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• W2785100376 abstract "Background and objectives Urinary tract infections are the most common bacterial infections in humans. In routine bacteriological laboratories the antibacterial activity of antibiotics against common urinary tract pathogens is determined by in vitro testing usually by disc diffusion test. However, in vitro antibiotic susceptibility tests cannot reflect the situation in vivo. In this investigation, the urine samples obtained in a single oral dose pharmacokinetic study were examined for their bactericidal activity against a range of relevant gram-positive urinary tract pathogens. The results of ex vivo tests (titers) were correlated with in vitro testing. Study population limits Six healthy volunteers received a sigle oral dose of ten oral antibiotics available at Croatian market: amoxycillin, amoxycillin-clavulanate, cephalexin, cefadroxil, cefuroxime, ceftibuten, ciprofloxacin, norfloxacin, cotrimoxazole (sulfametoxazol/trimethoprim) and linezolid. Urine samples were taking every two hours during the whole dosing interval of the particular antibiotic. The wash- out period between receiving two different antibiotic regimens was at least four weeks. 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 antibioticThe volunteers participated after written informed consent had been obtained, after physical examination and when haematologic, biochemical, ECG and EEG test were within normal. Urine samples were sterilised by filtration. Dosing intervals of the antibiotics used in this study are as follows according to the manufacturer's recommendations: amoxycillin 8 h, amoxycillin-clavulanate, cephalexin, cefuroxime, cefadroxil, norfloxacin, ciprofloxacin, cotrimoxazole and linezolid 12 h, and ceftibuten 24 h. Setting Experiments were performed on bacteria isolated from urinary tract infections in 2002-2003 at Clinical Hospital Center Zagreb: Escherichia coli 2080/79 non ESBL, Escherichia coli 4199/198 ESBL, Klebsiella pneumoniae 287/286 non ESBL, Klebsiella pneumoniae 1951 ESBL, Proteus mirabilis-4335/334, Serratia marcescens 4920/9199, Enteobacter cloacae -1211, Acinetobacter baumannii 4473/472, Pseudomonas aeruginosa 3579/578, Enterococcus faecalis 2252/251, Enterococcus faecium 162/161 and Staphylococcus saprophyticus 582. Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 29213 were used as quality control strains. Methods The susceptibility tests for Enterococcus faecalis, Enterococcus faecium, Staphylococcus saprophiticus and Staphyloccus epidermidis were determined by disc-diffusion and broth microdilution method. The ex vivo urinary bactericidal activity was tested by determination of urinary bactericidal titers. A titer of ≥ 1:8 was taken as significant because it has been shown to predict a therapeutic success. Study design: Ex vivo study Results Amoxycillin alone and combined with clavulanic acid had significant urinary bactericidal activity against E. faecium, S. saprophiticus and S. aureus. Older cephalosporins had moderate activity against staphylococci but no antibacterial activity against enterococci. Their peak titers in urine were high but they decreased very quicky during the dosing interval. Ceftibuten showed lower but persistent titers in urine against staphylococci compared to older compounds. Fluoroquinolones (ciprofloxacin and norfloxacin) had strong and persistent urinary bactericidal activity which covered the whole dosing interval for staphlylococci and E. faecalis but not against E. faecium. Linezolid was the only antibiotic having significant titers (≥ 1:8) in urine against E. faecium which was maintained throughout the whole dosing interval. The results of ex-vivo experiments were well correlated with those of the in vitro testing. The susceptible strains had significant urinary bactericidal titers (≥ 1:8). Conclusions Persistent urinary bactericidal activity of fluoroquinolones and ceftibuten maintained during the whole dosing interval is due to their high concentrations in urine and long elimnation half life. No urinary bactericidal activity of cephalosporins against enterococci was observed as expected because of their intrinsic resistance to cephalosporins. High range of urinary bactericidal titers can be explained by variable urinary antibiotic concentrations achieved by the volunteers. It can be concluded that positive therapeutic outcome can be predicted if in vitro tests show susceptibility for majority of patients but some which display low titers and thus probably achieve lower urinary antibiotic concentrations can be expected to have therapeutic failures. Average urinary bactericidal activity can be predicted from in vitro susceptibility testing but we can expect there will be patients with low level of urinary bactericidal activity due to variable antibiotic concentrations in urine." @default.
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• W2785100376 title "Urinary Bactericidal Activity of Linezolid Against Gram-Positive Cocci in Comparison with other Oral Antibiotics" @default.
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