Method

In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained.

Method

Mitomycin C was conjugated to a commercially available antibody against S. aureus via a disulfide linkage, with a drug release occurred via thiol-disulfide exchange.

ADC as tested against S. aureus under various growth conditions (planktonic, persisters and biofilm). In vitro toxicity of ADC vs MMC was measured using a human cell line (MOLT-4).

Finally, two independent in vivo experiments were performed in a murine implant-associated osteomyelitis model. In experiment one ADC treatment was compared NaCl, vancomycin and vancomycin + ADC (n=10 for all groups). Subsequently, ADC was compared to NaCl, the antibody used in the ADC construction, MMC and a novel ADC constructed with a non-S. aureus antibody (n=10 for all groups). All treatments were started day 7 post inoculation and were administered for 3 days. CFU enumeration was done following sonication to quantify bacterial load.

Method

15 female pigs received a stainless-steel implant in the right proximal tibia and were randomized into two groups. Infection was introduced by inoculating the implant with Staphylococcus aureus as previously described¹. On day 7 post surgery, all pigs were revised with implant removal, debridement of implant cavity and insertion of a sterile implant. 7 days of treatment was then initiated with either moxifloxacin 400 mg iv q.d. (M) or moxifloxacin and rifampicin 450 mg iv b.i.d. (RM). At day 14, animals were sedated and microdialysis was applied for continuous sampling of moxifloxacin concentrations during 8 h in five compartments: the implant cavity, cancellous bone in both the infected and non-infected proximal tibia, and adjacent subcutaneous tissue on both the infected and non-infected side using a previously described setup². Venous blood samples were collected. Implant and adjacent bone were removed for analysis.