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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 199 records · Page 11Linked to original sources
PubMed1985

Antimicrobial activity, bacterial resistance, and antimicrobial pharmacology. Is it possible to use new agents cost-effectively?

Perusal of the various journals devoted to antimicrobial agents and to the chemotherapy of infectious diseases reveals an increasing number of articles devoted to the analysis of the pharmacology of antimicrobial agents and the relationships of antimicrobial activity and pharmacologic properties. However, most attention to the pharmacokinetic properties of antimicrobial agents in the past decade has focused on the toxic properties of these agents, and there has been little work devoted to improving methods of administration. The availability of nontoxic antibiotics that are extremely active at low concentrations and of agents with markedly extended half-lives should cause us to reevaluate some of our current dosing practices. In many ways, a major adverse influence on appropriate antimicrobial therapy of ordinary infections has been the febrile neutropenic patient. Lessons learned from the care of these patients are inappropriately applied to the treatment of other patients. The neutropenic patient requires frequent administration of antibiotics at maximally tolerated doses. Many patients at risk for infection do not require antimicrobial therapeutic programs in which the antibiotic always exceeds the minimal inhibitory concentration. Indeed, the concept that the drug must be present in the serum well above the minimal inhibitory concentration for the entire interval of infection is derived from studies of neutropenic patients infected with Pseudomonas aeruginosa. Increasing resistance of hospital-acquired bacteria to older antibacterial agents will alter the initial and subsequent selection of antimicrobial agent. Combination drug therapy, which has a prominent role in the neutropenic patient, frequently results in greater cost to the health care system than is seen with single agents that are active against resistant bacteria. There are clear areas in which new antibacterial agents will be beneficial. We may be at a stage in which use of the older agents can no longer be viewed as the best clinically and economically. Better use of twice- or once-daily dosing programs of new agents coupled with use of intramuscular and oral administration of antibiotics can help reduce nosocomial infections that contribute to rising health costs.

Anti-Bacterial Agents↗
PubMed1985

Carbapenems: special properties contributing to their activity.

Imipenem is a beta-lactam antibiotic that inhibits most clinical isolates of staphylococci, Enterobacteriaceae, and streptococci, excluding enterococci, at 1 microgram/ml or less. Resistance can develop in methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens, albeit infrequently. Pseudomonas maltophilia is intrinsically resistant to imipenem. Many strains of Enterobacter cloacae, Clostridium freundii, and S. marcescens resistant to the aminothiazolyl cephalosporins are susceptible to imipenem, but tend to have higher minimal inhibitory concentrations. In general, imipenem inhibits organisms resistant to other beta-lactams and aminoglycosides. Imipenem binds to PBP-2 and rapidly kills most bacteria which it inhibits. Imipenem is highly stable against attack by beta-lactamases of both plasmid and chromosomal origin, and is more stable by several thousand-fold than earlier beta-lactamase stable compounds. It acts as a suicide inhibitor of beta-lactamases. Imipenem does induce beta-lactamases, but the activity of imipenem against isolates containing induced beta-lactamases is not decreased and it appears not to be susceptible to the trapping that occurs with some of the cephalosporins. Imipenem acts synergistically with aminoglycosides against a wide variety of bacteria, but this is most readily demonstrated for Streptococcus faecalis, S. aureus, and P. aeruginosa organisms which show a difference between inhibition and killing. Overall, the excellent activity of imipenem is the result of (1) the lack of a permeability barrier; (2) high affinity for PBP-2, a critical protein in cell wall synthesis in gram-negative bacteria, and for critical penicillin-binding proteins of gram-positive species; and, above all, (3) its great beta-lactamase stability.

Aminoglycosides↗
PubMed1985

Current state of infectious diseases--potential areas of directed therapy with aztreonam.

Gram-negative bacillary organisms have continued to be a major source of hospital infections. Beta-lactamase-producing species have rendered many older beta-lactam antibiotics impotent. Aztreonam is a monocyclic beta-lactam antibiotic that inhibits aerobic gram-negative bacilli, including beta-lactamase-producing species. The agent has been used in the treatment of infections due to Enterobacteriaceae and Pseudomonas aeruginosa. Potential areas of use of aztreonam are as sole therapy for urinary tract infections, gram-negative pneumonias, and bone and joint infections. It can be used in combination with other antibiotics as empiric therapy of respiratory, intra-abdominal, skin structure, and gynecologic infections. Aztreonam offers a new approach to the use of beta-lactam antibiotics.

