Multidrug resistant bacteria: An independent prognostic variable for failure in lower limb joint arthoplasty?

1 Introduction

Arthroplasty procedures, particularly of the hip and knee, have demonstrated high levels of patient satisfaction and have been proven to be cost effective in relieving the disability of severe arthritis.¹ Despite improvements in peri operative care, periprosthetic joint infection (PJI) remains a serious although thankfully rare complication.² The significance of PJI has ramifications for the patient, with a significant reduction in patient reported outcomes³ and the need for revision of the prosthesis with a concurrent reduction in function. For society as a whole, PJI has a significant impact on health care provision. The evolution of bacteria in response to the widespread use of antibiotics has resulted in an increase in PJI secondary to multidrug resistant organisms.⁴ This has had signifcant soci-economic and health impacts. An evaluation by the World Health Organisation (WHO) suggests the economic impact of resistant bacteria equates up to 1.6% of gross domestic product.⁵

A recent international consensus⁶ defined the presence of resistance to at least one agent in three different families of antibiotics as constituting a multi –drug resistant (MDR) microbe. This international consensus also classified resistant microbes as extensively drug resistant (XDR), defined as microbes showing sensitivity to two or less agents, and pan-drug resistant microbes (PDR) resistant to all categories of antibiotics.⁶

To date, there has been relatively little reported on the impact of PJI secondary to MDR microbes.^7,8 What limited evidence that exists highlights the need for prolonged antimicrobial treatment and aggressive, often multiple revision procedures if eradication of infection is to be achieved. The aim, therefore, of this study was to compare the outcomes, defined by eradication of infection, following treatment for a PJI due to a MDR bacterium with those of a PJI secondary to a non-MDR (NMDR) organism. Where variation existed between these outcomes, we aimed to identify the presence of an MDR organism as an independent predictor for failure to eradicate the infection.

2 Method

The study comprised a retrospective analysis of a prospectively maintained database in a single institution, which collects all details relating to patients diagnosed and treated for a PJI in a tertiary referral orthopaedic centre. All adult patients diagnosed and treated for a PJI of either hip or knee arthroplasty between January 2011 and December 2014 with a minimum 1 year follow up having completed treatment, were included in the study. All patients were managed through a specialist bone and joint infection multidisciplinary team.

All patients were diagnosed with a PJI according to the criteria of the Musculoskeletal Infection Society.⁹ Patients underwent one of three possible surgical strategies, defined by the International Consensus Meeting on Periprosthetic Joint Infection.¹⁰ Patients underwent either a staged revision comprising implant removal, debridement and insertion of an antibiotic loaded cement spacer, with additional antibiotics based on the preoperative culture, where known, or empirically, where the organism was not known, or a single stage revision consisting of removal of existing metalwork, debridement and re-implantation. The decision to undergo either single-stage or two-stage revision was governed by patient criteria, microbiology criteria, the soft tissue condition and the degree of bone loss. Patients presenting with acute symptoms of a PJI with symptom duration less than 4 weeks, without a sinus or evidence of implant loosening or bone loss, underwent debridement and implant retention (DAIR), as described by Byren et al.¹¹

All patients were treated with broad spectrum IV antibiotics until definitive microbiology culture of specimens taken at the time of surgery were known. At this stage, patients were converted to an anti-microbial regimen based on the infecting organism and its sensitivity. Where inflammatory markers did not normalise, or persistent discharge continued from the wound following the first stage, this procedure was repeated revising the antibiotic cement spacer. The time to re-implantation for two-stage revisions was governed by the clinical and biochemical response and was considered when inflammatory markers had normalised. Following reimplantation, antibiotics were continued until microbiology cultures of specimens taken at the time of the second stage confirmed no growth. For those where organisms were identified at the time of reimplantation, antibiotics were continued for a minimum period of 3 months but were only discontinued once inflammatory markers had normalised. In the case of one-stage revisions and those treated by DAIR, antibiotics were discontinued once inflammatory markers had normalised after a minimum period of 3 months.

