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Prolonged suppressive antibiotic therapy is successful in the management of prosthetic joint infection

Authors:
Nemandra Sandiford at Southland Hospital
Nemandra Sandiford
Jonathan Hutt at University College London Hospitals NHS Foundation Trust
Jonathan Hutt
D. O. Kendoff
D. O. Kendoff
D. O. Kendoff
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P. A. Mitchell
P. A. Mitchell
P. A. Mitchell
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Introduction Prosthetic joint infection (PJI) remains one of the major challenges facing orthopaedic surgeons. There is a paucity of evidence on non-operative management of PJI. We present the results of prolonged antibiotic suppression therapy (PSAT) in PJI from a single centre. Methods A retrospective study was performed. Twenty-six patients were included. Two patients were excluded due to the lack of follow-up data. Failure was defined as admission for sepsis from the joint or amputation. Results Average age was 72 years (range 35–93). Mean Charlson co-morbidity index was 4.3. Mean follow-up was 3.2 years (range 1.3–5.7). Staphylococcal species were isolated in 11 cases (44%) (MRSA 1, MSSA 5, Staph. epidermidis 4 and Staph Pasteuri 1). Other bacteria included E. Coli (2), Streptococci spp. (3), Propionebacterium acnes (1) and Pseudomonas aeruginosa (1). Four cases were polymicrobial infection (16%), and no organisms were identified in two cases (8%). Candida albicans was identified in one case. All cases of bacterial infection were treated with prolonged oral doxycycline or amoxicillin. Twenty patients (80%) received 6 weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics. Two patients experienced persistent symptoms and required amputation (both TKA). Two patients experienced sepsis but were treated successfully with IV antibiotics alone. The success rate of PSAT was 84% (21/25) successful at an average 3.2-year follow-up. Discussion and conclusion Prolonged suppressive antibiotic therapy is a viable option for the management of PJI with a low incidence of complications.
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Vol.:(0123456789)
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European Journal of Orthopaedic Surgery & Traumatology (2020) 30:313–321
https://doi.org/10.1007/s00590-019-02559-4
ORIGINAL ARTICLE • KNEE - ARTHROPLASTY
Prolonged suppressive antibiotic therapy issuccessful
inthemanagement ofprosthetic joint infection
N.A.Sandiford1 · J.R.Hutt1· D.O.Kendo2· P.A.Mitchell1· M.Citak3· L.Granger1
Received: 21 April 2019 / Accepted: 23 September 2019 / Published online: 1 October 2019
© Springer-Verlag France SAS, part of Springer Nature 2019
Abstract
Introduction Prosthetic joint infection (PJI) remains one of the major challenges facing orthopaedic surgeons. There is a
paucity of evidence on non-operative management of PJI. We present the results of prolonged antibiotic suppression therapy
(PSAT) in PJI from a single centre.
Methods A retrospective study was performed. Twenty-six patients were included. Two patients were excluded due to the
lack of follow-up data. Failure was defined as admission for sepsis from the joint or amputation.
Results Average age was 72years (range 35–93). Mean Charlson co-morbidity index was 4.3. Mean follow-up was 3.2years
(range 1.3–5.7). Staphylococcal species were isolated in 11 cases (44%) (MRSA 1, MSSA 5, Staph. epidermidis 4 and Staph
Pasteuri 1). Other bacteria included E. Coli (2), Streptococci spp. (3), Propionebacterium acnes (1) and Pseudomonas aer-
uginosa (1). Four cases were polymicrobial infection (16%), and no organisms were identified in two cases (8%). Candida
albicans was identified in one case. All cases of bacterial infection were treated with prolonged oral doxycycline or amoxi-
cillin. Twenty patients (80%) received 6weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics.
Two patients experienced persistent symptoms and required amputation (both TKA). Two patients experienced sepsis but
were treated successfully with IV antibiotics alone. The success rate of PSAT was 84% (21/25) successful at an average
3.2-year follow-up.
Discussion and conclusion Prolonged suppressive antibiotic therapy is a viable option for the management of PJI with a low
incidence of complications.
