RESUMO

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs' activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.

RESUMO

BACKGROUND: Prosthetic joint infection (PJI) caused by Acinetobacter baumannii (Ab) has become a growing concern due to its overwhelming ability to express resistance to antibiotics and produce biofilm. AIM: This study aimed to identify independent risk factors (RFs) associated with Ab-associated PJI and their role in the treatment outcome. METHODS: This was a single-centre, retrospective cohort study of PJI patients diagnosed between January 2014 and July 2018. A PJI diagnosis was made based upon the MSIS 2018 criteria. To estimate RFs associated with Ab-associated PJI, multivariate analyses with a level of significance of p < 0.05 were performed. To evaluate treatment failure, Kaplan-Meier analysis and log-rank test were performed. RESULTS: Overall, 98 PJI cases were assessed, including 33 with Ab-associated PJI and 65 with PJI involving other microorganisms (non-Ab-associated PJI). Independent RFs associated with Ab-associated PJI were revision arthroplasty [odds ratio (OR) = 3.01; 95% confidence interval (CI) = 1.15-7.90; p = 0.025] and nonelective arthroplasty (OR = 2.65; 95% CI = 1.01-7.01; p = 0.049). Ab-associated PJI was also more likely than non-Ab-associated PJI to be classified as a chronic late infection (OR = 5.81; 95% CI = 2.1-16.07; p = 0.001). Ab-associated PJI was not associated with treatment failure (p = 0.557). CONCLUSIONS: Late chronic infections, surgical revision and nonelective arthroplasty are well-known predictors of PJI but were also independently associated with Ab-associated PJI. Infections caused by Ab and surgical treatment with debridement, antibiotics and implant retention were not associated with PJI treatment failure. TRIAL REGISTRATION: Study data supporting our results were registered with the Brazilian Registry of Clinical Trials ( https://www.ensaiosclinicos.gov.br/rg/RBR-6ft5yb/ ), an open-access virtual platform for the registration of studies on humans performed in Brazil. Registration no. RBR-6ft5yb .

Assuntos

Acinetobacter baumannii , Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Brasil/epidemiologia , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/terapia , Reoperação , Estudos Retrospectivos

RESUMO

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan-Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.