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

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 arthrotomy 1 , 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.

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. 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 ). PRISMA flow diagram, showing the assessment of eligibility for inclusion in the review. 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 ). Risk of bias assessment using the Cochrane Risk of Bias 2 tool. 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.

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. Overall, 12 RCTs 9 - 20 were included in the review: six on prosthetic 9 - 14 and six on native 15 - 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 diabetes 11 , 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. General overview of the included articles. 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. 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 nine 9 , 11 , 14 - 20 studies investigating short-course antibiotic therapy and nine 9 - 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 prosthetic 9 , 11 , 14 and native 18 - 20 joint. General overview of the treatments used in the included articles. DAIR, debridement, antibiotics, and implant retention; N/A, not available; Na, native ; Pr, prosthetic . 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. Summary of the comparative surgical treatment failure rates in long- and short-term antibiotherapy. 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 ). Meta-analysis of short compared with long antibiotic treatments success of septic arthritis: 1) General uncontrolled infection: fewer with long course. 2) Uncontrolled infection in adults: fewer with long course. 3) Uncontrolled infection with debridement, antibiotics, and implant retention (DAIR) procedure: equivalent. df, degrees of freedom; IV, inverse variance. 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). Meta-analysis of short compared with long antibiotic treatments of prosthetic septic arthritis. 1) Treatment success: fewer therapeutic failures with long-course antibiotic therapy compared with short-course therapy. 2) Complications: equivalent complication rates. 3) Death: fewer deaths associated with long-course antibiotic therapy. df, degrees of freedom; IV, inverse variance. 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). Meta-analysis of short compared with long antibiotic treatments of native septic arthritis. 1) Treatment success: equivalent therapeutic failures between long-course antibiotic therapy compared with short-course therapy. 2) Complications: more complications with long-course antibiotic therapy compared with short-course therapy. df, degrees of freedom; IV, intravenous.

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 enterobacteria 4 , 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 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). 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 strategy 7 , 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. 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 profile 40 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). Relationship between Age-Joint-Immunity-Surgery-Sensitivity (AJISS) score and predicted probability of therapeutic success. Personalized Age-Joint-Immunity-Surgery-Sensitivity decision guide score to estimate the duration of antibiotic therapy in septic arthritis. 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. 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.