Abdomen↗
PubMed1985

The pharmacokinetics and serum and urine bactericidal activity of ciprofloxacin.

Ciprofloxacin is an investigational quinolone agent possessing an impressive antibacterial spectrum. Its pharmacokinetics were studied in six volunteers after 250-mg and 500-mg single oral doses, and its bactericidal activity compared to that of trimethoprim-sulfamethoxazole given to the same volunteers. Mean peak serum levels were 1.45 micrograms/mL and 2.46 micrograms/mL for 250-mg and 500-mg doses, and time to peak was 1 and 1.3 hours. The 12-hour levels were 0.12 micrograms and 0.22 microgram. Half-life (T1/2)alpha were 0.32 and 0.43 with T1/2 beta were 3.97 and 4.15 and volume of distribution (area) were 80L and 90L, respectively. Area under the concentration curve (AUC) was 5.65 h X micrograms/mL and 10.37h X micrograms/mL. Serum clearance was 23L for both doses. Approximately 49% of the 250-mg dose and 43% of the 500-mg dose was recovered in the urine. Bactericidal levels were determined against clinical isolates. Sera at 1.5 hours after the 500-mg dose averaged bactericidal levels of 1:20 or better for an Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and beta-lactamase producing Haemophilus influenzae and Branhamella catarrhalis. Urinary bactericidal levels at eight to 12 hours were greater than or equal to 1:157 for E coli, K pneumoniae, gentamicin-piperacillin resistant P aeruginosa, Staphylococcus aureus, and 1:20 for Streptococcus faecalis. Serum bactericidal levels were superior, and urine bactericidal levels were superior or equal to the bactericidal levels obtained with trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Stevens-Johnson syndrome due to Mycoplasma pneumoniae in an adult.

A case of Stevens-Johnson Syndrome (erythema multiforme major) due to Mycoplasma pneumoniae infection in a 45-year-old man is presented. This association has been previously reported only in children and young adults. A brief review of erythema multiforme, including the Stevens-Johnson syndrome, is described. M. pneumoniae should be added to the list of causes of the Stevens-Johnson syndrome in adults with pneumonia.

Humans↗
PubMed1985

Use of aztreonam in the treatment of serious infections due to multiresistant gram-negative organisms, including Pseudomonas aeruginosa.

Aztreonam is a novel antimicrobial agent belonging to the monobactam class of antibiotics. It inhibits both beta-lactamase-producing and non-beta-lactamase-producing aerobic gram-negative bacilli, but it has no activity against gram-positive species or against anaerobic species. The efficacy of aztreonam in the treatment of infection in 76 patients and its safety in 87 patients was evaluated. The majority (91 percent) of patients had significant underlying disease, and 47 percent were critically ill. Aztreonam produced an overall clinical response of 86 percent, with 10 of 11 cases of bacteremia cured, including four due to Pseudomonas aeruginosa, seven of eight cases of pneumonia, and seven of nine episodes of osteomyelitis. Infections due to bacteria resistant to ampicillin, carbenicillin, cefazolin, cefamandole, cefoxitin, and gentamicin were cured. Although 15 of 18 patients with exacerbations of pulmonary infection due to P. aeruginosa showed clinical improvement, bacteriologic cure was not achieved, as has been noted with other drugs. Similarly, patients with major underlying structural abnormalities of the urinary tract showed early relapses of bacteriuria. Aztreonam combined with antistaphylococcal, antistreptococcal, or antianaerobic agents provided an alternative to aminoglycoside use in these non-neutropenic patients. Administration of 1 or 2 g every eight hours yield serum bactericidal levels well in excess of 1:8 against all Enterobacteriaceae and some P. aeruginosa strains. There was a low incidence of adverse side effects, none serious. Overall, aztreonam is a useful alternative to the drugs available for use in hospital-acquired gram-negative infections and provides a chance for more directed therapy.

Adolescent↗
PubMed1985

Primary cutaneous aspergillosis in six leukemic children.

