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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 73 records · Page 4Linked to original sources
PubMed1991

The development of macrolides: clarithromycin in perspective.

Macrolide antibiotics have been available and used clinically since 1952. The class of drugs originated from a soil sample obtained from the City of Ilo-Ilo on the Island of Paray in the Philippines. Erythromycin has been the most widely used agent of this class called 'macrolides' because they possess the macrocyclic lactone nucleus. Many esters of erythromycin are well established as agents to treat a variety of respiratory and cutaneous infections, particularly in children. There has been a resurgence of interest in macrolides as a result of the recognition of pathogens such as Legionella, Chlamydia and Campylobacter spp. A number of new 14-membered macrolides have been synthesised in recent years with the goal of overcoming some of the problems of the older erythromycin agents. There has been variable activity of erythromycin against Haemophilus influenzae; there has been gastrointestinal irritation, particularly in adults; and the older agents are administered four times a day. Clarithromycin has increased activity against Legionella, and Branhamella spp., and Pasteurella multocida, and, with its 14-OH metabolite, inhibits Haemophilus spp. It is also more active against chlamydia and against anaerobic species while retaining excellent activity against streptococci including Streptococcus pneumoniae. It has increased plasma peak levels and a sufficiently long half-life for twice daily administration. Furthermore, it is well tolerated. Thus clarithromycin offers potential for use in those areas in which a safe, well tolerated macrolide will be used, namely respiratory, skin structure and selected diarrhoeal and genital infections.

Anti-Bacterial Agents↗
PubMed1991

In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin.

GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.

Cephalosporins↗
PubMed1991

In vitro activity of sparfloxacin.

Sparfloxacin, a new fluoroquinolone, inhibited the majority of members of the family Enterobacteriaceae at less than or equal to 1 microgram/ml. It was less active than ciprofloxacin but more active than ofloxacin. Against Pseudomonas aeruginosa, it was less active than ciprofloxacin but twofold more active than ofloxacin. It inhibited Staphylococcus aureus and most Streptococcus pneumoniae and Streptococcus pyogenes isolates at 0.25 micrograms/ml, whereas ciprofloxacin and ofloxacin inhibited these isolates at 2 micrograms/ml. Bacteroides fragilis was inhibited by less than or equal to 2 micrograms/ml. Sparfloxacin was less active at an acidic pH and in the presence of Mg2+. Resistance to sparfloxacin was produced by repeated exposure, although the frequency of single-step mutants was less than 10(-9).

Anti-Infective Agents↗
PubMed1991

Activity of mersacidin, a novel peptide, compared with that of vancomycin, teicoplanin, and daptomycin.

Mersacidin, a new peptide antibiotic, was four- to eightfold less active (MIC for 90% of isolates, 8 micrograms/ml) than vancomycin, teicoplanin, or daptomycin against Staphylococcus aureus. Coagulase-negative staphylococci were inhibited by 8 micrograms/ml, and the MICs of mersacidin for hemolytic streptococci and Streptococcus pneumoniae were 4 to 8 micrograms/ml. The mersacidin MICs for anaerobic organisms were as follows: Clostridium perfringens, 4 micrograms/ml; Propionibacterium acnes, 8 micrograms/ml; peptococci, 1 microgram/ml; and peptostreptococci, 8 micrograms/ml. Mersacidin had no activity against members of the family Enterobacteriaceae, Neisseria and Haemophilus species, or Pseudomonas aeruginosa. The size of the inoculum, the pH of the assay (5.5 to 7.5), the type of medium, and the anaerobic conditions had minimal effects on the MICs and MBCs of mersacidin. Overall, mersacidin proved less active than available glycopeptides and peptolides.

Anti-Bacterial Agents↗
PubMed1991

Microbiologic aspects of fluoroquinolones.

Fluoroquinolones are both old and new antimicrobial agents. The prototype agent of the class, nalidixic acid, was synthesized in 1962, whereas the new fluoroquinolones began to be used in the latter 1980s. During the past six years, orally administered fluoroquinolones have been used extensively in Japan and Europe to treat both community- and hospital-acquired infections. Most recently, one of the fluoroquinolones, ciprofloxacin, has also become available for parenteral and topical ophthalmic use. This article reviews the chemistry, antimicrobial activity, pharmacology, and clinical use of the fluoroquinolones.

4-Quinolones↗
PubMed1991

The place of quinolones in bacterial infections.

The quinolone antimicrobial agents are important therapeutic compounds for many infections. They have potential as substitutes for many parenteral agents, particularly in treating urinary tract, diarrheal, bone and joint, and some respiratory tract infections. The quinolones are important prophylactic agents for neutropenic patients. Adverse reactions to these compounds have been exceedingly infrequent. Important drug-drug interactions occur, and the absorption of the compounds can be markedly impaired by antacids. Resistance to quinolones is already a serious problem in some countries. Improper use in the United States will rapidly make the new quinolones ineffective treatment for staphylococcal, Pseudomonas, and even some Enterobacteriaceae infections. Careful attention to those situations in which resistance has been shown to develop is necessary.

