Search PubMed⌕ Search

Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 361 records · Page 20Linked to original sources

The comparative beta-lactamase resistance and inhibitory activity of 1-oxa cephalosporin, cefoxitin and cefotaxime.

The beta-lactamase stability and inhibitory activity of 1-oxa cephalosporin, (6R,7R)-7-[[carboxy(4-hydroxyphenyl)acetyl]amino]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, was investigated and compared to that of cefoxitin and cefotaxime. There was no detectable beta-lactamase hydrolysis of 1-oxa cephalosporin, cefotaxime and cefoxitin when incubated with beta-lactamases of plasmid or chromosomal origin which were primarily cephalosporinases or enzymes which hydrolyzed both penicillins and cephalosporins. The beta-lactamase inhibitory activity of 1-oxa cephalosporin was comparable to that of cefoxitin and cefotaxime. At equal molar concentration of substrate and inhibitor, cefoxitin, cefotaxime and 1-oxa cephalosporin effectively inhibited cephalosporinase hydrolysis of cephaloridine. Cefoxitin and cefotaxime were more effective inhibitors than the 1-oxa cephalosporin against a Providencia enzyme, whereas cefotaxime and 1-oxa cephalosporin were more effective inhibitors of a Citrobacter cephalosporinase.

Bacteria↗

Diagnosis and treatment: drugs five years later. Amoxicillin.

Amoxicillin is an aminopenicillin available in the United States only for oral use. It has an antibacterial activity and spectrum similar to that of ampicillin and is destroyed by gram-positive and gram-negative beta-lactamases. It is more active against enterococci and salmonellae than ampicillin, but less active against Shigella. It is better absorbed than ampicillin from the gastrointestinal tract with blood levels two to two and one half times those of ampicillin. Amoxicillin is an excellent agent to treat otitis media, bacterial sinusitis, bacterial exacerbations of bronchitis, acute lower-urinary-tract infections, gonorrhea, and typhoid. In special settings it may be useful as oral therapy of endocarditis, septic arthritis, and osteomyelitis and as prophylaxis to prevent endocarditis. When the cost of amoxicillin approaches that of ampicillin, it should replace that agent as the oral aminopenicillin of first choice.

Amoxicillin↗

Kinetics of netilmicin and gentamicin.

The kinetic parameters of netilmicin were studied in normal human subjects. In the intravenous study a steady-state was obtained in 4 subjects by the constant infusion of 2 mg/kg of netilmicin during the first hour followed by 0.5 mg/kg/hr for each of three successive hours. Creatinine clearance was greater than the simultaneous serum and renal clearance of netilmicin. In the intramuscular study 6 subjects received a single injection of 1 mg/kg of netilmicin followed by the same dose of gentamicin 1 wk later. A mean peak serum levels of 3.9 microgram/ml was found for both antibiotics, but the mean serum half-life of netilmicin was shorter than that of gentamicin. Doubling the intramuscular dose of netilmicin approximately doubled the peak serum level. In both studies 75% to 90% of the netilmicin was recovered in the urine within the first 24 hr. Netilmicin appears to be primarily excreted by glomerular filtration. The apparent volume of distribution was similar to that reported for other related aminoglycosides. Netilmicin and gentamicin have similar kinetic parameters. There were wide individual differences among normal subjects with both drugs.

Female↗

Kinetics of mezlocillin and carbenicillin.

The kinetics of mezlocillin, a semisynthetic acylureido penicillin, more active than carbenicillin against many gram-negative bacteria, were compared with those of carbenicillin. Following an intravenous infusion of 4 gm in 5 min to 8 normal men there was an average serum level of 294 microgram/ml for mezlocillin and 365 microgram/ml for carbenicillin. The t1/2 for mezlocillin was 47 min and that for carbencillin was 70 min. The apparent volume of distribution was 13.4 L for mezlocillin and 14.4 L for carbenicillin. The mean urinary recovery of mezlocillin was 72% and that for carbenicillin was 92%. Constant infusion of 5 mg of mezlocillin over 2 hr gave steady-state levels of 234 microgram/ml. Half-life, apparent volume of distribution, and serum and renal clearance of mezlocillin after constant infusion were in the same range as those after rapid infusion.

Adult↗

The epidemiology of hepatitis B infection in housestaff.

