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Biomedical subjects

R S Hare

Publications and source records attributed to R S Hare.

49 records · Page 3Linked to original sources
PubMed1986

Effect of NaCl supplementation of Mueller-Hinton broth on susceptibility of staphylococci to aminoglycosides.

The addition of NaCl to cation-supplemented Mueller-Hinton broth increased the MICs of gentamicin, amikacin, and netilmicin for coagulase-positive and -negative staphylococci in a concentration-dependent manner. At 2% NaCl, geometric mean MICs were elevated 14.1- to 25.6-fold. Mueller-Hinton broth containing added NaCl should not be used for testing the susceptibility of staphylococci to aminoglycosides.

Amikacin↗
PubMed1985

Evaluation of the in-vivo efficacy of Sch 34343.

Sch 34343 showed a linear dose response (with respect to AUCs) in mice following both intravenous and subcutaneous administration. It was 100% bioavailable following subcutaneous administration. Peak serum levels, AUCs, beta-phase half-life and recovery of Sch 34343 from the urine of mice indicated that it was similar to cephalothin and cefamandole. In experimental mouse infections, against Gram-negative strains, Sch 34343 was more active than cephalothin, equal to or more active than cefamandole and cefoxitin, but less active than latamoxef (moxalactam) and cefotaxime following single or multiple dose therapy. It was the most active compound against Staphylococcus. Sch 34343 was equally active against strains sensitive to beta-lactams and strains producing beta-lactamases. In an anaerobic abscess model in mice, Sch 34343 was more active than cefoxitin and clindamycin against Bacteroides fragilis. In Escherichia coli meningitis in rabbits, it cured rabbits with a single intravenous dose of 50 mg/kg.

Animals↗
PubMed1985

In-vitro activity of Sch 34343 against Gram-negative bacteria producing characterized beta-lactamases.

The activity of Sch 34343 against 13 strains producing large amounts of characterized beta-lactamases was compared with that of imipenem, latamoxef (moxalactam), aztreonam and other third-generation cephalosporins. Sch 34343, like imipenem, was active against all strains, including many resistant to all other beta-lactams. MICs of Sch 34343 determined for 16 different inocula were rarely increased even at very high inocula. Sch 34343 was rapidly bactericidal against Escherichia coli TEM-2, Enterobacter agglomerans (with an induced beta-lactamase) and two strains of Bacteroides fragilis with highly active cephalosporinases. Like cefoxitin, Sch 34343 was only slowly inactivated by concentrated crude penicillinases which inactivated cefotaxime within 1 h. Sch 34343 was even more stable to cephalosporinases than was cefoxitin. Stability of the antibiotics to the different beta-lactamases was also determined by pre-incubating them with dilutions of the beta-lactamases before determination of MICs against E. coli 25922. Very large amounts of all enzymes were required to increase the MICs significantly for Sch 34343 and imipenem. These results indicate the good stability of Sch 34343 to beta-lactamases.

Anti-Bacterial Agents↗
PubMed1985

Comparison of aminoglycoside resistance patterns in Japan, Formosa, and Korea, Chile, and the United States.

The resistance mechanisms of more than 2,000 aminoglycoside-resistant gram-negative aerobic bacteria were estimated by a method that assigned a biochemical mechanism based on susceptibility to selected aminoglycosides. Strains from hospitals in Japan, Formosa, and Korea (the Far East) were compared with strains from Chile and the United States. Of the strains from Chile, 90% had an aminoglycoside resistance pattern indicative of the 3-N-acetyltransferase [AAC(3)-V] enzyme. Of the strains from the Far East, 78% had susceptibility patterns suggesting the presence of AAC(6') enzymes. In contrast, strains from the United States had a wider variety of resistance mechanisms including 2''-O-adenylyltidyltransferase [ANT(2'')], AAC(3), AAC(6'), and AAC(2'). Reflecting these differences in resistance patterns, the frequencies of resistance to gentamicin, tobramycin, dibekacin, and amikacin in strains from the United States were different from those in strains from the Far East. These differences seem to be correlated with different aminoglycoside usage in the two regions. In the United States, where gentamicin was the most widely used aminoglycoside, 92% of the strains were resistant to gentamicin, 81% were resistant to dibekacin, and 8.8% were resistant to amikacin. In the Far East, dibekacin and kanamycin were widely used in the past and more recently amikacin has been frequently used. Of the strains from this region, 99% were resistant to dibekacin, 85% were resistant to gentamicin, and 35% were resistant to amikacin.

