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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 163 records · Page 9Linked to original sources
PubMed1987

Editors' roundtable: Current formulas for P & T Committee success (Part 1).

In this roundtable discussion, the four editors of Hospital Formulary--Arthur G. Lipman, Pharm D, Harold C. Neu, MD, Bramah N. Singh, MD, PhD, and Michael Weintraub, MD--share their views on key issues that affect hospital P & T Committees. They agree that the P & T Committee is both highly visible and functions well, and they predict that its influence in the health care system wil heighten as prospective reimbursement continues. Challenges P & T Committees are confronted with today, such as therapeutic entities from new technologies, use of approved drugs for unapproved indications, and the need for educating and re-educating the medical staff are discussed. Cost containment continues to become a more and more important consideration with maintained patient care quality. Successful strategies for coping with and benefiting from these challenges are presented.

Conflict, Psychological↗
PubMed1987

Penicillin-binding proteins and beta-lactamases: their effects on the use of cephalosporins and other new beta-lactams.

Alteration of PBPs has proved an effective way for gram-positive bacteria to become resistant to beta-lactams. The gram-positive species have not been able to use decreased permeability or synthesis of novel beta-lactamases to overcome the advances by medicinal chemists. Nonetheless, altered PBPs have proved to be a formidable form of resistance for staphylococci, enterococci, and even some S. pneumoniae. Although isolated examples of resistance of gram-negative species to beta-lactams have been seen for E. coli, Serratia, or P. aeruginosa, in general this form of resistance has not been used by the gram-negative species except by N. gonorrhoeae. Conversely gram-negative bacteria have used beta-lactamases as an effective weapon to overcome the advances in medical chemistry that have provided beta-lactamase inhibitors and structurally stable cephalosporins, monobactams, and carbapenems. Derepression or induction of beta-lactamases has provided species such as E. cloacae and P. aeruginosa the ability to resist destruction by new cephalosporins. The original concept of beta-lactamase as a trap or sponge has been shown to be inaccurate, and we realize that the high concentration of beta-lactamase in the periplasmic space combined with a decreased or slow entry of the beta-lactam allows an efficient acylation of the so-called stable cephalosporins with hydrolysis of these compounds. Although the PBPs and beta-lactamases are clear problems, there is the potential for future modification of beta-lactam structures to increase affinity to PBPs and decrease beta-lactamase affinity. Bacterial populations do have the ability to create transferable resistance even to extended spectrum beta-lactams. It will be necessary to carefully monitor the development of resistance to new beta-lactams. However, advances in the chemistry of beta-lactams should offer solutions to these real but potentially controllable problems.

Anti-Bacterial Agents↗
PubMed1987

The post-antimicrobial suppressive effect of quinolone agents.

A post-antimicrobial effect (PAE) was seen with all of the new 4-quinolones studied: ciprofloxacin, ofloxacin, Cl-934, Ro 23-6240, A-56619 and S-25930. The post-antimicrobial suppression of growth was for 4-8 h in the case of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa. PEA was demonstrated both in Mueller-Hinton broth at pH 7.4 and in urine at pH 5.5 with a Mg2+ concentration of 9.5 mM. Resistant organisms, with MICs greater than 4 micrograms/ml, showed a PAE after a 2-h exposure to 200 micrograms/ml of 4-quinolones. This demonstrates that PAE is seen for 4-quinolones even under conditions in which they are less active.

Anti-Bacterial Agents↗
PubMed1987

In vitro antibacterial activity and beta-lactamase stability of CL 118523, an aminothiazolyl iminomethoxy cephalosporin.

