Simultaneous Bilateral Methicillin-Resistant Staphylococcus aureus Infection After Total Knee Arthroplasty Successfully Treated with Continuous Local Antibiotic Perfusion: A Case Report

Introduction

Periprosthetic joint infection (PJI) is one of the most destructive complications following total knee arthroplasty [1–3]. Although guidelines for its management have been proposed, its treatment remains controversial and can require prolonged hospital stays, antibiotic therapy, and multiple surgical procedures [4]. PJI has serious adverse effects, including difficulties in performing daily activities. Most previous studies recommend treating chronic infection with a 2-stage revision arthroplasty or debridement, antibiotics, and implant retention (DAIR), with reported treatment success rates of 71.1% to 82.8% [5,6] and 9% to 62% [6,7], respectively. Recent studies have shown that the 5-year survival rate for patients with PJI is 87.3%, which is lower than that of patients with some types of cancer [8]. Treatment outcomes remain unsatisfactory, highlighting the urgent need to introduce new treatment methods to improve patient prognosis. Furthermore, simultaneous bilateral infections are rarely reported, resulting in a lack of guidance on determining appropriate treatment strategies.

In continuous local antibiotic perfusion (CLAP) therapy, a bone marrow needle and double-lumen tube are placed in the infected area, and an appropriate concentration of an antimicrobial agent is constantly perfused [9,10]. Soft-tissue and bone infections are managed using intra-soft tissue antibiotic perfusion and intra-medullary antibiotics perfusion, respectively [9–12]. CLAP therapy has shown good eradication outcomes in the treatment of bone and soft-tissue infections [9–12]. CLAP administered to the joint is referred to as intra-joint antibiotic perfusion (iJAP) [13]. Although this is specific to fungal infections after total hip arthroplasty, treatment outcomes using CLAP therapy, including iJAP, have been reported [14]. These results indicate the efficacy of CLAP in the treatment of PJI.

Two-stage exchange replacement surgery, the standard approach especially for chronic infection, would have required multiple surgeries and imposed physical and financial burdens on the patient [7]. On the other hand, DAIR is regarded as a patient-friendly approach, offering economic and physical advantages by preserving the implant through a single, minimally invasive surgical procedure [15]. Furthermore, although DAIR treatment for chronic infections is known to yield poorer outcomes in cases involving high-virulence organisms than in those involving low-virulence or culture-negative infections [15], the addition of CLAP may help to overcome this limitation.

We present the case of a 69-year-old patient with bilateral PJI who was successfully treated for implant retention and resolution of the PJI using DAIR combined with iJAP. To the best of our knowledge, this is the first report of simultaneous bilateral PJI treated in this manner. The successful combination of DAIR and iJAP in the treatment of chronic bilateral simultaneous infections caused by resistant bacteria suggests a new treatment method for such cases.

Case Report

A 69-year-old man with no history of febrile illness but with a history of cerebral palsy and end-stage osteoarthritis in both knees, who had total knee arthroplasty (left, 12 months earlier; right, 9 months earlier), was referred to our hospital. Ambulation was assisted with a walker prior to the onset of PJI. He noticed difficulty walking 2 weeks before presentation, and 3 days prior he developed a fever and worsening respiratory symptoms, prompting him to visit his previous doctor. At that time, the doctor performed a blood culture and detected gram-positive cocci, raising suspicion of PJI. Therefore, the patient was referred to our hospital.

Physical examination showed a 15-cm vertical surgical scar from the primary total knee arthroplasty, with bilateral swelling, warmth, effusion, and tender knee joints. The patient’s vital signs were as follows: heart rate, 86 beats per min; blood pressure, 157/71 mmHg; respiratory rate, 15 breaths per min; saturation without additional oxygen, 98%; and temperature, 38.2°C. Laboratory test results revealed a white blood cell count of 12 820/μL, C-reactive protein level of 16.27 mg/dL, and erythrocyte sedimentation rate of 70 mm/h. Plain radiographs revealed no radiolucency (Figure 1).

Based on the suspicion of infection, we performed joint aspiration. Approximately 20 mL of purulent exudate was aspirated from both the left and right knee joints, and gram-positive cocci were isolated from the joint fluid cultures. No uric acid crystals or pyrophosphate crystals were detected in the synovial fluid sample; however, an increase in the number of white blood cells and neutrophil ratio in the synovial fluid was observed. Therefore, based on the Musculoskeletal Infection Society diagnostic criteria, PJI was diagnosed and surgical intervention was performed.

Intraoperatively, pyogenic exudates and acute synovitis were observed in both knees, and methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the joint fluid cultures of both knees. As was later discovered, the MRSA isolates were susceptible to vancomycin (minimum inhibitory concentration [MIC] 1.0 μg/mL), teicoplanin, gentamicin, albicansin, minocycline, and trimethoprim/sulfamethoxazole, but were resistant to ampicillin, cefazolin, erythromycin, clindamycin, levofloxacin, imipenem/cilastatin, and ampicillin/sulbactam. Because there was no loosening of the femoral and tibial prosthesis, both implants were retained, and thorough synovectomy and irrigation were performed. Subsequently, the polyethylene insert was removed, posterior synovectomy was performed, and a new insert was implanted. Next, 22-Fr double-lumen tubes (Salem Sump tube; Coviden, Tokyo, Japan) were placed from the distal and medial joint capsules to the side of the medial epicondyle and to the side of the lateral epicondyle (Figure 2). The Salem Sump tubes were connected using a Y-tube attached to a suction device (SB bag; SB-Kawasumi Laboratories Inc, Tokyo, Japan). Upon the patient’s return to the ward, continuous local administration of gentamicin (1200 μg/mL) was initiated through 2 Salem sampling tubes inserted into each knee, with an infusion rate of 2 mL/h per tube (total 8 mL/h). Bilateral continuous passive motion (Gadelios Medical Co, Ltd, Tokyo, Japan) was maintained throughout the duration of the CLAP therapy. The setting on the continuous passive motion device was adjusted from 0 to 30 degrees immediately after surgery, and then the range of motion was gradually increased.

