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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 289 records · Page 16Linked to original sources
PubMed1982

Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam.

The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam. beta-Lactamase-containing Escherichia coli resistant to mecillinam was synergistically inhibited by both clavulanic acid and sulbactam. beta-Lactamase-containing Enterobacter was synergistically inhibited, but strains lacking beta-lactamases were not synergistically inhibited. Synergistic inhibition was noted for beta-lactamase-containing, mecillinam-resistant Klebsiella, Citrobacter, Serratia, and Salmonella isolates, but only 18% of beta-lactamase-containing Proteus mirabilis, Providencia rettgeri, Providencia stuartii, and Morganella morganii were synergistically inhibited by the combinations.

Amdinocillin↗
PubMed1982

Synergy of fosmidomycin (FR-31564) and other antimicrobial agents.

Fosmidomycin (FR-31564), a phosphonic acid derivative, was combined with cefazolin, cephalexin, ampicillin, carbenicillin, ticarcillin, gentamicin, and trimethoprim. Synergy between fosmidomycin and penicillins or cephalosporins was found for 37 to 52% of the Enterobacteriaceae tested. Synergy with trimethoprim was found against 55% of bacteria isolated, but only 17% of the strains showed synergy between formidomycin and gentamicin. Synergy between fosmidomycin and ticarcillin was shown for 35% of the Pseudomonas isolates. Cefazolin-, ampicillin-, and gentamicin-resistant isolates of various species were synergistically inhibited by fosmidomycin, as were ticarcillin- and gentamicin-resistant isolates. Antagonism was not encountered. This study illustrates another example of synergistic activity of compounds which attack different mechanisms in bacterial cells.

Anti-Bacterial Agents↗
PubMed1982

Inactivation of digoxin by Eubacterium lentum, an anaerobe of the human gut flora.

Digoxin is converted to cardioinactive reduced metabolites (DRP) in vivo and in vitro by the human gut flora. Digoxin inactivation is mediated by Eubacterium lentum, a normal inhabitant of the gastrointestinal flora. E. lentum appears to be the sole organism performing this reaction. Fecal bacteria that convert digoxin to DRP in vitro have been found to be present in some subjects who fail to make DRP in vivo. DRP-forming E. lentum have been isolated from the stools of two such subjects. When increasing amounts of arginine are supplied as a growth substrate to E. lentum, bacterial growth and DRP production vary inversely. Further study will be required to identify the factors which determine why digoxin is inactivated in vivo by the gut flora of certain patients and not by others.

Adult↗
PubMed1981

The inhibitory quotient. A method for interpreting minimum inhibitory concentration data.

A method for reporting minimum inhibitory concentration (MIC) data that facilitates interpretation by the clinician unfamiliar with clinically achievable drug levels is described. This system uses the inhibitory quotient, which is a number reflecting the multiple of the MIC that would be achieved. Inhibitory quotients are determined for blood, urine, bile, and CSF and reflect achievable drug levels in those body fluids. The use of inhibitory quotients can be extremely helpful to the physician in the rational selection of an appropriate antimicrobial agent.

Aminoglycosides↗
PubMed1981

Use of cefotaxime, a beta-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms.

Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents.

Adult↗
PubMed1981

A review and summary of the pharmacokinetics of cefoperazone: a new, extended-spectrum beta-lactam antibiotic.

Cefoperazone is a new piperazine cephalosporin derivative which has a broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative cocci and bacilli, including Pseudomonas aeruginosa. In studies of the intramuscular (i.m.) administration of cefoperazone at doses of 0.25, 0.5, and 1 g, mean peak serum concentrations were 22, 33, and 67 micrograms/ml at 1 hr. At 8 hr, serum levels were 2.1, 4.8, and 5.6 micrograms/ml, respectively, for the three doses. The mean half-life after intramuscular injection was 108-154 min. Urinary recovery ranged from 14 to 18% of an administered dose. Intravenous (i.v.) administration of cefoperazone by rapid (3-5 min) infusion produced serum levels at 15 min of 76, 156, and 244 micrograms/ml after doses of 0.5, 1, and 2 g, respectively. Concentrations of cefoperazone at 8 hr were 2.4, 6.5, and 11.8 micrograms/ml after these respective doses. Serum half-life was 115-120 min and urinary recovery, 29-33%. Levels determined at 5 min after bolus injection were 200 micrograms/ml for 1 g, 275 micrograms/ml for 2 g and 518 micrograms/ml for 3 g. Intravenous infusion studies of cefoperazone in which 2 g of the drug has been infused over 15, 30, or 120 min have yielded levels of 250-260 micrograms/ml. At 12 hr, levels of 1-2 micrograms/ml were still present. The half-life found in these studies ranged from 1.6 to 2.38 hr. Urinary recovery was 25-30%. Serum clearances have been 80-90 ml/min and renal clearances, 18-30 ml/min. The apparent volume of distribution of the compound has ranged from 10 to 16 liters. Comparative studies have shown that cefoperazone produced higher serum levels than cefazolin, cefamandole, cefotaxime, and moxalactam. Biliary concentrations exceed 400 micrograms/ml and are two to four times the levels found with cefazolin or cefamandole. In the presence of renal failure there is a minimal increase in serum half-life; but in the presence of biliary obstruction, serum half-life may reach 11 hr, depending on the degree of biliary obstruction. In the presence of biliary obstruction, the drug is 90% removed from the body by renal excretion.

Cefoperazone↗
PubMed1981

Comparative pharmacokinetics of cefoperazone and cefamandole.