Ninety-nine medical and surgical house officers were prospectively evaluated during internship and residency for the development of hepatitis B virus (HBV) infection. The overall incidence of hepatitis B was 10.2% per year. Eighty-six percent of episodes were subclinical. The greatest risk factor appeared to be frequent hand-to-mouth activity such as smoking or licking requisition labels. The presence of a hemodialysis or transplantation unit may be an additional institutional risk factor. HBV infection was not associated with a history of needle-sticks or contact with known antigen-positive patients. Educational efforts to minimize HBV infection should concentrate on handwashing techniques and discouragement of hand-to-mouth activity in patient care areas.

Habits↗

Therapy of serious infections with cefamandole.

Forty-four patients with serious bacterial infections were treated with cefamandole in a dose 1--2 g every four to six hours. Thirty-two patients were cured and six were markedly improved. Three of six failures were due to superinfection with cephalothin-resistant microorganisms. The over-all bacteriologic response was 80%. In 12 of 13 patients with bacteremia the blood was sterilized. Ten of 14 patients with gram-negative bacillary infections responded to treatment. Six of these were due to cephalothin-resistant microorganisms, three of which responded. Fifteen patients who were treated had a history of penicillin allergy. There were no serious reactions although skin rash did develop. Phlebitis was uncommon.

Adolescent↗

A comparative study of ticarcillin plus tobramycin versus carbenicillin plus gentamicin for the treatment of serious infections due to gram-negative bacilli.

The combination of ticarcillin plus tobramycin (TT) or carbenicillin plus gentamicin (CG) was used to treat 82 patients with severe systemic gram-negative infection in a prospective, randomized study. Pseudomonas aeruginosa was the primary pathogen in 7 (93 per cent) of these patients. Patients treated with TT responded more frequently (92 per cent or 37 of 40) than patients treated with CG (71 per cent or 30 of 42) (p is less than 0.05). This difference was primarily due to a greater response to TT in patients with pulmonary infections (93 per cent versus 68 per cent) and infections due to Pseudomonas (92 per cent versus 70 per cent). Severity of underlying disease was also an important determinant of response. Except for a greater incidence of hepatotoxicity with CG (23 per cent versus 3 per cent; p is less than 0.02), there was no difference in toxicity, colonization with drug-resistant microorganisms or superinfection between the two treatment groups. The combination of TT appears to be superior to CG for the treatment of pulmonary infections due to Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

A comparative study of the activity of cefamandole and other cephalosporins and analysis of the beta-lactamase stability and synergy of cefamandole with aminoglycosides.

The antibacterial activity of cefamandole against 445 clinical isolates was investigated and compared with the activity of other known cephalosporins (cephalothin, cephaloridine, cephalexin, and cefazolin) and of two penicillins (ampicillin and carbenicillin). Cefamandole was the most active antibiotic against isolates of Citrobacter, Enterobacter, and Shigella, and its activity against Staphylococcus aureus, Bacteroides, and some members of the Enterobacteriaceae was comparable to that of the other antibiotics tested. The stability of cefamandole with respect to beta-lactamase was investigated and compared with that of cephalothin, cefazolin, and cephalexin. Cefamandole was stable with respect to the beta-lactamases of Enterobacter and some other members of the Enterobacteriaceae. No significant correlation was found between the antibacterial activity and the beta-lactamase stability of cefamandole, except with Enterobacter. The synergistic activity of cefamandole combined with gentamicin or amikacin was demonstrated by killing-curve techniques, isobolograms, and susceptibility data. Although 12%--46% of the isolates were synergistically inhibited by either combination, antagonism was not observed. No correlation between the hydrolysis of cefamandole by beta-lactamase and the synergistic activity of cefamandole combined with amikacin was demonstrated.

Acinetobacter↗

Comparison of the pharmacokinetics of cefamandole and other cephalosporin compounds.

The pharmacokinetic properties of cefamandole were determined and compared with the properties of other cephalosporin agents. Cefamandole was found to be approximately 70% bound to protein. The mean peak concentration in serum after intramuscular (im) injection of 1 g of cefamandole was 20 microgram/ml at 0.5 hr, whereas the level at 6 hr was 1 microgram/ml. After intravenous (iv) infusion of 1 g of cefamandole, levels in serum ranged from 68 to 147 microgram/ml depending on the period of infusion. At 4 hr after infusion, levels were less than 1 microgram/ml. Probenecid elevated serum levels and prolonged excretion. The half-life (t1/2) of cefamandole after im injection ranged from 1 to 1.5 hr and from 0.45 to 1.2 hr after iv injection. Rates of serum and renal clearance of cefamandole ranged from 210 to 300 microliter/min per 1.73 m2. The apparent volume of distribution ranged from 12.4 to 17.9 liters/1.73 m2. Urinary excretion was rapid, with 60% of a dose excreted in the first 2 hr after injection. In 6 hr 90% of a dose was excreted. The pharmacokinetic properties of cefamandole were similar to those of cephalothin and cefoxitin, but the serum t1/2 was shorter than that reported for cefazolin and cefuroxime. Correlation of in vitro studies with pharmacokinetic properties revealed that cefamandole would inhibit most susceptible gram-positive and gram-negative bacteria if given by suggested im or iv regimens.