CL 118523 is an aminothiazolyl cephalosporin which contains a 1, 2, 3-thiadiazol radical at position 3 of the cephem nucleus. It was as active as cefotaxime, ceftazidime and aztreonam against most Enterobacteriaceae, MIC 90% less than 1 mg/l, and more active, 8 to 32-fold, than cefoperazone and cefoxitin. Enterobacter species resistant to the other agents were resistant to CL 118523. CL 118523 did not inhibit Pseudomonas aeruginosa, Pseudomonas maltophilia, MIC greater than 128 mg/l. It had excellent activity against hemolytic streptococci of groups A, B, C, and G, and methicillin-susceptible Staphylococcus aureus, but failed to inhibit enterococci and methicillin-resistant staphylococci. CL 118523 was minimally hydrolyzed by plasmid and chromosomally-mediated beta-lactamases, and was a poor beta-lactamase inducer.

Bacteria↗
PubMed1986

Antibiotics in the second half of the 1980s. Areas of future development and the effect of new agents on aminoglycoside use.

Articles in this supplement have examined in detail the role of aminoglycosides in the therapy of infections, addressing problems of resistance, toxicity, and efficacy. This article discusses other agents and their potential utility and effect on aminoglycosides. Penem antibiotics, which have activity against only aerobic gram-negative bacteria, have recently been synthesized. These agents have proved effective in animal experiments; to date, however, results of human clinical trials are not available. Carboxypenicillins and ureidopenicillins will still have to be administered with aminoglycosides in patients with serious life-threatening infections or in those institutions in which organisms such as Klebsiella, Enterobacter, and Pseudomonas exhibit high levels of resistance. What will be the role of aminothiazolyl cephalosporins? In some institutions, these agents might be used as sole therapy, particularly if they become less costly as a result of competition. In other settings, concern over the resistance of organisms, such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa, will result in the use of aminoglycosides with these relatively beta-lactamase-stable cephalosporins. It will be necessary to monitor the development of resistance to the new antibiotics and to determine whether the use of aminoglycosides plus third-generation cephalosporin combinations results in decreased resistance. Other agents to be considered include the directed therapy monobactams aztreonam and carumonam, the broad-spectrum carbapenem imipenem, and the penems under development. It is unclear whether these compounds might be used with aminoglycosides in critically ill, infected patients. It is also unclear what role oral beta-lactamase-stable cephalosporins will have in the therapy of nosocomial infections, since they probably will not be effective against many of the urinary or cutaneous infections that are treated with aminoglycosides. Quinolone agents can be used successfully against many infections. However, the likelihood of bacterial resistance developing and their potential for toxicity are still unknown. Thus, despite the emergence of many new agents, it appears that the time-tested aminoglycosides will continue to play an important role in antimicrobial therapy for some time to come.

Aminoglycosides↗
PubMed1986

Oral ciprofloxacin therapy of infections due to Pseudomonas aeruginosa.

The efficacy and safety of oral ciprofloxacin, a fluoroquinolone, were evaluated in the treatment of infection due to Pseudomonas aeruginosa. 96 infections in 71 patients were treated. Substantial underlying disease was present in most of the patients, and 25 (35%) were seriously ill. 52% of pseudomonas isolates were carbenicillin-resistant, and 31% gentamicin-resistant. The overall clinical response rate was 77%-28 of 35 exacerbations of cystic fibrosis respiratory disease, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 11 of 15 soft tissue infections. The bacteriological cure rate was 34%-0 of 35 cystic fibrosis, 4 of 17 respiratory infections, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 8 of 15 soft tissue infections. Ps aeruginosa developed resistance to ciprofloxacin in 25 of 96 infections. Side-effects were generally slight with nausea in 14 (15%) the most common, and there were only two substantial superinfections.

Administration, Oral↗
PubMed1986

Synergy of ciprofloxacin and azlocillin in vitro and in a neutropenic mouse model of infection.