Keywords PJI· Infection· Prosthetic joint infection· Suppressive antibiotics· Revision· PSAT
Introduction
The incidence of prosthetic joint infection (PJI) is 1–2% and
followed by total joint arthroplasty is expected to rise as the
total number of primary hip and knee arthroplasties per-
formed each year increases [1]. It remains one of the main
reasons for revision total hip and revision total knee arthro-
plasty. Management is often prolonged, resource intensive
and expensive. If treatment strategies such as debridement
and implant retention (DAIR) and single- or two-stage
revision fail, the surgeon may be forced to consider sal-
vage options such as excision arthroplasty, arthrodesis or
amputation [2]. However, if the patient is not fit for surgery,
declines further surgery or all surgical options have been
exhausted, suppression therapy with long-term antibiotics
has been described [3]. Several terms have been coined for
long-term administration of suppressive antibiotics includ-
ing prolonged antibiotic suppression therapy (PSAT) and
antibiotic suppression therapy (AST). Antibiotic suppres-
sion therapy can be defined as the administration of antibi-
otics for an extended period, potentially lifelong, to prevent
episodes of sepsis arising from the joint, improve symp-
toms and prevent or prolong progression to further surgery.
Indications for PSAT are a defined organism and sensitiv-
ity profile; a safe oral antibiotic that is compatible with the
organism susceptibility; and a system to facilitate continued
follow-up and monitoring of the patient in the community.
* N. A. Sandiford
nemsandiford@gmail.com
1 The Complex Arthroplasty Unit, St George’s Hospital,
London, UK
2 Chefarzt Zentrum für Orthopädie und Unfallchirurgie, Berlin,
Germany
3 Helios EndoKlinik, Hamburg, Germany
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Periprosthetic joint infection (PJI) remains a severe complication of arthroplasty, associated with a relevant morbidity and mortality (1)(2)(3)(4)(5)(6). Despite many advances and standardizations in treatment, therapy failures remain a frequent issue, particularly when treatment options are limited by surgical aspects or by comorbidities (5,(7)(8)(9)(10)(11) antibiotic suppression therapy remains an option in case of failure to eradicate PJI (9,12,13). However, prolonged administration of antibiotics is associated with a relevant rate of adverse reactions, and suppression of the infection may not be successful (4,12,13). ...
... Despite many advances and standardizations in treatment, therapy failures remain a frequent issue, particularly when treatment options are limited by surgical aspects or by comorbidities (5,(7)(8)(9)(10)(11) antibiotic suppression therapy remains an option in case of failure to eradicate PJI (9,12,13). However, prolonged administration of antibiotics is associated with a relevant rate of adverse reactions, and suppression of the infection may not be successful (4,12,13). Bacteriophages offer new treatment options, particularly considering increasing evidence for a synergistic effect of bacteriophages and antibiotics (14)(15)(16)(17). Though, there is still a lack of evidence to better define their appropriate use and therapeutic role of their administration as well as the posology in musculoskeletal infections (14,15). ...
... Classical surgical and antibiotic options may not be sufficiently effective or tolerable to treat successfully PJI, particularly when comorbidities limit therapeutic possibilities (4, 5, 7-11, 15, 19). Antibiotic suppression would be the classical option in case of treatment failure without surgical options (9,12,13). However, adequate drugs may not always be available or tolerated by the patient (4,13), and antibiotic suppression may also not be sufficient to prevent overt recurrence of infection (12,13,20). ...
Bacteriophage therapy created the necessary conditions for successful antibiotic suppression in a periprosthetic hip joint infection: a Case Report
Article
Full-text available
  • Apr 2025
Introduction Treatment failure remains an issue in periprosthetic joint infection (PJI). Bacteriophages offer new treatment options. However, there is still a lack of evidence to better define their usefulness and administration. We report a case in which antibiotic suppression was successful only after administration of bacteriophages. Case description Antibiotic suppression was the only option for a 94-year-old male with methicillin-resistant Staphylococcus aureus (MRSA) PJI of the hip and of the knee. As the hip PJI could not be suppressed adequately, bacteriophages were administered locally and systemically together with daptomycin. This combined approach led to sufficient clinical improvement for further oral antibiotic suppression, although without infection eradication. Conclusion The administration of bacteriophages may be a valuable, less-invasive adjunct therapy to successfully suppress PJI. Bacteriophage selection, preparation and administration, however, remains associated with administrative obstacles, greatly limiting availability and practicability. Nevertheless, research and developments in this domain should be pursued, particularly considering issues with future antibiotic limitations and cost associated with treatment failure in PJI.
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... Staphylococcus aureus is most frequently described as the infecting organism in PJI in the literature, followed by Coagulase negative Staphylococcus. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Beta-lactams and tetracyclines are the most commonly prescribed antibiotics for SAT. 15, 16, 18, 20, 22-27, 29, 31, 32 Historically, SAT for PJI was associated with poor outcomes, 14, 15 but success rates from the past decade have ranged between 60-93%. ...