Aminoglycosides↗
PubMed1984

Modification of interpretive breakpoints for netilmicin disk susceptibility tests with Pseudomonas aeruginosa.

Regression analysis of data correlating 30-micrograms netilmicin disk zone diameters with microdilution MICs, obtained by testing close-interval dilution steps, was performed with 77 selected strains of Pseudomonas aeruginosa, each tested in three independent laboratories. A zone of greater than or equal to 15 mm correlated with an MIC of less than or equal to 12 micrograms/ml (susceptible), and a zone of less than or equal to 12 mm correlated with an MIC of greater than 16 micrograms/ml (resistant). Additional disk tests were performed with 256 strains having known resistance mechanisms and 280 susceptible strains: the majority were appropriately categorized by these interpretive zone standards. The previously recommended standards of greater than or equal to 17 mm (MIC, less than or equal to 8.0 micrograms/ml) for the susceptible category inappropriately placed a significant number of truly susceptible P. aeruginosa strains in the intermediate category.

Drug Resistance, Microbial↗
PubMed1980

Evaluation of netilmicin susceptibility discs using bacteria with known aminoglycoside resistance patterns: correlation of in vitro and in vivo test results.

Data obtained with 30 micrograms netilmicin discs on Mueller-Hinton agar have been compared to MIC values obtained in Mueller-Hinton broth. Regression analysis was used to determine susceptibility cutoff points for Pseudomonas and non-Pseudomonas gram-negatives. The utility of these cutoff points for the determination of netilmicin sensitivity was evaluated in tests with 1405 clinical isolates. These tests employed 897 sensitive isolates and 508 strains with known aminoglycoside resistance patterns. Netilmicin was shown to be active against sensitive isolates and those strains with resistance patterns corresponding to the presence of: ANT(2"), ANT(2")+AAC(6'), ANT(4'), APH(2")+AAC(6'), APH(3')-IV and AAC(3)-I modifying enzymes. PD50 values obtained in experimental mouse infection studies with gentamicin, tobramycin and amikacin as well as netilmicin confirmed the excellent activity of netilmicin against strains with the above-mentioned resistance patterns. The good correlation between disc sensitivity test results and MIC and PD50 values suggest that a 30 micrograms netilmicin disc can be used to predict the netilmicin susceptibility of clinical isolates.

Aminoglycosides↗
PubMed1977

Characteristics of a cytochrome P-450-dependent fatty acid omega-2 hydroxylase from bacillus megaterium.

The fatty acid (omega-2) hydroxylase from Bacillus megaterium ATCC 14581 was examined with respect to some general enzymatic properties attributed to an intact complex isolated in a partially purified state. Hydroxylase specific activity was found to increase with increasing protein concentration in a manner consistent with a reversible association of the components in the complex. There was a substantial kinetic lag phase for palmitate hydroxylation which was abolished by a substrate preincubation in the absence of NADPH. The substrate bound and presumably activated the hydroxylase complex without the formation of a substrate-derived intermediated. The oxidation of NADPH and the hydroxylation of palmitate were found to occur in a one to one molar ration, independent of the protein concentration. Finally, a cytochrome P-450 component of the complex was identified on the basis of its CO-binding difference spectrum. It appears, that this cytochrome P-450 component is not identical to P-450 meg of the steroid hydroxylase system of B. megaterium ATCC 13368, since progesterone, an active substrate for the latter, is not hydroxylated by the preparation from B. megaterium ATCC 14581.

Bacillus megaterium↗