In vitro time-kill activities of ciprofloxacin alone and in combination with the iron chelator deferasirox against Vibrio vulnificus

Abstract

Iron plays a major role in the growth and virulence of ferrophilic organisms like Vibrio vulnificus. People who reside in the coastal areas with raw fish eating habits have a high risk of Vibrio infection and aggressive therapy can only reduce their mortality. We investigated the in vitro efficacy of ciprofloxacin, a bactericidal drug used in V. vulnificus patients, and the orally active iron chelator deferasirox against V. vulnificus infection. We performed in vitro time-kill studies on two ATCC strains and one clinical isolate of V. vulnificus collected from a patient admitted to Chosun University Hospital with either ciprofloxacin or iron chelator deferasirox alone and the two drugs in combination. The combination of an iron chelator plus an antibiotic creates a novel form of synergism at 24 h. The antimicrobial effect of deferasirox may be ascribed to its ability to deplete iron that would otherwise be used for bacterial growth. Combination therapy with ciprofloxacin plus deferasirox has potential clinical application by lowering the iron availability against a ferrophilic organism like V. vulnificus infections.

Antibacterial Activities of Iron Chelators against Common Nosocomial Pathogens

“…Previous studies with iron chelators have demonstrated a bacteriostatic effect on bacterial growth (10,14,16). We performed a time-kill assay to see if this was also true of the iron chelators evaluated in this study.…”

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

“…9). This said, how synergistic a combination is does depend on the exact speciation of the liganded iron; surprisingly, the iron chelator deferasirox promoted the antibacterial activity of ciprofloxacin against V. vulnificus (Neupane and Kim 2010), as did deferiprone with various azoles against Aspergillus fumigatus , while deferoxamine was antagonistic to azoles (Zarember et al 2009). As with any complex system, the interactions can be highly dosedependent (Hegreness et al 2008; Kohanski et al 2010; Yeh et al 2009).…”

In vitroantimicrobial activity of hydroxypyridinone hexadentate-based dendrimeric chelators alone and in combination with norfloxacin

“…In the case of bacterial and fungal resistance to antimicrobial agents, where entire classes of antibiotics are no longer treatment options (Hogan & Kolter, 2002;Spellberg et al, 2008), drug combinations offer a promising strategy to overcome bacterial resistance mechanisms and to restore antibiotic effectiveness. Moreover, the combination of iron chelators with antibiotics has also been demonstrated to have clinical potential (van Asbeck et al, 1983;Neupane & Kim, 2010;Zhu et al, 2013).…”