Pornpen Labthavikul

The Pharmacokinetics and Serum and Urine Bactericidal Activity of Ciprofloxacin

Ciprofloxacin is an investigational quinolone agent possessing an impressive antibacterial spectrum. Its pharmacokinetics were studied in six volunteers after 250‐mg and 500‐mg single oral doses, and its bactericidal activity compared to that of trimethoprim‐sulfamethoxazole given to the same volunteers. Mean peak serum levels were 1.45 μg/mL and 2.46 μg/mL for 250‐mg and 500‐mg doses, and time to peak was 1 and 1.3 hours. The 12‐hour levels were 0.12 μg and 0.22 μg. Half‐life (T1/2)α were 0.32 and 0.43 with T1/2β were 3.97 and 4.15 and volume of distribution (area) were 80L and 90L, respectively. Area under the concentration curve (AUC) was 5.65 h · μg/mL and 10.37h · μg/mL. Serum clearance was 23L for both doses. Approximately 49% of the 250‐mg dose and 43% of the 500‐mg dose was recovered in the urine. Bactericidal levels were determined against clinical isolates. Sera at 1.5 hours after the 500‐mg dose averaged bactericidal levels of 1:20 or better for an Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,and beta‐lactamase producing Haemophilus influenzae and Branhamella catarrhalis. Urinary bactericidal levels at eight to 12 hours were 1:157 for E coli, K pneumoniae, gentamicin‐piperacillin resistant P aeruginosa, Staphylococcus aureus, and 1:20 for Streptococcus faecalis. Serum bactericidal levels were superior, and urine bactericidal levels were superior or equal to the bactericidal levels obtained with trimethoprim‐sulfamethoxazole. Ciprofloxacins in vitro activity and human pharmacology should permit a twice or once daily dosing schedule for system 1C infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas, and S aureus, and once daily for urinary gastrointestinal infections.

Comparative in vitro activity of the new oral macrolide azithromycin

The in vitro activity of the new oral macrolide azithromycin was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, andStreptococcus pneumoniae were inhibited by 0.5 µg/ml. Activity of azithromycin was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin was more active than erythromycin againstHaemophilus influenzae (MIC90 1 µg/ml) andNeisseria gonorrhoeae. It inhibitedCampylobacter spp. andPasteurella multocida, and had an MIC50 of 8 µg/ml forEscherichia coli, Salmonella spp.,Shigella spp. andYersinia enterocolitica compared to an erythromycin value of > 64 µg/ml.

The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, enterobacteriaceae and pseudomonas aeruginosa

SummaryThein vitro activity of cefpirome, a new cyclopyridinium cephalosporin, was evaluated against 947 aerobic and anaerobic bacteria. Cefpirome inhibited 90% ofEscherichia coli, Klebsiella spp.,Citrobacter diversus, Morganella morganii, Proteus vulgaris, Proteus mirabilis, Aeromonas spp.,Salmonella spp.,Shigella spp. andHaemophilus andNeisseria species at ≤0.4 mg/l. It had activity comparable to that of cefotaxime, ceftizoxime, ceftazidime, aztreonam, and moxalactam against these species. Only a fewCitrobacter freundii, Enterobacter spp. andSerratia marcescens had MICs above 3.1 mg/l. The activity of cefpirome againstPseudomonas aeruginosa, 90% MIC of 12.5 mg/l, was superior to piperacillin, moxalactam, cefotaxime and cefoperazone. The 90% MIC againstStaphylococcus aureus was 0.8 mg/l, but methicillin-resistant staphylococci were not inhibited. Cefpirome was not significantly hydrolyzed by most plasmid beta-lactamases (TEM, SHV-1, PSE, OXA) nor by chromosomal enzymes (P99,Branhamella catarrhalis, Kl). Cefpirome did not inhibit chromosomal or plasmid betalactamases. Mice systemically infected withE. coli, Klebsiella pneumoniae, P. aeruginosa andS. aureus were protected by concentrations of cefpirome ranging from 0.85 mg/kg forK. pneumoniae to 4.467 mg/kg forP. aeruginosa.ZusammenfassungCefpirom, ein neues Cyclopyridin-Cephalosporin, wurdein vitro auf seine Aktivität gegen 947 aerobe und anaerobe Bakterien geprüft. In Konzentrationen von ≤0,4 mg/l hemmte Cefpirom 90% der Stämme vonEscherichia coli, Klebsiella sp.,Citrobacter diversus, Morganella morganii, Proteus vulgaris, Proteus mirabilis, Aeromonas spp.,Salmonella spp.,Shigella spp. undHaemophilus undNeisseria species. Seine Aktivität gegen diese Species war mit der von Cefotaxim, Ceftizoxim, Ceftazidim, Aztreonam und Moxalactam vergleichbar. Die MHK-Werte lagen nur für einigeCitrobacter freundii, Enterobacter spp. undSerratia marcescens über 3,1 mg/l. Die Aktivität von Cefpirom gegenPseudomonas aeruginosa war der von Piperacillin, Moxalactam, Cefotaxim und Cefoperazon überlegen; für 90% der Stämme lagen die MHK-Werte bei 12,5 mg/l. 90% der MHK-Werte fürStaphylococcus aureus betrugen 0,8 mg/l, methicillinresistente Staphylokokken wurden jedoch nicht gehemmt. Eine hydrolytische Spaltung von Cefpirom kam weder durch die Mehrzahl der plasmidgebundenen Betalactamasen (TEM, SHV-1, PSE, OXA) noch durch chromosomal gebundene Enzyme (P 99,Branhamella catharrhalis, K1) in signifikantem Ausmaß zustande. Chromosomale oder plasmidgebundene Betalactamasen wurden von Cefpirom nicht gehemmt. Bei systemischer Infektion mitE. coli, Klebsiella pneumoniae, P. aeruginosa undS. aureus hatte Cefpirom protektive Wirkung in Dosen, die von 0,85 mg/kg beiK. pneumoniae bis 4,467 mg/kg beiP. aeruginosa reichten.

Antibacterial Activity of Amifloxacin (WIN 49, 375), a New Quinolone Agent

The in vitro activity of amifloxacin, a quinolone antimicrobial agent was compared with those of ciprofloxacin, enoxacin, ofloxacin and norfloxacin against gram-positive and gram-negative bacteria. Ninety percent of Escherichia coli, Klebsiella species, Aeromonas, Salmonella, Shigella, Citrobacter, Enterobacter species, Proteus mirabilis, Serratia marcescens, and Morganella morganii were inhibited by less than or equal to 0.5 microgram/ml. Amifloxacin inhibited Branhamella, Haemophilus, and Neisseria at less than or equal to 0.25 microgram/ml, and 90% of Pseudomonas aeruginosa, including gentamicin- and carbenicillin-resistant isolates, at 4 micrograms/ml. It also inhibited staphylococci, including methicillin-resistant isolates, but was less active against streptococci and Bacteroides species. Amifloxacin had in vitro activity similar to enoxacin, ofloxacin, and norfloxacin, but was less active than ciprofloxacin. Like other quinolones, it was less active at acid pH and in the presence of urine.

Antimicrobial activity and β-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.