Antibiotic duration in native and periprosthetic joint infections : a systematic review and meta-analysis of randomized controlled trials.

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Abstract

AimsThe optimal duration of antibiotic therapy in joint infection remains controversial, particularly as native joint septic arthritis and periprosthetic joint infection (PJI) differ substantially in pathophysiology, surgical management, and prognosis. While short antibiotic courses have been advocated for native joints after adequate drainage, prolonged therapy is often recommended for PJIs due to biofilm-related infection. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to compare short- with long-course antibiotic strategies in both native and prosthetic joint infections.MethodsFollowing PRISMA guidelines, a systematic search was performed across PubMed, Embase, Web of Science, and the Cochrane Library. Only RCTs were included. Studies were assessed for inclusion using predefined population, intervention, comparison, outcomes, and study (PICOS) criteria. Meta-analyses were conducted using MedCalc, and treatment failures were analyzed using odds ratios (ORs) with 95% CIs.ResultsA total of 12 RCTs involving 1,414 patients (native 577; periprosthetic 837) were included, with six eligible for meta-analysis. For PJIs, long-course therapy (≥ 12 weeks) significantly reduced treatment failure compared with short courses (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011), while complication and mortality rates were similar. In contrast, for native joints, short-course therapy (≤ four weeks) achieved comparable infection control with prolonged regimens (OR 1.347; p = 0.565) when combined with adequate surgical drainage, particularly in paediatric populations. Surgical strategy (e.g. debridement, antibiotics, and implant retention vs one- or two-stage exchange) influenced outcomes more than antibiotic duration alone.ConclusionOptimal antibiotic duration should be individualized based on joint type and surgical approach. Short courses are effective for native septic arthritis with proper drainage, whereas PJIs generally require extended therapy due to biofilm-related complexity. We propose the Age-Joint-Immunity-Surgery-Sensitivity (AJISS) score as a decision-making tool to guide treatment duration, warranting prospective validation.
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Abstract

Aims The optimal duration of antibiotic therapy in joint infection remains controversial, particularly as native joint septic arthritis and periprosthetic joint infection (PJI) differ substantially in pathophysiology, surgical management, and prognosis. While short antibiotic courses have been advocated for native joints after adequate drainage, prolonged therapy is often recommended for PJIs due to biofilm-related infection. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to compare short- with long-course antibiotic strategies in both native and prosthetic joint infections.

Methods

Following PRISMA guidelines, a systematic search was performed across PubMed, Embase, Web of Science, and the Cochrane Library. Only RCTs were included. Studies were assessed for inclusion using predefined population, intervention, comparison, outcomes, and study (PICOS) criteria. Meta-analyses were conducted using MedCalc, and treatment failures were analyzed using odds ratios (ORs) with 95% CIs.

Results

A total of 12 RCTs involving 1,414 patients (native 577; periprosthetic 837) were included, with six eligible for meta-analysis. For PJIs, long-course therapy (≥ 12 weeks) significantly reduced treatment failure compared with short courses (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011), while complication and mortality rates were similar. In contrast, for native joints, short-course therapy (≤ four weeks) achieved comparable infection control with prolonged regimens (OR 1.347; p = 0.565) when combined with adequate surgical drainage, particularly in paediatric populations. Surgical strategy (e.g. debridement, antibiotics, and implant retention vs one- or two-stage exchange) influenced outcomes more than antibiotic duration alone.

Conclusion

Optimal antibiotic duration should be individualized based on joint type and surgical approach. Short courses are effective for native septic arthritis with proper drainage, whereas PJIs generally require extended therapy due to biofilm-related complexity. We propose the Age-Joint-Immunity-Surgery-Sensitivity (AJISS) score as a decision-making tool to guide treatment duration, warranting prospective validation. Cite this article: Bone Jt Open 2026;7(3):394–406. Take home message This study clarifies the differential impact of antibiotic duration according to joint type (native or prosthetic) and surgical strategy, providing robust evidence to optimize the management of joint infections. The introduction of the Age-Joint-Immunity-Surgery-Sensitivity score offers a decision‑making model based on key clinical parameters, with the potential to standardize practice and improve therapeutic stratification.

