Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-015-2388-8

REVIEW

Is prosthesis retention effective for chronic infections in hip arthroplasties? A systematic literature review M. Maillet 1 & P. Pavese 1 & D. Bruley 1 & A. Seigneurin 2 & P. François 2

Received: 4 March 2015 / Accepted: 10 April 2015 # Springer-Verlag Berlin Heidelberg 2015

Abstract The success rate of prosthesis removal as the standard approach to manage chronic infection in hip arthroplasties (HA) is 80–90 %. The effectiveness of prosthesis retention, with or without surgical debridement, to treat patients with chronic HA infection (symptom duration of more than 4 weeks) has not been well established, whereas this strategy is sometimes used in clinical practice. This study aimed to explore the cumulative incidence of failure of chronic HA infections treated with prosthesis retention, with or without debridement. A systematic literature review was conducted in accordance with the methods described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies concerning patients with chronically infected HA treated with prosthesis retention were included. The primary outcome was the cumulative risk of failure. We searched the MEDLINE, Embase, and Cochrane

databases up to April 2014. The database searches provided a total of 1,213 studies for potential inclusion in the review. Six relevant studies were finally identified, corresponding to 29 patients included. Their treatments consisted of prosthesis retention with debridement. This strategy failed for 14 out of these 29 patients after a 1-year follow-up. The failure rate of the prosthesis retention approach associated to debridement for chronic infection in HA is 48.3 % in this review. Debridement and prosthesis retention in association with prolonged antimicrobial treatment may be an advantageous alternative to arthroplasty exchange for frail patients. The difficulty in finding relevant studies illustrates the challenges of interpreting the existing literature for the management of chronic prosthetic joint infection (PJI).

Introduction Electronic supplementary material The online version of this article (doi:10.1007/s10096-015-2388-8) contains supplementary material, which is available to authorized users. * M. Maillet [email protected] * P. Pavese [email protected] D. Bruley [email protected] A. Seigneurin [email protected] P. François [email protected] 1

Infectious Diseases Department, Grenoble University Hospital, CHU de Grenoble BP 218, 38043 Grenoble Cedex 9, France

2

Public Health Department, Grenoble University Hospital, Grenoble, France

Current recommendations for chronic prosthetic joint infection (PJI) (symptom duration longer than 4 weeks [1]) management are based on non-randomized clinical trials, cohort or case-controlled retrospective studies, time-series, or expert opinions [2]. The effectiveness assessment of the different surgical approaches is difficult because of confounding variables, such as site of infection, study population and comorbidities, previous treatment histories, prosthesis stability, soft-tissue conditions, the microorganism involved, and sensitivity to antibiotics. Moreover, the success or failure definitions sometimes differ across studies [3–5]. For chronic PJI, clinical studies have mainly evaluated oneand two-stage exchange strategies through cohorts treated with one or the other strategy [6]. Two meta-analyses showed a success rate of prosthesis removal to manage infection in hip arthroplasties (HA) of 80–90 % [6, 7], and prosthesis removal

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is now recommended as the standard therapeutic approach [2]. In contrast, debridement, antibiotics, and implant retention (DAIR) is now recommended for patients presenting with an acute PJI with a well-fixed prosthesis without a sinus tract [2]. The success rate of DAIR for early or late acute infections after hip or knee prosthesis is reported to be 45.9 and 52 %, respectively [8]. Nevertheless, adherence to recommendations is not complete for chronic infections, especially for less invasive strategies [5, 9]. Indeed, a few patients treated with a prosthesis retention strategy are sometimes found within cohorts including patients treated with the exchange strategy [10–12]. Furthermore, in clinical practice, the debridement and retention strategy is sometimes preferred for patients who refuse to undergo further major surgeries or for whom alternative surgical strategies are unacceptable or high risk because of frailty, or poor functional results are expected after prosthesis exchange. However, prosthesis retention, with or without surgical debridement, has not been thoroughly investigated for chronic infections in HA. With DAIR, relapse of infection seems more likely [13, 14]. The prosthesis retention strategy, with or without surgical debridement, increases the risk of failure the longer the symptoms lasted [13, 15, 16]. The rapid formation of a biofilm on material devices reduces the effectiveness of host defense and antibiotics: the special life conditions within the biofilm generate phenotypic changes of the microorganisms, including target modification, efflux, secretion of inactivating enzymes, and stationary growth phase [17, 18]. This is a reason why prosthesis retention may be suboptimal. Nevertheless, some studies have reported that implant retention was not associated with a worse outcome compared to their removal, with a success rate of 50–78 % for acute and chronic infections combined [5, 19]. A less aggressive approach with open debridement and prosthesis retention may be an alternative to avoid exchange arthroplasty, which is associated with a higher rate of procedure-related morbidity, more immobilization, and greater need for rehabilitation. From a medical-economic perspective, retention strategies should be less expensive than prosthesis removal [20–22]. We aimed to review evidence on the effectiveness of the prosthesis retention strategy (with or without debridement) for the treatment of patients with chronic infection in HA, in terms of cumulative incidence of failure.

