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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 55 records · Page 3Linked to original sources

The in-vitro activity of new streptogramins, RP 59500, RP 57669 and RP 54476, alone and in combination.

RP 59500 is a 30:70 mixture of RP 57669 and RP 54476. The activity of RP 59500 and its two components against Gram-positive and Gram-negative organisms was compared with that of clarithromycin, roxithromycin, azithromycin and rokitamycin. RP 59500 inhibited 90% of erythromycin-susceptible and resistant Staphylococcus aureus and coagulase-negative staphylococci at less than or equal to 1 mg/L (range 0.06-2 mg/L). Both inducibly and constitutively-resistant strains of S. aureus, as well as strains resistant to rifampicin, gentamicin and ciprofloxacin, were inhibited. Streptococcus pyogenes, including erythromycin-resistant isolates, and group C and G streptococci were inhibited by 0.5 mg/L. Streptococcus pneumoniae and viridans group streptococci were inhibited by 1 mg/L. The MIC90 was 4 mg/L for Haemophilus influenzae and 1 mg/L for Moraxella catarrhalis. RP 59500 did not inhibit Enterobacteriaceae or Pseudomonas aeruginosa. The activity of RP 59500 against streptococci was less than that of the four other macrolides. Clostridium perfringens strains were highly susceptible, as were Bacteroides spp. RP 59500, when combined with ciprofloxacin, cefotaxime or gentamicin, did not have altered activity against susceptible species or alter the activity of the other component of the combination against susceptible species. MBCs in serum were increased two- to four-fold for S. pyogenes, S. pneumoniae and S. aureus, compared with MBCs in broth, but RP 59500 was as active at pH 6 as at pH 7, and there was not an appreciable inoculum effect. RP 59500 has potential use as an agent against inducibly and constitutively erythromycin-resistant isolates of Gram-positive species and selected anaerobic organisms.

Azithromycin↗

In vitro activity of OPC-17116.

The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal to 0.25 microgram/ml. At less than or equal to 2 micrograms/ml, 90% of the Enterobacteriaceae were inhibited, which was comparable to or better than the activities of fleroxacin, ofloxacin, and lomefloxacin but less than the activity of ciprofloxacin. OPC-17116 inhibited 90% of the staphylococci tested at less than or equal to 0.25 micrograms/ml, but it did not inhibit methicillin-resistant, ciprofloxacin-resistant Staphylococcus aureus or Staphylococcus epidermidis. Group A, B, C, F, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.5 microgram/ml, being four-fold more active than ciprofloxacin and ofloxacin. Tosufloxacin was the most active agent tested against gram-positive cocci. OPC-17116 inhibited Bacteroides fragilis at 4 micrograms/ml. There was a minimal effect of inoculum size on MIC, and the MBCs were within 1 dilution of the MICs. The activity of OPC-17116 was decreased at pH 6 and in the presence of high Mg2+ concentrations, but it was unaffected by human serum. OPC-17116 showed a postantibiotic effect against Pseudomonas aeruginosa and Staphylococcus aureus similar to the postantibiotic effects reported for other fluoroquinolones. The frequency of spontaneous single-step resistance was low (less than 10(-9)), but repeated passage of organisms in the presence of OPC-17116 resulted in the selection of resistant isolates.

Anti-Infective Agents↗

In vitro activity and susceptibility to hydrolysis of S-1006.

The in vitro activity of S-1006, the active component of a new orally absorbed cephalosporin, S-1108, inhibited 90% of Staphylococcus aureus isolates at less than or equal to 2 micrograms/ml, 90% of group A, B, C, F, and G streptococci and Streptococcus pneumoniae isolates at less than or equal to 0.12 microgram/ml, and all Haemophilus influenzae isolates at less than or equal to 0.06 microgram/ml. Although 50% of the members of the family Enterobacteriaceae were inhibited by less than or equal to 2 micrograms of S-1006 per ml, Enterobacter spp. and Citrobacter freundii resistant to ceftriaxone were resistant to S-1006. The MICs of S-1006 for approximately 20% of Providencia, Proteus vulgaris, and Serratia isolates were 4 micrograms/ml. S-1006 was hydrolyzed by the plasmid TEM-3, TEM-5, PSE-1, and PSE-4 beta-lactamases and by the chromosomal beta-lactamase of Enterobacter and Morganella spp. and P. vulgaris.

Bacteria↗

In vitro activity and beta-lactamase stability of LJC 10,627.

The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.

Carbapenems↗

In vitro activity of MC-352, a new 16-membered macrolide.

