Assessment of differences in antimicrobial effect determined with two in vitro pharmacodynamic models: impact of surface area to volume ratio.
OBJECTIVE
To measure the influence of different surface area:volume ratios (SA:Vs) on antibiotic penetration and subsequent antibacterial effect.


METHODS
In vitro laboratory experiment.


METHODS
Two academic research laboratories.


METHODS
The two models with effective SA:Vs of 5.34 and 4.80 cm(-1) were evaluated by conducting a time-kill experiment with Pseudomonas aeruginosa ATCC 27853 and ceftazidime.


RESULTS
Ceftazidime was administered by constant infusion into the central compartment. Its penetration into the peripheral compartment and bacterial counts were determined over 24 hours, and antibacterial effect was quantified. Antibiotic penetration, calculated using central compartment and peripheral compartment area under the concentration-time curves, and effect, quantified as the relationship between the areas under growth and kill curves, differed between the models. Antibiotic penetration into the peripheral compartment was 53% greater over the first 4 hours of the experiment in the model with the larger SA:V. This was associated with antibacterial effects that were 64% and 38% greater in the 0-4-hour and 0-24-hour time periods, respectively.


CONCLUSIONS
Differences in antibiotic penetration and effect observed between these models are likely explained by differences in SA:V
Anti-Infective Research Laboratories, College of Pharmacy, Medical University of South Carolina, Charleston 29425, USA. whiterl@musc.edu
Roger L
RL
White
Charles R
CR
Bonapace
Lawrence V
LV
Friedrich
Michael J
MJ
Rybak
Diane M
DM
Cappelletty
Renee-Claude
RC
Mercier
Heather H
HH
Houlihan
Jeffrey R
JR
Aeschlimann
John A
JA
Bosso
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002442:Ceftazidime / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010865:Pilot Projects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013499:Surface Properties; D013997:Time Factors
D000900:Anti-Bacterial Agents; D002442:Ceftazidime