No abstract

Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (fT > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 μg/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12–18 h). Blood samples were collected as reference. Results: CI resulted in fT > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 μg/mL. In Group STI, >72% fT > MIC was reached for MIC = 4 μg/mL in all investigated compartments, while for MIC = 16 μg/mL only subcutaneous tissue exhibited fT > MIC > 50%. Conclusion: CI of piperacillin resulted in higher fT > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.

Background: Peri and postoperative antibiotics are key adjuvant treatment tools in the management of periprosthetic joint infection (PJI). The aim of this study was to evaluate the effect of rifampicin on the area under the moxifloxacin concentration-time curve from 0 to 24 hours (AUC 0-24 ) in the synovial fluid of the knee joint, tibial bone, and adjacent subcutaneous tissue under steady-state conditions using microdialysis in a porcine model.Methods: Twenty female pigs were randomized to receive oral treatment with moxifloxacin monotherapy (Group A, n = 10) of 400 mg once daily for 3 days or a combination therapy (Group B, n = 10) of 400 mg of moxifloxacin once daily for 3 days and 450 mg of rifampicin twice daily for 7 days. Microdialysis was used for sampling the synovial fluid of the knee joint, tibial cancellous and cortical bone, and adjacent subcutaneous tissues. Plasma samples were taken as a reference. Measurements were obtained for 24 hours.Results: Coadministration of moxifloxacin and rifampicin resulted in reductions of the moxifloxacin AUC 0-24 in all targeted tissue compartments by 67% to 85% (p < 0.05). The corresponding change in plasma was 20% (p = 0.49). For both groups, the tissue penetration (the ratio of tissue free fraction AUC 0-24 to plasma free fraction AUC 0-24 [fAUC tissue /fAUC plasma ]) was incomplete in all investigated compartments. The highest moxifloxacin tissue penetration was in the knee joint synovial fluid: 0.59 (Group A) and 0.24 (Group B). The lowest tissue penetration was in the cortical bone: 0.17 (Group A) and 0.03 (Group B). Conclusions:We found a significant reduction of the moxifloxacin concentration, expressed as the AUC 0-24 , in tissues relevant to acute PJI treatment when coadministered with rifampicin.Clinical Relevance: The concentrations within the targeted tissue compartments were reduced significantly more than the concentrations in plasma, which may be particularly important as plasma concentrations are used in clinical practice to assess moxifloxacin treatment sufficiency. Joint replacement alleviates pain and enhances joint function for numerous patients every year. Although infection related to arthroplasty procedures is rare (European intercountry range, 1% to 3%) 1 , the number of procedures is rising, and infections result in high morbidity rates and expenditures associated with their treatment 2,3 . Current treatment protocols for acute periprosthetic joint infection (PJI) include surgical debridement, antibiotics, and implant retention (DAIR) 4 . Periand postoperative antibiotics are key adjuvant treatment tools, and the optimal selection, mode of administration, and duration of treatment are dependent on multiple factors 4,5 .Quinolones combined with rifampicin are recommended internationally as the first-line antibiotic therapy in acute staphylococcal PJI, the most prevalent type of PJI 4,6 . In comparison to older quinolones, moxifloxacin exhibits lower epidemiological cutoff values (ECOFFs) for staphylococci and a lower potential for antibiotic-...