Efficacy of sparfloxacin and autoradiographic diffusion pattern of [14C]Sparfloxacin in experimental Staphylococcus aureus joint prosthesis infection

Abstract

Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment regimen was started 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1 microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were 3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment, animals were sacrificed and tibias were removed, pulverized, and quantitatively cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10 CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21 log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was significantly more effective than pefloxacin (P = 0.025). The autoradiographic pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with prostheses and in infected animals 15 days after inoculation. Sixty minutes after completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals the highest levels of radioactivity were detected around the prosthesis, in femoral cartilage, and in articular ligaments. Radioactivity was slightly less intense in bone marrow and muscles and was very weak in compact bone. The distribution of sparfloxacin in uninfected rabbits was similar. Thus, sparfloxacin may represent a valid alternative therapy in these infections provided that it is carefully monitored for potential side effects.

From in vitro to in vivo Models of Bacterial Biofilm-Related Infections

“…Another preventive approach relying on a minocycline/rifampin-impregnated bioresorbable polymer implant coating has been shown to reduce biofilm formation [ 289 ]. Another key contribution of these models is the study of distribution and efficacy of frequently used antibiotics such as fluoroquinolones [ 290 ].…”

Prophylaxis of implant‐related staphylococcal infections using tobramycin‐containing bone cement

“…Such a minimal detection limit is a relative drawback of all studies that evaluate implantrelated infections using a comparable plating and counting technique. 22,[38][39][40][41][42][43][44][45] However, many studies do not mention the minimal detectable level of bacteria. Early experiments have shown that, in the presence of a foreign body, a number of 100 CFU of a staphylococcal strain is enough to produce an infection in man.…”

Current Status of Molecular Imaging in Infections

“…Radiolabeled antibodies performed poorer compared to autologous leukocyte scintigraphy (accuracy ranging from 75-86%), while no data on the use of [ 18 F]FDG-PET and PET/CT in primary appendicular osteomyelitis are available (exect for chronic, see below) [10]. Tc-ciprofloxacin (Infecton TM , a radiolabeled broad-spectrum fluoroquinolone that inhibits the DNA-gyrase and/or 8 topoisomerase IV of bacteria) have been used in pediatrics patients with clinical suspicion of osteomyelitis (98% sensitivity and 100% specificity, with a 100% positive predictive value and a 87% negative predictive [22]) despite the low specificity for osteoarticular infections (aspecific accumulation in growth plates, non-infected prosthetic knees, pseudoarthrosis, palindromic rheumatism, and postoperative fibrosis of the lumbar spine, avascular hip necrosis, fibrous dysplasia, non-union fracture, and uninfected prosthetic joints [23][24][25][26][27][28] (those resultshad also been reported in animal model with another radiolabeled quinolone, 14 C-sparfloxacin [29]). Preliminary results of 68 Ga-citrate PET/CT compared to different combinations of diagnostic procedures (MRI, radiography, CT, or labeled WBC scintigraphy), biopsy (when diagnostic), and follow-up data (at least 1 year), have been reported in 31 patients with suspected osteomyelitis or diskitis.…”

“…Additionally, 99m Tc-ciprofloxacin results at the end of therapy had the highest sensitivity (83%), accuracy (70%) and negative predictive value (95%) in predicting infection resolution or recurrence as compared to ESR assessment and clinical examinations [155]. UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] was also employed to differentiate infection from aseptic loosening of prostheses [156] as well as to assess response to antibiotic therapy with reduction in radiopharmaceutical uptake after treatment as compared to baseline scan in the responder group [157].…”

“…Preliminary results with 99m Tc-ubiquicidin [29][30][31][32][33][34][35][36][37][38][39][40][41] have been reported in patients with suspected SD. The sensitivity and specificity for detecting SD were 100% and 87%, respectively with a positive predictive value of 95% and a negative predictive value of 100%.…”