Introduction

Antibiotic therapy is central to managing septic arthritis,1 eliminating infection locally and systemically. Depending on the context, it may be empirical or targeted based on the pathogen.1-3 Although the approach differs considerably depending on whether the infection involves a native joint (septic arthritis (SA)) or a periprosthetic joint infection (PJI),4 the use of an short- compared with long-course antibiotic therapy remains a subject of debate in both SA and PJI.3,4 Antibiotic treatment is frequently paired with surgical intervention to decompress the joint and remove debris potentially affecting prognosis.1 In native joints, surgical strategies include simple joint lavage (irrigation), with or without synovectomy, performed via arthrotomy1,3,5 or arthroscopy.1,3,5 In PJIs, options include debridement, antibiotics, and implant retention (DAIR) and one- or two-stage prosthetic arthroplasties.3 This wide therapeutic arsenal has led some authors to propose adapting antibiotic therapy to joint type and surgical approach used. Definitions of short therapy vary depending on joint type: in native joints, short therapy is typically defined as < four weeks;3,5,6 in prosthetic joints, there is no consensus on short-treatment duration, which varies between six and 12 weeks.7,8 Despite the central role of antibiotics in septic arthritis treatment, evidence regarding the optimal strategy remains limited. Most existing literature focuses on surgical techniques or observational outcomes, with few comparing antibiotic regimens. This lack of standardized guidance is particularly significant given the increasing prevalence of PJIs and the rise of antimicrobial resistance. Therefore, the aim of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of various antibiotic strategies in the treatment of septic arthritis, including both native and prosthetic joints. By focusing on high-level evidence, this review seeks to clarify the roles of short- compared with long-term duration, and the impact of adjunctive corticosteroid use.

Methods

Search strategy and information source This study was registered with the Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420250635375. The literature search was conducted following PRISMA guidelines. A systematic search was performed in PubMed, Embase, Web of Science, and the Cochrane Library to identify eligible studies. The search used medical subject heaings (MeSH) terms and relevant keywords, including ‘septic arthritis’, ‘short-term antibiotic therapy’, ‘long-term antibiotic therapy’, and ‘randomized controlled trial’. Ethical approval and informed consent were not required for this study, as it is a systematic review and meta-analysis of published data. Inclusion and exclusion criteria Eligible studies compared different surgical interventions and/or antibiotic regimens, and reported clinical outcomes such as infection eradication, complications, or treatment failure. Meta-analysis articles meeting the following patient, intervention, comparator, outcome, studies (PICOS) criteria were selected: 1) population: patients with septic arthritis; 2) intervention: short course of antibiotics; 3) comparator: long course of antibiotics; 4) outcome: at least one of the following outcomes indicating treatment failure was reported: uncontrolled infection, death, or complication; 5) study design: only RCTs were included. We excluded studies performed in animals or published in a language other than English and French. In cases of multiple publications from the same dataset, only the most recent study was included (Figure 1). Data extraction Two authors (CDM, FG) independently reviewed the titles and abstracts of the studies and initially identified and assessed the full texts of these studies against the inclusion criteria. Disagreements were resolved by a third reviewer. The following data were extracted for each included study: author’s name, year of publication, country, study design, sample size, sex, age, prosthetic joint, native joint, long- and short-course antibiotic treatment, and surgical procedure. Each RCT was evaluated using the Cochrane Risk of Bias Tool, considering the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential sources of bias (Figure 2). Statistical analysis Analyses were performed using MedCalc (Belgium). All p-values < 0.05 were considered statistically significant. For I² values less than 50%, the p-value used was based on the fixed-effect model. For I² values greater than 50%, the p-value used was based on the random-effect model. Treatment failures were expressed as dichotomous data in the form of odds ratios (ORs) with 95% CIs. The results are presented as forest plots, illustrating the effect estimates for each individual study as well as for all studies combined.

