[Escherichia coli eradication from the blader urine by amoxicillin-sulbactam. Intrinsic activity of the inhibitor].
BACKGROUND
At urine concentrations obtained after the oral administration of amoxicillin-sulbactam (500/500 mg) this combination inhibits roughly 90% of Escherichia coli and Proteus mirabilis strains.


OBJECTIVE
To administer amoxicilin-sulbactam 875/125 mg and to determine: a) minimum inhibitory concentration (MIC) of sulbactam for E. coli and P. mirabilis; b) urine inhibitory titres power (UIT) against amoxicillin-resistant E. coli or P. mirabilis; c) urine concentrations of sulbactam; and to verify whether sulbactam 125 mg as single drug, attains a high enough UIT to support the intrinsic action of the inhibitor; and to compare the activity of amoxicillin-sulbactam and amoxicillin-clavulanate and that of sulbactam and clavulanate.


METHODS
Twelve healthy volunteers received a single oral dose of amoxicillin-sulbactam 875/125 mg or amoxicillin-clavulanate 875/125 mg, according to a randomized cross-over design. Urine samples were drawn at: 0 (basal), 2, 4, and 6 hours after dosing. Urine pH, specific gravidity and UIP were assessed. Thirty nine strains isolated from urine samples were used: 30 TEM-1 producing E. coli strains and 3 extended spectrum CTX-M-2 betalactamase-producing E. coli; and 6 P. mirabilis resistant to both combinations. In 6 healthy volunteers, sulbactam 125 mg was administered orally and UIT against E. coli (MIC amoxicillin > 2048 mg/l) was assessed.


CONCLUSIONS
MIC-90 for amoxicillin plus sulbactam or clavulanate were similar to those for sulbactam or clavulanate alone, without any difference attributable to the chemical composition of the urine. The activity of amoxicillin plus the inhibitors could be due, not only to the inhibition of betalactamase but also to the intrinsic effect of the inhibitor. Both combinations showed an equivalent inhibitory activity. Two-hour UIT remained high for the entire 6-h evaluation period. Sulbactam concentration far exceed sulbactam MIC for the 6h-period, inhibiting urine E. coli. We disagree with the cut-off limit proposed for intermediate values of NCCLS, which, for these antimicrobial are 16/8, a value lower than those obtained in urine samples after the administration of betalactamase inhibitors. This may be an explanation for the beneficial effect of amoxicillin-sulbactam in the recovery of uncomplicated lower urinary tract infections in women when the involved strains were considered resistant by diffusional methods.
Casellas
J M
JM
Centro de Estudios en Antimicrobianos, Alvear Martínez, San Martin, Argentina. casellasjm@cpsarg.com
Visser
M
M
Tomé
G
G
Cohen
H
H
Soutric
J
J
Arenoso
H
H
D000328:Adult; D000658:Amoxicillin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D011513:Proteus mirabilis / Q000187:drug effects; D013407:Sulbactam / Q000493:pharmacokinetics / Q000494:pharmacology*; D014552:Urinary Tract Infections / Q000188:drug therapy; D014556:Urine / Q000382:microbiology*
D000658:Amoxicillin; D013407:Sulbactam