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H C Neu

Publications and source records attributed to H C Neu.

At least 37 records · Page 2Linked to original sources

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

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

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

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

Kinetics of intravenous amoxicillin in patients on long-term dialysis.

The kinetics of intravenous amoxicillin was studied in 8 patients with creatinine clearances of less than 7 ml/min who were on long-term hemodialysis. Kinetic parameters were determined using a 2-compartment linear model. The serum half-life (t1/2) of amoxicillin in these patients ranged from 7.5 to 21 hr. The t1/2 fell to 2.84 +/- 0.45 hr during dialysis. Approximately 30% of the dose was recovered in the dialysate during 4 hr of dialysis and there was a 25% reduction per hour in serum concentration. We present a dosage schedule for intravenous amoxicillin in patients with reduced renal function who are undergoing hemodialysis.

Adolescent

Kinetics of intravenous mezlocillin in chronic hemodialysis patients.

The kinetics of intravenous mezlocillin was studied in 8 patients with creatinine clearances under 7 ml/min who were undergoing chronic hemodialysis. Kinetic parameters were determined using a 2-compartment linear model. The mezlocillin serum half-life (t 1/2) in these patients ranged from 2.9 to 7.8 hr (mean, 5.4). The t 1/2 decreased to 1.57 +/- 0.09 hr during dialysis. Approximately 18% of the dose was recovered in the dialysate in 4 hr of dialysis. There was a 30% reduction per hour in serum concentration. The kinetics of mezlocillin, due to removal by nonrenal mechanisms, more closely resemble the kinetics of penicillin G and ampicillin than of carbenicillin and ticarcillin. A dosage schedule for use of intravenous mezlocillin in patients undergoing hemodialysis is presented.

Adult

Lepromatous leprosy masquerading as disseminated tuberculosis.

A patients with disseminated leprosy is described. A 57 year old man from Cuba presented with fever and pancytopenia. Bone marrow aspirate showed numerous acid-fast bacilli and a liver biopsy specimen contained multiple granulomas. The patient was considered to have tuberculosis and was treated with isoniazid and rifampin, with initial clinical improvement, only to have the fever recur and to show deterioration in hematologic and hepatic function. Failure to grow M. tuberculosis suggested a diagnosis of leprosy which was proved by skin biopsy. How lepromatous leprosy can masquerade as disseminated tuberculosis is discussed.

Biopsy

Clinical evaluation of netilmicin therapy in serious infections.

Netilmicin, a new semisynthetic aminoglycoside, was evaluated in the therapy of 33 episodes of infection in 30 patients. Eighteen patients had documented bacteremia. Infection sites included pulmonary, urinary tract and soft tissue areas. A complete bacteriologic and clinical cure rate of 85 per cent was achieved. No treatment failures occurred in the bacteremic group. Although netilmicin is less effective than gentamicin in vitro against Pseudomonas, it was clinically and bacteriologically effective. Netilmicin bacteriologic cures occurred in patients whose organisms were inhibited by 6.2 microgram/ml or less of netilmicin. Despite a uniform dosing protocol, a wide range of netilmicin serum levels was obtained. Adverse effects were limited to one case of transient nephrotoxicity and one Candida urinary suprainfection. Netilmicin appears to be an effective, safe agent for the therapy of serious infections.

Adult

Mezlocillin in the therapy of serious infections.

Mezlocillin, a new semisynthetic penicillin chemically related to ampicillin which is more active than carbenicillin against Ps. aeruginosa, B. fragilis and Strep. faecalis and which inhibits many Klebsiella, was evaluated in the therapy of 34 episodes of infection in 26 patients. Infection sites included pulmonary, urinary tract and tissue infections, including peritonitis. Seven patients had bacteremia. Clinical cures were achieved in 83 per cent and bacteria cures in 76 per cent of infections. Cure was achieved with mezlocillin in patients with infections caused by carbenicillin-resistant species. Adverse effects of therapy were minimal, one rash and one episode of reversible neutropenia. Serum and body flevels of susceptible organisms.uid levels were easily maintained above the inhibitory levels of susceptible organisms. Mezlocillin was a safe, well tolerated and effective antibiotic in the treatment of infections due to susceptible organisms.

Adolescent

Antibiotic-associated pseudomembranous colitis in children.

Antibiotic-associated colitis is a rare complication of antimicrobial therapy in children. Ampicillin, penicillin, and clindamycin are the drugs most frequently reported to cause pseudomembranous colitis in pediatric patients. This diagnosis should be suspected in any child with significant diarrhea during or after a course of antimicrobial therapy, especially if the diarrhea persists after the drug has been discontinued. The diagnosis is established by proctoscopic findings of typical plaques of pseudomembranes. Most cases resolve promptly when the implicated antibiotic is stopped; however, the disease can be fulminant, progressing to toxic megacolon, peritonitis, and shock. Therapy of patients who have persistent diarrhea after the offending antibiotic has been discontinued should include oral vancomycin. Close fluid management is crucial for survival.

Ampicillin