DOI: 10.6084/m9.figshare.29927720.v1
title: <b>P</b><b>olimycrobial Infection as a p</b><b>oor outcome of suppressive antibiotic therapy</b><b> (SAT) among patients with o</b><b>rthopaedic implant</b><b>-associated </b><b>infection</b><b>s</b><b> (OI</b><b>A</b><b>I): A cohort study </b><b> </b>

description: Study design and population: In this single-center prospective cohort study with a retrospective analysis, patients with OII who underwent SAT were monitored at the musculoskeletal infection outpatient clinic of the Department of Orthopaedics and Traumatology of a large tertiary academic hospital, in São Paulo, Brazil between August 2019 and May 2025. [The patients were monitored for a period of one year and categorised into two groups based on the outcome of suppressive antimicrobial therapy (SAT), with group allocation determined immediately upon the occurrence of therapy failure. Patients aged over 18 with a history of OII according to the European Bone and Joint Infection Society (EBJIS) criteria for FRI, PJI and IASA and eligible for SAT were included. Patients aged under 18 and those who lost outpatient follow-up were excluded. The review of medical records and the research project were conducted in full compliance with the principles of the Declaration of Helsinki of the World Medical Association, Good Clinical Practices (GCP), and within the laws and regulations of the ethics and research committee of the hospital where the research was carried out, in accordance with CONEP standards and approved by the ethics and research committee (CAAE: 79347124.7.0000.5479). All data generated during this study will remain confidential, and investigators at the centre will not use this data for any purpose other than the execution of the study. Variables studied: Epidemiological variables, type and place of infection, aetiology of the infection and microbiological profile, reasons for indicating SAT, antibiotics used in the therapy, reasons for SAT failure and treatment after failure were collected. Moreover, the duration of SAT (in weeks), clinical evolution, adverse events and therapy changes were also analysed. All the data was collected during the initial evaluation and follow-up visits at three, six and twelve months after the start of SAT. 3.3 Diagnostic Criteria and adopted definitions: Definition of FRI followed the consensus publication by Metsemakers et al ​​. The diagnosis of PJI was based upon the European Bone and Joint Infection Society (EBJIS) published in 2021. Meanwhile, diagnosis of spinal implant infections was established according to the definitions by Divi et al. SAT was defined as the systemic (oral or parenteral) administration of one or more antibiotics for an indefinite period, initiated with the intention of controlling infection in cases not suitable for standard surgical treatment​. Drug selection and dosage were based on the in vitro susceptibility of cultured pathogens or empirically according to local epidemiology in cases of culture-negative infections. The decision to initiate SAT was individualized, considering comorbidities, patient allergies, drug interactions, drug bioavailability, tolerance, and adherence capacity. For PJI, SAT was indicated under the following conditions: a) Inadequate surgical management (e.g., removal of the prosthesis was not feasible, incomplete, or performed outside the recommended time frame); b) Suboptimal curative antibiotic therapy (e.g., lack of an active drug for biofilm treatment); c) Patients not candidates for new surgical interventions (DAIR, implant exchange, resection arthroplasty, or arthrodesis) due to risks such as limb threat, systemic comorbidities contraindicating surgery, or patient refusal​​. In the case of FRI and IASA, SAT was indicated in the following scenarios: a) To assist in fracture consolidation in patients who did not receive appropriate clinical and/or surgical treatment or who failed and for whom implant removal was unfeasible due to non-union; b) To control local damage and maintain limb functionality in patients who did not receive appropriate clinical and/or surgical treatment, failed, and for whom implant removal was contraindicated due to limb threat, systemic comorbidities contraindicating surgery, or patient refusal​. Failure of SAT was defined as the presence of at least one of the following criteria: a) Need for new surgical intervention due to persistence or recurrence of infection; b) Absence of fracture consolidation in the context of FRI; c) Persistence or recurrence of local signs and symptoms (e.g., fistula, surgical wound dehiscence, or joint pain reported in the last follow-up visit); d) Fever and/or signs of sepsis during suppressive therapy; e) Death due to infection-related causes​​. Statistic analysis: Quantitative variables were presented in mean, median, and interquartile intervals. Qualitative variables were presented as absolute (n) and relative (%) frequencies. Logistic regression using the stepwise forward method was used to identify independent variables. In the pre-selection process, a bivariate analysis was performed, using when appropriate the Chi-square test, Fischer’s exact test, T-Student test or Mann-Whitney test, and admitting p&lt;0,20 as a selective criterion to a further multivariate analysis. In all steps, p&lt;0,05 was considered statistically significant. Statistical analysis was made in the SPSS program (version 25.0).