Bactericidal activity of amoxicillin against non-susceptible Streptococcus pneumoniae in an in vitro pharmacodynamic model simulating the concentrations obtained with the 2000/125 mg sustained-release co-amoxiclav formulation.
OBJECTIVE
To investigate the bactericidal activity against Streptococcus pneumoniae of simulated amoxicillin serum concentrations obtained in humans after 2000/125 mg sustained-release (SR) and 875/125 mg co-amoxiclav administered twice and three times a day, respectively.


METHODS
An in vitro computerized pharmacodynamic simulation was carried out and colony counts were determined over 24 h. Ten strains non-susceptible to amoxicillin (four of them exhibiting an MIC of 4 mg/L, five strains with an MIC of 8 mg/L and one strain with an MIC of 16 mg/L) were used.


RESULTS
With amoxicillin 2000 mg, an initial inoculum reduction >99.99% was obtained for strains with an MIC of 4 mg/L, > or =99% for strains with an MIC of 8 mg/L and 70.6% for the strain with an MIC of 16 mg/L at 24 h sampling time. At this sampling time, no reduction of initial inocula was obtained with amoxicillin 875 mg/8 h for two of the four strains with an MIC of 4 mg/L, three of the five strains with an MIC of 8 mg/L or for the strain with an MIC of 16 mg/L.


CONCLUSIONS
The new co-amoxiclav 2000/125 mg SR formulation appears to offer advantages versus previous formulations with respect to bactericidal activity against current amoxicillin non-susceptible strains.
Sevillano
David
D
Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain.
Calvo
Almudena
A
Giménez
María-José
MJ
Alou
Luis
L
Aguilar
Lorenzo
L
Valero
Eva
E
Carcas
Antonio
A
Prieto
José
J
D000658:Amoxicillin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000493:pharmacokinetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010403:Penicillin Resistance; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development*
D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin