Data from 10 patients (eight men, two women) were collected. The mean age at the time of fracture operation was 59.9 (range, 22–80) years, and the mean follow-up duration was 2.5 (1.0–5.0) years. Comorbidities included diabetes mellitus (three patients), hepatitis C (one patient), chronic renal failure requiring dialysis (one patient), and epilepsy (one patient). The affected bones were the tibia in eight patients and the humerus and fibula in one patient each. Open fractures were present in three patients. Osteosynthesis was performed in seven patients by plates and in three patients by intramedullary nail. The initial internal fixation was performed at an average of 7.5 (0–27) days after the injury. Deep infections developed on average of 29.9 (14–63) days after the initial internal fixation.
A summary of the characteristics of the 10 patients is presented in Table 1. The pathogenic bacteria were methicillin-susceptible Staphylococcus aureus (MSSA) in six patients, MRSA in two patients, and unknown in two patients. Antibiotics administered through iMAP were astromicin (800–1000 mg/day), arbekacin (150 mg/day), and gentamicin (60–300 mg/day) in three, one, and eight patients, respectively; the average duration of iMAP was 17.1 (range, 8–28) days. A summary of administered antibiotics is shown in Table 2. In all patients, the deep infections could be eradicated with the implants preserved, leading to fracture union. During the observation period, there were no complications or recurrence of infection, and no patient required arthrodesis and amputation of the affected limb. The blood concentration of gentamicin needed to be adjusted in one of the patients (patient 7 in Table 2). The transition of gentamicin concentration in the blood and drainage fluid of the patient is shown in Fig. 2. The gentamicin concentration in the blood was adjusted to an appropriate level by promptly slowing down the rate of gentamicin administration. By contrast, the concentrations in the drainage fluid, used as a reference for local concentration, were maintained at a high level throughout the administration period.
Case presentation 1 (patient 1 in Table 1)
The patient was a 75-year-old woman with diabetes mellitus. She sustained left closed tibial and fibular distal shaft fractures in a traffic accident (Fig. 3a). Pre-injury activities of daily living were T-cane gait exercises. We performed open reduction and internal fixation (ORIF) for both fractures using locking plates on the 5th day after the injury (Fig. 3b). On the 14th postoperative day, purulent discharge was observed from the surgical wound (Fig. 3c), and deep infection to the implant and fracture site was considered; thus, emergency surgery was performed on the same day. A subcutaneous pocket filled with necrotic tissue and infected fluid was curetted. A drainage tube was placed subcutaneously, and iMAP needles were inserted proximal and distal to the fracture site in the tibia (Fig. 3d). We confirmed that the injected saline through the iMAP needles was properly drained through the tibial fracture site to the drainage tube. A solution of 120 mg of gentamicin in 50 mL saline was injected locally at 2 mL/h from two iMAP needles in a sustained manner using syringe pumps, with the implants preserved (Fig. 3e). The pathogenic bacterium was MSSA. Local findings improved promptly after the initiation of iMAP, and iMAP needles were removed 14 days after insertion. Intravenous and oral administration of antibiotics was continued for 4 weeks and 8 weeks after iMAP needle removal, respectively. At 1 year after surgery, no signs of infection recurrence were observed, and fracture union was achieved. The patient was able to walk with a T-cane as before the injury (Fig. 3f).
Case presentation 2 (patient 5 in Table 2)
The patient was a 22-year-old man with hepatitis C who could walk independently before the injury. He was injured in a traffic accident and was diagnosed with right closed tibial and fibular shaft fractures (Fig. 4a). ORIF with an intramedullary nail was performed for the tibial fracture on the 9th day after the injury (Fig. 4b). High-grade fever was observed on the 14th day after internal fixation, and localized swelling with heat was noted around the fracture area and the knee. Purulent discharge was observed upon the puncture of both areas (Fig. 4c). The infection was suspected to have spread to the knee joint via an intramedullary nail, and emergency surgery was performed on the same day. Two incisions were made around the fracture site, and curettage was performed. After placement of the subcutaneous drainage tube, iMAP needles were inserted in the proximal and distal parts of the fracture area (Fig. 4d). Bone marrow infusion was started at the same dose as in Case 1, and purulent leachate was drained. Two drainage tubes were placed in the knee joint after intra-articular irrigation during arthroscopy (Fig. 4e). The pathogenic bacterium was MSSA. Local findings improved promptly after iMAP was applied, and the iMAP needles were removed 27 days after insertion. Intravenous and oral administrations of antibiotics were continued for 2 weeks and 8 weeks after iMAP needle removal, respectively. There were no signs of recurrence of infection at 5 years after the treatment. Fracture union was achieved, and the patient could walk without pain (Fig. 4f).