Combinations of ciprofloxacin with azlocillin, piperacillin and ticarcillin were tested in vitro against clinical isolates. Azlocillin plus ciprofloxacin showed synergy against 30% of Pseudomonas aeruginosa isolates; it was either synergistic or additive against 78% of all isolates tested even those resistant to the beta-lactam. Synergism was rarely noted for Klebsiella pneumoniae, Escherichia coli, Enterobacter spp. or Branhamella spp. isolates. Minimum inhibitory concentrations of ciprofloxacin plus azlocillin, plus piperacillin and plus ticarcillin against Pseudomonas spp. were reduced 4 or 2 fold, respectively. However, the combination azlocillin plus ciprofloxacin showed primarily indifference against gram-positive strains. Neutropenic mice infected with a lethal challenge of Pseudomonas spp. were protected by a combination of azlocillin and ciprofloxacin. Its additive and/or synergistic effects and expanded spectrum of activity against streptococci, methicillin-resistant staphylococci and JK corynebacteria may provide an alternative to traditional therapy.

Animals↗
PubMed1986

Histoplasmosis in patients with the acquired immune deficiency syndrome.

Five patients with disseminated histoplasmosis are reviewed. Four of five had the acquired immune deficiency syndrome (AIDS) and one was receiving steroid therapy. All were immigrants to the United States from Puerto Rico, the Dominican Republic, or South America, and none had a history of travel to regions of the United States where Histoplasma is endemic. Histoplasma complement fixation titers to mycelial antigen were not demonstrable in three of three patients in whom they were measured. Of the four patients with AIDS, Histoplasma capsulatum was isolated from bone marrow aspirates in two patients and from lymph node and liver biopsy specimens in one patient each. One of the bone marrow specimens showed organisms on Gomori-methenamine silver stain. In the other three cases, results of staining were falsely negative and diagnosis awaited culture results weeks later. Amphotericin B therapy resulted in rapid clinical improvement in the three patients that were treated. Intravenous therapy was followed by treatment with oral ketoconazole. Follow-up has not been long enough to determine the ultimate efficacy of ketoconazole. Disseminated histoplasmosis should be considered in all patients from the Caribbean or South America with AIDS or who are receiving immunosuppressive therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Antimicrobial activity and beta-lactamase stability of SK&F 88070 compared with other agents.

The in vitro activity and beta-lactamase stability of SK&F 88070 (7-[[2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[ [1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio]methyl]-3- cephem-4-carboxylic acid) a new parenteral cephalosporin was investigated against 780 types of bacteria. SK&F 88070 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, Shigella species, Morganella morganii, and Citrobacter diversus at less than or equal to 0.5 micrograms/ml. Its activity against these species was similar to cefotaxime and moxalactam and superior to cefoperazone and piperacillin. It was less active than cefoperazone against Pseudomonas aeruginosa and less active than cefotaxime or cefoperazone against Staphylococcus aureus. SK&F 88070 inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.12 micrograms/ml. Enterobacter species, Citrobacter freundii, and Serratia, which were resistant to cefotaxime and moxalactam were resistant to SK&F 88070. It was not hydrolyzed by plasmid beta-lactamases, but was hydrolyzed by the Proteus vulgaris type 1c enzyme. SK&F 88070 inhibited Richmond-Sykes type 1a beta-lactamases.

Anti-Bacterial Agents↗
PubMed1986

The activity of BMY 28142 a new broad spectrum beta-lactamase stable cephalosporin.

The in-vitro activity of BMY 28142, an iminomethoxy, aminothiazolyl cephalosporin containing a methyl pyrrolidinio C-3 was compared with that of cefotaxime, ceftazidime, aztreonam, imipenem and tobramycin against various bacteria. BMY 28142 was the most active agent tested against the Enterobacteriaceae inhibiting 90% at less than or equal to 1 mg/l. The in-vitro activity of BMY 28142 was equal to or superior to cefotaxime against the highly susceptible members of the Enterobacteriaceae and several-fold superior to ceftazidime and aztreonam. BMY 28142 inhibited many Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cefotaxime, ceftazidime and aztreonam. BMY 28142 was more active than imipenem against Proteus, Providencia and Morganella species. Ceftazidime and imipenem were more active than BMY 28142 against Pseudomonas aeruginosa, but it inhibited piperacillin and tobramycin-resistant isolates. BMY 28142 inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae. BMY 28142 was more active than ceftazidime against streptococcal and staphylococcal species, but it did not inhibit or kill most methicillin-resistant Staphylococcus aureus. BMY 28142 did not inhibit most Bacteroides species. BMY 28142 was not hydrolyzed by common plasmid and chromosomal beta-lactamases, but it bound poorly to Enterobacter beta-lactamase, was a poor inhibitor of the TEM plasmid beta-lactamase and was a poor inducer of beta-lactamases.

