Outpatient Parenteral Antibiotic Therapy in Primary Hip and Knee Arthroplasty Infection Managed with Debridement and Retention of Prosthesis: A Retrospective Cohort Study

Abstract

Background:

Attempted joint salvage of infected primary arthroplasty traditionally has utilized joint washouts in combination with costly long-term inpatient parenteral antibiotic regimens. Outpatient and home parenteral antibiotic therapy (OHPAT) represents a potential alternative. However, there is a lack of published data on its value for primary deep arthroplasty infection. This paper describes the surgical and microbiologic outcomes of a cohort of patients with deep arthroplasty infections treated with OHPAT after surgical washout and debridement.

Methods:

Local OHPAT records identified all patients who underwent attempted joint salvage of a primary hip or knee replacement complicated by a deep post-operative infection between February 2006 and February 2009. Minimum follow-up for all patients was 24 mos. For each patient, hospital records were reviewed to ascertain the effectiveness of treatment.

Results:

In total, 14 patients (10 total knee replacements; four total hip replacements) were identified from the records. Eleven joints (79%) were salvaged. There was a trend toward a higher salvage rate with early infection (<6 mos after primary surgery), with eight of nine joints (89%) being salvaged, versus 60% (three of five) for later presentation. Methicillin-sensitive Staphylococcus aureus was the most common organism identified (43% of cases), and 57% of infections were polymicrobial. The average duration of OHPAT was 58 days. Two patients were readmitted because of clinical deterioration, both of whom later required revision. All patients, regardless of their outcomes, stated they were satisfied with the OHPAT service and believed it was more convenient than inpatient treatment. We estimate OHPAT saved approximately £13,000 per patient episode.

Conclusions:

Use of OHPAT for deep infection after primary arthroplasty has a high success rate. It is effective at identifying patients failing treatment, is cost-effective, and has a high level of patient satisfaction.

Since it was first described in the 1970s [1] the use of outpatient and home parenteral antibiotic therapy (OHPAT) has grown, and it now represents a useful treatment option for a variety of infective indications. The technique has been shown consistently to be safe and cost-effective compared with inpatient treatment [2 –4]. Clinics offering such treatment allow frequent parenteral or oral antibiotic administration or both in addition to clinical review and monitoring of biochemical and hematologic markers of infection. Patients are treated as outpatients unless admission is dictated by clinical or biochemical deterioration.

Infection after primary joint arthroplasty is a substantial cause of arthroplasty revision and patient morbidity. Modern estimates for the incidence of deep post-operative infection range from 0.2% to 1% [5,6]. This is significantly lower than the 6.9% [7] reported only 50 years ago, largely because of advances in aseptic theater technique, theater design, antibiotic prophylaxis, and antibiotic-impregnated cement. Initial surgical management of the infected primary arthroplasty traditionally has involved open or arthroscopic washout with debridement, providing an opportunity to take samples for culture. This is followed by a sustained course of antibiotics, usually administered parenterally in order to sustain sufficient bioavailability. This protocol often necessitates an extended and ill-defined inpatient stay, which is inconvenient for patients and represents a substantial monetary burden [8].

Although there have been reports of OHPAT effectiveness in the treatment of osteomyelitis [9] and skin and soft tissue infections [10], there is a lack of published data for its use for primary deep arthroplasty infection. We therefore undertook this retrospective cohort study with the intention of describing the surgical and microbiologic outcomes of a cohort of patients with deep arthroplasty infections treated, after surgical debridement, using the OHPAT service at our local institution. We aimed to identify the causative organisms and describe their subsequent treatment, including details of re-admission rates from OHPAT, salvage rates, and patient satisfaction alongside an analysis of cost-effectiveness.

Patients and Methods

Using local OHPAT records, we identified all patients who had undergone primary hip or knee replacement complicated by a deep post-operative infection and treated via the OHPAT service at our institution between February 2006 and February 2009. Inclusion criteria for OHPAT are that the patient requires parenteral antibiotics and that a once-daily regimen is available. Patients excluded from OHPAT are intravenous (IV) drug users, alcoholics, patients who cannot safely have IV access at home (e.g., some confused patients without adequate caregivers), and patients unwilling or incapable of daily travel for treatment. All patients for whom an initial attempt at joint salvage was made were included. All patients were treated on an outpatient basis in an OHPAT clinic based at a university teaching hospital. Clinical progress, is monitored closely by a consultant in infectious diseases present in the clinic at regular intervals. The treatment commences within 24 h of discharge for all patients. Peripheral access consisted of a tunneled Hickman catheter or peripherally-inserted central catheter and was obtained by the local radiology department while the patient was hospitalized. No catheter-associated complications were reported.

