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K E Price

Publications and source records attributed to K E Price.

At least 37 records · Page 2Linked to original sources
PubMed1974

Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics.

One hundred fifty-two bacterial strains that possess resistance to kanamycin A, gentamicin, or tobramycin, or to more than one of these antibiotics, were collected from various sources in Canada, Europe, Japan, and the United States. This collection was composed of Staphylococcus aureus and Pseudomonas aeruginosa and members of the Enterobacteriaceae family. Their susceptibility to BB-K8 (amikacin), a new broad-spectrum semisynthetic derivative of kanamycin A, and to the other agents, was determined on Mueller-Hinton Medium by the twofold agar dilution method. Test results revealed that 60.5% of the isolates were resistant to 8 mug of tobramycin per ml, 67.1% to 8 mug of gentamicin per ml, 86.2% to 20 mug of kanamycin A per ml, and only 8.6% to 20 mug of amikacin per ml. Of interest is the fact that the amikacin-resistant strains were generally resistant to all of the other aminoglycosides. The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through O-phosphorylation, O-adenylylation, or N-acetylation. A number of susceptibility profiles were obtained when the organisms were tested against a series of nine aminoglycosides. The majority of these profiles resembled those found for organisms that possess known mechanisms of enzymatic inactivation.

Aminobutyrates↗
PubMed1973

Effect of assay medium on the antibacterial activity of certain penicillins and cephalosporins.

It is well known that the composition of the assay medium greatly affects the antimicrobial activity of aminoglycoside antibiotics. A similar response has now been observed with certain penicillins and cephalosporins. In the case of these compounds, this effect is apparently governed by the chemical nature of the penicillin 6- and cephalosporin 7-side chains. In comparison with their activity in Nutrient Broth, the activity of some of the beta-lactam antibiotics that have a weakly basic or basic group in their side chain was reduced as much as 40-fold in one or more of the following media: Mueller-Hinton, Trypticase soy, antibiotic assay, and heart infusion broths. In contrast, the assay medium had no effect on the activity of those compounds possessing an acidic or a nonionizable function in their side chain. The extent to which medium influences the antibacterial activity was also dependent upon the assay method and the organism, the effect being more pronounced in broth dilution than in agar dilution tests and occurring more frequently with gram-negative than with gram-positive organisms.

Cephalosporins↗
PubMed1973

Microbiological properties of a new cephalosporin, BL-S 339: 7-(phenylacetimidoyl-aminoacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-ylthiomethyl)ceph-3-em-4-carboxylic acid.

BL-S 339 is a new broad-spectrum, parenterally effective cephalosporin whose expression of antibacterial activity in vitro is markedly affected by the nature of the assay medium. When assayed in nutrient agar, BL-S 339 was more active than cephalothin against strains of Diplococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter, and indole-positive Proteus sp. However, when assayed in Mueller-Hinton medium, its activity, especially against gram-negative bacteria, was reduced substantially, whereas the activity of cephalothin was virtually unaffected by the assay medium. The in vivo activity of BL-S 339 correlated well with its activity in nutrient agar; when administered subcutaneously to mice, it was therapeutically more efficacious than cephalothin in infections caused by both gram-positive and gram-negative bacteria. When BL-S 339 was administered intramuscularly to mice, the concentrations achieved in the blood were three times those achieved with cephalothin. BL-S 339 was bound to human serum proteins to the same extent as cephalothin. Recovery of BL-S 339 in the urine within the 24-hr period after intramuscular administration to rats was three times that of cephalothin.

Animals↗
PubMed1973

BL-20803, a new, low-molecular-weight interferon inducer.

BL-20803 induced interferon in mice when administered via oral or parenteral routes. During multiple dosing with the drug at 48-h intervals, animals exhibited a hyporesponsive state to the third treatment. Inhibition of vaccinia virus infection was correlated with interferon induction.

Animals↗
PubMed1972

Structure-activity relationships among a group of 7-(alpha-(N,N'-substituted-amidinothio)-acetamido) cephalosphoranic acids.

Structure-activity relationships were examined for a number of 7-[alpha-(N,N'-substituted-amidinothio)-acetamido] cephalosporanic acids, including several wherein the amidino group was cyclized into six, seven, and eight-membered rings and a series wherein alkyl, cycloalkyl, alkenyl, and alkynyl radicals were substituted on the nitrogens of the noncyclized amidino group. Derivatives containing an unsubstituted cyclized amidino group had comparable antibacterial activity in vitro and in general had a spectrum of activity broader than that of cephalothin, especially against cephalothin-resistant strains of Escherichia, Klebsiella, and Proteus. When administered parenterally, the cephalosporin with the six-membered cyclized amidino group was as effective as cephalothin in experimental infections of mice produced by cephalothin-sensitive gram-negative organisms and more efficacious in infections caused by cephalothin-resistant strains. Among the cephalosporins with noncyclized amidino groups, those with an ethyl substituent on one of the nitrogens and a C(2)-C(4) alkyl radical, particularly propyl on the other, were the most active. They not only had a better profile of activity in vitro than cephalothin and the cephalosporin derivatives having a cyclized amidino group, but were also more efficacious in infections of mice.

