Search PubMed⌕ Search

Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 181 records · Page 10Linked to original sources
PubMed1986

Antimicrobial activity and beta-lactamase stability of foramidocillin.

Foramidocillin is a 6-alpha-formamido penicillin with a 6-beta-acylureido side chain. The majority of the Enterobacteriaceae were inhibited by less than or equal to 1 microgram of foramidocillin per ml, and Pseudomonas aeruginosa was inhibited by 4 micrograms/ml. Foramidocillin had activity comparable to those of ceftazidime, imipenem, and aztreonam against beta-lactamase-producing members of the Enterobacteriaceae and P. aeruginosa, and it inhibited organisms resistant to piperacillin. Foramidocillin did not inhibit gram-positive species or anaerobic gram-negative bacteria. Foramidocillin was not hydrolyzed by the common plasmid-mediated beta-lactamases TEM-1, TEM-2, OXA-2, PSE-4, and SHV-1, by the chromosomal beta-lactamases P99 of Enterobacter cloacae and K1 of Klebsiella oxytoca, or by the Sabath-Abraham enzyme of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1986

In vitro activity of CI-934, a new quinolone, compared with that of other quinolones and other antimicrobial agents.

The in vitro activity of CI-934, a new 4-quinolone, was determined against gram-positive and gram-negative bacteria. The MICs for 90% of the isolates tested were 0.25 microgram/ml for Streptococcus pneumoniae, 0.5 microgram/ml for Streptococcus faecalis, 0.25 microgram/ml for staphylococci, including methicillin-resistant strains, and less than or equal to 1.0 microgram/ml for Escherichia coli, Salmonella and Shigella spp., Klebsiella spp., Proteus spp., and Citrobacter spp. CI-934 had activity superior to that of other quinolones against streptococci by four- to eightfold. Against members of the family Enterobacteriaceae, ciprofloxacin was 2- to 18-fold more active; ofloxacin and norfloxacin were twofold more active or similar to CI-934. CI-934 inhibited ampicillin-cephalothin-resistant urinary isolates of E. coli, Klebsiella pneumoniae, and Proteus mirabilis and cefoxatime-resistant Acinetobacter spp., Citrobacter freundii, Enterobacter cloacae, Proteus vulgaris, and Morganella morganii. The medium, inoculum size, and oxygen concentration, as well as the addition of serum, had not major effect on the activity of CI-934. Magnesium at a concentration of 9 mM increased MICs and MBCs four- to eightfold, and testing at pH 6 increased MICs as much as 32- to 64-fold for some organisms in comparison with MICs at pH 7. The frequency of spontaneous mutation to resistance was comparable to that for other new quinolones, but resistant isolates could be selected by repeated subculture.

Anti-Bacterial Agents↗
PubMed1986

Factors influencing the in vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620.

The in vitro activity of difloxacin (A-56619) and A-56620, two new aryl-difluoroquinolones, was decreased by magnesium at 9 mM and in assay at pH 5.5 or in urine. Resistance was seen with members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus repeatedly exposed to subinhibitory concentrations of the compounds. The frequency of resistance was similar to that found for other new quinolones.

Anti-Bacterial Agents↗
PubMed1986

In vitro activity and beta-lactamase stability of two oral cephalosporins, ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074).

Ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074), two new orally administered aminothiazolyl imimomethoxy cephalosporins, inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.5 micrograms/ml but were less active against staphylococci than were cephalexin and cefaclor. They did not inhibit S. faecalis, S. faecium, Listeria monocytogenes, Corynebacterium JK species, or Pseudomonas aeruginosa. Haemophilus influenzae, Branhamella catarrhalis, and Neisseria gonorrhoeae, including ampicillin-resistant isolates, were inhibited at less than 0.25 micrograms/ml. Both agents inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Salmonella species, Shigella species, Citrobacter diversus, and Aeromonas hydrophila resistant to ampicillin, cephalexin, and cefaclor at less than or equal to 2 micrograms/ml, although many isolates of Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens resistant to cefotaxime were not inhibited by these agents. A marked inoculum effect was noted for Enterobacteriaceae carrying the Richmond-Sykes type 1A chromosomally mediated beta-lactamases, but plasmid-mediated beta-lactamases did not hydrolyze the compounds. Both drugs inhibited the chromosomally mediated beta-lactamase of E. cloacae, P99.

Bacteria↗
PubMed1986

In vitro activity and beta-lactamase stability of a new difluoro oxacephem, 6315-S.

