Ciprofloxacin and Rifampin Dual Antibiotic-Loaded Biopolymer Chitosan Sponge for Bacterial Inhibition

Abstract

Complex extremity wounds in Wounded Warriors can become contaminated with microbes, which may cause clinical outcomes resulting in amputation, morbidity, or even fatality. Local delivery of multiple or broad-spectrum antibiotics allows practicing clinicians treatment solutions that may inhibit biofilm formation. Propagation of vancomycin-resistant Staphylococcus aureus is also a growing concern. The development of vancomycin-resistant S. aureus has become a critical challenge in nosocomial infection prevention in the USA, but to date has seen little occurrence in osteomyelitis. As an alternative, locally delivered ciprofloxacin and rifampin were investigated in a preclinical model for the prevention of biofilm in complex extremity wounds with implanted fixation device. In vitro assays demonstrated ciprofloxacin and rifampin possess an additive effect against Gram-negative Pseudomonas aeruginosa and were actively eluted from a chitosan sponge based local delivery system. In an in vivo orthopedic hardware-associated polymicrobial model (S. aureus and Escherichia coli) the combination was able to achieve complete clearance of both bacterial strains. E. coli was detected in bone of untreated animals, but did not form biofilm on wires. Results reveal the clinical potential of antibiotic-loaded chitosan sponges to inhibit infection through tailored antibiotic selection at desired concentrations with efficacy towards biofilm inhibition.

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…26 An alternative, more effective approach to antibiotic monotherapy is combination antibiotics. [27][28][29] Rifampin has been studied in combinations with linezolid, vancomycin, cloxacillin, and ciproflaxin. [27][28][29] Dual therapy of rifampin with either linezolid or vancomycin for in vivo tibial infections resulted in reduced bacterial load compared to rifampin monotherapy.…”

“…[27][28][29] Rifampin has been studied in combinations with linezolid, vancomycin, cloxacillin, and ciproflaxin. [27][28][29] Dual therapy of rifampin with either linezolid or vancomycin for in vivo tibial infections resulted in reduced bacterial load compared to rifampin monotherapy. 27 In another study, rifampin and ciproflaxin together completely cleared a combination S. aureus and Escherichia coli coinfection.…”

“…27 In another study, rifampin and ciproflaxin together completely cleared a combination S. aureus and Escherichia coli coinfection. 29 Thus, combinations of antibiotics may offer better treatment outcomes.…”

“…Sponges for local and rapid treatment of osteomyelitis appears to be a growing area of interest, particularly in military applications, as they are readily available to pack into traumatic wounds and rapidly deliver therapeutics directly to the site of infection. 29 Reported materials of sponges include chitosan, chitosan-polycaprolactone blends, and collagen, which have been used to deliver gentamicin, 116,152 ciprofloxacin, 29,153 amikacin, 154,155 vancomycin, [154][155][156] rifampin, 29 and others. 157 In two comparative studies in humans, gentamicin loaded collagen sponges matched the efficacy of traditionally used PMMA beads in osteomyelitis treatment, while reducing the need for secondary surgical procedures.…”

“…Furthermore, efficacy against biofilm was also noted. 29 Thus, sponges as delivery vehicles for antimicrobials may be a promising area for future research. History has shown that bacteria will continue to develop resistance to commonly used antibiotics, so it is imperative that we continue to explore alternative means of infection mitigation.…”