Osteomyelitis Treatment with Nanometer-Sized Hydroxyapatite Particles as a Delivery Vehicle for a Ciprofloxacin- Bisphosphonate Conjugate; New Fluoroquinolone-Bisphosphonate Derivatives Show Similar Binding Affinity to Hydroxyapatite and Improved Antibacterial Activity Against Drug-Resistant Pathogens

Orthopaedic injuries comprise a majority of combat injuries seen in recent US military conflicts. The development and increased use of modern body armor, which has been correlated with decreased chest and upper abdominal injuries (Mabry et al., 2000), will likely continue to result in an increased r...

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Bibliographic Details
Main Authors: McPherson, III, James C, Runner, Royce R, Shapiro, Brian A, Walsh, Douglas S, Buxton, Thomas B
Format: Report
Language:English
Subjects:
ABDOMEN
ACINETOBACTER BAUMANNII
BACTERIA
BONE FRACTURES
CALCIUM
CIPROFLOXACIN RESISTANCE METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
CIPROFLOXACIN SUSCEPTIBLE METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
CIPROFLOXACIN-BISPHOSPHONATES
CONTAMINATION
CONTRAST
DRUG TOLERANCE
EXTREMITIES
FLUOROQUINOLONE-BISHOPHNATE
GERMICIDES
GRAM NEGATIVE BACTERIA
GRAM POSITIVE BACTERIA
HIGH ENERGY
HYDROXXYAPATITE
IN VITRO ANALYSIS
IN VIVO ANALYSIS
INFECTIOUS DISEASES
Medicine and Medical Research
Microbiology
MILITARY INTELLIGENCE
MRSA(METHICILLIN RESISTANT STAPHYLOCCUS AUREUS)
MUSCULOSKELETAL DISEASES
OM(OSTEOMYELITIS)
PATHOGENIC MICROORGANISMS
Pharmacology
PHOSPHATES
STAPHYLOCOCCUS AUREUS
TCP(TRICALCIUM PHOSPHATE)
TRAUMA
WOUNDS AND INJURIES
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Summary:Orthopaedic injuries comprise a majority of combat injuries seen in recent US military conflicts. The development and increased use of modern body armor, which has been correlated with decreased chest and upper abdominal injuries (Mabry et al., 2000), will likely continue to result in an increased relative rate of extremity injuries. These injuries commonly present with significant open bone fractures of the limbs and substantial contamination with bacteria from high energy trauma. Once bone infection is established, one fourth of open fractures will progress to osteomyelitis (OM) (Lew and Waldvogel, 1997; Wolski, 2004; Buxton et al., 2004). We developed a novel local drug-delivery system consisting of ciprofloxacin-bisphosphonate conjugate (E41) bound to calcium phosphate (CP) bone particles. In situ, the conjugate dissociates from CP and maintains its antibacterial activity. This topical granulated antibiotic delivery system reduced infection rates in our in vivo OM model. Current studies contrast two CP homeostatic bone-substitute particles, nanometer-sized hydroxyapatite NanOss(Trademark) (Nan), and mu-sized tricalcium phosphate Skelite(Trademark) (TCP) in vitro for binding to E41, and in vivo for E41-CP blockade of rat OM. See also ADM002187. Proceedings of the Army Science Conference (26th), held in Orlando, Florida on 1-4 December 2008. Sponsored in part by U.S. Army Medical Research Acquisition Activity, Fort Detrick MD.