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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 235 records · Page 13Linked to original sources
PubMed1984

Antibacterial activity of coumermycin alone and in combination with other antibiotics.

Coumermycin has been shown to inhibit Staphylococcus aureus and Staphylococcus epidermidis strains that are susceptible and those that are resistant to methicillin at concentrations less than or equal to 0.05 micrograms/ml. Listeria monocytogenes and Corynebacterium spp. resistant to cephalosporins were inhibited by less than or equal to 1.6 micrograms of coumermycin ml, and streptococcal species, with the exception of Streptococcus faecalis, were inhibited by 0.1 micrograms/ml. Cross-resistance with beta-lactams or aminoglycosides was not found. Coumermycin acted synergistically with ofloxacin, norfloxacin, and enoxacin against S. aureus but did not show synergy when combined with nafcillin, vancomycin, or rifampin. Coumermycin did not inhibit members of the family Enterobacteriaceae or Pseudomonas aeruginosa.

Aminocoumarins↗
PubMed1984

Comparative in vitro activity and beta-lactamase stability of FR 17027, a new orally active cephalosporin.

FR 17027, a new orally absorbed cephalosporin ester, inhibited group A and B streptococci and Streptococcus pneumoniae at less than or equal to 0.1 micrograms/ml, which is similar to the inhibition concentration of amoxicillin and cefaclor, and was more active than cephalexin. It was less active (MIC, 25 micrograms/ml) against staphylococci than was cephalexin, and it did not inhibit Streptococcus faecalis or Listeria monocytogenes. FR 17027 inhibited beta-lactamase-producing isolates of Neisseria gonorrhoeae, Haemophilus influenzae, and Branhamella catarrhalis at less than 0.1 micrograms/ml and was more active than cefaclor or cephalexin against these bacteria. FR 17027 inhibited Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Providencia stuartii, Providencia rettgeri, and Citrobacter diversus at less than or equal to 1 microgram/ml, including isolated resistant to amoxicillin, cephalexin, and cefaclor, but it was less active than ceftizoxime. Some strains of Enterobacter cloacae, Enterobacter agglomerans, Citrobacter freundii, and Enterobacter aerogenes were resistant (MIC, greater than 25 micrograms/ml). FR 17027 did not inhibit Pseudomonas aeruginosa, other Pseudomonas species, Acinetobacter species, or Bacteroides species. Activity was minimally affected by growth conditions. FR 17027 was not hydrolyzed by the common beta-lactamases present in many of the pathogens causing respiratory and urinary tract infections in outpatients.

Amoxicillin↗
PubMed1984

Cefotaxime and desacetylcefotaxime: an example of advantageous antimicrobial metabolism.

Although the antibacterial activity of desacetylcefotaxime (des-CTX), the principal metabolite of cefotaxime (CTX), is eightfold lower than cefotaxime, the metabolite inhibits many B-lactamase-producing Enterobacteriaceae and unusual Pseudomonas species resistant to agents such as cefamandole, cefoxitin, and cefoperazone. des-CTX is more stable than CTX to attack by beta-lactamases of some species such as Bacteroides fragilis, Proteus vulgaris, and the k-1 enzyme of Enterobacter-Klebsiella. des-CTX acts synergistically with CTX against many Enterobacteriaceae and Streptococcus faecalis. The antibacterial activity of the combination of CTX/des-CTX indicates that the drug can be administered every 8-12 hr and provides excellent, broad-spectrum antimicrobial activity.

Bacteria↗
PubMed1984

In vitro activity of pefloxacin compared to that of quinolones and other antimicrobial agents.

Pefloxacin is a new methyl-4-piperazinyl quinolone. It had MIC90 values of less than 0.01 to 0.8 micrograms/ml for the majority of Escherichia coli, Klebsiella, oxytoca, Citrobacter, Providencia, Enterobacter cloacae, Enterobacter aerogenes, Morganella and Proteus mirabilis. It inhibited ampicillin, cephalexin and nalidixic acid resistant isolates of these species. Against Pseudomonas the pefloxacin MIC90 was 3.1 micrograms/ml. Staphylococcus aureus had a MIC50 of 0.4 micrograms/ml and a MIC90 of 0.8 micrograms/ml and S. faecalis had a MIC90 of 3.1 micrograms/ml. Pefloxacin inhibited Salmonella spp., Salmonella typhi, Shigella spp., Yersinia, Aeromonas, toxigenic E. coli at concentrations of less than 0.05 to 1.6 micrograms/ml, including ampicillin and trimethoprim resistant strains. There was a minimal difference in MIC and MBC values in broth or serum, but major changes in MIC and MBC values occurred in acid urine. Increase in MIC values occurred with repeated transfer in broth or urine.