4-Quinolones↗
PubMed1990

Antibacterial therapy: problems and promises, Part II.

Numerous antibacterial agents recently or soon to be available are reviewed: new quinolones, macrolides, aminoglycosides, glycopeptides, and lipopeptides. Overall, these agents do much to improve antibacterial activity against problem organisms, overcome resistance, and reduce toxicity and frequency of administration. Many are orally administered and will shorten hospital stays.

Aminoglycosides↗
PubMed1990

Antibacterial therapy: problems and promises, Part I.

Agents approved for clinical use in the past five years and others most likely to be available in the near future are evaluated in this two-part review. This installment is devoted entirely to the beta-lactam antibiotics--penicillins, cephalosporins, monobactams, and carbapenems. There are more similarities than differences among them, but the variations give each agent a range of appropriate uses.

Anti-Bacterial Agents↗
PubMed1990

Pathophysiologic basis for the use of third-generation cephalosporins.

After 10 years of use, the third-generation cephalosporins remain excellent antibiotics. They have superior activity against selected streptococcal species compared with other cephalosporins, and superior activity against Haemophilus, Neisseria, Branhamella, and other less common oral gram-negative aerobic species. Despite a very broad spectrum of activity, the third-generation cephalosporins, like all other cephalosporins, have only poor activity against enterococci, Listeria, Corynebacterium jekeium, and methicillin-resistant staphylococci. Over the past 10 years, the activity of the third-generation cephalosporins against Escherichia coli, Klebsiella, Proteus, Providencia, Serratia, Haemophilus, and Neisseria has remained excellent. Equally as important, though perhaps less well recognized, is the activity of some of these agents against mouth anaerobic species and the anaerobic Bacteroides and Clostridium spp. of the pelvic area. At present, there are two main threats to the continued use of the third-generation cephalosporins. These are the increasing number of infections due to Enterobacter spp., which constitutively produce large amounts of a beta-lactamase that hydrolyzes cephalosporins, and the recent appearance of Klebsiella spp. in many parts of the world that possess new plasmid-mediated beta-lactamases that destroy cefotaxime, ceftazidime, and related third-generation parenteral cephalosporins. Correlation of pharmacologic properties with in vitro activity provides information as to reasonable dosage regimens for the third-generation cephalosporins. For most serious infections cefotaxime, ceftizoxime, and ceftazidime should be given three times a day provided that the patient has relatively normal renal function. Ceftriaxone can be administered once daily in less severe infections. The use of lower doses or less frequent dosing with cefotaxime, ceftizoxime, or ceftazidime is recommended in aged patients whose renal function is impaired. The unique interaction of cefotaxime with its active metabolite, desacetylcefotaxime, allows cefotaxime to be administered less frequently than three times a day in selected anaerobic infections. Correlation of the antibacterial activity and pharmacology of cephalosporins will help us to tailor their use more appropriately, so that the third-generation cephalosporins will remain useful antimicrobial agents for a further decade.

Bacteria↗
PubMed1990

Aztreonam activity, pharmacology, and clinical uses.

Aztreonam, the first monobactam, has been used extensively in the treatment of a variety of infections caused by gram-negative pathogens. It has been shown to be highly effective against susceptible bacteria without causing serious adverse reactions. Its pharmacologic profile can be attributed to its unique chemical properties and mechanisms of action, which differ substantially from those of the bicyclic beta-lactams, such as the penicillins and cephalosporins. Administered parenterally, aztreonam provides peak serum concentrations for most Enterobacteriaceae and Pseudomonas aeruginosa. It is widely distributed throughout the body. Excretion is largely dependent on renal mechanisms, so dosage can be adjusted in the presence of renal impairment. The clinical uses of aztreonam include treatment of urinary tract, lower respiratory tract, and intraabdominal infections, as well as septicemia, endometritis, pelvic cellulitis, and skin and skin structure infections due to aerobic gram-negative organisms. It is concluded that aztreonam can be used with confidence in the single-drug treatment of susceptible aerobic, gram-negative pathogens. In the treatment of mixed infections, or those of unknown etiology, however, combination therapy is recommended to ensure coverage of gram-positive and anaerobic bacteria.

Aztreonam↗
PubMed1990

Third generation cephalosporins: safety profiles after 10 years of clinical use.

Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic than the penicillins. Nephrotoxicity has not been a problem at recommended doses. Some third generation agents can cause hypoprothrombinemia if not administered with vitamin K, and disulfiram-like reactions occur with some agents because of the presence of a thiomethyl tetruzole moiety affixed to the cephem nucleus. There is a greater incidence of diarrhea associated with the agents excreted through a primarily biliary route, and this may contribute to the selection of drug resistant bacteria. Some agents are less active against staphylococci and their use may result in an increased incidence of superinfection or overgrowth of enterococci. If attention is given to the potential for adverse effects, many of these problems can be avoided and the third generation cephalosporins can be used safely in hospitals, nursing homes, and home care settings.