Search strategy and eligibility criteria All types of study design were accepted for inclusion, without restrictions on publication date or status. The review was restricted to articles published in English. Studies concerning patients with chronically infected HA treated with prosthesis retention were included. Chronic infection was defined by symptom duration longer than 4 weeks [1]; prosthesis retention was considered with or without surgical debridement. Studies reporting data for hip and knee, or acute and chronic infections, or prosthesis retentions and prosthesis removals combined were included if data on patients treated for a chronically infected HA with prosthesis retention were available. Exclusion criteria were fungal infection pathogens, mycobacterial infections, prolonged suppressive antibiotic therapy, or less than 1 year of follow-up. The primary outcome was treatment failure (at least persistence or recurrence of infectious symptoms) within the followup period.

Information sources and search strategy We searched the MEDLINE, Embase, and Cochrane databases up to April 2014. The search strategy is described in Table 1 [6, 25]; the results were stored in an Excel database. One review author (MM) scanned the titles and abstracts. Potentially relevant articles were acquired for fulllength text and authors were contacted when the article was not available.

Data processing Information was extracted from each study by one review author (MM) and checked by another author (PP), including: (1) characteristics of study participants (age, gender, duration of symptoms, microorganisms, prosthesis loosening, sinus tract, follow-up), and the study inclusion and exclusion criteria; (2) surgical therapy and antimicrobial treatment regimen; (3) treatment failure definition; (4) number of patients meeting the inclusion criteria; and (5) outcomes. Disagreements were resolved by discussion between them.

Summary measures

Materials and methods The study was conducted with methods described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [23, 24].

The cumulative incidence of failure was computed using extracted data from the relevant studies. It was defined as the number of treatment failures during follow-up over the number of patients with chronic hip PJI treated with a prosthesis retention approach.

Eur J Clin Microbiol Infect Dis Table 1 Search strategy applied in the MEDL INE, Embase, and Cochrane databases

Search performed in the following numerical order #1 #2 #3 #4 #5 #6 #7 #8 #9 #10

infection infections hip prostheses and implants arthroplasty replacement prosthesis hip arthroplasties hip arthroplasty hip replacement

#11 #12 #13 #14 #15 #16 #17 #18 #19 #20 #21 #22 #23 #24 #25 #26 #27 #28

hip replacements replaced hip hip implant hip implants hip joint replacement total hip prosthesis hip prosthesis hip prostheses prosthesis related infection conservative debridement retention suspensive treatment #1 OR #2 #4 OR #5 OR #6 OR #7 #3 AND #25 AND #26 #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 #25 AND #28 #3 AND #19 #20 OR #21 OR #22 OR #23 #24 AND #31 #27 OR #29 OR #30 #32 AND #33

#29 #30 #31 #32 #33 #34

No limits applied for the search strategy. The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp) was searched for ongoing, terminated, or completed trials using: hip/infection AND arthroplasty/infection

Risk of bias The surgical procedures, the antibiotic regimen, and the outcome definitions were evaluated in the included studies. Publication bias could not be assessed by a funnel

plot considering the very low number of patients in each study.

