent than erythromycin against most organisms that have been tested. The correlation of zone size diameters and MICs of A-56268 for 461 strains of bacteria isolated from clinical specimens was investigated. Based on anticipated levels in human serum of 2 micrograms/ml, 15-microgram disks have been recommended with zone size standards of greater than or equal to 15 mm for susceptibility (MIC correlate, less than or equal to 2.0 micrograms/ml) and less than or equal to 11 mm for resistance (MIC correlate, greater than or equal to 8 micrograms/ml). Selection of these tentative breakpoints resulted in no very major errors (false susceptible), a major error (false resistant) rate of 0.22%, and an acceptable minor error (intermediate) rate of 2.82%. MIC ranges and zone diameter limits for quality control organisms used in the standardized agar dilution and disk diffusion susceptibility tests with A-56268 are given.

Clarithromycin↗

In vitro evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones.

The in vitro antibacterial potencies of A-56619 and A-56620, two new aryl-fluoroquinolones, were compared with the potency of norfloxacin against a broad spectrum of organisms. Cefotaxime, aztreonam, piperacillin, imipenem, penicillin, and gentamicin were also tested for reference purposes. The MICs required to inhibit at least 90% of the strains tested ranged from 0.25 to 4 micrograms/ml for A-56619 and from 0.06 to 0.5 microgram/ml for A-56620 for members of the Enterobacteriaceae. A-56619 was generally twofold less potent and A-56620 was twofold more potent than norfloxacin against most aerobic gram-negative bacilli, including members of the Enterobacteriaceae and Pseudomonas aeruginosa. Against indole-positive Proteus, Morganella, Providencia rettgeri, and Serratia strains, A-56619 was at least 8- to 16-fold less potent than norfloxacin. A-56619 and A-56620 were four- to eightfold more potent than norfloxacin against Staphylococcus aureus and equally potent to fourfold more potent against Streptococcus species, Haemophilus influenzae, and Neisseria gonorrhoeae. The MICs of A-56619 and A-56620 were only slightly affected by increased inoculum size or by the addition of various cations at physiologic concentrations. A-56619 was three- to fivefold less active at pH 8.0 than at pH 6.5 or 7.2. A-56620 was twofold less active at pH 6.5 than at pH 8.0 or 7.2 against members of the Enterobacteriaceae and Pseudomonas aeruginosa; similar pH variations did not affect A-56620 activity against gram-positive cocci. The potencies of A-56619, A-56620, and norfloxacin were less in urine than in Mueller-Hinton broth; however, this effect was more pronounced with norfloxacin. Human serum at a concentration of 50% caused a 4- to 64- fold decrease in the potency of A-56619 and an average 4-fold decrease in the potency of A-56620, compared with no effect on the potency of norfloxacin. A-56619, A-56620, and norfloxacin were bactericidal and, at four times the MIC, reduced the viable cell counts of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by approximately 99.9% within 2 h. A-56619, A-56620, and norfloxacin showed no significant synergistic activity and no antagonism when they were aminoglycoside or beta-lactam antimicrobial agents.

Anti-Infective Agents↗

In vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide.

The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.

Administration, Oral↗

Microcomputers and computer-based instruction.

With the advent of low-cost modular microcomputer technology, discussions of computer-based instruction (CBI) have taken on a new direction. Earlier efforts at computer-based instruction were successful in the technical area, but the expense of starting and maintaining the programs deterred the widespread application of CBI. The initial low purchase price and minor maintenance expenses of microcomputers have lessened financial concerns about equipment purchases. The smaller size and the capability of the microcomputer have allowed CBI system developers to focus on more specific (rather than monolithic) projects so that the time and the cost for program development have been reduced. Although students have demonstrated high interest in CBI, faculties expressed some reservation about entering the field because of the new technology and the lack of supporting evidence for the value of this teaching modality. The microcomputer may be the answer to the economic and attitudinal deterrents to the success of previous attempts at CBI.

Computer-Assisted Instruction↗

API and Minitek systems in identification of clinical isolates of anaerobic gram-negative bacilli and Clostridium species.

A comparison of the API and Minitek methods of biochemical testing was made on a variety of anaerobic bacteria. Although API and Minitek results were not compared to more standardized or conventional procedures of identification, multiple repeat testing of the two systems was done on routine clinical isolates and known organisms to determine (i) whether the reactions were reliably consistent, (ii) the ease of reading the two systems with respect to the frequency of questionable results, and (iii) the percentage of routine clinical isolates for which each system yielded an identification. The Minitek system gave a much lower incidence of difficult to interpret reactions. The two systems were comparable in terms of reproducibility and capability of yielding an identification of the anaerobic gram-negative bacilli and Clostridium species, but were unsatisfactory for routine use on most of the other anaerobic bacteria isolated.

Bacterial Infections↗

Modified agar dilution method for rapid antibiotic susceptibility testing of anaerobic bacteria.