Bacterial Infections↗
PubMed1990

In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522.

The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 2 micrograms/ml, compared to MICs of greater than or equal to 8 micrograms/ml for the other cephalosporins tested. It was more active against Streptococcus pyogenes (MIC less than or equal to 0.06 microgram/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at less than or equal to 0.12 microgram/ml, while the MI"90 for Streptococcus bovis and viridans streptococci was 0.5 and 2 micrograms/ml, respectively. The MIC90 for enterococci and Listeria monocytogenes was 8 micrograms/ml. Clostridium perfringens was inhibited by 0.12 microgram/ml, but most Bacteroides spp. were resistant. The MIC90 for beta-lactamase positive Escherichia coli (producing primarily TEM-1) was greater than 64 micrograms/ml and for beta-lactamase negative strains 16 micrograms/ml. The MIC90 for high-level beta-lactamase producing Klebsiella pneumoniae was greater than 64 micrograms/ml versus 4 micrograms/ml for other isolates. The MIC90 for Moraxella catarrhalis was 2 micrograms/ml, for Haemophilus influenzae 1 micrograms/ml, and for Neisseria gonorrhoeae 4 micrograms/ml. Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. and Pseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.

Administration, Oral↗
PubMed1990

Antimicrobial activity and beta-lactamase stability of BMY-28232, parent compound of an oral cephalosporin.

BMY-28232, an aminothiazolyl imino methoxy cephalosporin which is available as an orally absorbed acetoxyethyl ester, inhibited strains of methicillin-susceptible Staphylococcus aureus, hemolytic streptococci, Streptococcus pneumoniae, Escherichia coli, Klebsiella species, and many strains of Proteus and Providencia stuartii at concentrations less than 1 microgram/ml, including isolates resistant to cephalexin and cefaclor. It had activity similar to that of cefixime, but was more active against methicillin-susceptible staphylococci. BMY-28232 was a poor substrate for beta-lactamases but was destroyed by the new TEM-3 enzyme, and had less activity against Enterobacter species, Citrobacter freundii, and Proteus vulgaris isolates. Methicillin-resistant staphylococci, Pseudomonas species, enterococci, Listeria monocytogenes, Corynebacterium jeikeium, Bacteroides fragilus and some strains of Clostridium species were resistant to BMY-28232.

Bacteria↗
PubMed1990

Beta-lactamases, beta-lactamase inhibitors, and skin and skin-structure infections.

beta-Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus. The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated beta-lactamases were recognized in the Enterobacteriaceae, Haemophilus, and chromosomally mediated beta-lactamases in Klebsiella, and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of beta-lactamases. Clavulanate is a beta-lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit beta-lactamase-producing bacteria and retain activity against Pseudomonas. Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other beta-lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate-amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections.

Bacteria↗
PubMed1990

Combination of ofloxacin and other antimicrobial agents.

We evaluated the combination of ofloxacin with piperacillin, gentamicin, vancomycin, rifampin, clindamycin, and metronidazole by the checkerboard agar dilution method against 165 isolates which included Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa, Providencia stuartii, Acinetobacter, Staphylococcus aureus, Bacteroides fragilis, and Citrobacter perfringens. Synergy of piperacillin-ofloxacin was demonstrated for 50% and 40% respectively of E. cloacae and P. aeruginosa. Some ofloxacin and piperacillin-resistant isolates were susceptible with the combination. Ofloxacin-gentamicin was indifferent for aerobic gram-negative species. Ofloxacin and vancomycin or gentamicin was indifferent for S. aureus and E. faecalis, but rifampin-ofloxacin showed addition. Combination of ofloxacin and metronidazole or clindamycin or erythromycin was indifferent for aerobic and anaerobic species. Ofloxacin could be combined with piperacillin with benefit against P. aeruginosa, but combination with aminoglycosides is not of benefit.

Anti-Infective Agents↗
PubMed1990

Bacteraemia--a New York perception.

Positive blood cultures (in total 7541) obtained from patients of varied social background in a New York medical centre between 1984 and 1989 are reviewed. Streptococcus pneumoniae predominated in community-acquired infections, and coagulase-negative staphylococci and Staphylococcus aureus in nosocomial infections, the latter often arising from intravenous lines. The reported trend towards Gram-positive isolates is confirmed in this series.

Cross Infection↗
PubMed1990

Quinolones in perspective.

Fluoroquinolones have been in use for the past five years. The agents inhibit Enterobacteriaceae, Pseudomonas aeruginosa, and staphylococci, but some agents lack activity against streptococci and none of the commercially available agents inhibits anaerobic species. The fluoroquinolones possess many pharmacological advantages which have made them excellent therapy for urinary, selected respiratory, gastrointestinal, skin, soft tissue, bone, and sexually transmitted infections. They have also proved useful as prophylaxis in neutropenic patients. A major problem for the future is that inappropriate and indiscriminate use of quinolones will cause rapid development of resistance, particularly among staphylococci and P. aeruginosa.

4-Quinolones↗