Continuous Cefazolin Infusion To Treat Bone and Joint Infections: Clinical Efficacy, Feasibility, Safety, and Serum and Bone Concentrations

Abstract

Cefazolin has been used for many years to treat bone and joint infections. Because of its time-dependent antimicrobial activity, continuous infusion would potentially be beneficial. We report on the feasibility, safety, and efficacy of prolonged continuous intravenous cefazolin therapy in a cohort of 100 patients, their serum cefazolin levels, and the concomitant bone cefazolin concentrations in 8 of them. This retrospective cohort study included all the patients treated for bone or joint infection with a continuous cefazolin infusion administered over a 12-h period twice daily for >2 weeks. Drug monitoring was performed at least twice for all the patients. Serum and bone cefazolin concentrations were determined by standardized disk diffusion microbiological assays. The absence of clinical, biological, and radiological signs of infection after 2 years of follow-up and the same criteria after 1 year of follow-up defined cures and probable cures, respectively. The median treatment duration was 42 days, and the median daily cefazolin dose was 6 g. Half of the patients received parenteral antibiotic therapy on an outpatient basis. Two moderate-grade adverse events were observed. The median serum cefazolin concentrations were 63 g/ml (range, 13 to 203 g/ml) and 57 g/ml (range, 29 to 128 g/ml) on days 2 to 10 and days 11 to 21, respectively. The median bone cefazolin concentration reached 13.5 g/g (range, 3.5 to 29 g/g). The median bone concentration/serum concentration ratio was 0.25 (range, 0.06 to 0.41). Among 88 patients with a median follow-up of 25 months (range, 12 to 53 months), 52 were considered cured and 29 were considered probably cured. Thus, the treatment of bone and joint infections with a prolonged continuous intravenous cefazolin infusion was feasible, effective, well-tolerated, safe, and convenient, making it a strong candidate for home therapy.

Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model

“…Second, we did not confirm biofilm formation on the prosthesis before the electrical stimulation protocol and it is recognized that clinically IAI might appear at a time later than POD 6 when more robust biofilms might be present. However, the results suggest antibiotic therapy alone did not effectively treat the implant bacterial burden in this model, which is consistent with biofilm-associated orthopaedic infections seen clinically [26]. We also must point out that the undetectable CFU levels presented in this study may not necessarily mean the infection was eradicated.…”

Large Cohort Study of Central Venous Catheter Thrombosis during Intravenous Antibiotic Therapy

“…Vancomycin was given as a high-dose continuous infusion, with target serum concentrations of 30 to 40 mg/liter, as previously described (18). Cefazolin (19), ceftazidime, piperacillin-tazobactam, and clindamycin (20) were also administered via continuous infusion.…”

Continuous Clindamycin Infusion, an Innovative Approach to Treating Bone and Joint Infections

“…For 47 patients, a second sample was obtained between days 8 and 28, with a minimum of 5 days between the times of collection of the two samples. Samples were assayed as described before (30). Multiresistant Staphylococcus aureus SJ11617 (rifampin MIC, Ͼ128 mg/liter; fosfomycin MIC, Ͼ512 mg/liter; fluoroquinolone MICs, Ͼ64 mg/liter; fusidic acid MIC, Ͼ256 mg/liter) was used as the indicator organism.…”