The minimum follow-up was 24 mos for all cases. This cohort included all patients regardless of where the primary procedure was performed and therefore included patients referred from other institutions. The 10 males and four females with a mean age of 63 years (range 39–81) underwent total knee replacement (TKR) in 10 cases and total hip replacement (THR) in four. Failure of treatment was defined as revision of any component excluding the polyethylene liner (acetabular component, tibial tray) or modular femoral head, which may have been exchanged at the time of initial surgical debridement. The decision to stop antibiotic treatment was made by a consultant in infectious diseases on the basis of persistent normalization of biochemical markers and clinical assessment.

The OHPAT records list detailed clinical information alongside biochemical, hematologic, radiologic, and microbiologic data. To ensure data accuracy, the OHPAT records were verified against patient notes and electronic data stored on the trust's pathology and radiology servers. For this review, we collected specific data on the surgical procedure (date of primary operation, date of infection presentation, date and type of initial surgical procedure), biochemical markers (C-reactive protein [CRP] at presentation and time to return to baseline [<5 mg/dL]), microbiologic results (organism and sensitivities, antibiotics used), and clinical outcome (joint salvaged or revised). In addition, all but one patient, who died of unrelated causes, was contacted via telephone at the end of treatment and questioned about the experiences and satisfaction with the OHPAT service.

Results

Rates of salvage

Overall, 11 joints (79%) were salvaged. These included seven of the 10 TKRs and all four THRs. Eighty-nine percent of the joints presenting within six months of the original procedure were salvaged. Of the five patients presenting after six months, only three (60%) progressed to salvage. Ten cases were treated with initial open washout with or without a liner exchange, of which 90% were salvaged. Of the four cases where percutaneous or arthroscopic washouts were used initially, only two were salvaged. All salvaged TKRs and three of the four THRs were cemented prostheses.

The trend in the decrease in CRP with time for the two groups is given in Figure 1A and specifically for the three failures in Figure 1B. Of the three failures, one patient (age 81; TKR) improved initially and appeared to have responded to treatment only to have a recurrence five months after initial presentation. A different organism was identified at recurrence, and the patient was treated subsequently with long-term suppressive antibiotics. The second patient (age 71; TKR) had an excellent clinical response to initial washout and liner exchange but had a persistently elevated CRP concentration with a noticeable spike at day 106 (Fig. 1B). The CRP concentration eventually normalized without need for further surgical intervention, but infection recurred 18 mos after presentation. The final patient (age 58; TKR) had known rheumatoid arthritis and developed infection with an atypical organism three years after primary surgery. Infection failed to abate despite three washouts and necessitated a two-stage revision performed seven weeks after re-presentation.

FIG. 1.

Change in serum C-reactive protein concentration. (A) Decrease with time for the two groups. (B) Trend for three patients in whom treatment failed.

Re-admission

During the course of OHPAT, four patients required re-admission. Two of these were for medical conditions unrelated to their treatment (urinary tract infection and hematemesis.) The other two (TKR aged 81, TKR aged 58) (see Fig. 1B) were re-admitted because of deterioration in the clinical status of their infected arthroplasty. Both of these patients eventually required a two-stage revision. There were no complications with tunneled catheters.

Causative organisms

In all the joints, at least one causative organism was identified by culture. In eight cases (57%), only one organism was identified, whereas six infections (43%) were polymicrobial. The most common organism was methicillin-sensitive Staphylococcus aureus, occurring in six of 14 cases (43%) and accounting for 30% of all organisms identified. In only one case was an atypical organism cultured (Lactococcus lactis). This was associated with persistent infection despite multiple washouts and eventually necessitated a two-stage revision.

Patient satisfaction

One patient had died of unrelated causes prior to questionnaire completion. Of the 13 patients contacted, all stated they were satisfied with the OHPAT service. All patients thought that OHPAT was more convenient than an inpatient stay and that should the same problem recur, they would undergo OHPAT again. All stated they would recommend the service to a friend under similar circumstances. There were no problems with attendance.