... 30 Several published literature reviews explore the use of SAT in PJI, often as a follow-on strategy after surgical debridement and implant retention (DAIR). 4,27,36,37 These reviews typically find favourable success rates ranging from 66% to 75%, but they acknowledge the difficulty in assessing the efficacy of SAT due to the heterogeneity of the literature at present. Namely, variations between medical and surgical management prior to commencement of SAT, definitions of what therapy actually constitutes SAT, and characterisation of treatment success or failure. ...
... 19 There is also anecdotal evidence in the literature of patients stopping SAT after an extended duration and remaining symptom free. 16,17,26,27,39 However there are currently no definitive guidelines to determine a clinically relevant stopping point, nor a biomarker that may indicate it is safe to cease suppressive antibiotic therapy. Markers such as a normalised ESR have been used to guide SAT cessation or to assess likely success of SAT as a therapeutic option 21 , however there have been instances in the literature of patients with a normal ESR having infection recurrence between 3 days to one month after stopping SAT. ...
The Use of Long-term Antibiotics for Suppression of Bacterial Infections
Article
  • Jun 2024
  • CLIN INFECT DIS
Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterised, but they include adverse drug effects ranging from mild to severe, the development of antibiotic resistant organisms and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in four common indications, examine the gaps in the current literature and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardised term to describe the use of long-courses of antibiotics to suppress hard-to-treat infections.
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... Oral tetracyclines are more likely to be used as an SAT against BJIs. A total of 10 retrospective studies have reported the efficacies of SATs, including oral tetracyclines, in patients with PJIs (Ceccarelli et al., 2023;Jang et al., 2024;Leijtens et al., 2019;Pradier et al., 2018;Prendki et al., 2014;Rao et al., 2003;Sandiford et al., 2020;Segreti et al., 1998;Siqueira et al., 2015;Wouthuyzen-Bakker et al., 2017). No prospective study was found. ...
... Most studies on the curative treatment of BJIs involved few patients, and the results should be interpreted with caution. Another significant issue is the lack of precision regarding the treatment duration and surgical management, which limits the interpretation of suc- Hip PJI, n = 14 CoNS, n = 11 SA, n = 4 P. acnes, n = 2 C. perfringens, n = 1 P. aeruginosa, n = 2 Corynebacterium, n = 1 GPR, n = 1 2.7/3.1 3/14 (21 %) leading to SAT discontinuation in one patient -Pruritus, n = 1 -Nausea, n = 1 -Thrombocytopenia, n = 1 Success, n = 8 (57 %) Failure, n = 6 (43 %) Sandiford et al. (2020) Retrospective study, n = 26 ...
Oral tetracyclines for bone and joint infections: what do we know?
Article
Full-text available
  • Apr 2025
Background and aim: Complex bone and joint infections (BJIs), including prosthetic joint infections (PJIs) and infections associated with osteosynthetic materials, present significant treatment challenges that often require surgical intervention and prolonged antibiotic therapy. In France, the incidence of PJIs in knee and hip arthroplasties ranges from 0.79 % to 2.4 %, with staphylococci being the primary pathogens involved. Recent studies have suggested that oral antibiotic therapy may be as effective as intravenous therapy and that 12 weeks of antibiotic treatment are needed. Tetracyclines, particularly doxycycline and minocycline, are of interest because of their broad-spectrum activities, good oral bioavailability, and potential efficacy in treating BJIs. We aimed to provide a literature review on the role of oral tetracyclines in the management of BJIs. Method: We performed a systematic review of the literature identified via an electronic search of PubMed and ScienceDirect. Results: A total of 648 articles were screened, and 31 studies were included. Pharmacological studies demonstrated that the bone to blood penetration ratio ranged from 0.06 to 0.75. Less than 20 % of strains implicated in BJIs exhibited resistance to oral tetracyclines. Four studies demonstrated potential inhibition of strain growth. Eight studies that included 62 patients reported curative treatment, with a success rate ranging from 82 % to 100 % for PJIs regardless of the surgical management. For suppressive therapy, 10 studies that included 201 patients reported success rates ranging from 57 % to 100 %. The rate of adverse effects ranged from 0 % to 14 % for curative treatment and from 0 % to 57 % for suppressive treatment, leading to treatment discontinuation in less than 20 % of cases. Conclusion: This review highlights that the number of studies supporting the use of oral tetracyclines for the treatment of BJIs is limited. More robust pharmacological and clinical studies are needed to confirm the safety and efficacy profiles of oral tetracyclines for the treatment of BJIs.