Results Study selection The MEDLINE, Embase, and Cochrane database searches provided a total of 1,474 studies for potential inclusion in the review (Fig. 1). After adjusting for duplicates, 1,213 studies remained. Of these, 1,029 studies were discarded after reading titles and reviewing abstracts. The Cochrane Library provided no relevant studies. Eighteen additional abstracts were identified by checking the references of the relevant papers. Among the unavailable full-text articles, no response was received from nine authors contacted. The full text of the remaining 201 citations was examined in greater detail. Of these, 195 studies did not meet the inclusion criteria, many of them lacking relevant patient information, such as precise information on which patients had chronic infections or hip infections, which patients had prosthesis retention, and a clear number of treatment failures for these patients (see exclusion reasons in the Supplementary Material). Six studies met the inclusion criteria. Study characteristics The study characteristics are summarized in Table 2 and Supplementary Tables 1 and 2 [10–12, 26–28]. Five retrospective and one prospective study enrolling 29 patients were included. The infection, inclusion, and exclusion criteria were well defined. The total number of patients, the sites of PJI, gender, age, and infection duration are described in Table 2. Most of the microorganisms involved were Staphylococcus and Streptococcus. Surgical therapy consisted of irrigation, debridement (sometimes repeated), and prosthesis retention; one study combined this with the implantation of resorbable gentamicin-loaded sponges. Various antimicrobial treatment regimens were prescribed according to the microorganisms involved for at least 3 months. Prosthesis loosening on Xrays or at initial debridement, or the presence of a sinus tract were sometimes specified. Information on treatment failure was clear. Cumulative incidence of failure Outcomes should be interpreted cautiously according to the antimicrobial treatment regimen, as well as the number and details of the surgical procedures. Aboltins et al. reported a debridement procedure for a chronic MRSA infection with a successful outcome after

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Studies identified through database searching Medline (n=518) Embase (n=830) Cochrane (n=126)

records after duplicate removed (n=1213)

Full text articles assessed for eligibility (n=184)

Additional included studies: Identified through bibliographic cross-reference of obtained articles (n=17)

Exclusion based on title and abstract (n=1029)

Exclusion based on: language of study other than English, study identified as oral or written presentation from meeting, non available article and no response from the contacted authors, lack of relevant patient information (such as precise information on which patients have chronic infections or hip infections, which patients have conservative treatments, clear number of treatment failure) (n=195)

Studies included in qualitative and quantitative synthesis (n=6) Fig. 1 Flow chart of the study selection process

2 years of follow-up [10]. It should be noted that the antimicrobial treatment duration was long (12 months). Bernard et al. reported one treatment failure in a 90-yearold woman, with a chronic MRSA hip prosthesis infection, treated with debridement without material removal [11]. It relapsed after 53 days of treatment; she received vancomycin alone, whereas current guidelines now recommend the combination with rifampicin whenever feasible [2, 29]. It is difficult to conclude that treatment failure was due to the prosthesis retention, given that the antibiotics were not optimal.

Barberán et al. observed seven treatment failures out of 19 patients treated for staphylococcal-infected HA [12]. The patients did not receive the recommended intravenous antimicrobial treatment; now, rifampicin administration is also recommended twice daily [2]. The treatment duration seemed appropriate. The surgical procedure consisting of debridement and irrigation in combination with resorbable gentamicin-loaded sponges (repeated up to three times) described by Kuiper et al. showed two treatment failures [26]. Nevertheless, the

Methicillin-resistant Staphylococcus aureus

Methicillin-susceptible Staphylococcus aureus

Retrospective, multicenter

b

1990/2005– 2008

Retrospective

Retrospective

a

Switzerland and Sweden

Sendi et al. [28]

2004–2009

1986–1992

The Netherlands

United States of America

Segreti et al. [27]

1998–2004

Spain

Barberán et al. [12] Kuiper et al. [26]

Retrospective

Prospective



Bernard et al. [11] France

Design

Retrospective cohort analysis of a prospectively compiled registry

Years of inclusion

1998–2003

Country

Summary of the included studies

Aboltins et al. [10] Australia

Authors

Table 2

34: 23 hips, 13 knees

18: 6 hips, 12 knees

34 hips

60: 32 hips, 28 knees

15: 10 hips, 3 tibias, 1 knee, 1 vertebrae

20: 13 hips and 7 knees

50

50

35

56.7

80

50

Total number of patients, Gender, % male sites of prosthetic joint infections

71

Mean 66 (31–83)