Results

Search output The database search identified 605 publications after duplicates were removed. Following a rigorous selection process, 554 studies were excluded, including those that did not meet the inclusion criteria. A total of 51 full-text articles were screened for potential eligibility, and 39 were excluded due to lack of relevant comparison or full text. In all, 12 RCTs were retained, of which six were selected for the meta-analysis comparing short with long antibiotic therapy. Characteristics of included studies Overall, 12 RCTs9-20 were included in the review: six on prosthetic9-14 and six on native15-20 joints. Studies were conducted on 1,414 patients (Table I) (837 patients with septic arthritis on the prosthetic joint and 577 on native joint). The overall mean age was 41.1 years (SD 31.7) (66.4 years (SD 7.45) for adult studies and 5.8 years (SD 2.88) for paediatric studies), and the majority of whom were adult males. The knee was most often affected, followed by hip and shoulder. The different classes of antibiotics used included beta-lactams,14,15,19 macrolides,14,20 tetracyclines,20 fluoroquinolones,9,11,20 glycopeptides,14,20 and sulfonamides.15,20 The authors identified six potential causes of morbidity in medical past history,9,11,12,14,18,20 diabetes11,12,14,20 being the most common. Correlation Pearson analysis revealed a strong positive relationship between comorbidity burden and adverse outcomes, particularly in PJIs. Diabetes showed the highest association with treatment failure (r ≈ 0.99), while immunosuppression strongly correlated with mortality (r ≈ 0.97). Chronic renal disease and cancer also demonstrated significant links to complications and death. In contrast, native septic arthritis (SA) cases had minimal comorbidity impact and very low mortality, indicating that comorbidities are a major prognostic factor primarily in PJIs. Table I. | Authors | Country | N | Sex ratio (M/F) | Age, yrs | Medical past | Joint | Na or Pr | Biology | Microbiology | Antibiotic therapy | || |---|---|---|---|---|---|---|---|---|---|---|---|---| | International nonproprietary name | Short | Long | |||||||||| | Bernard et al, 2021 | England | 410 | 2.08 | 68.94 | Obesity | H: 255 K: 149 | Pr | CRP; blood culture | Staphylococcus aureus; CoNS; Streptococcus species; Gram-negative organisms | IV: Methicillin/ cephalosporin Oral: Rifapicin/ fluoroquinolone | 393 | 389 | | Blom et al, 2022 | UK, Sweden | 140 | 1.41 | 71 | N/A | H: 140 | Pr | N/A | Monomicrobial culture; negative culture; polymicrobial culture | N/A | 0 | 140 | | Tamayo et al, 2016 | Spain | 63 | 0.90 | 72 | Diabetis; chronic heart disease; chronic liver disease; chronic renal disease; cancer | H: 20 K: 24 | Pr | N/A | Polymicrobial infection; Staphylococcus aureus; CoNS | Rifampicin Levofloxacin | 30 | 33 | | Espeland et al, 2020 | Norway | 48 | 2 | 68.5 | Diabetis; immunosuppressor treatment; smoking | H: 31 K: 9 | Pr | CRP; ESR | MSSA; MRSE; Staphylococcus lugdunensis; Staphylococcus capitis | Rifampicin Cloxacilin | 0 | 48 | | Valenzuela et al, 2021 | USA | 116 | 1 | 67.1 | N/A | H: 44 K: 88 | Pr | N/A | N/A | N/A | 116 | | | Manning et al, 2023 | Australia | 60 | 1.73 | 67 | Diabetes mellitus; chronic renal impairment; cancer; cirrhosis; rheumatoid arthritis; congestive cardiac failure; ischaemic heart disease, present; cerebrovascular disease | N/A | Pr | CRP | Methicillin-susceptible Staphylococcus aureus; Group B Streptococcus; group C/G Streptococcus; Staphylococcus lugdunensis; other CoNS | Flucloxacilin/ cefazolin ampicillin/penicillin Vancomycin Teicoplanin Ceftriaxone pipericelin | 21 | 29 | | Odio et al, 2003 | Costa Rica | 123 | 1.04 | 5.68 | N/A | H: 47 K: 40 S: 4 E: 24 A: 5 | Na | CRP; joint fluid (WBC, LDH, Gram+ stained smear) | Staphylococcus aureus, Haemophilus influenza, Staphylococcus pneumoniae, Staphylococcus pyogene | Ampicillin Oxacillin Trimethoprim – Sulfamethoxazole | 100 | 0 | | Harel et al, 2011 | Israël | 49 | N/A | 1 | N/A | N/A | Na | N/A | N/A | Cefuroxim | 49 | 0 | | Hamidreza arti et al, 2014 | Iran | 60 | 2.75 | 8.06 | N/A | N/A | Na | N/A | N/A | 60 | 0 | | | Smith et al, 2002 | Maliwi | 61 | 2.81 | 8 | HIV; drepano-cytosis | S: 61 | Na | N/A | Salmonella typhimurium; Salmonella enteridis; Staphylococcus aureus; type-B haemophilus; group-A streptococcus; Streptococcus pneumoniae; klebsiella | 21 | N/A | | | Heikki Peltola et al, 2009 | Finland | 130 | 1.36 | 6.2 | N/A | H: 48 K: 32 S: 6 E: 8 A: 30 W/O: 2 | Na | CRP; ESR; WBC | Staphylococcus aureus; Haemophilus influenzae type b; Streptococcus pyogenes; Streptococcus pneumoniae | Clindamycin Amoxicillin Cephalosporin | 31 | 30 | | Ergys Gjika et al, 2019 | Switzerland | 154 | 1.61 | 50 | Diabetis; cirrhosis; cancer; steroid medication | H: 1 K: 14 S: 7 E: 1 A: 3 W/O: 98 | Na | CRP; bacteraemia | Staphylococcus aureus; Staphylococcus aureus infection; streptococci; Gram negative(s) | Ceftriaxon Vancomycin Co-amoxicilline Quinolone Cotrimoxazole Clindamycine Doxycicline | 63 | 67 | - A, ankle; CoNS, coagulase-negative staphylococcus; E, elbow; H, hip; IV, intravenous; K, knee; LDH, lactate dehydrogenase; MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermisis; MSSA, methicillin-sensitive Staphylococcus aureus; Na, native ; N/A, not available; Pr, prosthetic ; S, shoulder; WBC, white blood cell; W/O, wrist and others. Therapeutic strategy The antibiotic treatment strategies reported in the included studies varied according to treatment duration, the use of adjunctive corticosteroids, and the causative pathogen. Antibiotic therapy was classified as either short- or long-term (based on duration), with or without corticosteroids, empirical or targeted. The definitions of short- and long-course antibiotic therapy differed depending on whether the infection involved a native or prosthetic joint. For native joints, therapy was considered short if administered for less than four weeks and long if extended beyond that (≥ four weeks), while for prosthetic joints, short-course therapy was defined as less than 12 weeks, and long-course therapy as six weeks or more. All of the authors identified nine9,11,14-20 studies investigating short-course antibiotic therapy and nine9-14,18-20 studies evaluating long-course therapy. Regarding PJIs (Table II), six studies employed long-course antibiotic therapy (12 weeks or more), of which three were comparative studies assessing long compared with short antibiotic regimens (< 12 weeks). For native septic arthritis (Table II), six studies used short-course antibiotic therapy (three weeks or less), of which three were comparative studies evaluating short compared with long antibiotic regimens (four weeks or more). Corticosteroids were administered as an adjunct in paediatric cases,15-17 and empirical antibiotic therapy was followed by pathogen-targeted treatment. Comparisons between treatment strategies were made across the included studies: long- compared with short-course antibiotic therapy on the prosthetic9,11,14 and native18-20 joint. Table II. | Authors | Country | N | Na or Pr | Short antibiotic therapy | Long antibiotic therapy | Surgical technique | Length of hospital stay (days) | Uncontrolled infection | Complications | Death | ||||||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---| | n | Duration, weeks | n | Duration, weeks | Arthrocenthesis | Arthrotomy | Arthroscopy | DAIR | One-stage | Two-stage | Short | Long | Short | Long | Short | Long | Short | Long | |||| | Bernard et al, 2021 | England | 410 | Pr | 190 | 6 | 188 | 12 | 151 | 146 | 91 | 14 | 32 | 15 | 46 | 35 | 10 | 10 | |||| | Blom et al, 2022 | UK, Sweden | 140 | Pr | N/A | 140 | > 12 | N/A | 65 | 75 | 17 to 24 | N/A | 34 | N/A | 70 | N/A | 7 | ||||| | Tamayo et al, 2016 | Spain | 63 | Pr | 30 | 8 | 33 | > 12 | 63 | N/A | N/A | N/A | 2 | 1 | 8 | 14 | 2 | 1 | |||| | Espeland et al, 2020 | Norway | 48 | Pr | N/A | 48 | > 12 | 48 | N/A | N/A | N/A | N/A | 13 | N/A | N/A | N/A | N/A | ||||| | Valenzuela et al, 2021 | USA | 116 | Pr | N/A | 116 | > 12 | N/A | 58 | 58 | 2 to 8 | N/A | 8 | N/A | 19 | N/A | 6 | ||||| | Manning et al, 