Anti-Bacterial Agents↗
PubMed1984

Cephalosporin antibiotics as applied in surgery of bones and joints.

New cephalosporin antibiotics will continue to be discovered as old forms are found to lose effectiveness. Cephalosporins currently account for a major part of any hospital pharmacy budget. They are often used inappropriately in treatment of both community and hospital infections. Cephalosporins should be used when penicillins are not effective and for particular infections. A major use of cephalosporins is in prophylaxis; cephalosporin antibiotics will not prevent infections caused by organisms that are resistant to these compounds. Infections caused by Enterobacter cloacae, Citrobacter freundii, and Pseudomonas aeruginosa, which are resistant to even third-generation cephalosporins and the monobactams and thienamycins, have been encountered. Wound infections with a deficient blood supply provide situations in which such organisms will grow. It is hoped that proper application of each generation of cephalosporins combined with careful surgical procedures will prevent rapid development of resistance and make it possible to have these drugs as a useful part of our armamentarium for more than just a few years.

Arthritis, Infectious↗
PubMed1984

The pharmacology of clavulanic acid and ticarcillin combined.

The pharmacokinetics of ticarcillin and clavulanic acid were studied in normal volunteers. Ticarcillin at 50 mg/kg was combined with clavulanic acid at 1.7 and 3.4 mg/kg and infused over 30 minutes. Peak serum levels of ticarcillin were 325 micrograms/ml and its pharmacokinetic parameters were similar when combined with either dose of clavulanic acid. Peak serum levels of clavulanic acid were 8 micrograms/ml for 1.7 mg/kg and 15.8 micrograms/ml for 3.4 mg/kg. Serum concentrations of clavulanic acid were greater than or equal to 1 microgram/ml for 2 h with the 1.7 mg/kg dose and for 3 h with the 3.4 mg/kg dose. Serum half-lives of ticarcillin and clavulanic acid were similar, 1.2 hours. Urinary concentrations of ticarcillin exceeded 100 micrograms/ml and clavulanic acid concentrations exceeded 1 microgram/ml for 6 h. The serum and urine levels were such that many beta-lactamase producing organisms would be inhibited by this combination.

Adult↗
PubMed1984

Contemporary antibiotic therapy in otolaryngology.

This article attempts to put into perspective the use of old and new antimicrobial agents important in otolaryngologic infections. Many of the older agents are still extremely useful, but advances in the development of new chemotherapeutic agents have provided compounds that should be of great use to the practicing otolaryngologist.

Anti-Bacterial Agents↗
PubMed1984

Trends in the development of beta-lactam antibiotics.

In many ways it is ironic that the first description of a beta-lactamase occurred in 1940 with an enzyme isolated from Escherichia coli since in recent years there has been a major interest in Gram-negative species and the development of agents to overcome the hydrolytic action of beta-lactamases of Gram-negative species. There have been four distinctly different approaches to the development of new beta-lactam antibiotics. These have been the search for inhibitors of beta-lactamases and agents such as clavulanic acid and sulbactam are examples of compounds which by virtue of Kcat function act as suicide inhibitors and make old antibiotics new. There has been the modification of the penicillin and cephem nucleus to increase beta-lactamase stability or failing that to improve the ability of the compounds to pass through the cell wall and increase affinity for critical beta-lactam receptors, i.e. penicillin-binding proteins. There has been the development of carbapenem type of agents such as imipenem which would have broad activity including aerobic, anaerobic, Gram-positive and Gram-negative species. There has been the discovery of the monobactam agents of which aztreonam is an example of a compound with great beta-lactamase stability but with activity limited to Gram-negative aerobic species. Bacterial resistance has indeed been the major factor that has modified use of beta-lactams and influenced the development of the aforementioned types of drugs. The widespread presence of beta-lactamases in common pathogens such as Haemophilus influenzae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella sp., Pseudomonas aeruginosa, and Bacteroides fragilis has made it necessary to have beta-lactamase stable compounds for initial therapy of infection. It is possible to analyze structure-activity relations of beta-lactam compounds to determine changes which will be most advantageous in light of known and expected resistance patterns. But the increased realization in recent years of the importance of the pharmacokinetics of beta-lactam drugs has made it essential that the development of new compounds be based on an integration of microbiological and pharmacokinetic parameters. Interest in the prevention of resistant flora has also affected the development of new drugs since it is increasingly appreciated that alteration of intestinal flora contributes to selection of drug resistant microorganisms. Finally, new toxicities or adverse effects associated with the use of certain new agents has modified the development of certain compounds.