73 (56–86)

Mean 74.6

61.7 (23–90)

76 (58–83)

Age, median, years (range)

Mean 35 (24–72)





2 patients

2/2

1 (male, 58 years old, MRSAa, 0/1 symptom duration 75 days, 1 debridement procedure, antibiotics for 12 months, follow-up 28 months) 1/1 1 (female, 90 years old, symptom duration 2 years, a MRSA , debridement without removal of foreign body, antibiotics for 184 days) 19 patients 7/19

Number of patients (chronic hip Treatment failure prosthesis infections treated without prosthesis removal)

>4 years of follow-up 1 with discontinued antibiotic 1/1 therapy (male, 37 years old, MSSAb, debridement procedure, clindamycin 4 months) >2 years 5 patients (symptom duration 3/5 34–68 days, 2 loose implants, 1 severe softtissue damage, 3 open debridements, 1 wound revision, 1 arthroscopic surgery, 2 revisions for 2 patients, antibiotic therapy for 12–18 months)

At least 1 year



8 acute infections, 10 chronic infections

Mean 14 (range 6– 20.6)

Median 32 (6–76)

Follow-up, months (range)

? (45–3,650)

38 (12–743)

Time with infection, median, days (range)

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antimicrobial treatment (2 weeks of intravenous antibiotics adapted to causative bacteria after each irrigation, followed by oral antibiotics for 3 months) was appropriate. In the study published by Segreti et al., one treatment failure was reported for a 37-year-old man with a methicillinsusceptible Staphylococcus aureus (MSSA) infection treated with a debridement procedure [27]. The antimicrobial regimen was not optimal in that he received clindamycin alone. Sendi et al. described two successful treatments for stable implants with moderate soft-tissue damage: open surgeries were performed and antibiotics lasted 12 and 13 weeks [28]. Three prosthesis retention treatments failed: one implant was stable with slight soft-tissue damage and wound revision only was performed; the two others had loose implants, one with severe soft-tissue damage was treated with two open surgeries, the other without soft-tissue damage underwent two arthroscopic surgeries. The antibiotic duration was 12 weeks for two patients and 18 weeks for the last one. Overall, prosthesis retention failed for 14 of 29 patients (48.3 %). Study quality Few studies were identified, without any randomized controlled trials. They were case studies mostly based on retrospective data collection. Due to the low number of patients included in each study, publication bias could not be assessed.

Discussion Summary of evidence The review results suggest that debridement and prosthesis retention is sometimes the approach adopted for chronic infection in HA. Patients treated in this way are usually not able to undergo major surgeries or decline further surgeries. This strategy may be an alternative to material exchange, with a cumulative incidence of failure of approximately 44 %, which is relatively high compared to the risk of failure reported for prosthesis removal [6, 7]. The value of current recommendations has been demonstrated elsewhere: inappropriate choice of material retention strategies such as debridement and retention and inadequate antimicrobial treatment are associated with failure [9]. Nevertheless, prosthesis removal is a major surgery: substantial mortality is associated with two-stage exchanges for HA infections [30]. Retention treatment could be considered as an initial option in selected cases of chronically infected HA, and patients who would benefit from this approach need to be identified. Unfortunately, the low number of patients in our review precluded the study of good prognosis factors. Even though some studies have highlighted a worse outcome for two-stage exchanges following a failed material retention approach [31, 32], it could

