[Influence of the displacement of protein binding by ibuprofen in the activity of a third-generation cephalosporin against Streptococcus pneumoniae].
The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitro bactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. The activity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporins in respiratory tract infections.
Cafini
F
F
Departamento de Microbiología, Facultad de Medicina, Universidad Complutense de Madrid.
González
N
N
Torrico
M
M
Echeverría
O
O
Sevillano
D
D
Alou
L
L
Giménez
M J
MJ
Aguilar
L
L
Gómez-Lus
M L
ML
D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001667:Binding, Competitive; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D013290:Streptococcal Infections / Q000097:blood / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D018440:beta-Lactam Resistance
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D002511:Cephalosporins; D012709:Serum Albumin; C073460:cefditoren; D007052:Ibuprofen