We report a cluster of primary cutaneous aspergillosis in six children with hematologic malignancy. When first seen, they had hemorrhagic bullae caused by Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger at the sites of insertion of intravenous cannulas or where arm boards had been taped to the extremities. Rapid diagnosis of cutaneous aspergillosis was made by direct examination of the blister roof with potassium hydroxide before it progressed to a necrotic ulcer. Intravenous amphotericin was instituted promptly in five of six patients, and none died of disseminated aspergillosis. Epidemiologic investigation tracked the source of aspergillus to a storeroom with a false ceiling that had recently been repaired for a water leak.

Amphotericin B↗
PubMed1985

Antibacterial activity of amifloxacin (WIN 49, 375), a new quinolone agent.

The in vitro activity of amifloxacin, a quinolone antimicrobial agent was compared with those of ciprofloxacin, enoxacin, ofloxacin and norfloxacin against gram-positive and gram-negative bacteria. Ninety percent of Escherichia coli, Klebsiella species, Aeromonas, Salmonella, Shigella, Citrobacter, Enterobacter species, Proteus mirabilis, Serratia marcescens, and Morganella morganii were inhibited by less than or equal to 0.5 microgram/ml. Amifloxacin inhibited Branhamella, Haemophilus, and Neisseria at less than or equal to 0.25 microgram/ml, and 90% of Pseudomonas aeruginosa, including gentamicin- and carbenicillin-resistant isolates, at 4 micrograms/ml. It also inhibited staphylococci, including methicillin-resistant isolates, but was less active against streptococci and Bacteroides species. Amifloxacin had in vitro activity similar to enoxacin, ofloxacin, and norfloxacin, but was less active than ciprofloxacin. Like other quinolones, it was less active at acid pH and in the presence of urine.

Anti-Bacterial Agents↗
PubMed1985

The in vitro activity and beta-lactamase stability of cefpiramide compared with other beta-lactam antibiotics.

The in vitro activity of cefpiramide, a new ureido cephalosporin antibiotic, was determined against 1128 gram-positive and gram-negative aerobic and anaerobic bacteria selected for resistance to ampicillin and cefazolin. Cefpiramide was less active on a milligram basis than cefotaxime, ceftazidime, moxalactam, and aztreonam against all of the members of the Enterobacteriaceae. Cefpiramide inhibited many Pseudomonas aeruginosa resistant to carbenicillin, piperacillin, and cefotaxime, but it was less active than ceftazidime and cefsulodin. Cefpiramide inhibited staphylococci and streptococci and had appreciable activity against Streptococcus faecalis and Listeria moncytogenes. It had less activity than cefoxitin against anaerobic species. Cefpiramide inhibited permeability mutants of Escherichia coli at lower concentrations than the parent strain, suggesting an effect of entry upon its activity. Although cefpiramide was resistant to attack by most chromosomal beta-lactamases, it was hydrolyzed by the common plasmid beta-lactamases TEM and SHV and by the chromosomal Proteus vulgaris, type Ic, cephalosporinase.

Anti-Bacterial Agents↗
PubMed1985

The pharmacokinetic and bactericidal characteristics of oral cefixime.

The pharmacokinetics of cefixime (FK 027), a broad-spectrum cephalosporin, were assessed in 12 normal subjects after single oral doses of 50, 100, 200, and 400 mg. Mean peak serum concentrations were 1.02, 1.46, 2.63, and 3.85 micrograms/ml after the four respective doses. Respective mean serum levels at 12 hours were 0.16, 0.33, 0.72, and 1.13 micrograms/ml. Volumes of distribution averaged 0.1 L/kg body weight, and the elimination t1/2 was 3 hours for all doses. The AUC was 7.01, 11.4, 22.5, and 36.4 micrograms X hr/ml for the four doses, respectively. Serum clearance averaged 0.4 mg/min/kg and mean 24-hour urinary recovery was 21%, 19%, 20%, and 16% for the four respective doses. Serum bactericidal titers at 4 hours exceeded 1:16 for Streptococcus pneumoniae, S. pyogenes, Hemophilus influenzae, and Branhamella catarrhalis. Urine bactericidal titers exceeded 1:8 for Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae resistant to the available oral cephalosporins.

Administration, Oral↗
PubMed1985

In-vitro activity and beta-lactamase stability and inhibitory properties of a new penem antibiotic, Sch 34343.