6315-S, a novel difluoromethyl thioacetamido oxacephem, had in vitro activity comparable to that of cefotaxime and moxalactam against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Citrobacter diversus, Salmonella spp., and Shigella spp., inhibiting 90% at less than or equal to 0.25 microgram/ml. It inhibited piperacillin- and cefoperazone-resistant isolates in these species. 6315-S did not inhibit cefotaxime- or moxalactam-resistant Citrobacter freundii, Enterobacter aerogenes, or Enterobacter cloacae (MICs for 90% of the strains tested were greater than or equal to 16 micrograms/ml). Proteus vulgaris resistant to cefotaxime was inhibited. Pseudomonas species and Acinetobacter species were resistant (MICs greater than 64 micrograms/ml). MICs for 90% of the Staphylococcus aureus and S. epidermidis isolates were 4 micrograms/ml. 6315-S was highly active against anaerobic species of Clostridium, Fusobacterium, Bacteroides, and peptostreptococci and was superior to other agents against these organisms. 6315-S was not hydrolyzed by the major plasmid and chromosomal beta-lactamases, but it induced chromosomal beta-lactamases in Enterobacter cloacae and Pseudomonas aeruginosa.

Bacteria↗
PubMed1986

In vitro activity against aerobic and anaerobic gram-positive and gram-negative bacteria and beta-lactamase stability of RS-533, a novel carbapenem.

RS-533 is a novel carbapenem antibiotic. Its activity was compared with that of imipenem and the new cephalosporins, aztreonam, piperacillin, and tobramycin. RS-533 had activity comparable to that of imipenem, inhibiting the majority of the Enterobacteriaceae, streptococci, staphylococci, and Bacteroides species at concentrations of less than or equal to 2 micrograms/ml. RS-533 inhibited Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens resistant to ceftazidime, aztreonam, and cefoperazone, but RS-533 did not inhibit all methicillin-resistant Staphylococcus aureus or Pseudomonas maltophilia. It inhibited tobramycin-resistant members of the Enterobacteriaceae and Pseudomonas aeruginosa. RS-533 was stable against attack by common chromosomal and plasmid-mediated beta-lactamases and was an effective inhibitor of many beta-lactamases.

Aztreonam↗
PubMed1986

In vitro activity of A-16686, a new glycopeptide.

A-16686 is a novel glycopeptide antibiotic derived from Actinoplanes. A-16686 inhibited hemolytic streptococci groups A, B, C, F, and G at concentrations of less than or equal to 0.06 to 0.5 microgram/ml, with 90% inhibited by 0.5 microgram/ml, including erythromycin-resistant isolates. S. bovis, various viridans groups streptococci, S. mitis, S. mutans, and S. sanguis were inhibited by less than or equal to 1 microgram/ml, and MICs of S. faecalis and S. faecium were 0.5-2 micrograms/ml. Most staphylococci, including methicillin-resistant strains, were inhibited by 1 or 2 micrograms/ml. A-16686 was bactericidal with minimal difference between MIC and MBC for gram-positive species. A-16686 did not inhibit Enterobacteriaceae or Pseudomonas.

Anti-Bacterial Agents↗
PubMed1986

Synergy of sulbactam and ampicillin against methicillin-resistant staphylococci.

Methicillin resistance in staphylococci is an increasing problem both for Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), which cause infections of the heart and after central nervous system surgery. Resistance seems to be due primarily to production of altered penicillin-binding proteins. The present study determined whether a combination of beta-lactamase inhibitor sulbactam and ampicillin or sulbactam and cefazolin would inhibit MRSA and MRSE. Sulbactam, ampicillin and cefazolin at 32 micrograms/ml did not inhibit MRSA or MRSE. At 8 micrograms/ml of each agent all isolates were inhibited. Synergy of sulbactam and ampicillin could be demonstrated against MRSA by the agar fixed ratio method, checkerboard dilution and by killing curves. This suggests that in certain situations MRSA and MRSE may be effectively eliminated by this method.

Ampicillin↗
PubMed1986

Comparative in vitro activity and beta-lactamase stability of CGP 31523A, a new aminothiazolyl cephalosporin.

The in vitro activity of CGP 31523A, an aminothiazolyl cephem, was compared to that of other cephalosporins--imipenem, aztreonam, carbenicillin, and gentamicin. CGP 31523A inhibited E. coli, K. pneumoniae, P. mirabilis, C. diversus, K. oxytoca, P. stuartii, Salmonella and Shigella at less than or equal to 0.25 micrograms/ml. It was equal or 2-fold more active than cefotaxime and ceftazidime, and 4-fold more active than imipenem against these organisms. It inhibited all carbenicillin and gentamicin-resistant isolates of these species. Neisseria and Haemophilus were inhibited by less than or equal to 0.12 micrograms/ml. Some C. freundii, E. cloacae, E. aerogenes, P. vulgaris, and P. penneri had MICs greater than or equal to 16 micrograms/ml similar to cefotaxime, ceftazidime and aztreonam. Pseudomonas were resistant, MIC 128 micrograms/ml. CGP 31523A inhibited streptococci at less than or equal to 0.25 micrograms/ml with the exception of S. faecalis, and staphylococci were inhibited by 0.5 micrograms/ml but methicillin-resistant isolates were resistant. Bacteroides and some Clostridium had MICs greater than or equal to 16 micrograms/ml. CGP 31523A was less stable than cefotaxime and ceftazidime to the plasmid TEM/SHV/PSE-4 beta-lactamases. Like cefotaxime it was hydrolyzed by the P. vulgaris type Ic beta-lactamase but not by the type Ia enzymes. CGP 31523A was not an effective beta-lactamase inhibitor nor did it induce beta-lactamases. It had overall activity comparable to available extended spectrum cephalosporins.