2023 | Australia | 60 | Pr | 31 | < 12 | 29 | 18 | 60 | N/A | N/A | N/A | 9 | 7 | 5 | 8 | 2 | 1 | |||| | Odio et al, 2003 | Costa Rica | 123 | Na | 100 | 2 | N/A | 100 | 7 | 18 | N/A | N/A | 0 | N/A | |||||||| | Harel et al, 2011 | Israël | 49 | Na | 49 | 3 | N/A | 49 | 9 to 12 | 0 | N/A | 2 | N/A | 0 | N/A | ||||||| | Arti et al, 2014 | Iran | 60 | Na | 60 | 3 | N/A | 60 | 9 to 12 | 0 | N/A | 0 | N/A | ||||||||| | Smith et al, 2002 | Maliwi | 61 | Na | 31 | 3 | 30 | 6 | 31 | 30 | N/A | 0 | 0 | 0 | 0 | 0 | 0 | ||||| | Peltola et al, 2009 | Finland | 130 | Na | 63 | 1 (10 days) | 67 | 4 (30 days) | 114 | 15 | 1 | 5 | 3 | 5 | 4 | 0 | 0 | ||||| | Gjika et al, 2019 | Switzerland | 154 | Na | 77 | 2 | 77 | 4 (30 days) | 154 | 4 | 6 | 4 | 4 | 27 | 33 | 0 | 0 | - DAIR, debridement, antibiotics, and implant retention; N/A, not available; Na, native ; Pr, prosthetic . Outcomes Differences in treatment failure rates were analyzed, and where appropriate, the findings were further supported by meta-analyses to identify the most effective treatment strategies. The analysis of failure proportions revealed a statistically significant difference in favour of paediatric patients compared with adults for both short-course (p = 0.023) and long-course (p = 0.001) antibiotic therapy. However, no significant difference was observed with the addition of corticosteroid therapy to antibiotics (p = 0.108). A statistically significant difference was observed for single-stage prosthetic arthroplasties compared with two-stage procedures when long-term antibiotic therapy was used (p = 0.021). Additionally, short-course antibiotic therapy showed a statistically significant advantage for irrigation over arthrotomy (p = 0.007), and for one-stage prosthetic (p < 0.001) arthroplasty over debridement and implant retention. Table III summarizes the comparative treatment failure rates across studies. Table III. | Variable | Irrigation vs arthrotomy | Irrigation vs arthroscopy | Arthrotomy vs arthroscopy | DAIR vs one stage | DAIR vs two stage | One vs two stage | |---|---|---|---|---|---|---| | Long-term antibiotherapy | |||||| | Difference | 5,440 | 8,840 | 14,280 | 4 | 4.9 | 9 | | 95% CI | -7,695 to 42,651 | -17,306 to 14,783 | -14,131 to 51,307 | -1.7 to 11.6 | 3.63 to 12.38 | 3.14 to 15.36 | | p-value | 0.626 | 0.305 | 0.211 | 0.179 | 0.241 | 0.021 | | In favour | N/A | N/A | N/A | N/A | N/A | One stage | | Short-term antibiotherapy | |||||| | Difference | 9,600 | N/A | N/A | 21 | 12 | 9 | | 95% CI | 1,898 to 22,123 | N/A | N/A | 10,845 to 30,559 | -4 to 24.1 | -1,461 to 23,292 | | p-value | 0.007 | N/A | N/A | 0.001 | 0.129 | 0.095 | | In favour | Irrigation | N/A | N/A | One stage | N/A | N/A | - DAIR, debridement, antibiotics, and implant retention; N/A, not available. The results of the meta-analysis, expressed as odds ratios, indicate a significant advantage for long-course antibiotic therapy compared with short-course therapy (OR 1.789, 95% CI 1.113 to 2.876; p = 0.016). This effect was particularly evident in adults (OR 1.783, 95% CI 1.080 to 2.944; p = 0.024), with low heterogeneity observed across studies (I² < 0.001). This effect was not evident in DAIR procedure (OR 1.660, 95% CI 0.89 to 3.08; p = 0.109) (Figure 3). For prosthetic septic arthritis (Figure 4), prolonged antibiotic therapy was associated with a significantly lower rate of therapeutic failure compared with short-course treatment (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011). Complication rates were similar between the two strategies (OR 1.05, 95% CI 0.69 to 1.59; p = 0.817), while mortality was reduced with longer antibiotic treatments (OR 1.17, 95% CI 0.53 to 2.58; p = 0.697). Conversely, for native joint septic arthritis (Figure 5), no significant difference was observed in therapeutic failure between short and prolonged antibiotic treatments (OR 1.347, 95% CI 0.49 to 3.72; p = 0.565). However, longer courses were linked to a higher incidence of complications without providing additional efficacy benefits (OR 0.811, 95% CI 0.45 to 1.46; p = 0.565).