3 Results

The study population comprised 240 patients who fulfilled the inclusion criteria. 74 (31%) patients were included in the MDR group and were compared to 166 (69%) in the N-MDR group. There was no significant difference in site of infection i. e hip or knee (p = 0.208) and gender (p = 0.398) between the MDR and N-MDR groups (Table 1).

4 Conclusion

Our study has shown that Multi Drug Resistant Bacteria infection in lower limb arthoplasty results in a significantly worse outcome for patients. We have demonstrated that the presence of an MDR organism is an overwhelmingly strong and independent predictor for poor outcome after at least one year.

The mean number of surgical procedures with the MDR patients highlights the complex management these patients are subjected to, which is in keeping with the current literature.^14,15 The data also indicates that the mean number of procedures is significantly higher in the MDR failure group versus the N-MDR failure group (7 vs 4 procedures respectively), which suggests that a number of 4 surgical attempts at salvage during a single infected episode should be the threshold level set when failure is becoming increasingly inevitable.

Historically, poor outcomes in infected arthroplasty have been linked to co-morbidities and have further been used as a factor when considering amputation.16^17,18 The demographic stratified data from our study has shown that neither age, sex nor co-morbidity had any bearing on the rates of failure for an MDR organism. Furthermore, only increased age was shown to be a significant factor for the N-MDR group in relation to failure rates.

The internationally recognised management strategies for peri-prosthetic infection are followed by our institution. Despite this uniformity, the MDR group has shown a higher rate of failure versus the NMDR across all treatment groups. Although this was shown to be significant in the staged revision group, the other groups are showing a trend towards statistical significance and greater patient numbers may be required to prove this. By examining the most acutely infected group, i.e. those suitable for DAIR, against the staged revision treatment group, we attempted to account for chronicity as a confounding factor. Although there was a higher rate of failure amongst all chronic patients, again in keeping with current evidence,^16,17 this was not found to be statistically significant and thus cannot be an independent factor for failure nor account for the significant difference in failure between both groups.

Existing literature has also established the polymicrobial element in patient infection to be a bad prognostic factor.¹⁸ Some studies have even noted a higher rate of MRSA and other resistant bacteria with polymicrobial infections.¹⁹ Our study confirms this finding, but the difference did not remain when analyzing the NMDR group. Therefore, we propose an interesting alternative to the widely held belief that the presence of more then one bacteria leads to a poor outcome. Our study suggests the presence of more than one organism, where one organism is an MDR, is the explanation behind existing and, indeed, our own findings. Despite this observation, more research is perhaps needed to examine the pathophysiological nature of MDR organisms with polymicrobial infections.

Due to the large number of MDR staphylococcal infections documented a direct comparison could only realistically be made to the staphylococcal infections in the N-MDR group. The significantly higher rate of failure when stratifying for the organism type (for staphylococcus aureus at least) again underlines the message that the multi drug resistance is the main driving factor behind the poor outcomes. This may be due, in part, to the polymicrobial relationship with other organisms but again this requires further research.

Within the MDR group we discovered the presence of XDR organisms and so called PDR organisms. We used the class sensitivity data available to the clinician from the database as these are what the clinician will utilize in their management protocol. We discovered that there was a significant rate of failure within the organisms with 2 or less class sensitivities. This has never been demonstrated in the orthopaedic literature and suggests that our current management strategy of surgical intervention and antibiotics may be ineffective. With fewer antibacterial agents in the clinician's arsenal this can explain a poorer outcome. However, further work is required to develop antibiotic and possibly surgical regimes to combat more resistant organisms.

In conclusion, this study has demonstrated that the presence of an MDR organism in infected hip and knee arthroplasty will lead to a long and protracted journey for the majority of patients. The worse outcomes, irrespective of demographics, treatment, chronicity or multiple organisms strongly suggest that the MDR organism itself is a significant factor for the failure of joint arthroplasty. Clinicians faced with this must risk stratify when determining their treatment and individually factor this threat into their assessments and counselling of the patient.

Statement

No conflict of interests declared.