The in vitro activity of MC-352, 3,4'-dideoxy-5-O-mycaminosyltylonolide, was compared with those of erythromycin, clarithromycin, and rokitamycin. The MC-352 MIC90 (MIC for 90% of isolates) for erythromycin-susceptible Staphylococcus aureus and Staphylococcus epidermidis was less than or equal to 1 microgram/ml, similar to those of the other agents. The MC-352 MIC50 for erythromycin-resistant S. aureus was 2 micrograms/ml, similar to that of rokitamycin. The MC-352 MIC90 (0.12 micrograms/ml) for Streptococcus pyogenes was similar to those of erythromycin and clarithromycin and superior to that of rokitamycin, and the MC-352 MIC90 for group B, C, and G streptococci was 0.25 microgram/ml. MC-352 and clarithromycin had an MIC90 of 0.12 microgram/ml for Streptococcus pneumoniae. Erythromycin-susceptible Enterococcus faecalis was inhibited by MC-352 at 1 microgram/ml, but the MIC for constitutively erythromycin-resistant isolates was greater than 16 micrograms/ml. Legionella pneumophila was inhibited by less than or equal to 0.25 microgram/ml. MC-352 was the most active agent against Bacteroides fragilis, with an MIC90 of 8 micrograms/ml, and was more active than the other agents against Haemophilus influenzae, with an MIC90 of 4 micrograms/ml. Moraxella spp. were inhibited by MC-352 at less than or equal to 0.25 microgram/ml. The MIC90 for Escherichia coli, Klebsiella pneumoniae, and Salmonella, Shigella, Yersinia, Enterobacter, Citrobacter, and Serratia spp. was greater than or equal to 32 micrograms/ml. MC-352 was bactericidal for S. pyogenes and S. pneumoniae, and its activity was not altered by human serum.

Anti-Bacterial Agents↗

Quinolone antimicrobial agents.

This chapter reviews the chemistry, microbiology, pharmacology, and clinical use of the fluoroquinolone antimicrobial agents. The molecular and clinical problems of bacterial resistance are reviewed. The clinical areas in which fluoroquinolones have been investigated are detailed, with particular attention to areas of appropriate and inappropriate use.

4-Quinolones↗

Use of antimicrobial agents to treat central nervous system infection.

When dealing with infections of the central nervous system (CNS), the clinician is often faced with a daunting diagnostic and therapeutic challenge. The clinical presentation can vary from an insidious course that allows time for a full diagnostic examination to fulminant catastrophic events that require immediate therapeutic intervention. Fortunately, a thorough clinical evaluation combined with current laboratory and imaging techniques often allows for a prompt provisional diagnosis of infection. Clinical experience and scientific investigation have laid the basis for rational empiric antimicrobial therapy of CNS infection. The role of antibiotics in the treatment of CNS infections is reviewed and updated, emphasizing current rationale for empiric therapy as well as the proper use of specific antibiotics for specific pathogens.

Anti-Bacterial Agents↗

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Mupirocin treatment of nasal staphylococcal colonization.

The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study. Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus. Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains. Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains. At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized. Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates. None of the subjects had serious adverse effects. Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated.

Adult↗

Clinical microbiology of azithromycin.

Azithromycin contains an aza-methyl substitution in the 15-membered aglycone ring and as such it is the prototype antibiotic of the azalide class, similar in mechanism of activity to the macrolides. It demonstrates a broad spectrum of activity against many aerobic and anaerobic Gram-positive species, and also inhibits a number of important aerobic and anaerobic Gram-negative bacteria. Significantly, azithromycin shows good activity against Haemophilus influenzae, an organism against which older macrolide antibiotics have proved disappointing. It is highly effective in inhibiting clinically significant intracellular pathogens such as Chlamydia trachomatis and Legionella. Bactericidal activity is seen for certain streptococci and for H. influenzae. Closely linked with azithromycin's microbiologic activity are its novel pharmacokinetics. Azithromycin moves rapidly from blood to tissue compartments where it remains for prolonged periods. Although serum concentrations remain low, the levels attained in the tissues (often greater than 2 mg/kg) are higher than the minimum inhibitory concentration for many common pathogens, and delivery of drug to infection sites by phagocytic cells contributes to these concentrations. This penetration into eukaryotic and prokaryotic cells may be responsible for azithromycin's expanded spectrum of activity, particularly against intracellular organisms. The use of antibiotic blood levels as breakpoints for susceptibility would appear to be inappropriate in the case of azalides. Rather, levels of drug at the tissue site of infection should be considered as guides to predicting efficacy. The in vitro activity of azithromycin, together with its unique tissue pharmacodynamics, define an agent that should demonstrate utility in infections of the respiratory tract, skin and skin structures, and certain sexually transmitted diseases.

