Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy

Abstract

Background: Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA.

Methods: Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis.

Results: According to bliss independent interaction, the synergistic interactions depended on ΔE values that showed the best for CIP was with AMB (ΔE = 55.14) followed with KET (ΔE = 41.23) and lastly ITR (ΔE = 39.67) at CIP = 150 mg/L. DOX was optimal with KET (ΔE = 42.11) followed with AMB (ΔE = 40.77) and the lowest with ITR (ΔE = 9.12) at DOX = 75 mg/L. MET is the best with AMB (ΔE = 40.95) and then with ITR (ΔE = 35.45) and finally KET (ΔE = 15.15) at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects.

Conclusion: This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.

Figure 1

In vitro pharmacodynamic effects of ciprofloxacin (mg/L) combined with amphotericin B (mg/L); ketoconazole (mg/L); itraconazole (mg/L) as log₁₀ concentration on candida isolated from patients with fixed orthodontic appliance.

Figure 2

In vitro pharmacodynamic effects of doxycycline (mg/L) combined with amphotericin B (mg/L); ketoconazole (mg/L); itraconazole (mg/L) as log₁₀ concentration on candida isolated from patients with fixed orthodontic appliance.

Figure 3

In vitro pharmacodynamic effects of metronidazole (mg/L) combined with amphotericin B (mg/L); ketoconazole (mg/L); itraconazole (mg/L) as log₁₀ concentration on candida isolated from patients with fixed orthodontic appliance.

Figure 4

The synergistic effects of antibiotics-antifungal combination according to bliss independence interaction analysis on clinical candida isolated from patients with fixed orthodontic appliance. AMB: amphotericin B (mg/L); KET: ketoconazole (mg/L); ITR: itraconazole (mg/L), CIP: ciprofloxacin, DOX: doxycycline, MET: metronidazole. The number of asterisks (∗) corresponds to the level of the statistical significance (^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001).