Anti-Bacterial Agents↗
PubMed1986

The in-vitro activity and beta-lactamase stability of carumonam.

Carumonam is a monobactam with a beta-carbamyloxmethyl group at position 4. It inhibited 90% of Enterobacteriaceae at less than or equal to 8 mg/l and had in-vitro activity similar to that of cefotaxime, ceftazidime and aztreonam. Fifty per cent of Enterobacter, Citrobacter and Serratia isolates were inhibited by 4 mg/l, but isolates resistant to aztreonam and ceftazidime were not inhibited. Carumonam, like aztreonam, did not inhibit Gram-positive or anaerobic species. Carumonam was not destroyed by the common plasmid- and chromosomally-mediated beta-lactamases and was more stable than aztreonam to attack by the K-1 beta-lactamase of Klebsiella oxytoca. Carumonam inhibited Richmond-Sykes type Ia and Id beta-lactamases but was a poor inhibitor of type III enzymes. It did not induce beta-lactamases.

Anti-Bacterial Agents↗
PubMed1986

Oral ciprofloxacin therapy of infection caused by multiply resistant bacteria other than Pseudomonas aeruginosa.

Of 125 patients treated with ciprofloxacin at the Columbia-Presbyterian Medical Center, New York, 34 had infections due to bacteria other than Pseudomonas aeruginosa. The mean age of the patients was 50 years (19-88 years) and most had significant underlying disease. There were nine lower respiratory infections, eight urinary tract infections, eight soft tissue infections, three osteomyelitis, and three intra-abdominal infections. The pathogens were: Escherichia coli, 7 (mean MIC 0.07 mg/l); Serratia marcescens, 6 (0.2 mg/l); Enterobacter spp., 5 (0.1 mg/l); Klebsiella pneumoniae, 3 (0.1 mg/l); Proteus mirabilis, 3 (0.06 mg/l); Cutrobacter freundii, 2 (0.06 mg/l), Staphylococcus aureus, 3 (0.5 mg/l); and one each of Acinetobacter anitratus. Haemophilus, influenzae, Salmonella enteritidis, Flavobacterium meningosepticum, and Streptococcus faecalis. Of these organisms 81% were resistant to ampicillin, 70% to carbenicillin, 22% to gentamicin, 49% to cefazolin and cephalexin, and 25% to cotrimoxazole. Ten patients had concomitant Ps. aeruginosa infections. Patients were treated orally with 500 mg or 750 mg ciprofloxacin every 12 h. The overall clinical response rate was 88%, and the bacteriological response 76%, and 65% if Ps. aeruginosa is included. Resistance to ciprofloxacin developed in one Staph. aureus and one Ser. marcescens (MIC greater than 2 mg/l). Toxicity was minor. Ciprofloxacin was effective and safe therapy of infections due to Gram-negative bacteria resistant to many of the currently available oral and parenteral agents.

Administration, Oral↗
PubMed1986

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.

Anti-Bacterial Agents↗
PubMed1986

Comparative antibacterial activity of an arylglycyl oral cephalosporin, LY164846.

LY164846 is a semisynthetic arylglycyl cephalosporin which can be absorbed orally. It had in vitro activity comparable to that of cefaclor against beta-hemolytic streptococcal species and was two- to fourfold more active than cephalexin. Enterococci and Listeria species were resistant, and its activity against staphylococci was similar to that of other oral cephalosporins. Although some Bacteroides species were inhibited, the MICs for 25% were greater than or equal to 16 micrograms/ml. LY164846 was hydrolyzed by Staphylococcus aureus beta-lactamase and by cephalosporinases, but it was more stable than cefaclor.

Administration, Oral↗