Discussion

The management of septic arthritis requires a multidisciplinary approach,21,22 combining appropriate antimicrobial therapy with surgical intervention.23-26 This systematic review aimed to identify the most effective antibiotic strategies, in terms of treatment duration and adjunctive corticosteroid use, based on randomized controlled trials. Our meta-analysis revealed a modest but statistically significant advantage in favour of long-course antibiotic therapy over short-course regimens, particularly in adults (OR 1.783, 95% CI 1.080 to 2.944; p = 0.024). These results suggest that longer durations may provide more robust infection control in this population, especially for PJIs, where biofilm-forming organisms such as Staphylococcus epidermidis are common.9,11,12 Empirical antibiotic therapy (against Staphylococcus aureus,4,9,11,12,14,15,18-20,27,28 streptococci,4,14,19,20,27,28 and enterobacteria4,17,27,28), typically initiated after joint fluid and blood cultures are obtained, remains essential.1,5,21-25 Once the pathogen and its susceptibility profile are known, targeted therapy should follow to optimize efficacy and reduce antimicrobial resistance risks.8,10-15,18,19 Native septic arthritis Early and intensive antibiotic therapy is essential to limit joint damage and preserve cartilage in the long term.29 Short antibiotic therapy (< four weeks) appears effective for native joint infections when combined with adequate surgical drainage and early intervention.1-3,5,6,18-20 Repeated arthrocentesis or arthroscopy are viable options in early-stage infections,1-3,5,6 with the latter allowing direct visualization and thorough lavage.23,25,30,31 In our review, short-course therapy combined with irrigation showed better outcomes than when paired with arthrotomy (p = 0.0075), particularly in paediatric populations, where infection control rates were significantly higher (p = 0.0232 and p = 0.0007 for short and long courses, respectively). Our meta-analysis found no significant difference in treatment failure between short and long courses (OR 1.347, 95% CI 0.49 to 3.72; p = 0.565). However, prolonged therapy was associated with a higher incidence of complications without additional benefit in infection control. Mortality differences were negligible across regimens. Adjunctive corticosteroid therapy remains a controversial topic. Its use is mostly restricted to paediatric populations.15-17,32 Several trials suggest that corticosteroids may reduce inflammation,22,32 pain, hospital stay, CRP normalization, and long-term sequelae,15-17,22,32 without compromising infection control.32,33 However, in adults, data are scarce, and potential immunosuppressive effects warrant caution.23 Our analysis did not show a statistically significant difference with corticosteroid use (p = 0.108). PJI PJIs present unique challenges due to biofilm formation and the complexity of surgical management.4,8,9 The clinical course of PJI is often categorized as acute (early or subacute), typically occurring within three months of implantation, and chronic (late), which develops beyond this period. This distinction is critical because it influences both surgical strategy and antibiotic duration.4 For acute PJIs, particularly those managed with implant retention (DAIR), shorter antibiotic courses have been explored. However, evidence remains mixed: our review found no clear benefit of extended therapy in DAIR cases,9,11,14 aligning with recent literature suggesting that shorter regimens may be acceptable under strict criteria such as early diagnosis, stable implant, and susceptible organisms.7,34-37 Conversely, chronic PJIs, often associated with mature biofilms and delayed presentation, require more aggressive management. Extended antibiotic therapy (≥ 12 weeks) remains the most widely adopted strategy7,9-14 and demonstrated a significant reduction in treatment failure compared with short courses (OR 2.04, 95% CI 1.18 to 3.54; p = 0.011). Complication rates were similar between regimens (OR 1.05; p = 0.817), while mortality showed a non-significant trend favouring prolonged therapy (OR 1.17; p = 0.697). Surgical approach strongly influenced outcomes: single-stage exchange under long-course coverage outperformed two-stage procedures (p = 0.021), whereas DAIR showed no clear benefit from extended antibiotic duration. These findings underscore the importance of tailoring antibiotic duration to infection timing and surgical strategy. Acute PJIs may allow for shorter courses when combined with effective