The Preservative Effects of "Antibiotic Concentration" and "Addition of BAK" on the Time–Kill Comparison of Moxifloxacin and Gatifloxacin

Abstract

Purpose: : The preservative effects of Moxifloxacin (MOX) and Gatifloxacin (GAT) were compared using time–kill studies to determine the effect of antibiotic concentration (0.5% vs 0.3%) and the addition of 0.005% benzalkoniun chloride (BAK) for eliminating Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Coagulase–Negative Staphylococcus (CNS).

Methods: : Standard time–kill studies were determined with 5 isolates each of SA, PA, and CNS at an initial inoculum of 1 x10⁶ cfu/ml. Bacteria survival was tested at hours 1, 2, 4, 6, 8 and 24 hours to: 1) Mueller Hinton broth (vehicle), 2) 0.005% BAK, 3) 0.5% MOX, 4) 0.5% GAT, 5) 0.3% MOX, 6) 0.3% GAT, 7) 0.3% GAT plus 0.005% BAK, 8) 0.5% MOX plus 0.005% BAK, 9) 8 µg/ml GAT, and 10) 8 µg/ml MOX. The main outcome measures were 1) time to kill and 2) killing rates. Data were analyzed with the Mood’s Median Test or ANOVA with significance set at p < 0.05.

Results: : MOX or GAT at either 0.5% or 0.3% equally eliminated SA, PA, and CNS. For SA and CNS, 0.005% BAK, 0.3 % GAT + 0.005% BAK, and 0.5% MOX + 0.005% BAK eliminated all growth within 1 hour. 0.3% GAT + 0.005% BAK (median 1 hr) eliminated bacteria faster than 0.5% MOX (median 4 hrs) (p=0.016). For PA, 0.3% GAT, 0.5% MOX, 0.3% GAT + 0.005% BAK, and 0.5% MOX + 0.005% BAK eliminated all growth within 1 hour while 0.005% BAK alone did not eliminate growth at 24 hours. The kill rates of MOX and GAT, that were tested at 8 µg/ml, were equivalent for SA (0.7), PA (3.0), and CNS (0.7) [log₁₀ (cfu+1)/hour].

Conclusions: : As a preservative, MOX and GAT have equivalent antibacterial activity at either 0.5% or 0.3%, and have equivalent killing rates at 8 µg/ml for SA, PA, and CNS. 0.005% BAK appears to complement GAT for eliminating SA and CNS while it has no effect on PA. GAT and MOX appear to act as self–preservatives against PA. The clinical effects of "antibiotic concentration" and the "addition of BAK" for MOX and GAT requires further in vivo studies.

Keywords: antibiotics/antifungals/antiparasitics • clinical laboratory testing