Animals↗

Bactericidal activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae and streptococcal pathogens.

The serum bactericidal activity of clarithromycin in six normal human volunteers was determined after oral doses of 500 mg. The mean plasma levels of clarithromycin plus 14-hydroxy clarithromycin were 2.11 micrograms/mL after the second dose and 4.36 micrograms/mL after the sixth dose. The mean serum bactericidal titer against Haemophilus influenzae after the second dose was 1:8 and after the sixth dose 1:16 when unheated serum was used. Similar values were obtained when serum to which clarithromycin and 14-hydroxy clarithromycin was added was tested. Mean serum bactericidal titers against H. influenzae determined in Haemophilus test broth or heated serum were 1:2 and 1:4, respectively. Against Streptococcus pneumoniae and Streptococcus pyogenes, there was greater than 1:16 serum bactericidal levels at 12 hours after the sixth dose of clarithromycin.

Administration, Oral↗

Cephalosporins--cefotaxime 10 years later, a major drug with continued use.

Cefotaxime has in the past decade proved to be a most useful agent. It has established the efficacy and safety suggested in the early in vitro, pharmacological and clinical papers. It remains an excellent agent to treat many community and hospital-acquired respiratory infections, urinary tract infections, meningitis, particularly in pediatrics, spontaneous bacterial peritonitis and selected abdominal and gynecological infections.

Bacterial Infections↗

Synergy and antagonism of combinations with quinolones.

Combinations of fluoroquinolones with other antimicrobial agents have been extensively investigated. Combinations of fluoroquinolones with aminoglycosides, beta-lactams, imidazoles, macrolides and clindamycin infrequently show synergy against Enterobacteriaceae and gram-positive bacteria. These combinations rarely show antagonism. Combinations of rifampin with fluoroquinolones tested against Staphylococcus aureus have been reported to show synergy and antagonism, and in vitro results have not correlated with results of animal infection experiments. Against Pseudomonas aeruginosa combinations of antipseudomonas penicillins or imipenem with fluoroquinolones are synergistic for 20% to 50% of isolates in vitro and also are synergistic in animal models of infection, whereas combinations of aminoglycosides with fluoroquinolones rarely show synergy against Pseudomonas aeruginosa. Against anaerobic species such as Bacteroides fragilis combinations of fluoroquinolones with clindamycin, anti-anaerobic penicillins, cephalosporins or imidazoles are occasionally synergistic but usually indifferent. Ciprofloxacin and ofloxacin combined with antituberculosis agents have activity against Mycobacterium tuberculosis and atypical mycobacteria. In general, fluoroquinolones should be combined with other agents not to achieve synergy, which is extremely variable, but to provide activity against bacteria inadequately inhibited by the fluoroquinolones.

4-Quinolones↗

In vitro activity of Ro 09-1428 compared to other cephalosporins.

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms. Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040. Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates. The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins. For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P-99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.

Cephalosporins↗

In vitro activity of cefcanel versus other oral cephalosporins.

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml. Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins. Clostridium spp. were inhibited by 0.25 micrograms/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp. The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime. Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases. Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1.

Administration, Oral↗

In-vitro activity of WIN 57273 compared to the activity of other fluoroquinolones and two beta-lactam antibiotics.

WIN 57273, a new fluoroquinolone, was four to 128-fold more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. The MIC90 for Staphylococcus aureus was 0.015 mg/l and for S. epidermidis, 0.03 mg/l. All Lancefield group A, B, C, & G streptococci, Streptococcus bovis and S. pneumoniae were inhibited by less than or equal to 0.06 mg/l compared to 0.5 mg/l for tosufloxacin and 2 mg/l for ciprofloxacin. For anaerobic bacteria WIN 57273 had an MIC90 for bacteroides of 1 mg/l, and for Clostridium spp. 0.015.mg/l. WIN 57273 was less active than ciprofloxacin against Enterobacteriaceae, with an MIC90 of 1 mg/l, including aminoglycoside and cephalosporin-resistant isolates. The MIC90 of WIN 57273 for Pseudomonas aeruginosa was 2 mg/l, compared to 0.5 mg/l for ciprofloxacin. Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. were inhibited by 0.06 mg/l. WIN 57273 was more active against Gram-negative bacteria at acid pH, but activity was decreased by magnesium ions and an increase in inoculum. Resistant strains were selected after passage on antibiotic-containing agar.

Anti-Infective Agents↗