be an advantageous alternative for frail patients. It could also have functional benefits and economic implications [20–22]. Regarding arthroscopy, it has been suggested to provide worse outcomes compared with open surgery [3, 33]. If prosthesis removal is impossible because of the patient’s poor general condition, unacceptable functional results expected after prosthesis removal, or because the patient declines further surgeries, chronic oral antimicrobial suppression may also play a role for the treatment of chronic infection in HA [2, 27, 34]. Indeed, Segreti et al.’s study evaluated prolonged antibiotic suppression: treatment success was defined as a functional prosthesis without symptoms, with or without prolonged antibiotic suppression. Thus, our review could only detect failure; some patients were not included because they had received prolonged suppressive antimicrobial therapy [27]. We chose to exclude it to keep the patient group homogeneous, given that we could not be sure of their successful outcome or treatment failure while receiving antibiotic suppression: the infection may only have been controlled. Nevertheless, this alternative needs to be considered for some cases. The ideal antibiotic regimen modalities and optimal duration need to be defined, as does its success rate. We believe that the antimicrobial therapy duration should not be less than 1 year and that a life-long suppressive antimicrobial therapy should be considered [27, 34]. A last option may be resection arthroplasty: infection cure reaches 80–100 % with the Girdlestone procedure [35]. However, mortality is important in this group of patients [36], pain may still be important, and most patients are unable to walk. Thus, this procedure may only seem appropriate for nonambulatory patients and impossible reimplantation because of unacceptable anesthetic or surgical risk or technical difficulties, as a salvation option after failed procedures [35–37]. Strengths and limitations, potential bias To our knowledge, this is the first systematic review of prosthesis retention strategy effectiveness for chronic HA infections. However, its limitations need to be considered. First, only six studies were included because very few studies met the inclusion criteria. Difficulties were encountered finding relevant information about symptom duration, site of infection, surgical approach, and outcome for each type of infection. In many studies, only intervals from operation to diagnosis of infection according to Tsukayama’s classification were specified [4], without information on the duration of symptoms. Therefore, it seems very important to standardize strict definitions for PJI (acute, chronic, early, and late infections) [1, 4], to specify this information in studies, and to give outcomes for each type of infection in order to compare or compile results whenever feasible. The follow-up period may be debatable, given that some studies chose to evaluate the outcome after 2 years of followup. When this time period is modified, the 2-year cumulative

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incidence of treatment failure is slightly worse, being 70 %, based on a lower number of patients (7/10). Many studies pooled hip and knee prosthesis infections. By choosing to mix them, the number of studies and patients included would have been more numerous. Nevertheless, even if the success rate does not seem to differ between total hip and knee arthroplasties [3, 6, 16, 38], we chose to restrict our review to HA infections because we expected to include more studies and medical treatment is not recommended for the same duration [2]. No controlled trials evaluating the prosthesis retention approach for chronic infection of HA were identified. Most studies were not designed for surgical approach evaluation and were based on retrospective data collection. Moreover, the studies reviewed included a low number of patients. The characteristics of the patients included in each study, the surgical procedures, and the antibiotic regimen, as well as the outcome definitions, differed across studies. Finally, publication bias cannot be ruled out. Because we restricted the review to articles in English, we may have overlooked studies published in national journals. We contacted each author of a potentially relevant study, but some of them did not reply. Selective outcome reporting may be a potential bias, as positive outcomes may have been more widely reported than negative ones, because prosthesis retention is not conventionally recommended. Nevertheless, it should be noted that the patients included were not case reports of successful results, but belonged to cohorts having other specific aims. Future research In our opinion, relevant patient information and specific outcome results for each type of infection need to be clearly identified in future publications in order to draw conclusions based on homogenous groups of patients. This seems quite important, since most recommendations are made on the basis of studies with a low level of evidence. It would be useful to conduct clinical trials targeting frail elderly patients to compare infection control rates between arthroplasty exchange and debridement, and prosthesis retention associated with prolonged antimicrobial treatment.

illustrate the challenges of interpreting the existing literature for chronic prosthetic joint infection (PJI) management. Conflict of interest None.

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Conclusions 12.

The cumulative failure incidence of the prosthesis retention approach for chronic infection in hip arthroplasties (HA) is 48.3 % in this review. This is consistent with theoretical expectations, since the success rate was 50–78 % in previous studies including acute and chronic infections [5, 19]. Debridement and prosthesis retention in association with prolonged antimicrobial treatment may be an advantageous alternative to arthroplasty exchange for frail patients. The problems finding relevant studies to respond to this question

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Is prosthesis retention effective for chronic infections in hip arthroplasties? A systematic literature review.

The success rate of prosthesis removal as the standard approach to manage chronic infection in hip arthroplasties (HA) is 80-90 %. The effectiveness o...
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