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... These bacterial biofilms are microscopic matrices that adhere to both living tissue and prosthetic surfaces [4,6], often forming rapidly after infection. This impairs achieving a complete cure, as these biofilms protect bacteria from both antimicrobial agents and the host immune system [7]. Bacteria in biofilms on prosthetic materials can evade detection by standard microscopy and culture techniques [4]. ...
Suppressive Antibiotic Therapy in Prosthetic Joint Infections: A Contemporary Overview
Article
Full-text available
  • Mar 2025
The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and offer future directions for research to optimize patient outcomes.
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... Fourth, antibiotics can be used to control the neutrophil response and even suppress synovial fluid and tissue culture results, but the use of antibiotics does not remove bacteria from a joint replacement, especially when biofilm is present [62,63]. However, when antibiotics are stopped, the bacteria re-emerge, as does the neutrophil response [30,54,[64][65][66]. ...
The mononuclear phagocyte system obscures the accurate diagnosis of infected joint replacements
Article
Full-text available
  • Nov 2024
  • J TRANSL MED
Introduction Diagnosing infected joint replacements relies heavily on assessing the neutrophil response to bacteria. Bacteria form biofilms on joint replacements. Biofilms are sessile bacterial communities encased in a protective extracellular matrix, making them notoriously difficult to culture, remarkably tolerant to antibiotics, and able to evade phagocytosis. Phagocytized bacteria dramatically alter cytokine production and compromise macrophage antigen presentation. We hypothesize that a subset of joint replacements have a dormant infection that suppresses the neutrophil response to bacteria but can be distinguished from uninfected joint replacements by the response of the mononuclear phagocyte system (MPS) within periarticular tissue, synovial fluid, and circulating plasma. Methods Single cell RNASeq transcriptomic and OLink proteomic profiling was performed on matched whole blood, synovial fluid, and periarticular tissue samples collected from 4 joint replacements with an active infection and 3 joint replacements without infection as well as 6 joint replacements with a prior infection deemed “infection-free” by the 2018 Musculoskeletal Infection Society criteria (follow-up of 26 ± 3 months). Results The MPS and neutrophil responses differ by infected state; the cellular distribution of the MPS response in the subset of joints with dormant infections resembled actively infected joints (p = 0.843, Chi-square test) but was significantly different from uninfected joints (p < 0.001, Chi-square test) despite the absence of systemic acute phase reactants and recruitment of neutrophils (p < 0.001, t-test). When compared to no infection, the cellular composition of dormant infection was distinct. There was reduction in classically activated M1 macrophages (p < 0.001, Fischer's test) and alternatively activated M2 macrophages coupled with an increase in classical monocytes (p < 0.001, Fischer’s test), myeloid dendritic cells (p < 0.001, Fischer’s test), regulatory T-cells (p < 0.001, Fischer’s test), natural killer cells (p = 0.009, Fischer’s test), and plasmacytoid dendritic cells (p = 0.005, Fischer’s test). Hierarchical cluster analysis and single-cell gene expression revealed that classically M1 and alternatively M2 activated macrophages as well as myeloid dendritic cells can independently distinguish the dormant and uninfected patient populations suggesting that a process that modulates neutrophil recruitment (C1QA, C1QB, LY86, SELL, CXCL5, CCL20, CD14, ITGAM), macrophage polarization (FOSB, JUN), immune checkpoint regulation (IFITM2, IFITM3, CST7, THBS1), and T-cell response (VISIG4, CD28, FYN, LAT2, FCGR3A, CD52) was occurring during dormant infection. Gene set variation analysis suggested that activation of the TNF (FDR < 0.01) and IL17 (FDR < 0.01) pathways may distinguish dormant infections from the active and uninfected populations, while an inactivation of neutrophil extracellular traps (NETs) may be involved in the lack of a clinical response to a dormant infection using established diagnostic criteria. Synovial inflammatory proteomics show an increase in synovial CXCL5 associated with dormant infection (p = 0.011, t-test), suggesting the establishment of a chronic inflammatory state by the MPS during a dormant infection involved in neutrophil inhibition. Plasma inflammatory proteomics also support a chronic inflammatory state (EGF, GZMN, FGF2, PTN, MMP12) during dormant infection that involves a reduction in neutrophil recruitment (CXCL5, p = 0.006, t-test), antigen presentation (LAMP3, p = 0.047, t-test), and T-cell function (CD28, p = 0.045, t-test; CD70, p = 0.002, t-test) that are also seen during the development of bacterial tolerance. Discussion All current diagnostic criteria assume each patient can mount the same neutrophil response to an implant-associated infection. However, the state of the MPS is of critical importance to accurate diagnosis of an implant-associated infection. A reduction in neutrophil recruitment and function mediated by the MPS may allow joint replacements with a dormant infection to be mischaracterized as uninfected, thus limiting the prognostic capabilities of all current diagnostic tests.
