Urine inhibitory titers against resistant Escherichia coli isolates after oral amoxicillin-sulbactam.
It has been previously shown that following the oral administration of amoxicillin-sulbactam (AXS) the urinary activity against Escherichia coli (Ec) is due to beta-lactamase inhibition (i.e. TEM-1) as well as to the intrinsic activity of sulbactam (SB). Similarly, it has been previously demonstrated in volunteers that a single oral dose of AXS 500/500 mg allows high urine inhibitory titers (UITs) against resistant Ec isolates. In this in vitro and ex vivo study we assessed the urinary activity of a new AXS proportion: 875/125 mg. Urine was collected from 12 volunteers at 0-2; 2-4; 4-6 h after a single oral dose of AXS 875/125 mg. Previous studies had shown that pooled urine from 12 volunteers did not differ significantly in the UIT as compared to the mean individual values. Urine pools for each period were prepared. Each pool was tested for UIT against 60 Ec isolates received from 10 different laboratories in South American countries: 10 susceptible (S) to AXS; 10 intermediate (I) and 40 resistant (R); the latter ranging 32/16-256/128 mg/l. Amoxicillin (AX) and SB urine concentrations were determined in all the samples. UIT ranged from 1/4 to > 1/32 for S and I strains and from 1/1 to 1/4 for R strains. For one strain (AXS, MIC 256/128 mg/l) the UIT titer was 1/1 at 2 and 4 h but it was not inhibited at 6 h. AX mean levels ranged from 1872 (2 h) to 522 mg/l (6 h) while SB ranged from 1075 (2 h) to 334 (6 h) mg/l. It is noteworthy that 59/60 strains were inhibited by 128 mg/l SB alone.


CONCLUSIONS
The AXS 875/125 proportion has a remarkable in vitro and ex vivo activity against Ec urinary isolates.
Casellas
José M
JM
Centro de Estudios en Antimicrobianos (CEA), San Martín, Argentina. casellasjm@cpsarg.com
Visser
Matías
M
MacDougall
Natalia
N
Tomé
Gabriela
G
Cohen
Hugo Sabban
HS
Soutric
Jorge
J
Arenoso
Héctor
H
D000284:Administration, Oral; D000328:Adult; D000658:Amoxicillin / Q000494:pharmacology* / Q000652:urine; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology* / Q000652:urine; D013407:Sulbactam / Q000494:pharmacology* / Q000652:urine; D014552:Urinary Tract Infections / Q000188:drug therapy; D014556:Urine / Q000737:chemistry* / Q000382:microbiology
D010406:Penicillins; D000658:Amoxicillin; D013407:Sulbactam