Effect of Ciprofloxacin on Killing ofActinobacillus actinomycetemcomitansby Polymorphonuclear Leukocytes

Abstract

Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs). It is susceptible to ciprofloxacin, which PMNs actively accumulate. This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A. actinomycetemcomitans than control PMNs. Isolated human PMNs were loaded by brief incubation with 0.5 g of ciprofloxacin/ml. Opsonized bacteria (ATCC 43718) were incubated at 37°C with control and ciprofloxacinloaded PMNs and in the presence and absence of 0.5 g of ciprofloxacin/ml. When assayed at bacteria-to-PMN ratios of 30:1 and 90:1, ciprofloxacin-loaded PMNs killed significantly more bacteria and achieved significantly shorter half times for killing than control PMNs (P < 0.05; Tukey's test). At ratios of 3:1 and 10:1, these differences were not significant.

Both leukotoxin and poly-N-acetylglucosamine surface polysaccharide protect Aggregatibacter actinomycetemcomitans cells from macrophage killing

“…These results are consistent with those of previous studies demonstrating that A. actinomycetemcomitans cells are resistant to killing by human PMNs [14,[32][33][34]. Infection of THP-1 cells with wild-type A. actinomycetemcomitans cells resulted in a highly reproducible 2-fold increase in bacterial CFUs, and a concomitant decrease in THP-1 cell viability.…”

Key Roles of Human Polymorphonuclear Cells and Ciprofloxacin in Lactobacillus Species Infection Control

“…These data confirm that CIP and probably other fluoroquinolones (such as moxifloxacin, prulifloxacin, pefloxacin, and sparfloxacin) can help the host defense in the outcome of infections because they accumulate and remain active inside PMNs (20,(24)(25)(26).…”

“…In particular, CIP has a broad antibacterial spectrum, with bactericidal activity toward Gram-positive and Gram-negative aerobes (5,19); it accumulates inside the PMNs and remains active, leading to a significant reduction in the number of intracellular bacteria, such as Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans) (20).…”

Garenoxacin-induced increase of CD11b expression on human polymorphonuclear neutrophils does not affect phagocytosis and killing of Staphylococcus aureus

“…Previous investigations of different quinolones revealed that these antibacterial agents have heterogeneous effects on the phagocytosis, the burst production, and the killing function of the respective phagocytes [4][5][6][7][8]. Because garenoxacin at therapeutic concentrations has been shown to significantly increase the CD11b expression of human PMN [5], we examined the effect of subtherapeutic to supratherapeutic concentrations of garenoxacin on phagocytosis and killing of S. aureus by human PMN.…”

“…From 1 to 17.65 ll of appropriate quinolone dilutions were added to 100 ll heparinized whole blood immediately after blood sampling to furnish final concentrations of 0.5, 5, 100, and 1,500 mg/l, respectively. While 0.5 and 5.0 mg/l are considered to represent sub-therapeutic and normally achievable peak plasma concentrations after oral dosing of 400 mg [11], the concentration of 100 mg/l was chosen to exclude effects with higher concentrations some multiples of the maximum achievable concentrations in individual patients and for comparability with other studies [4][5][6][7][8]. In contrast, the 1,500 mg/l concentration is far outside the range of concentrations which are considered of clinical value.…”