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... Moreover, there is no uniform definition of SAT and the optimal treatment duration is unknown (1). The considerable global variation in the use of SAT for PJI belies this lack of data (5)(6)(7)(8)(9)(10)(11)(12)(13). ...
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... CSA is used as a suppressive therapy for a variety of hardware infections, including spinal hardware infections, prosthetic joint infections, and vascular graft infections when the hardware cannot be removed surgically (12)(13)(14)(15). In this study, we hypothesized CSA might reduce the incidence of recurrent VADI, thereby reducing the frequency of hospital readmission. ...
Clinical impact of the use of chronic suppressive antibiotics against recurrent ventricular assist device infections
Article
Full-text available
  • Oct 2024
Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18–0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12–0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10–3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events. IMPORTANCE Ventricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice.
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... Clinical use of tetracyclines has focused mainly on suppression therapy following surgical debridement and implant retention. A few cohorts have demonstrated adequate suppression rates of infection with these agents (Pradier et al., 2018;Leijtens et al., 2019;Sandiford et al., 2020;Ceccarelli et al., 2023). Also, it should be noted that a substantial number of patients in these studies that experienced infection relapse had to suspend the suppressive antibiotic weeks or months beforehand due to adverse effects. ...
Antibiotics with antibiofilm activity – rifampicin and beyond
Article
Full-text available
  • Aug 2024
The management of prosthetic joint infections is a complex and multilayered process that is additionally complicated by the formation of bacterial biofilm. Foreign material provides the ideal grounds for the development of an intricate matrix that hinders treatment and creates a difficult environment for antibiotics to act. Surgical intervention is often warranted but requires appropriate adjunctive therapy. Despite available guidelines, several aspects of antibiotic therapy with antibiofilm activity lack clear definition. Given the escalating challenges posed by antimicrobial resistance, extended treatment durations, and tolerance issues, it is essential to ensure that antimicrobials with antibiofilm activity are both potent and diverse. Evidence of biofilm-active drugs is highlighted, and alternatives to classical regimens are further discussed.
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... Pavoni et al. (2004, n = 29) reported a cure rate of 66 % after stopping SAT within 1 year, but the indication for initiating SAT was not clearly defined in that paper. No relapses were reported by Bene et al. (2018) in 24 Five other observational studies with a combined total of 120 patients reported sporadic SAT cessation after 6 to 36 months in 15 patients with one subsequent relapse (7 %) (Goulet et al., 1988;Segreti et al., 1998;Rao et al., 2003;Leijtens et al., 2019;Sandiford et al., 2019). Byren et al. (2009, n = 112) found a fourfold increase in relapse in the first 4 months after stopping SAT after a median time of 15 months in patients with PJI treated with DAIR; however, this occurred only in a minority of patients, and most of the patients were actually cured. ...
Dosing and treatment duration of suppressive antimicrobial therapy in orthopedic implant infections: a cohort study
Article
Full-text available
  • Jun 2024
Introduction: Limited data inform about the optimal dosing and duration of suppressive antimicrobial therapy (SAT) for orthopedic implant infection (OII). We aimed to compare the effectiveness of low-dosage with standard-dosage SAT and evaluate the safety of stopping SAT. Methods: All patients with OII treated with SAT from 2011 to 2022 were retrospectively included. Data were extracted from electronic patient files. Low-dosage SAT was defined as antimicrobial therapy dosed lower than the standard dosage recommended for OII. The association of dosing strategy and other factors with failure-free survival were assessed by Kaplan–Meier and Cox proportional hazard models. Results: One-hundred-and-eight patients were included. The median follow-up time after SAT initiation was 21 months (interquartile range (IQR) 10–42 months). SAT was successful in 74 patients (69 %). Low-dosage SAT (n=82) was not associated with failure in univariate (hazard ratio (HR) 1.23, 95 % confidence interval (CI) 0.53–2.83) and multivariate analyses (HR 1.24, 95 % CI 0.54–2.90). In 25 patients (23 %), SAT was stopped after a median treatment duration of 26 months. In this group, one patient (4 %) developed a relapse. Conclusions: In this study, low-dosage SAT was as effective as standard dosage SAT. Moreover, stopping SAT after 2 to 3 years may be justified in patients with a good clinical course. These findings warrant further research on optimal dosing and duration of SAT and on the durability of in vivo biofilms.