debridement and implant retention, while chronic infections generally require prolonged therapy and often prosthesis exchange. Clinical implications These findings underscore the need for individualized treatment strategies rather than a uniform approach. We propose a practical decision-making tool (Age-Joint-Immunity-Surgery-Sensitivity (AJISS) guide) incorporating age,5,9-20,38,39 immune stats,11,12,14,20,21 type of surgery, joint involved,5,9-20 and microbiological profile40 to tailor antibiotic duration. The AJISS score is based on a strong predictive rationale for estimating the optimal duration of antibiotic therapy in septic arthritis (Table IV). Data from the meta-analysis demonstrate an almost linear inverse correlation (Figure 6) between the score and the probability of success (r ≈ –0.96), confirming that each additional point increases the risk of failure and justifies prolonged treatment. The statistical power of the model is acceptable (≈ 80%) and its discriminative ability satisfactory (area under the curve (AUC) ≈ 0.78), with thresholds (0 to 2, 3 to 5, 6 to 9) clearly separating recommended durations (three to four, six to eight, and ≥ 12 weeks), although, consistent with observed trends (global OR 1.789; p = 0.016). Table IV. | Criteria | Points | |---|---| | A – Age | | | Elderly (aged > 75 years) | + 2 | | Adult (aged 15 to 75 years) | + 1 | | Child (aged < 15 years) | 0 | | J – Type of joint | | | Prosthetic joint | + 1 | | Native joint | 0 | | I – Immune status | | | Immunosuppressed (e.g. HIV 10 mg/day) | + 2 | | Controlled immunocompromised (e.g. HIV > 200 CD4, controlled diabetes) | + 1 | | Immunocompetent | 0 | | S – Surgical option (0 to 3) | | | Prosthesis retained (DAIR or simple washout) with the involvement of mature biofilm (ex: chronic septic arthritis) | + 3 | | Prosthesis removed (one- or two-stage exchange) with the involvement of mature biofilm (ex: chronic septic arthritis) | + 2 | | Incomplete decontamination without the involvement of mature biofilm (ex: native joint with incomplete debridement or DAIR in early PJI) | + 1 | | Native joint with complete debridement | 0 | | S – Sensibility of antibiotic (0 to 2) | | | Multiresistant strain (R): find intravenous active antibiotics | + 2 | | Sensible with high-dose requirement (SDD/I) | +1 | | Sensible (S) | 0 | | Score interpretation | | | Total score | Recommended antibiotic duration | | 0 to 2 | 3 to 4 weeks | | 3 to 5 | 6 to 8 weeks | | 6 to 9 | ≥ 12 weeks | - DAIR, debridement, antibiotics, and implant retention; PJI, periprosthetic joint infection. This tool should be validated in multicentre cohorts, integrating biological markers (e.g. CRP), imaging (e.g. persistent abscess, osteolysis), and drug toxicity considerations.41 It offers a rational, adaptable framework to optimize treatment length in both native and prosthetic septic arthritis. First, the number of high-quality RCTs available for inclusion was small, which reduces the statistical power and generalizability of the findings. Second, there was considerable heterogeneity across studies in defining ‘short’ compared with ‘long’ antibiotic courses, surgical strategies, and outcome measures, making direct comparisons challenging. Third, sub-group analyses were limited by incomplete reporting of patient-level data, such as comorbidities, microbiological profiles, and immune status, which are critical determinants of treatment success. Fourth, most included trials were conducted in high-resource settings, potentially limiting applicability to low-resource environments where diagnostic and surgical options differ. Further multicentre studies are needed to refine duration thresholds. Despite these constraints, our findings support a more individualized, evidence-based approach to antibiotic duration. In conclusion, this meta-analysis of RCTs reveals two distinct patterns in antibiotic management for septic arthritis. For native joints, short-course antibiotic therapy appears effective when combined with adequate surgical drainage, particularly in paediatric populations. In contrast, prosthetic joint infections demonstrate a clear benefit from prolonged antibiotic regimens, reflecting the complexity of biofilm-related infections and the need for sustained antimicrobial coverage. These findings underscore that treatment duration should not follow a one-size-fits-all approach but rather be tailored to joint type, surgical strategy, and patient characteristics, paving the way for individualized decision-making tools such as the AJISS score.

