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D A Preston

Publications and source records attributed to D A Preston.

50 records · Page 3Linked to original sources

Delineation of the relative antibacterial activity of cefamandole and cefamandole nafate.

By conventional laboratory evaluation procedures, the in vitro antibacterial activities of cefamandole and its O-formyl ester, cefamandole nafate, appear virtually identical. When the activities of these two compounds were examined for their ability to lyse log-phase cultures of susceptible bacteria, however, cefamandole was found to be about 10 times more active than cefamandole nafate. Cefamandole nafate was shown to be rapidly converted to cefamandole in bacteriological media, with a half-life of less than 1 h at a pH of 7.0 or above. At pH 6.0, in log-phase inhibition experiments, however, cefamandole nafate is more stable, allowing delineation of the activity between cefamandole and cefamandole nafate. The efficacy of cefamandole was identical to that of cefamandole nafate in treating experimental animal infections, indicating that rapid conversion of cefamandole nafate to cefamandole occurs in vivo.

Animals↗

Evaluation of antibiotic efficacy using electron microscopy: morphological effects of guanylureido cephalosporin, chlorobenzoylureido cephalosporin, BL-P1654, and carbenicillin on Pseudomonas aeruginosa.

The response of Pseudomonas aeruginosa to carbenicillin, BL-P1654, and two cephalosporins (112384 and 112883) was evaluated by minimal inhibitory concentration determinations, [(14)C]leucine uptake studies, morphological studies of colonial growth, and mouse intraperitoneal inoculations. Spheroplast formation and bacterial lysis were not the early response; instead, cell division was inhibited and long filaments were formed. Spheroplast formation and bacterial lysis were not observed in the first 7 h of incubation in minimal inhibitory concentrations of antibiotic.

Animals↗

Evaluation of antibiotic efficacy using electron microscopy: morphological effects of guanylureido cephalosporin, BL-P1654, and carbenicillin on Escherichia coli.

Early response of Escherichia coli to minimal inhibitory concentrations of 112883, BL-P1654, and carbenicillin was determined by [(14)C]leucine uptake and scanning electron microscopy morphology studies. [(14)C]leucine uptake was inhibited later by carbenicillin than by BL-P1654 or 112883. Cellular swelling at 30 min, septal region swelling, and lysis were the progressive morphological changes with BL-P1654 and 112883. Carbenicillin-treated cells showed septal region swelling, beaded chains, and lysis.

Carbenicillin↗

Rapid detection of ampicillin-resistant Haemophilus influenzae and their susceptibility to sixteen antibiotics.

Ampicillin-resistant and -susceptible strains of Haemophilus influenzae were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 mug/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of H. influenzae were less susceptible (MIC, 4 to 32 mug/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 mug/ml). A rapid assay for beta-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of H. influenzae.

Ampicillin↗

New synthetic antibacterial compound, 1-(2-hydroxyethyl)-3-nitro-4-pyrazole carboxamide.

A series of 3-nitropyrazole compounds represent a new class of synthetic antibacterial agents. One member of this series, 1-(2-hydroxyethyl)-3-nitro-4-pyrazolecarboxamide, exhibited an antibacterial spectrum similar to that of nitrofurantoin. The inhibitory concentrations of this nitropyrazole were lower than those required for nitrofurantoin. Single oral doses of 20 mg/kg resulted in peak nitropyrazole concentrations of 5.8 and >1,000 mug/ml in mouse blood and urine, respectively. In dogs, 87% of a 10 mg/kg oral dose was recovered in urine during a 24-h period with a peak serum concentration of 13.6 mug/ml. This nitropyrazole was highly effective against experimental bacterial infections in mice. The low acute toxicity in mice, rats, or dogs and significant antibacterial activity lead to the conclusion that further evaluation of this compound is warranted.

Amides↗

Compound 64716, a new synthetic antibacterial agent.

Compound 64716, 1-ethyl-4 (1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, is a new synthetic antibacterial agent. The antibacterial spectrum of this compound includes gram-negative bacteria that are most frequently isolated from urinary tract infections. Minimal inhibitory concentration values of 64716 for isolates of Escherichia coli and Proteus sp. ranged from 2 to 4 and 2 to 8 mug/ml, respectively, and the compound was bactericidal at concentrations close to the minimal inhibitory concentration values. In vivo, doses required for successful therapy of experimental mouse infections were comparable to those for nalidixic acid. After oral administration of 40 mg/kg, peak concentrations of this compound in mouse blood reached 19.2 mug/ml. Within 30 min after doses of 20 mg/kg, bacteriologically active drug concentrations of 64716, nalidixic acid, and oxolinic acid in mouse urine were >1,000, 170, and <1.5 mug/ml, respectively. Resistant bacteria were not selected when bacteria were exposed to 500 mug/ml of 64716. Compound 64716 was less bound by human serum proteins than was nalidixic acid. Equivalent antibacterial activity along with superior pharmacological properties of 64716 when compared with nalidixic acid lead to the conclusion that this new compound is a promising antibacterial agent.