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Outcomes after suppressive antimicrobial therapy for prosthetic joint infection: a prospective cohort study
Article
The objective of this study was to describe the use of and outcomes after suppressive antimicrobial therapy (SAT) in a large prospective peri-prosthetic joint infection (PJI) cohort. SAT was defined as antimicrobial therapy continuing beyond 12 months from PJI diagnosis or where there was an early intention for SAT. The primary outcome was “treatment failure” at 24 months, defined as any of (i) clinical evidence of (ii) further surgery for or (iii) death from PJI. Secondary outcomes included quality of life (QOL) scores using Short Form 12 (SF-12) and Oxford hip (OHS) and knee (OKS) scores. SAT was prescribed for 223 of 720 (31.0%) in the cohort. Patients prescribed SAT were more likely to be older, have comorbidities, chronic PJI, higher C-reactive protein, sinus tract, or be treated with debridement and implant retention. The most frequently prescribed antimicrobials for SAT were ciprofloxacin (64 [21%]), amoxicillin (42 [14%]), and rifampicin (35 [12%]). Treatment failure was more common in the SAT group (75/185 [40.1%] vs 85/447 [19.0%]). After propensity score-adjusted analysis, SAT remained associated with higher rates of treatment failure (aOR 2.48, 95% CI [1.66–3.72]). Although 24-month QOL scores were lower in the SAT group, there were similar improvements from baseline in functional joint scores in SAT and non-SAT groups (OHS median interquartile range [IQR] +8.5 [19.0] vs +7.0 [22.0]; P = 0.78 and OKS +8.0 [20.0] vs +7.0 [22.0]; P = 0.53). SAT use for PJI is common, and in this study, it was not associated with improved outcomes. Identifying patients most likely to benefit from SAT should be explored in carefully designed controlled trials.
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Efficacy of indefinite chronic oral antimicrobial suppression for prosthetic joint infection in the elderly: a comparative study
Article
Full-text available
  • May 2017
Objectives: During prosthetic joint infection (PJI), surgical management is sometimes impossible, indefinite chronic oral antimicrobial suppression (ICOAS) may sometimes be the only option. We evaluated the outcome of elderly patients who benefited from ICOAS for a strictly palliative goal METHODS: We performed a national retrospective cohort study in France of patients aged >75years old with PJI, and managed with ICOAS planned for life long from 2009 to 2014, and compared the population with an event versus the population free of event. Event was defined as a composite outcome in patients under ICOAS, including: local or systemic progression of the infection; death or discontinuation of antimicrobial therapy because of adverse drug reaction. Results: Twenty-one patients were included, with a median age of 85 (IQR: 81; 88) years old. There were 8/21 patients with an event: 1 patient with adverse drug reaction; 3 patients had systemic progression of sepsis; and 2 had local progression. A total of 2/21 patients died. No deaths were related to ICOAS or infection. There was no significant difference (p >0.05) between the population with an event and free of event considering demographic, clinical and microbiological characteristics. Conclusions: In our cohort, ICOAS seems to be an effective and safe option.
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Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study
Article
Full-text available
  • Sep 2017
  • EUR J CLIN MICROBIOL
During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.