A simplified method has been developed for agar dilution antimicrobial susceptibility testing of anaerobic bacteria, designed to economize on time and money when only a few isolates need to be tested. The procedure is based on the principle of using filter paper disks as carriers of the antibiotic and 35- by 10-mm petri dishes which, when inoculated with the Steers replicator, can test up to four organisms per plate. The procedure was run in parallel with conventional agar dilution techniques and showed 95% agreement to within one dilution for all minimal inhibitory concentrations recorded on fresh anaerobic isolates from clinical specimens. The technique was further simplified by using commercially available antibiotic-containing disks, thereby alleviating the tedious and time-consuming procedure of preparing the disks. The data indicated that 48- to 72-h diffusion periods were sufficient to achieve a uniform concentration of the antibiotic in the petri plate and that the antibiotics were stable at room temperature for that period of time. In terms of applicability and relevance to the needs of the clinical microbiology laboratory, the modified agar dilution method for rapid antimicrobial susceptibility testing of individual anaerobic isolates was found to be superior to the broth dilution method since it was easier to read and required considerably less set up time.

Agar↗

Comparison of the Minitek test system with a conventional screening procedure for identification of Enterobacteriaceae.

A Minitek basic 9 disc/11 test system plus arabinose, inositol and rhamnose was compared with a conventional six tube screening system for identification of members of the family Enterobacteriaceae. Correlation varied from 88.3 to 100% with the various substrates when studied against 737 strains of these and other gram-negative bacteria recently isolated in our clinical laboratory. Two discs, citrate and ornithine, which originally gave a correlation of 88.3 and 95.5% respectively were modified so that a final correlation of 99.4 and 96.3% was obtained. The average correlation using the eleven discs was 97%.

Bacteriological Techniques↗

Evaluation of enrichment, storage, and age of blood agar medium in relation to its ability to support growth of anaerobic bacteria.

By measuring the colony size of a variety of anaerobic bacteria isolated from clinical specimens, an evaluation was made of the benefits derived from the addition of several enrichments to blood agar medium commonly used for the growth of anaerobes. Similar methods were used to study the effects of various storage conditions and age of the medium. The results were compared with those obtained on freshly prepared and enriched blood agar plates as well as commercially available blood agar plates. Freshly prepared and enriched blood agar was found to give substantially larger colonies than could be grown on commercially obtained blood agar plates when both were inoculated and incubated under identical conditions. Storage of plating media under CO2 for periods of up to 72 h had only a minor effect on the growth of the anaerobic bacteria studied, but longer periods of storage under CO2 resulted in a less efficient plating medium. Nonenriched brain heart infusion (BHI) was found to be a better basal medium than Trypticase soy agar (TSA) medium. Colony size on fully enriched BHI blood agar plates was greater than nonenriched BHI greater than nonenriched TSA greater than commercially prepared nonenriched TSA plates. The data suggest that freshness of the plates may be as important as using rich media.

Bacteroidaceae↗

Intracellular and extracellular nucleotides and related compounds during the development of Myxococcus xanthus.

Changes in nucleotide pools and extracellular nucleotides during the developmental cycle of the myxobacterium Myxococcus xanthus were determined using a high-pressure liquid chromatography nucleotide analyzer. A general increase in all nucleotide pools occurred during the morphological phase of glycerol conversion of vegetative cells to myxospores. The levels of the nucleoside triphosphate pools remained high as the myxospore matured and throughout subsequent germination. Oxidized nicotinamide adenine dinucleotide levels were elevated in the dormant myxospore and then declined during germination. The adenylate energy charge value was 0.85 +/- 0.02 for vegetative cells, germinating myxospores, and 6-h-old myxospores. It was interesting that the value for the so-called dormant myxospore was the same as that characteristic of physiologically active cells. The germinating myxospores excreted large quantities of uracil along with lesser quantities of purine nucleoside monophosphates. Although the source of the extracellular uracil cannot be determined from these experiments, it may have been derived from a shift in base ratios accompanying an assumed ribonucleic acid turnover during germination.

Adenine Nucleotides↗

Outcome-based justification for implementing new point-of-care tests: there is no difference between magnesium replacement based on ionized magnesium and total magnesium as a predictor of development of arrhythmias in the postoperative cardiac surgical patient.

OBJECTIVE: To determine whether introducing a new laboratory test, ionized magnesium (iMg++), would affect outcome, where outcome was defined as the rate of arrhythmias in a population of postoperative cardiopulmonary bypass (CPB) patients. DESIGN: A prospective randomized trial. SETTING: Cardiothoracic surgical intensive care unit of a university hospital. PATIENTS: One hundred fifty consecutive post-CPB patients with randomized to two groups, one of which received routine reporting of iMg++ levels on all postoperative electrolyte requests while the other had access to total magnesium (tMg++) levels on demand and no access to iMg++ levels. Groups were compared for rate of arrhythmias, total amount of magnesium repleted, and demographics. MEASUREMENTS AND MAIN RESULTS: Eighty-five patients were randomized to the tMg++ group and 65 to the iMg++ group. The two groups did not differ in the rate of arrhythmias (chi-square test): 13/85 (15%) of the tMg++ patients and 12/65 (18%) of the iMg++ patients developed an arrhythmia. The groups also did not differ in the amount of magnesium sulfate (MgSO4) administered (2 tailed t-test): tMg++ patients received 1.5 +/- 0.15 (SEM) gm of MgSO4, whereas iMg++ patients received 1.3 +/- 0.15 gm. CONCLUSION: The study does not support the hypothesis that magnesium repletion titrated to iMg++ reduces arrhythmia development in post-CPB patients. The lack of a difference in the amount of magnesium replacement between the two groups suggests that tMg++ level is a reasonable indicator of iMg++ level. Routine measurement of iMg++ does not, therefore, appear to have advantages over tMg++ in the postoperative management of CPB patients.

Aged↗