Cost analysis

A cost analysis was performed using the OHPAT business plan and costs provided by the orthopedics department management team. We calculated the average duration of treatment within the OHPAT service for our patients as 58 d. The average cost of our local OHPAT service is £24/d, and thus the average cost of OHPAT treatment was £1,392. The cost of an inpatient bed for 24 h is estimated at £250. For ease of calculation, consultant salary was not included in our calculations. The average cost of an inpatient stay for the same duration was therefore £14,500. Assuming consumables (e.g., drug and catheter costs, blood tests, laboratory support, subsequent clinic appointments) are equivalent for inpatient treatment and OHPAT, this equates to a savings of £13,108 per patient in favor of OHPAT. Some units might provide a different model of care, with two weeks of inpatient intravenous antibiotic followed by discharge and completion of therapy on an oral antibiotic (clinical assessment allowing.) In this case, the savings would have been £2,108 per patient in favor of OHPAT.

Discussion

Deep prosthetic infection is the scourge of the arthroplasty surgeon. It is costly, time and resource consuming, and difficult to treat. Attempted prosthetic salvage using a combination of initial aggressive surgical debridement with prosthetic retention, followed by a long-term course of parenteral antibiotic therapy delivered in an outpatient setting is an attractive alternative to revision. Our experience using this method suggests that this is an effective option, with a high overall success rate (70% TKR and 100% THR), especially in patients presenting within six months of primary surgery who were treated with initial open washout. In addition, we found the protocol to be effective at identifying patients failing treatment, safe, cost-effective, and associated with a high level of patient satisfaction.

Despite including all patients with infection of a primary implant treated with attempted joint salvage using OHPAT over a three-year period, we were able to identify only 14 patients. Although this number is small, this is, to our knowledge, the largest study of OHPAT and deep prosthetic infection reported in the literature. We also benefit from a minimum 24-mo follow-up of all salvaged joints to ensure no relapses occurred after cessation of treatment. It should be recognized that these patients present in a variety of ways and can demonstrate differences in co-morbidities, medical treatments, and immunologic status. The retrospective nature of this analysis meant that this information was not available or could not have been analyzed meaningfully because of the small numbers. Standardization of surgical technique and operative management were beyond the control of this study.

Previous work has shown that OHPAT is safe and cost-effective in the treatment of osteomyelitis [9], endocarditis [11 –13], skin and soft tissue infections [10], and bone and joint infections [14.] However, there is no examination of outcomes with attempted salvage after deep prosthetic infection [15]. A recent study examining salvage rates after inpatient-treated prosthetic joint infections reported a salvage rate of 79% at two years [16]. The results of OHPAT in our series demonstrate similar success, with 79% of primary joints salvaged regardless of time to presentation. Indeed, the salvage rate was even greater in patients presenting within six months of primary surgery and who were treated with aggressive initial open washout and debridement.

In this series, the most common causative organisms were methicillin-sensitive S. aureus, and coagulase-negative staphylococci. This is similar to the findings of Phillips et al. [17], who reported that 36% of deep prosthetic infections were caused by coagulase-negative S. aureus and 25% by methicillin-sensitive S. aureus in their series of more than 10,000 arthroplasty procedures. The figure also is consistent with the prevalence reported in the literature [18,19]. Our study found that patients were highly satisfied and were overwhelmingly positive when asked about the OHPAT service. In their series of 276 patients undergoing OHPAT for a variety of soft-tissue indications, Chapman et al. [20] found similarly high rates of satisfaction, with almost 99% of patients rating the service very good or excellent.

As part of this investigation, we performed a crude cost analysis comparing the savings achieved by using OHPAT instead of traditional inpatient parenteral treatment. This demonstrated that per day, OHPAT costs approximately 10% that of a comparable inpatient stay, exclusive of consumables costs, which were assumed to be equivalent. Similar cost analysis performed using OHPAT services dealing primarily with skin and soft tissue infections have found cost to be only 47% that of a comparable inpatient stay [10]. The discrepancy from our own findings is likely to be attributable to local variations in costing and treatment and the much shorter duration of OHPAT for many common soft-tissue infections. A third arm of cost analysis examining a scenario in which patients are provided with parenteral antibiotics for two weeks also showed a financial benefit, although loss of other benefits of OHPAT (frequent follow-up and biochemical monitoring by an experienced team, reduced antibiotic bioavailability) should not be underestimated.

In conclusion, this study has shown that high salvage rates, equivalent to those of traditional inpatient-based treatments, can be achieved using a combination of aggressive surgical debridement followed by outpatient parenteral antibiotics delivered by an OHPAT service. This treatment modality is associated with both high levels of patient satisfaction and significant cost savings. Thus, OHPAT for the management of deep primary prosthetic infection is safe, patient-friendly, and cost-effective.

Footnotes

Author Disclosure Statement

None of the authors has any commercial associations that might create a conflict of interest in connection with this paper.

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