Naslov
Bactericidal Activity of Oral Antibiotics in ex vivo Model.

Autori
Bedenić, Branka ; Topić, Marijana ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the World Conference on dosing of Antiinfectives. Paul Ehrlich Symposium. / - Nürnberg, 2004

Skup
World Conference on dosing of Antiinfectives. Paul Ehrlich Symposium.

Mjesto i datum
Nürnberg, Njemačka, 09.09.2004. - 12.09.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Amoxycillin/clavulanate; cephalexin; cefuroxime; cefadroxil; ceftibuten; norfloxacin; supphametoxazole/trimethoprim; urinary bactericidal titers; urinary tract infections

Sažetak
Background: Urinary tract infections are the most common bacterial infections in humans. Their frequency varies with the age, gender and the condition of the urinary tract. In the assesment of an antibiotic, the bactericidal activity of plasma, urine and other body fluids is a relevant pharmacodynamic parameter, being an integration of pharmacokinetic properties with in vitro activity. In routine bacteriological laboratories the antibacterial activity of antibiotics is determined by in vitro testing usually by disc diffusion test. However, in vitro antibiotic susceptibility tests cannot reflect the situation in vivo. In vitro the bacteria are exposed to fixed concentrations of antibiotics whereas in vivo there is a more gradual decrease in antibiotic levels depending on the elimination half-life of the antibiotic. Furthermore, the bactericidal compounds of human immune system are not present in the arteficial medium. For that reason ex-vivo models better predict the therapeutic efficency of particular antibiotics. In this investigation, the urine samples obtained in a single oral dose pharmacokinetic study were examined for their bactericidal activity agains a range of relevant urinary tract pathogens. Methods: Eight oral antibiotics available at Croatian market were tested: amoxycillin, amoxycillin/clavulanate, cephalexin, cefuroxime, cefadroxil, ceftibuten, norfloxacin and sulphametoxazole/trimethoprim. Their in vitro against common community acquired and hospital urinary tract pathogens activity was determined by broth microdilution method. Ex vivo bactericidal activity was tested by determination of urinary bactericidal titers. Six healthy volunteers (females, age range 40-55) received a single oral dose of amoxycillin/clavulanate – 875/125 mg, cephalexin - 500 mg, cefuroxime - 500 mg, cefadroxil - 500 mg, ceftibuten - 400 mg, norfloxacin-400 mg, and sulphametoxazole/trimethoprim-400/80 mg, respectively. The wash- out period between receiving two different antibiotic regimens was at least four weeks. Strenuous physical activity, smoking and acohol intake was prohibited from 24 h before until 24 h after drug administration. The test drug was taken after fasting for 12 h and the first meal was served 2 h after drug administration. The urine samples were collected in different time intervals post dose (0-2, 2-4, 4-6, 6-8, 8-10, 10-12 and 12-24 h) depending on the dosing interval of a particular antibiotic. A titer of 1:8 was taken as clinically relevant since it was shown to predict a successful therapeutic outcome. Results: All antibiotics except of amoxycillin and sulphametoxazole/trimethoprim displayed high titers in urine against Escherichia coli ( non ESBL), Klebsiella pneumoniae ( non ESBL), Proteus mirabilis and Staphylococcus saprophiticus. The titers of antibiotics with shorter t1/2 (cephalexin) decreased faster than of those with longer elimination half-life (ceftibuten). Only amoxycillin and amoxycillin/clavulanate showed measurable titers in urine against Enterococcus feacalis. Norfloxacin was the only antibiotic having significant titers in urine against hospital urinary tract pathogens Pseudomonas aeruginosa and Acinetobacter baumannii which were maintained during the whole dosing interval period (12 h). Ceftibuten and norfloxacin demonstrated good bactericidal activity in urine against Serratia marcescens, Enterobacter cloacae and ESBL positive K. pneumoniae and E. coli. The bactericidal titers in urine were in concordance with the results of in vitro testing. The antibiotics with lower MICs had higher titers against particular pathogens. Conclusions: 1. According to our results oral beta-lactam antibiotics could be antibiotics of choice for the treatment of uncomplicated urinary tract infections caused by E. coli and P. mirabilis due to their low toxicity. 2. Ceftibuten as third generation cephalosporin, was the only beta-lactam displaying high activity against ESBL producing E. coli and Klebsiella pneumoniae in urine during the whole dosing interval (24 h), but according to the NCCLS recommendations, beta-lactams except of carbapenems are not recommended for the therapy of infections caused by ESBL producing Enterobacteriaceae even when in vitro tests show susceptibility. 3. Urinary tract infections caused by Enterococcous feacalis should be treated with amoxycillin alone or combined with clavulanate. Enterococci show intrinsic resistance to all cephalosporins. 4. Fluoroquinolones are the antibiotics of choice for the treatment of hospital acquired urinary tract infections when P. aeruginosa, E. cloacae, S. marcescens, A. baumanii or ESBL positive Enterobacteriaceae are isolated from urine as pathogens because they demonstrate excellent in vitro and ex vivo activity and achieve high concentrations in urine. Their main drawback compared to beta-lactams is causing more adverse effects. Apart of that they cannot be administered in pregnancy and childhood contrary to beta-lactams.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA