The activity of the extended spectrum cephalosporin cefpirome (HR 810) was compared with that of other beta-lactams and gentamicin. A total of 524 clinical isolates and strains known to be resistant to certain agents were studied. Against the Enterobacteriaceae, Haemophilus influenzae and Neisseria spp. cefpirome was highly active (MIC90 less than or equal to 0.5 mg/l), generally being as active or slightly more active than ceftazidime and cefotaxime, and 8 to 32 times more active than cefuroxime. Against Pseudomonas aeruginosa cefpirome (MIC90 8 mg/l) was four-fold less active than ceftazidime. Staphylococcus aureus was susceptible to cefpirome (MIC90 2 mg/l) and cefpirome was the only cephalosporin tested with significant activity against Lancefield Group D streptococci. Bacteroides spp. (with the exception of Bact. ureolyticus) were resistant to cefpirome. The compound was bactericidal to all the susceptible strains studied with the exception of Lancefield Group D streptococci. The major target site for cefpirome was PBP 3 and the protein binding was low.
6-β-bromo penicillanic acid and 6-β-iodo penicillanic acid, two simple penicillanic acid derivatives were compared with clavulanic acid and sulbactam as to their β-lactamase inhibitory properties. Characterized β-lactamase producing strains were used. Generally the two novel compounds were as potent β-lactamase inhibitors as clavulanic acid and inhibited the same range of enzymes. The possibility of β-lactamase inhibitor/β-lactam ester-linked compounds (mutual pro-drugs) is discussed.
Journal Article The pharmacokinetics and tissue penetration of intravenously administered CGP 31608 Get access R. Wise, R. Wise Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Webberley, J. M. Webberley Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Andrews, J. M. Andrews Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. P. Ashby J. P. Ashby Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 21, Issue 1, January 1988, Pages 85–91, https://doi.org/10.1093/jac/21.1.85 Published: 01 January 1988 Article history Received: 04 June 1987 Accepted: 11 September 1987 Published: 01 January 1988
The pharmacokinetics of rufloxacin after a single 400 mg oral dose were studied in eight volunteers, measuring plasma, inflammatory fluid and urine concentrations. Mean peak plasma concentrations of 4.4 mg/L were achieved at a mean time of 1.9 h after administration. The mean plasma elimination half-life was 28.2 h. Mean peak levels in inflammatory fluid reached 3.2 mg/L after 3.5 h, and 30.7% of the dose was eliminated in urine by 96 h. The apparent mean volume of distribution of rufloxacin, at steady state, was 109.5 L. The mean percentage penetration of rufloxacin into the inflammatory exudate, as measured by ratios of AUC0-50 h was 90%.
Pirbenidihin, a semi-synthetic penicillin, structurally related to ampicillin, was investigated as to its in vitro activity. The drug was found to exhibit a higher degree of activity against Pseudomonas aeruginosa, being approximately eight times more active than carbenicillin and four times more active than ticarcillin. The new drug was about fourfold more active than carbenicillin against other Entero bacteriaceae with the exception of Proteus spp. The drug is somewhat more stable in serum than carbenicfflin. Pirbenicillin does not appear to inactivate gentamicin as rapidly as carbenicillin.
Journal Article Bactericidal activity of sparfloxacin and ciprofloxacin under anaerobic conditions Get access M. A. Cooper, M. A. Cooper Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Andrews, J. M. Andrews Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Wise R. Wise * Department of Medical Microbiology, Dudley Road HospitalBirmingham, UK *Corresponding author Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 28, Issue 3, September 1991, Pages 399–405, https://doi.org/10.1093/jac/28.3.399 Published: 01 September 1991 Article history Received: 25 February 1991 Accepted: 17 April 1991 Published: 01 September 1991
The pharmacokinetics of cefpodoxime were determined after a single oral dose of 261 mg of cefpodoxime proxetil, equivalent to 200 mg of cefpodoxime, was given to each of six healthy male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak level in plasma was 2.1 micrograms/ml, attained at a mean time of 2.9 h. The mean half-life of elimination from serum was 2.2 h. The inflammatory exudate was penetrated moderately rapidly, the mean peak level being 1.7 micrograms/ml at 3.5 h. The mean percent penetration of the inflammatory exudate was 103.7. The mean 24-h urine recovery of cefpodoxime was 32.2%. This study suggests that cefpodoxime proxetil taken once or twice daily will be sufficient to treat urinary or systemic infections caused by susceptible pathogens.
The in-vitro activity of gemifloxacin, a new fluoroquinolone, against a wide range (c. 700) of recent clinical isolates, was compared with that of three other fluoroquinolones and other relevant agents. Gemifloxacin inhibited 90% of the Enterobacteriaceae strains at 0.5 mg/L or less, exceptions being Serratia spp. (MIC90 1 mg/L) and strains possessing a putative mechanism of resistance to fluoroquinolones. Ninety per cent of Pseudomonas aeruginosa were inhibited by 4 mg/L. Gemifloxacin had good activity against respiratory pathogens, with 90% of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis being inhibited by 0.06 mg/L or less. Staphylococcus aureus (MSSA) were highly susceptible (MIC90 0.06 mg/L) but MRSA less susceptible (MIC90 8 mg/L) to gemifloxacin. Enterococcus spp. were markedly more susceptible to the study agent than to ciprofloxacin. Gemifloxacin showed good activity against Bacteroides fragilis (MIC90 0.5 mg/L) and anaerobic cocci. A tentative in-vitro breakpoint of 0.5 mg/L was studied using a 1 µg disc content for all genera except Pseudomonas where a 5 µg disc content was employed. The false sensitivity reporting rate was 0.5% and false resistance rate was 6.0%, which was considered acceptable. In conclusion, gemifloxacin is a highly active fluoroquinolone that should prove clinically useful in the treatment of a wide range of infections. Susceptibility testing criteria have been developed that should prove robust in a clinical laboratory.
The activity of clavulanic acid alone and in combination with penicillin, amoxycillin, and carbenicillin was studied. Marked reductions in the minimum inhibitory concentrations (MICs) for a wide spectrum of beta-lactamase-producing clinical isolates were found. Of particular interest were the decreased MICs of penicillin for Bacteroides fragilis and beta-lactamase-producing strains of Neisseria gonorrhoea in the presence of the clavulanic acid. Beta-lactamase-producing strains of Escherichia coli, Klebsiella spp., and indole-negative Proteus also showed considerably increased susceptibility to amoxycillin in combination with clavulanic acid. Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid.
HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus spp. (indole positive), Enterobacter spp., Salmonella typhi, Serratia marcescens, Providencia stuartii , and Staphylococcus aureus . In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of Streptococcus pyogenes , Lancefield group D streptococci, and Neisseria gonorrhoeae ; with ampicillin against Haemophilus influenzae ; and with cefoxitin against Bacteriodes fragilis . HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against S. pyogenes ; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms ( P. aeruginosa and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 μg/ml. A series of seven transfers of selected strains of E. coli, Klebsiella spp., S. aureus , and P. aeruginosa through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium.
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