Between August 2014 and December 2018, 33 patients provided with DAP (Cubicin®, MSD K.K., Tokyo, Japan) as a treatment for a PHI at our institution. DAP was administered when an infection was suspected, right after aspiration of the joint for subsequent cell culture. However, some of those patients changed the antibiotic treatment to a more appropriate one after the identification of the pathogen. In cases where no identification was made by joint aspiration, DAP therapy was initiated, and if the C-reactive protein (CRP) levels decreased, the treatment continued. Thus, a retrospective study for the treatment of infections caused by gram-positive pathogens with DAP was conducted in only 20 patients (follow-up rate of 100%) (Fig. 1). In accordance with the IDSA guideline , the implant retention was initially selected, but the final decision was made intraoperatively by the surgeons. Rifampicin (RFP) was added whenever possible.
Surgical options included implant retention in 9 patients (no surgery in 4 and only debridement in 5) and implant removal in 11 patients (one-staged and two-staged revisions in 3 and 8, respectively). The implant retention group included 3 men and 6 women, with a mean age of 69 years (range, 36–85 years) and a mean follow-up period of 24 months (6–39 months). The mean duration of DAP therapy was 30 days (12–106 days), at a mean daily dose of 5.6 mg/kg/day (3.8–8.3 mg/kg/day). The implant removal group included 4 men and 7 women, with a mean age of 69 years (range, 53–88 years) and a mean follow-up period of 23 months (4–50 months). The mean duration of DAP therapy was 37 days (1–60 days), at a mean daily dose of 5.8 mg/kg/day (3.8–10.0 mg/kg/day) (Table 1). The study was approved by our institutional review board. All patients provided informed consent for study participation and publication of findings.
Bacterial infection diagnosis
PHI was diagnosed according to the criteria of the Musculoskeletal Infection Society . PHI was classified into four clinical categories: Type I (early postoperative infection), Type II (late chronic infection), Type III (acute hematogenous infection), and Type IV (positive intraoperative cultures) [5, 6]. An early postoperative infection was defined as a wound infection that developed less than one month after surgery. A late chronic infection corresponded to an infection that developed one month or more after the index operation and that had an insidious clinical course. An acute hematogenous infection was associated with a documented or suspected antecedent bacteremia and was characterized by an acute onset of symptoms in the affected joint with the prosthesis. A patient was considered to be in the Type IV group if at least two specimens obtained at the time of revision surgery were positive on culture.
After antibiotic administration, patients were followed-up at weeks: 1, 2, 3, 4, 8, and 12, at months 6 and 9, at 1 year, and annually thereafter. Data were retrospectively analyzed by two orthopaedic surgeons who were blinded to the treatment regimens. Pathogens causing PHIs, reasons for the discontinuation of an antibiotic, and infection control rates were evaluated. Infection control was defined as the lack of clinical signs, symptom, and radiological signs of infection, a CRP level <10 mg/L and an erythrocyte sedimentation rate <20 mm/h. Therefore, a successful case was defined as one not requiring implant removal after treatment; failure was defined as implant removal due to recurrent infection.
For the laboratory assessment, CRP levels (mg/L) were investigated. Furthermore, the risk of recurrent infection was evaluated using the scoring system  (Fig. 2), based on six parameters: 1) general condition, 2) duration of infection, 3) wound complication, 4) presence of microorganisms, 5) CRP levels, and 6) necessity for bone grafting. Each parameter was rated from 0 to 2 points, giving a maximum score of 12 points for low-risk.
Two-group comparison were conducted using Student t-test or Mann-Whitney U test. To compare qualitative variables, Fisher exact test was applied. The Wilcoxon signed-rank test was used to compare differences in parameters before and after patient treatment. Statistical significance was defined as P < 0.05. All analyses were performed using SAS 9.2 (SAS Institute Inc., Cary, NC, USA).