Comparative Evaluation of Three In Vitro Techniques in the Interaction of Ampicillin and Ciprofloxacin against Staphylococcus aureus and Escherichia coli

Purpose: The study was designed to evaluate the consistency of interpretation of results of interaction between ampicillin and ciprofloxacin against S. aureus and E. coli using three in vitro techniques. Methods: The interaction between ampicillin and ciprofloxacin was studied using three in vitro methodsCheckerboard technique, Overlay Inoculum Susceptibility Disc technique (OLISD) and the Decimal Assay for Additivity technique (DAA). Results: In the Checkerboard technique, fractional inhibitory concentration (FIC) indices show that the ampicillin/ciprofloxacin combination is synergistic against the test organisms. In the DAA approach, a target IZD of 15 mm yielded Biological Equivalent Factors (BEF) of 1.35 μg (amp/Staph), 6.74 μg (cipro/Staph), 9.62 μg (ampicillin/E. coli), and 5.45 μg (cipro/E. coli). Statistical analyses show that all decimal combinations of ampicillin and ciprofloxacin were additive (p< 0.05). The overlay inoculum susceptibility disc method shows inhibition zone diameter increments ranging between 36 ± 8.00 % to 69.2 ± 23.08 % for S. aureus and 28.12 ± 3.13 % to 50 ± 12.50 % for E. coli. These increments are consistent with reported criteria for synergism in the OLISD method. Conclusion: The study suggests a possible clinical use for the combination of ampicillin and ciprofloxacin against infections caused by these organisms. Equally, the apparent disagreement between DAA and the other two methods raises questions as to the consistency of inferences drawn on interaction studies when different techniques are used.