The pharmacokinetics of cefoperazone, a new beta-lactam antibiotic, were studied in normal volunteers and compared with the pharmacokinetics of cefamandole. After a 30-min infusion of 2 g of cefoperazone, the mean serum level was 256 micrograms/ml; at 4 h, the serum level was 20 micrograms/ml, and at 24 h, the level was 1.25 micrograms/ml, compared with levels of cefamandole of 188 micrograms/ml at the end of infusion, 1.8 micrograms/ml at 4 h, and none detected thereafter. The mean half-life of cefoperazone was 1.6 h, compared with 0.7 h for cefamandole. The area under the curve was 356 micrograms/ml per h for cefoperazone, which was three times that for cefamandole. The apparent volume of distribution for cefoperazone was 9.9 liters/1.73 m2 compared with 12.5 liters/1.73 m2 for cefamandole. Serum clearance of cefoperazone was 85 ml/min, and renal clearance was 25 ml/min, compared with a serum clearance of 224 ml/min and a renal clearance of 213 ml/min for cefamandole. Urine levels exceeded 25 micrograms/ml in the first 8 h after injection. Renal recovery of cefoperazone was only 29%.

Adult↗
PubMed1981

Pharmacokinetics of moxalactam and cefazolin compared in normal volunteers.

The pharmacokinetics of moxalactam, a new beta-lactam antibiotic with an unusually broad spectrum of activity, were studied in normal volunteers and compared with the pharmacokinetics of cefazolin. After a 1,000-mg intramuscular injection of moxalactam, a mean peak serum level of 49 +/- 10 micrograms/ml was achieved at 30 to 60 min which was equivalent to the level achieved with 0.5 g of cefazolin. Serum levels of 4.57 +/- 0.63 micrograms/ml, above the inhibitory levels for most organisms, were present at 8 h. The half-life of moxalactam was 2.3 h. After a 30-min intravenous infusion of 1 g, the serum level of moxalactam was 60 +/- 18.8 micrograms/ml. This compares with a serum level of 70 micrograms/ml obtained with an infusion of 0.5 g of cefazolin. At 6 h, 3.59 +/- 0.68 microgram/ml of moxalactam was present. The half-life of moxalactam was 2.3 h, similar to that of cefazolin. By 1 h after administration, serum levels of moxalactam were higher after intramuscular administration than after intravenous delivery. Urinary recovery of the drug was 76% after intramuscular injection and 74% after intravenous infusion, with the majority of the drug having been excreted in the first 4 h after administration. Urinary recovery of cefazolin was 85%. The pharmacokinetics of moxalactam are similar to those of cefazolin.

Adult↗
PubMed1981

Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase-stable cephalosporin.

The in vitro activity of ceftriaxone (Ro 13-9904), a parenteral cephalosporin, was compared with that of other beta-lactam antibiotics. the compound was less active against Staphylococcus aureus and Staphylococcus epidermidis than was cephalothin or cefamandole, but it was comparable to cefoxitin, cefotaxime, and moxalactam in inhibiting most isolates of S. aureus at 3.1 microgram/ml. Ro 13-9904 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at concentrations below 0.25 microgram/ml, but Streptococcus faecalis required concentrations above 25 microgram/ml. Neisseria gonorrhoeae and Haemophilus influenzae were inhibited at concentrations similar to those of cefotaxime, less than 0.1 microgram/ml. Ro 13-9904 was as active as cefotaxime and moxalactam against most Enterobacteriaceae and was the most active agent tested against Proteus, inhibiting all strains tested at 0.006 microgram/ml. Ro 13-9904 was slightly less active than moxalactam or cefoxitin against Bacteroides fragilis, requiring more than 100 microgram/ml to inhibit 90% of isolates, and it was less active than cefoperazone against Pseudomonas aeruginosa. Presence of serum, alteration of pH, and use of various media did not change the inhibitory levels. Bactericidal concentrations were similar to inhibitory levels. Ro 13-9904 was stable to most plasmid-mediated beta-lactamases, but was hydrolyzed by some Enterobacter, Proteus, and Bacteroides beta-lactamases of chromosomal origin.

Bacteria↗
PubMed1981

In vitro and in vivo antibacterial activity of FR-31564, a phosphonic acid antimicrobial agent.

The in vitro and in vivo activity of FR-31564 [sodium hydrogen 3-(N-hydroxyformamido)propylphosphate] against gram-positive and -negative aerobic and anaerobic bacteria was investigated and compared with that of fosfomycin, cephalexin, carbenicillin, and trimethoprim-sulfamethoxazole. The in vitro activity of FR-31564 was markedly enhanced when combined with glucose 6-phosphate or fructose 6-phosphate, but not when combined with ribose phosphate, adenosine monophosphate, or glycerol phosphate. In vitro activity of FR-31564 also was enhanced by human or horse blood, but not by human serum. The type of medium had a great effect on the minimal inhibitory concentration, with the lowest minimal inhibitory concentrations achieved on nutrient agar, 8- to 16-fold less than with Mueller-Hinton, heart infusion, or Trypticase soy agars. FR-31564 was more active than fosfomycin, cephalexin, carbenicillin, or trimethoprimsulfamethoxazole against Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, E. aerogenes, and Citrobacter. It was less active than fosfomycin against Serratia marcescens and Proteus mirabilis and did not inhibit gram-positive cocci or anaerobic species. FR-31564 inhibited a number of E. coli, K. pneumoniae, and some Pseudomonas aeruginosa strains resistant to the other agents. In the presence and absence of human blood FR-31564 showed bactericidal activity, and P. aeruginosa exposed to FR-31564 for 3 h showed a 6-h lag in regrowth. FR-31564 administered by the subcutaneous route was more active in protecting mice challenged with P. aeruginosa than was fosfomycin, carbenicillin, or cefoperazone. It was as active by the oral route in protecting mice challenged with E. coli as was fosfomycin, ampicillin, cephalexin, or trimethoprimsulfamethoxazole.

Animals↗