Aztreonam↗
PubMed1986

Synergy of fosfomycin with beta-lactam antibiotics against staphylococci and aerobic gram-negative bacilli.

Fosfomycin inhibits bacterial cell wall synthesis at the initial stage. It can act synergistically with beta-lactams. The effect of the combination of fosfomycin and selected penicillins and cephalosporins against staphylococci, Pseudomonas aeruginosa, Pseudomonas cepacia and selected Gram-negative bacteria was determined. Synergy was determined by agar dilution and checkerboard titration methods; synergy was defined as an FIC index less than or equal to 0.5 and partial synergy greater than 0.5 to 0.75. Concentrations of drugs used were those that would be reached in man by intravenous and oral routes. Fosfomycin combined with nafcillin and with cefotaxime against staphylococci showed synergy for most isolates. For methicillin-resistant Staphylococcus aureus, synergy or partial synergy was found for 90% of isolates. Synergy was less frequently found with Staphylococcus epidermidis. The MICs for S. aureus were reduced from greater than or equal to 32 micrograms/ml to less than or equal to 1 microgram/ml. Fosfomycin was synergistic with ticarcillin, piperacillin, azlocillin, ceftazidime, aztreonam and imipenem against 31 to 61% of P. aeruginosa. MICs were reduced from greater than or equal to 128 micrograms/ml to 8-32 micrograms/ml, depending upon the agent. Although fosfomycin acted synergistically with azlocillin, piperacillin and ceftazidime against some P. cepacia, most often there was an indifferent interaction and MICs were in the resistant range, greater than or equal to 128 micrograms/ml. The interaction of fosfomycin and ampicillin was synergistic against a number of strains of Enterobacteriaceae, Proteus vulgaris and Providencia rettgeri, yielding MICs in an achievable range. The combination of fosfomycin with beta-lactams may be clinically useful in selected situations, particularly for methicillin-resistant staphylococci and beta-lactam-resistant P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1986

The effect of the combination of erythromycin with new beta-lactam antibiotics against gram-negative aerobic respiratory pathogens.

The effect of erythromycin on the in vitro activity of cefotaxime, ceftizoxime, cefoperazone, moxalactam, ceftazidime, cefmenoxime, aztreonam, imipenem, piperacillin, and gentamicin against 89 bacteria isolated from sputum and tracheal aspirates of patients admitted to intensive care units was evaluated. There were 30 Pseudomonas aeruginosa, 27 Klebsiella pneumoniae, 9 Enterobacter cloacae, 5 Escherichia coli, 4 Enterobacter aerogenes, 3 each of Klebsiella oxytoca, Pseudomonas maltophilia, Serratia marcescens, 2 each of Morganella morganii, Acinetobacter anitratus; 1 Proteus mirabilis. All isolates were resistant to erythromycin. Organisms were screened for synergy by fixed erythromycin concentration at 1, 8 and 16 micrograms/ml. There were 16 isolates that showed a greater than four-fold difference in MICs. These strains were analyzed by the checkerboard broth method. No antagonism was seen for any drug combination with erythromycin. One Enterobacter cloacae showed synergy of ceftizoxime and erythromycin, and 1 E. cloacae showed synergy with cefotaxime. Addition was found for 2 P. aeruginosa, 1 each E. aerogenes, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. At concentrations of erythromycin achievable in blood or pulmonary tissue, the activity of newer beta-lactams and gentamicin is not altered by erythromycin.

Anti-Bacterial Agents↗
PubMed1985

Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases.

Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades. Virtually all Staphylococcus aureus, and many Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Enterobacteriaceae, and Bacteroides species possess beta-lactamases that hydrolyze penicillins and cephalosporins. The most common plasmid-mediated beta-lactamase is the TEM enzyme (Richmond-Sykes type IIIa), which is present in Hemophilus, Neisseria, and Enterobacteriaceae. One technique to overcome bacterial resistance has been the development of beta-lactamase inhibitors. Clavulanic acid is a beta-lactamase inhibitor that inhibits the beta-lactamases of S. aureus, Hemophilus, Neisseria, Branhamella, Eschericia coli, Klebsiella, and Bacteroides. Clavulanate acts as a "suicide" inhibitor, forming a stable enzyme complex that binds to serine at the active site of the enzyme. Clavulanate readily crosses the outer cell wall of most Enterobacteriaceae to interact with beta-lactamases in the periplasmic space. Clavulanate does not inhibit beta-lactamases such as the Richmond-Sykes type I enzymes found in Pseudomonas aeruginosa, Enterobacter, and Citrobacter species, which are inducible enzymes that function primarily as cephalosporinases.

Anti-Bacterial Agents↗
PubMed1985

Pharmacology of ticarcillin combined with clavulanic acid in humans.

Serum and urine levels of ticarcillin and clavulanic acid after administration of doses of 50 mg/kg and 1.7 mg/kg or 50 mg/kg and 3 g/0.1 g, respectively, are potentially toxic to susceptible bacteria. Both compounds are widely distributed in body tissues and fluids, with concentrations exceeding the minimal inhibitory concentrations of most pathogens. Excretion is primarily renal, although there is some metabolism of clavulanate in the body. Due to accumulation, dosage adjustment is required for patients with renal insufficiency. Both ticarcillin and clavulanic acid are cleared by hemodialysis.

Clavulanic Acid↗
PubMed1985

Ticarcillin plus clavulanic acid in the treatment of pneumonia and other serious infections.

Clavulanic acid is a potent inhibitor of bacterial beta-lactamases, and ticarcillin is a potent antipseudomonal penicillin. The combination of ticarcillin disodium and clavulanate potassium provides an excellent spectrum of activity against the majority of bacterial pathogens responsible for serious infections in both normal and abnormal hosts. Eighteen courses of therapy were administered to 16 patients; 35 percent of the patients were in poor or critical condition, and all but one had severe underlying disease. Thirteen separate episodes of pneumonia were treated, of which nine were in patients with cystic fibrosis, and 11 involved Pseudomonas aeruginosa. Of the 13 cases of pneumonia, 11 showed clinical cure or improvement, whereas only three showed bacteriologic cure. Of the four nonpulmonary cases, three showed clinical improvement or cure, and one showed a bacteriologic cure. In two patients, phlebitis developed at the site of intravenous infusion. The combination of ticarcillin and clavulanic acid is safe and effective therapy for pneumonia in anatomically compromised hosts.

Adolescent↗
PubMed1985

Relation of structural properties of beta-lactam antibiotics to antibacterial activity.

There has been remarkable progress in the development of new antimicrobial agents as the result of structural modifications of the cephalosporin nucleus. It has been possible to predict many aspects of the antimicrobial activity of new agents and to recognize the structural modifications that contribute to overcoming the continued problem of bacterial resistance. The activity of beta-lactams against gram-positive species depends primarily on their affinity for the enzymes referred to as penicillin-binding proteins. Resistance of gram-positive species to beta-lactams is either due to altered penicillin-binding proteins or, more commonly, due to the presence of beta-lactamases, which are usually plasmid-mediated and inducible. The activity of beta-lactams against gram-negative aerobic and anaerobic bacteria is the result of the way in which the compounds pass through the porin channels in the outer wall, resist inactivation by beta-lactamases, and bind to the penicillin-binding proteins. The basic cephalosporin nucleus consists of the essential beta-lactam ring fused to a dihydrothiazine ring. It is possible to modify this structure to increase antibacterial activity. Changes in moieties at position 3 affect pharmacologic activity but can also cause a marked increase or decrease in activity against staphylococci and Pseudomonas species. The presence of the thiomethyltetrazole group at position 3 has been associated with an alteration in prothrombin synthesis and with disulfiram reactions. Modifications of the cephem nucleus at position 7 by addition of methoxy groups increase beta-lactamase stability but decrease activity against gram-positive species because of lower affinity for penicillin-binding proteins. The more useful acyl side chains have been those that contain a 2-aminothiazolyl moiety, which causes increased affinity of the molecules for penicillin-binding proteins of gram-negative bacteria and streptococcal species. Iminomethoxy groups provide beta-lactamase stability against the common plasmid beta-lactamases such as those of Staphylococcus aureus and the TEM, SHV-1, OXA, and PSE enzymes found in Enterobacteriaceae and Pseudomonas aeruginosa, as well as the chromosomally mediated K-1 and P99 enzymes of Enterobacter. A propylcarboxy group increases beta-lactamases stability and also provides activity against P. aeruginosa and some Acinetobacter. Conversely, this particular grouping reduces the beta-lactamase induction capabilities of a compound, as well as its ability to function as a beta-lactamase inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