Anti-Bacterial Agents↗
PubMed1983

Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death.

The activity of penicillins against bacteria is in large part related to binding to specific receptor proteins involved in cell wall biosynthesis. These proteins have been designated penicillin-binding proteins. They can be separated into distinct entities through the use of acrylamide gel electrophoresis and binding of radioactive 14C-labeled penicillin G. Six major proteins have been defined in the Enterobacteriaceae, penicillin-binding proteins 1 to 6. Selection of mutants has shown that there are three essential proteins: penicillin-binding protein 1, which is divided into penicillin-binding protein 1Bs, a peptidoglycan transpeptidase, and penicillin-binding protein 1A, which acts as a replacement for penicillin-binding protein 1Bs. Penicillin-binding protein 2 is a murein-elongation initiating enzyme and penicillin-binding protein 3 is a septal murein-synthesizing enzyme. Penicillin-binding proteins 4, 5, and 6 are not essential for bacterial survival. Binding of penicillins to penicillin-binding protein 1Bs produces lysis, binding to penicillin-binding protein 2 produces round cells, and binding to penicillin-binding protein 3 produces long filaments. Amdinocillin is a beta-amidino penicillanic acid derivative that binds specifically to penicillin-binding protein 2. The compound is more beta-lactamase stable than ampicillin and has no major delay in entry into the periplasmic space as do some penicillins. Amdinocillin inhibits most of the Enterobacteriaceae, with the exception of some indole-positive Proteus species, but it does not inhibit gram-positive cocci or Pseudomonas aeruginosa. Amdinocillin produces spherical bacterial cells that eventually lyse. Its activity in vitro is markedly affected by ionic content of media. This agent acts synergistically with many penicillins, such as ampicillin, carbenicillin, and the like, and with cephalosporins, cefazolin, cefamandole, or cefoxitin to inhibit gram-negative bacilli, probably on the basis of binding to different proteins needed for the production of the peptidoglycan of the bacterial cell wall. Amdinocillin possesses a number of the essentials for effective antimicrobial activity and, by virtue of its enhancement of the activity of other beta-lactams, may prove to be a useful agent in the chemotherapy of certain infections.

Amdinocillin↗
PubMed1983

Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers.

The pharmacokinetic parameters of amdinocillin and pivamdinocillin were studied in 12 normal volunteers. Plasma amdinocillin concentrations were determined by microbiologic assay and urine concentrations by high performance liquid chromatography. Pharmacokinetic parameters were calculated by a two-compartment open model for the intravenous infusion and by a one-compartment model with zero-order absorption for the oral doses. The mean peak serum level after the intravenous infusion of 500 mg was 39 micrograms/ml. At one and a half hours after the oral administration of 250 mg and 500 mg doses, mean peaks were 1.93 and 2.66 micrograms/ml respectively. Half-life was one hour for all doses. Maximal plasma concentration did not increase proportionally with dose. Bioavailability was 45 percent after the 250 mg dose and 38 percent after the 500 mg dose.

Administration, Oral↗
PubMed1983

Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics.

Amdinocillin is a semisynthetic derivative of 6-beta-amidinopenicillanic acid, which has bactericidal activity against a broad spectrum of gram-negative bacteria. We report the results of a multicenter study evaluating the safety and efficacy of amdinocillin in combination with other beta-lactam antibiotics in the treatment of 120 serious gram-negative bacterial infections. Amdinocillin was safe and well tolerated and, in combination with other beta-lactam antibiotics, was effective in the treatment of a broad range of gram-negative bacterial infections. Therapy with amdinocillin and other beta-lactam antibiotics was often associated with a demonstrable synergistic effect. Thus, amdinocillin holds promise as an effective antibiotic with synergistic potential when used in combination with penicillins and cephalosporins.