Animals↗

Biological properties of three 3-heterocyclic-thiomethyl cephalosporin antibiotics.

Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties. All three compounds are active in vitro against a variety of gram-positive and gram-negative bacteria. Minimal inhibitory concentrations (MIC) of these bactericidal antibiotics were not significantly affected by changes in pH or NaCl content of nutrient broth, or by the use of different inoculum sizes. However, agar-dilution MIC values were generally two- to fourfold lower than the MIC values in comparable broth-dilution tests. Stability to cephalosporinase by two of the compounds extended their antibacterial spectra over cephalothin and cephaloridine to include strains of Enterobacter sp. and indole-positive Proteus sp. Binding to serum proteins of the new cephalosporins was intermediate between cephalothin and cephaloridine. Excellent concentrations of the antibiotics were attained in mouse blood, after subcutaneous administration of 20 mg per kg. In vitro biological characteristics of the antibiotics were verified by successful therapy of experimental mouse infections. Regression lines were calculated to show the correlation of agar-dilution MIC values with zones of inhibition by the disc testing procedure. Because each of the three new cephalosporins has certain advantageous properties over cephalothin and cephaloridine, additional toxicological and pharmacological data should be obtained for all three compounds.

Amidohydrolases↗

Specific assay of aminoglycosidic- or polymyxin-type antibiotics present in human sera in combination with cephalosporins.

Monitoring of serum concentrations of aminoglycosidic or polymyxin antibiotics when administered concurrently with cephalosporins or penicillins requires a special assay technique. Selective enzymatic degradation of the beta-lactam antibiotic from the serum specimen allows subsequent assay of the antibiotic being monitored. This report gives details of a simple procedure for laboratory production of a crude enzyme capable of degrading cephalosporins or penicillins. An assay procedure for quantitating aminoglycosidic or polymyxin antibiotics after enzymatic degradation of a coexisting beta-lactam antibiotic is described.

Amidohydrolases↗

Differences among moxalactam, cefoperazone, and cefotaxime in activity against multiple-antibiotic-resistant gram-negative bacteria.

In vitro evaluations have shown that moxalactam, cefoperazone, and cefotaxime, three new beta-lactam antibiotics, have certain potency and antibacterial spectral characteristics in common. Results of parallel tests of these antibiotics against routine clinical isolates have suggested that these compounds could be tested with one disk that is representative of this spectral class. The key requirement for this class concept in disk testing is that there be no bacterial resistance mechanism that can operate against one, but not all, members of the proposed class. The results of an 11-center study of approximately 500 isolates of multiple-antibiotic-resistant Enterobacteriaceae responsible for nosocomial infections illustrated that cross-resistance to moxalactam, cefoperazone, and cefotaxime is highly variable from center to center. Thus, the spectral class concept of disk susceptibility testing would be inappropriate for this group of drugs.

Bacteria↗

Microbiological aspects of erythromycin.

Almost 35 years after its discovery, erythromycin remains highly active against most strains of a broad array of clinically important organisms. Many strains of Gram-positive and Gram-negative aerobic, facultative and anaerobic bacteria, as well as Mycoplasma, treponemes and Chlamydia, are susceptible to this agent. Erythromycin acts by binding to the ribosomes of the target organisms, thereby inhibiting protein synthesis. Although a pharmacokinetically superior erythromycin estolate has been shown to be a less potent antibiotic prior to hydrolysis, it appears to contribute significantly to the therapeutic response following administration of erythromycin estolate. Clinical laboratory susceptibility testing or erythromycin may be done using standardized methods, but the laboratorian is cautioned to remember the adverse effect of acidic test conditions on the apparent activity of this antibiotic.

DNA Transposable Elements↗

Global surveillance of bacterial susceptibility to cefaclor: 1988-1990.

In vitro data on bacterial susceptibility to cefaclor were collected from clinical trials conducted in 15 European countries, South Africa, Canada, and the United States. Among the respiratory pathogens, 94% of Haemophilus influenzae, 98.6% of Streptococcus pneumoniae, 98.8% of Streptococcus pyogenes, and 98.1% of Moraxella catarrhalis were susceptible to cefaclor. Over 90% of the tested isolates of the most common urinary tract pathogen, Escherichia coli, were susceptible to cefaclor. Virtually all of the pathogens that may infect skin and soft tissues, S pyogenes and Staphylococcus aureus (methicillin-susceptible strains), were cefaclor susceptible. These data confirm that the major pathogens in bacterial infections of the upper and lower respiratory tract, of the skin and related structures, and of the urinary tract remain susceptible to cefaclor after more than 13 years of widespread clinical use.

Bacteria↗