Assessment of Differences in Antimicrobial Effect Determined with Two In Vitro Pharmacodynamic Models: Impact of Surface Area to Volume Ratio

Study Objective. To measure the influence of different surface area:volume ratios (SA:Vs) on antibiotic penetration and subsequent antibacterial effect. Design. In vitro laboratory experiment. Setting. Two academic research laboratories. Intervention. 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. Measurements and Main 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. Conclusion. Differences in antibiotic penetration and effect observed between these models are likely explained by differences in SA:V.