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Efficacy of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection
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Full-text available
  • Jan 2017
Introduction: For chronic prosthetic joint infections (PJI), complete removal of the infected prosthesis is necessary in order to cure the infection. Unfortunately, a subgroup of patients is not able to undergo a revision surgery due to high surgical risk. Alternatively, these patients can be treated with antibiotic suppressive therapy (AST) to suppress the infection. Aim: To evaluate the efficacy and tolerability of AST. Methods: We retrospectively collected data (period 2009-2015) from patients with a PJI (of hip, knee or shoulder) who were treated with AST at the University Medical Center Groningen, the Netherlands. AST was defined as antibiotic treatment for PJI that was started after the usual 3 months of antibiotic treatment. The time of follow-up was defined from the time point AST was started. Treatment was considered as failed, when the patient still experienced joint pain, when surgical intervention (debridement, removal, arthrodesis or amputation) was needed to control the infection and/or when death occurred due to the infection. Results: We included 21 patients with a median age of 67 years (range 21 - 88) and with a median follow-up of 21 months (range 3 - 81). Coagulase negative staphylococci (CNS) (n=6), S. aureus (n=6) and polymicrobial flora (n=4) were the most frequently found causative pathogens. Most patients with CNS and S. aureus were treated with minocycline (67%) and clindamycin (83%) as AST, respectively. Overall, treatment was successful in 67% of patients. Failure was due to persistent joint pain (n=1), surgical intervention because of an uncontrolled infection (n=3), and death due the infection (n=3). We observed a treatment success of 90% in patients with a 'standard' prosthesis (n=11), compared to only 50% in patients with a tumor-prosthesis (n=10). Also, treatment was successful in 83% of patients with a CNS as causative microorganism for the infection, compared to 50% in patients with a S. aureus. Patients who failed on AST had a higher ESR in comparison to patients with a successful treatment (mean 73 ± 25SD versus 32 ± 19SD mm/hour (p = 0.007), respectively. 43% of patients experienced side effects and led to a switch of antibiotic treatment or a dose adjustment in almost all of these patients. Conclusions: Removal of the implant remains first choice in patients with chronic PJI. However, AST is a reasonable alternative treatment option in a subgroup of patients with a PJI who are no candidate for revision surgery, in particular in patients with a 'standard' prosthesis and/or CNS as the causative micro-organism.
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Salvage Procedures for Management of Prosthetic Joint Infection After Hip and Knee Replacements
Article
Full-text available
  • Nov 2016
  • Open Orthop J
Background The increasing load placed by joint replacement surgery on health care systems makes infection, even with the lowest rates, a serious concern that needs to be thoroughly studied and addressed using all possible measures. Methods A comprehensive review of the current literature on salvage procedures for recurrent PJIs using PubMed, EMBASE and CINAHL has been conducted. Results Prolonged suppressive antibiotic therapy (PSAT), resection arthroplasty and arthrodesis were the most common procedures performed. Suppressive antibiotic therapy is based on the use of well tolerated long term antibiotics in controlling sensitive organisms. Resection arthroplasty which should be reserved as a last resort provided more predictable outcomes in the hip whereas arthrodesis was associated with better outcomes in the knee. Various methods for arthrodesis including internal and external fixation have been described. Conclusion Despite good union and infection control rates, all methods were associated with complications occasionally requiring further surgical interventions.
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Single Stage Knee Arthroplasty Revision Surgery: A Systematic Review of the Literature
Article
Full-text available
  • Sep 2015
  • Open Orthop J
Total Knee Arthroplasty is an increasingly common procedure and revision surgery, particularly for infection, is associated with significant morbidity and healthcare costs. The current gold standard is a two stage revision procedure but single stage revision is increasingly being used in some departments to improve patient outcomes. We conducted a systematic review of the literature to determine the up-to-date evidence underlying the use of a single stage knee approach in revision surgery. A total of 12 studies were included in this review amounting to 433 revision surgeries. This is the largest review of single stage knee revision surgery. The procedures described were heterogenous and included the 'two-in-one' technique as well as other single stage revision procedures. There were also differences in implants and antibiotic regimens. The mean re-infection rates described in 10 studies was 9.4% (range 0-19.2%) after a mean follow-up of 40.3 months (range 7-180 months). The re-infection rates in the studies published over the last 30 years are falling, and this is not accounted for by any significant change in duration of follow-up during this period. The outcome scores varied, but patients generally showed an improvement. The Knee Society Score and the Oxford Knee Score were the most commonly used in five and three studies respectively. We conclude that the current evidence for single stage revision is variable and there is a lack of good quality evidence to address whether single stage revisions is thorough enough to eradicate deep infection and is able to restore adequate function. There is a need for larger prospective studies with standardised procedures and protocol, and with adequate follow-up. Till then, patients considered for a single stage approach should be thoroughly assessed and the surgery should be performed by a senior surgeon with experience in single stage knee revisions.