On day 14 after CLAP initiation, the 2 Salem Sump tubes and SB bags were removed. Local findings improved during the procedure, and the inflammatory response normalized on postoperative day 25. In combination with the systematic administration of antibiotics via CLAP, vancomycin was administered intravenously on the day of surgery and continued until postoperative day 31. Walking training began on postoperative day 51. Subsequently, oral minocycline was commenced and continued for 6 months. The patient was discharged on postoperative day 64, and the range of motion at that time was 0 degrees in extension and 130 degrees in flexion on both sides (Figure 3). He was able to walk with a walker when he was discharged from the hospital. After discharge, monthly laboratory tests, imaging, and physical examinations were performed, with no signs of infection observed. As a result, the patient remained symptom-free and without recurrence 1 year later. Given the complete resolution of symptoms and normalization of inflammatory markers, additional surgical treatment was deemed unnecessary.

Figure 4 shows the changes in white blood cell count and C-reactive protein levels from the time of hospital admission to the time of transfer to another hospital, as well as the treatment administered.

Discussion

In recent years, treatment methods for PJI have been established [16,17]. However, only 4 cases of bilateral simultaneous infection have been reported [18–21], and there is no standard treatment strategy. Furthermore, 1 of the 4 cases of bilateral MRSA infection was hematogenous infection [18], and there have been no reports of chronic infection. In general, MRSA infections are reported to be more difficult to treat than non-MRSA infections in terms of implant retention and postoperative knee function [22,23]. Considering these points, the present case report provides useful information, as the incidence of PJI in both knees caused by MRSA is quite low and typically difficult to treat. Notably, in the present case, good treatment results were achieved with a single surgery.

This case was classified as a chronic infection according to Tsukayama et al [24]. Two-stage revision surgery is considered the standard treatment for chronic infection without implant loosening [24]. In a case series involving DAIR and 2-stage revision for treatment of chronic infection due to MRSA, the reported treatment success rate for the initial surgery was 0% [22], and postoperative loss of knee function was likely [23]. The success rate of 2-stage revision surgery for MRSA-related infections is only 22.4% [25]. The success rate of treatment remains low regardless of the method used, making the present case is a rare example of the successful resolution of late-stage symptoms of chronic bilateral MRSA infection of the knee using a novel therapy.

The conventional 2-stage revision surgery, which involves removing the implant, placing an antibiotic-containing cement spacer, and then reinserting the implant in a second surgery, has several disadvantages. First, antibiotic-impregnated cement achieves high local antibiotic concentrations; however, these levels rapidly decline within a few days and fall below the minimal biofilm eradication concentration (MBEC) [26], which is the concentration required to destroy biofilms. This concentration has been shown to be 100 to 1000 times higher than that of the MIC, which is the lowest concentration required to inhibit bacterial growth [26,27]. Prolonged exposure to sub-MIC levels of antibiotics can promote the selection of multidrug-resistant organisms, which can form biofilms on the cement surface and compromise treatment outcomes. Second, the cement spacer is in place for a long period during which the knee joint cannot be moved [7], potentially limiting its range of motion. Third, the need for 2 operations, both with significant anesthetic and surgical risks [7], is a concern for patients. Therefore, as shown in this case report, a single operation to eradicate an infection is ideal for preserving knee function and reducing the occurrence of various complications.

CLAP therapy can continuously deliver concentrations of antibacterial drugs above the MBEC directly to an infected area. In addition, to prevent shortcuts in perfusion fluid in the joint and preserve range of motion, we introduced continuous passive motion during CLAP therapy. Depending on the local findings and laboratory test results, local antibiotics should be administered for 1 to 2 weeks before being terminated [11]. Only a single operation is required, unless the infection flares. We believe that CLAP therapy can compensate for the disadvantages of 2-stage revision surgery. Furthermore, the MBEC of gentamicin for staphylococci, including MRSA, is reported to be up to 256 times higher than the MIC. This suggests that gentamicin can achieve the required MBEC at a lower concentration [28]. Therefore, it is thought that even infections caused by resistant bacteria can be controlled with gentamicin treatment at concentrations exceeding the MBEC. As a result, the bilateral MRSA infection in our case was resolved with a single surgery. In chronic PJI, for which 2-stage revision surgery is usually recommended, it is noteworthy that CLAP was able to control the infection with a single-stage treatment.

Although we described the usefulness of CLAP therapy, this case present only a single case of late chronic infection. Therefore, the effectiveness of this therapy for all simultaneous bilateral total knee arthroplasty infections remains to be determined. Long-term follow-up and accumulation of more cases are needed.

Conclusions

We reported a case of simultaneous bilateral PJI after total knee arthroplasty caused by MRSA that was successfully treated with CLAP therapy in combination with DAIR. This surgical method, if successful, can reduce the number of surgeries required and reduce the associated financial and physical burdens. Therefore, CLAP may be a viable treatment option for PJI caused by MRSA after total knee arthroplasty. Continued follow-up and accumulation of cases will provide further evidence supporting the effectiveness of this surgical method.