Bacterial Infections↗

Bone and joint infections due to Salmonella.

A search of the records at the New York City Department of Health and the charts of patients at Columbia Presbyterian Hospital identified 37 cases of bone infection and nine cases of joint infection due to Salmonella between 1964 and 1978. Factors that apparently contributed to the development of either osteomyelitis or septic arthritis in 23 of the patients included hemoglobinopathy, previous trauma or surgery, connective tissue disorder, and lymphoma. Salmonella typhimurium and Salmonella enteritidis were the most common serotypes involved with bone infections, whereas members of the C1 serogroup were the most common cause of septic joint infections. Isolates of C1 serogroup Salmonella were represented in both bone and joint infections with frequencies (24% and 67%, respectively) disproportionate to the numbers of Salmonella isolated from other sources during this period. Therapy for joint infections was usually successful, with minimal residual damage. Therapy for acute osteomyelitis was unaccountably inadequate, with many patients (47%) developing chronic infections. Use of inappropriate therapy or an insufficient period of therapy were the most important factors contributing to poor outcome.

Adolescent↗

Piperacillin, a new penicillin active against many bacteria resistant to other penicillins.

The in vitro activity of piperacillin, a new semisynthetic piperazine penicillin derivative, was evaluated against 626 clinical isolates and compared with the activity of other beta-lactam antibiotics. At a concentration of 0.1 microgram/ml, piperacillin inhibited all streptococci except enterococci. Non-beta-lactamase-producing staphylococci were inhibited by 1.6 microgram or less per ml. Both beta-lactamase- and non-beta-lactamase-producing Haemophilus were inhibited by 0.1 microgram/ml. Piperacillin inhibited non-beta-lactamase-producing Escherichia coli, Salmonella, and Shigella at a concentration of 6.3 micrograms/ml, but 20% of strains of these species containing type III beta-lactamase were not inhibited by 100 micrograms/ml. Piperacillin at 25 micrograms/ml, inhibited 83% of Citrobacter, 58% of Klebsiella, 88% of Enterobacter, and 50% of indole-positive Proteus, Acinetobacter, and Providencia. At 25 micrograms/ml, piperacillin inhibited 95% of Pseudomonas aeruginosa and 78% of Bacteroides fragilis. The minimal inhibitory concentration of piperacillin against Pseudomonas was affected by increasing the inoculum size and by pH. Minimum bactericidal concentrations against Pseudomonas and Serratia often were eightfold greater than the minimum inhibitory concentrations. Piperacillin was equal in activity to ampicillin against enterococci. It was more active than carbenicillin against E. coli, Klebsiella, Enterobacter, and Bacteroides. It was the most active penicillin against Pseudomonas and inhibited many strains of Pseudomonas for which the MICs of carbenicillin were above 200 micrograms/ml. Piperacillin was hydrolyzed by many different beta-lactamases. Synergistic activity of piperacillin was demonstrated when it was combined with amikacin, gentamicin, and cefazolin against P. aeruginosa and members of the Enterobacteriaceae. No antagonism was observed when piperacillin was combined with aminoglycosides; however, antagonism was observed rarely against E. coli when piperacillin was combined with cefazolin.

Chemical Phenomena↗

Cefaclor: in vitro spectrum of activity and beta-lactamase stability.

The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against Haemophilus strains than did cephalexin and inhibited beta-lactamase-producing Haemophilus isolates. Cefaclor was more active than cephalexin or cephalothin against Escherichia coli, Salmonella, and Shigella isolates but did not act against Serratia, Acinetobacter, indole-positive Proteus, or Bacteroides isolates. Cefaclor was resistant to type III (TEM) beta-lactamases but was destroyed by type I beta-lactamases and, to a lesser degree, by type IV and type V beta-lactamases.

Amidohydrolases↗