Sch 34343 is a new penem antibiotic. Its in-vitro activity was determined against Gram-positive and -negative aerobic and anaerobic isolates. Sch 34343 inhibited 90% of strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella spp, Citrobacter spp. and Shigella spp. at less than 1 mg/1. Ninety per cent of strains of Enterobacter, Morganella and Providencia spp. were inhibited by less than 4 mg/1. Sch 34343 did not inhibit Pseudomonas spp., and it had slightly less activity against Enterobacteriaceae than did cefotaxime or latamoxef (moxalactam), but it inhibited organisms resistant to cefoxitin, cefoperazone and piperacillin. Sch 34343 inhibited methicillin-susceptible Staphylococcus aureus at less than or equal to 0.25 mg/1, and it inhibited haemolytic streptococci at less than or equal to 0.06 mg/1. Sch 34343 inhibited Bacteroides fragilis at 0.06 mg/1, including some cefoxitin-resistant isolates. Sch 34343 was not hydrolysed by plasmid- or chromosomally-mediated beta-lactamases, was an excellent inhibitor of Richmond-Sykes type Ia beta-lactamases, and also inhibited, although less effectively, the common plasmid beta-lactamases. It induced beta-lactamases, but inhibited Enterobacter and Citrobacter spp. in which it induced beta-lactamase activity.

Anti-Bacterial Agents↗
PubMed1985

The in-vitro activity of EN 272, a quinolone-7-carboxylic acid, in comparison with other quinolones.

The in-vitro activity of EN 272, a quinolone-7-carboxylic acid was determined and compared with that of enoxacin, ofloxacin, norfloxacin, ampicillin, cephalexin and trimethoprim. EN 272 inhibited the majority of the Enterobacteriaceae at concentrations of less than or equal to 1.6 mg/l. EN 272 was four- to 32-fold less active than the other new quinolones, but it inhibited organisms resistant to nalidixic acid, ampicillin and cephalexin. EN 272 had poor activity against Pseudomonas aeruginosa and streptococcal species, but it did inhibit most staphylococci at less than or equal to 6.3 mg/l. EN 272 was less active at pH 5.5 and in urine as are other quinolones.

Anti-Bacterial Agents↗
PubMed1985

The in-vitro activity of a novel penem FCE 22101 compared to other beta-lactam antibiotics.

FCE 22101 is a penem antibiotic which inhibits the majority of Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae at concentrations of 0.5-4 mg/l. It inhibits staphylococci, haemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.25 mg/l. Pseudomonas aeruginosa and other Pseudomonas species are resistant. Bacteroides fragilis and Clostridium species are inhibited by less than or equal to 1 mg/l. FCE 22101 is not hydrolyzed by the common plasmid and chrosmosomal beta-lactamases. It shows minimal discrepancy between MIC and MBC values and there is minimal effect of inoculum size. Although FCE 22101 is generally less active against Enterobacteriaceae than are cefotaxime and ceftazidime, it does inhibit some Enterobacter spp. resistant to these agents. FCE 22101 and imipenem are similar in activity against Gram-positive and anaerobic species.

Anti-Bacterial Agents↗
PubMed1985

In-vitro activity of ofloxacin, a quinolone carboxylic acid compared to other quinolones and other antimicrobial agents.

Ofloxacin is a new quinolone carboxylic acid compound. Its activity against 900 bacterial isolates was determined. It inhibited 90% of Escherichia coli, Klebsiella sp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Citrobacter spp., Enterobacter spp., Morganella morganii, Proteus mirabilis, Yersinia enterocolitica at less than or equal to 0.8 mg/l. Branhamella catarrhalis, Haemophilus sp., Neisseria sp. were inhibited by less than or equal to 0.1 mg/l. Pseudomonas aeruginosa and other Pseudomonas species were inhibited by less than or equal to 6.3 mg/l. Although most staphylococcal species, including methicillin-resistant staphylococci were inhibited by 3.1 mg/l, many streptococcal species had higher MIC values, and most Bacteroides species were inhibited at less than or equal to 6.3 mg/l. The overall activity of ofloxacin was similar to enoxacin and norfloxacin. Ofloxacin inhibited organisms resistant to nalidixic acid, ampicillin, cephalexin, piperacillin, and gentamicin including Enterobacter spp., Citrobacter freundii and Serratia marcescens resistant to cefotaxime. The activity of ofloxacin was lower at an acid pH and in urine, but serum had no effect on MICs or MBCs. Increase in ofloxacin MICs for various bacteria could be achieved by repeated subculture in the presence of ofloxacin.

Animals↗