Amdinocillin↗
PubMed1983

Digoxin-inactivating bacteria: identification in human gut flora.

Digoxin, the most widely used cardiac glycoside, undergoes significant metabolic conversion in many patients to cardioinactive metabolites in which the lactone ring is reduced. This appears to occur within the gastrointestinal tract. An attempt was made to isolate and identify the organisms capable of reducing digoxin from stool cultures obtained from human volunteers. Of hundreds of isolates studied, only Eubacterium lentum, a common anaerobe of the human colonic flora, converted digoxin to reduced derivatives. Such organisms were also isolated in high concentrations from the stools of individuals who did not excrete these metabolites when given digoxin in vivo. When the growth of E. lentum was stimulated by arginine, inactivation of digoxin was inhibited. Neither the presence of these organisms alone nor their concentration within the gut flora appeared to determine whether digoxin would be inactivated by this pathway in vivo.

Arginine↗
PubMed1983

What do beta-lactamases mean for clinical efficacy?

beta-Lactamases have proved to be extremely important in influencing therapy with penicillins and cephalosporins against gram-positive and gram-negative aerobic and anaerobic species. Both plasmid mediated beta-lactamases which are primarily of a constitutive penicillinase type and the inducible chromosomal enzymes which are primarily cephalosporinases are important. The use of penicillins to treat Haemophilus, Neisseria gonorrhoeae, Escherichia coli, Klebsiella, Salmonella, Shigella and Pseudomonas infections must be based upon the relative incidence of beta-lactamase producing strains. In the same manner cephalosporins can be used to treat infections due to Enterobacter, Serratia and Bacteroides only if the compounds are beta-lactamase stable and not good inducers of beta-lactamase activity. Although altered permeability is important in the resistance of some Pseudomonas and Enterobacter to beta-lactams, the resistance really is due to a combination of reduced entry of molecules and strategically placed beta-lactamases. It is only in some Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus faecalis strains that altered penicillin-binding proteins make a significant contribution to the resistance to beta-lactams. beta-lactamases will continue to be the most important factor in clinically significant resistance of bacteria to both penicillins and cephalosporins.

Bacillus cereus↗
PubMed1983

Beta-lactamase stability of cefoxitin in comparison with other beta-lactam compounds.

The beta-lactamase stability of cefoxitin, the second-generation cephamycin compound, was compared with that of cefamandole, cefoperazone, cefotaxime, moxalactam, carbenicillin, and piperacillin. Unlike cefamandole, cefoperazone, carbenicillin, and piperacillin, cefoxitin was not hydrolyzed by the common plasmid beta-lactamases, TEM-1, TEM-2, OXA-2, and SHV-1. Cefoxitin and moxalactam were the only agents stable to all chromosomal beta-lactamases, whereas cefamandole, cefoperazone, cefotaxime, carbenicillin, and piperacillin were destroyed by cephalosporinases of Proteus vulgaris and Bacteroides fragilis.

Anti-Bacterial Agents↗
PubMed1983

Considerations about the relationship of inhibitory concentrations and the pharmacologic and toxic properties of antimicrobial agents.

Too little attention has been given to the correlation of antimicrobial susceptibility tests and the pharmacokinetics of antimicrobial agents. Ability to perform and provide reproducible, rapid, minimal inhibitory concentration data, combined with the knowledge of serum levels, can be used to yield inhibitory quotients which will improve the chemotherapy of serious infections. Antimicrobial susceptibilities have to be provided rapidly for the life-threatening infections that occur in certain clinical settings. Antimicrobial susceptibilities also must be provided in a manner that demonstrates that one may not be able to achieve therapeutic concentrations with certain drugs. We have reached an era in which knowledge of an organism being susceptible or resistant is no longer adequate.

Anti-Bacterial Agents↗
PubMed1983

New penicillins and their use in pediatrics.

The new penicillins have not been a breakthrough for the pediatrician. Indeed, 20 years ago with the introduction of ampicillin and methicillin and 15 years ago with the introduction of carbenicillin, the pediatrician was given the penicillins that he has used so well to treat trivial and life-threatening infections. The drugs discussed in this article are small steps forward, and whether mezlocillin, azlocillin, or piperacillin will prove more helpful to the pediatrician than have carbenicillin or ticarcillin will be learned in the next few years.

Child↗