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One-stage versus two-stage exchange arthroplasty for infected total knee arthroplasty: a systematic review
Article
Full-text available
  • Sep 2015
  • KNEE SURG SPORT TR A
Purpose Infection complicating total knee arthroplasty (TKA) has serious implications. Traditionally the debate on whether one- or two-stage exchange arthroplasty is the optimum management of infected TKA has favoured two-stage procedures; however, a paradigm shift in opinion is emerging. This study aimed to establish whether current evidence supports one-stage revision for managing infected TKA based on reinfection rates and functional outcomes post-surgery. Methods MEDLINE/PubMed and CENTRAL databases were reviewed for studies that compared one- and two-stage exchange arthroplasty TKA in more than ten patients with a minimum 2-year follow-up. Results From an initial sample of 796, five cohort studies with a total of 231 patients (46 single-stage/185 two-stage; median patient age 66 years, range 61–71 years) met inclusion criteria. Overall, there were no significant differences in risk of reinfection following one- or two-stage exchange arthroplasty (OR −0.06, 95 % confidence interval −0.13, 0.01). Subgroup analysis revealed that in studies published since 2000, one-stage procedures have a significantly lower reinfection rate. One study investigated functional outcomes and reported that one-stage surgery was associated with superior functional outcomes. Scarcity of data, inconsistent study designs, surgical technique and antibiotic regime disparities limit recommendations that can be made. Conclusion Recent studies suggest one-stage exchange arthroplasty may provide superior outcomes, including lower reinfection rates and superior function, in select patients. Clinically, for some patients, one-stage exchange arthroplasty may represent optimum treatment; however, patient selection criteria and key components of surgical and post-operative anti-microbial management remain to be defined. Level of evidence III.
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The outcome of infected arthroplasty of the knee
Article
  • Mar 1986
In order to define the predisposing factors and outcome of infected arthroplasty of the knee, a retrospective analysis of a consecutive series of 471 knee arthroplasties was performed. There were 23 cases of superficial wound infection and 25 of deep infection. Superficial wound infection alone resulted in a painfree gait, with little limitation of movement. Rheumatoid arthritis, the use of constrained prostheses and the presence of a superficial wound infection, all predisposed to deep infection. Deep infection was eradicated by long-term antibiotics in only two patients in whom skin cover was successfully provided by a gastrocnemius musculocutaneous flap. Excision of a sinus track, wound debridement and exchange arthroplasty were universally unsuccessful. Arthrodesis, however, in 11 out of 12 cases, provided the painfree gait these patients desire.
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Outcome following Debridement, Antibiotics and Implant Retention (DAIR) In Hip Peri-Prosthetic Joint Infection – An 18-year experience
Article
  • Mar 2017
Background: Debridement-antibiotics-and-implant-retention (DAIR) may be considered a suitable surgical option in periprosthetic joint infections (PJIs) with soundly fixed prostheses, despite chronicity. This study aims to define the long-term outcome following DAIR in hip PJI. Methods: We reviewed all hip DAIRs performed between 1997 and 2013 (n = 122) to define long-term outcome and identify factors influencing it. Data recorded included patient demographics, medical history, type of DAIR performed (+/- exchange of modular components), and organisms identified. Outcome measures included complications and/or mortality rate, implant survivorship, and functional outcome (Oxford Hip Score). Results: Most DAIRs (67%) were of primary arthroplasties and 60% were performed within 6 weeks from the index arthroplasty. Infection eradication was achieved in 68% of the first DAIR procedure. In 32 cases, more than one DAIR was required. Infection eradication was achieved in 85% of the cases (104/122) with the (single or multiple) DAIR approach. The most common complication was PJI-persistence (15%), followed by dislocation (14%). Very good functional outcomes were obtained, especially in primary arthroplasties. All streptococcus infections were resolved with DAIR and had better outcome. Twenty-one hips have been revised (17%) to-date, 16 were for persistence of PJI. The 10-y implant survivorship was 77%. Early PJI and exchanging modular components at DAIR were independent factors for a 4-fold increased infection eradication and improved long-term implant survival. Conclusion: DAIR is, therefore, a valuable option in the treatment of hip PJI, especially in the early postoperative period (≤6 weeks), with good outcomes. However, DAIR is associated with increased morbidity; further surgery may be necessary and instability may occur. Where possible, exchange of modular implants should be undertaken.
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A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation
Article
  • Jan 1987
  • J Chron Dis
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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Chronic Suppression of Periprosthetic Joint Infections with Oral Antibiotics Increases Infection-Free Survivorship
Article
  • Aug 2015
  • J BONE JOINT SURG AM
The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval [CI] = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio [HR] = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit. Therapeutic Level III. See the Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.
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