Acetamides↗
PubMed1972

7-(Alpha-(1-methyl-4-pyridinothio)-acetamido) cephalosporanic acid.

7-[alpha-(1-Methyl-4-pyridiniothio)-acetamido] cephalosporanic acid, referred to herein as BL-S 217, is a new broad-spectrum semisynthetic cephalosporin that offers several advantages over cephalothin. A comparison of the activity in vitro of these antibiotics indicates that BL-S 217 is about eightfold more effective against Streptococcus pyogenes and Diplococcus pneumoniae. Against gram-negative bacteria, BL-S 217 possesses a broader antibacterial spectrum than cephalothin, particularly against members of the Enterobacteriaceae family; e.g., BL-S 217 inhibited over 20% more strains of both Escherichia coli and Klebsiella than cephalothin and also showed some advantage in tests against Salmonella and Enterobacter. Overall, of 208 strains of Enterobacteriaceae tested, 172 were susceptible to BL-S 217 compared to 149 for cephalothin. BL-S 217 was less bound to human serum proteins than cephalothin and gave higher peak blood levels in mice after intramuscular administration. The LD(50) of BL-S 217 in mice after subcutaneous administration was in excess of 4,000 mg/kg. When administered by the same route to mice experimentally infected with cephalothin-sensitive bacterial strains, this new cephalosporin was 20 times more effective than cephalothin in S. pyogenes and D. pneumoniae infections and 3 to 4 times more efficacious in an E. coli infection. Its therapeutic efficacy was comparable to that of cephalothin in infections produced by strains of Staphylococcus aureus, Klebsiella pneumoniae, and Proteus mirabilis.

Acetamides↗
PubMed1970

Semisynthetic coumermycins: structure-activity relationships.

The relative antimicrobial activity of a large series of semisynthetic coumermycins has been determined. Most of the derivatives, which were 3-substituted-4-hydroxy-8-methyl-7-[3-O-(5-methyl-2-pyrrolylcarbonyl) noviosyloxy] coumarins, had an in vitro antibacterial spectrum similar to that of the parent compound, coumermycin A(1), but were generally less potent in minimal inhibitory concentration (MIC) tests. Derivatives with an alkylcarboxamido, arylcarboxamido, or arylsulfonamido group in the 3 position had considerably greater in vitro activity than those possessing an amino-, aryl-, or alkyureido substituent. Efficacy in Staphylcoccous aureus Smith infections of mice was greater for those compounds with branched-chain alkylcarboxamido, unsubstituted, mono- or disubstituted aryl- and heteroaryl-carboxamido groups than for derivatives having an n-alkylcarboxamido, aralkyl-carboxamido, arylsulfonamido, or trisubstituted arylcarboxamido substituent. Significant in vitro activity against Klebsiella pneumoniae and other gram-negative species was restricted to those compounds having a 3-(3-n-alkyl-4-hydroxy-phenyl-carboxamido) group. Only the n-hexyl homologue demonstrated in vivo activity in a K. pneumoniae infection. Many derivatives were two- to threefold more active than coumermycin A(1) in orally treated mouse infections, despite the fact that their MIC values were considerably higher. This result was undoubtedly a reflection of the markedly greater oral absorbability possessed by many of the derivatives. Although peak oral mouse blood levels of some compounds were > 25 times higher than those of coumermycin A(1), their toxicity for the host was no greater. In addition, the semisynthetic coumermycins caused much less local irritation than coumermycin A(1) when administered parenterally.

Animals↗
PubMed1969

Antipseudomonal activity of alpha-sulfoaminopenicillins.

A series of penicillins characterized by the presence of a sulfoamino or a modified sulfoamino group in the side chain was subjected to in vitro antimicrobial screening tests. Although the most potent members of the series were less active than benzylpenicillin against gram-positive bacteria and comparably active against most gram-negative bacteria, they were, on the average, 8 to 16 times more effective against strains of Pseudomonas aeruginosa. In other comparative laboratory tests against P. aeruginosa, these compounds were about as active as carbenicillin and four to eight times more active than ampicillin. An examination of structure-activity relationships indicated that maximal potency was obtained with penicillins having an alpha-(aromatic or heteroaromatic)-alpha-sulfoaminoacetamido side chain. The compound with an alpha-phenyl group was comparable in activity to those having an alpha-(2- or 3-thienyl) group, whereas any modification in position or structure of the alpha-sulfoamino group reduced activity. Results of studies with a cell-free P. aeruginosa beta-lactamase suggest that the marked inhibitory effects of alpha-sulfoamino penicillins for P. aeruginosa can be attributed, at least in part, to their high degree of resistance to this enzyme. Some derivatives, however, had weak antipseudomonal activity, despite possessing a high degree of beta-lactamase resistance.

Ampicillin↗