References

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Duration of antibiotic therapy in the intensive care unit . J Thorac Dis . 2016 ; 8 ( 12 ): 3774 – 3780 . Crossref PubMed Google Scholar 41. Mu W , Xu B , Wang F , Maimaitiaimaier Y , Zou C , Cao L . Low incidence of acute kidney injury with combined intravenous and topical antibiotic infusions in periprosthetic joint infection after total knee arthroplasty . Bone Joint Res . 2024 ; 13 ( 10 ): 525 – 534 . Crossref PubMed Google Scholar Author contributions F. M. Bombah: Conceptualization, Data curation, Investigation, Methodology, Project administration, Visualization, Writing – original draft R. Buzisa Mbuku: Data curation, Formal analysis C. Dongmo Mayopa: Data curation, Formal analysis G. Fodjeu: Data curation, Formal analysis L. Fonkoue: Supervision, Writing – review & editing T. Van den Wyngaert: Data curation, Formal analysis, Writing – review & editing H. Poilvache: Writing – review & editing T. Schubert: Supervision, Writing – review & editing C. Detrembleur: Conceptualization, Data curation, Investigation, Methodology J. Yombi: Supervision, Writing – review & editing O. Cornu: Conceptualization, Methodology, Supervision, Writing – review & editing Funding statement The author(s) disclose receipt of the following financial or material support for the research, authorship, and/or publication of this article: the open access was funded byThe author(s) disclose receipt of the following financial or material support for the research, authorship, and/or publication of this article: the open access was funded by ICMJE COI statement The authors confirm that they have no conflicts of interest to disclose. Data sharing All data generated or analyzed during this study are included in the published article and/or in the supplementary material.

Acknowledgements

During the preparation of this work, the author(s) used ChatGPT (OpenAI, USA) in order to assist with language refinement. After using this tool, the authors reviewed and edited the content as needed, and took full responsibility for the content of the publication. Open access funding The open access fee as funded by Académie de Recherche et d’Enseignement Supérieur (ARES), the fund for Research Training in Industry and Agriculture (FRIA) of the F.R.S. FNRS, and the CAI doctoral scholarship programme of UCLouvain, Belgium. © 2026 Bombah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/ © 2026 Bombah et al.

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