Aim. A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system function and ultimately shifting genetic predisposition to clinical outcome. Therefore, we hypothesized that a similar interaction could affect the occurrence of acute and chronic periprosthetic joint infections (PJI). Method. Multiple biomarkers of gut barrier disruption were tested in parallel in plasma samples collected as part of a prospective cohort study of patients undergoing revision arthroplasty for aseptic or PJI (As defined by the 2018 ICM criteria). All blood samples were collected before any antibiotic was administered. Samples were tested for Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) using commercially available enzyme-linked immunosorbent assays. Statistical analysis consisted of descriptive statistics and ANOVA. Results. A total of 96 patients were consented and included in the study. 32 were classified as PJI (23 chronic and 9 acute), and 64 as aseptic. Both Zonulin and LPS were found to be increased in the acute PJI group 8.448 ± 7.726 ng/mL and 4.106 ± 4.260 u/mL, compared to chronic PJI (p<0.001) and aseptic revisions (p=0.025). sCD14 was found to be increased in both chronic (0.463 ± 0.168 ug/mL) and acute PJI (0.463 ± 0.389 ug/mL) compared to aseptic revisions (p<0.001). Conclusions. This prospective ongoing study reveals a possible link between gut permeability and the ‘gut-immune-joint axis’ in PJI. If this association continues to be born out with larger cohort recruitment, it would have a massive implication in managing patients with PJI. In addition to the administration of antimicrobials, patients with PJI and other orthopedic infections may require gastrointestinal modulators such as pro and prebiotics

Aim. Bone and joint infections (BJI) need frequently prolonged antibiotic treatment at high dosage for a total of 6 or 12 weeks depending the type of infection. Impact of such prolonged antibiotic exposure on the gut microbiota has never been assessed. Method. We performed a national multicentric prospective study of patients with BJI to monitor the gut microbiota dynamic all along antimicrobial treatment. Clinical data and stool collection were performed at the baseline visit (B) within 24h before starting antibiotics, at the end of the treatment (EOT) and 2 weeks after antibiotic withdrawal during a follow-up visit (FU). Microbiota composition was determined by shotgun metagenomic sequencing. Biological markers of gut permeability and inflammation were monitored at each time point. Results. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI and 21 prosthetic joint infections (PJI). At EOT there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI but not in patients with osteosynthesis-related BJI (p<0.05, Wilcoxon test). At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. Principal Component Analysis (PCoA) of the Bray Curtis distance, showed a significant change of the gut microbiota at the end of treatment compared to baseline (p<0.01, PERMANOVA) that only partially recover at FU. The taxonomic analysis showed that microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks to patients treated for 12 weeks. No particular antibiotic (especially fluoroquinolones) was associated with a lower Shannon index or distinct dynamic of recovery at the end of treatment. PCoA analysis of the Bray Curtis distance shows that patients with elevated plasma level of CRP (≥5mg/L) at EOT had a distinct gut microbial composition compared to others. Conclusions. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery 2 weeks after antibiotic withdrawal, independently on the duration of the therapy and on the type of the antibiotic used. Elevated CRP at EOT might reflect persistent alteration of the gut microbiota. Assessment of long-term impact after the end of treatment is on-going

Aim. A large body of evidence is emerging to implicate that dysregulation of the gut microbiome (dysbiosis) increases the risk of surgical site infections. Gut dysbiosis is known to occur in patients with inflammatory bowel disease (IBD), allowing for translocation of bacteria across the inflamed and highly permeable intestinal mucosal wall. The null hypothesis was that IBD was not associated with increased risk of periprosthetic joint infection (PJI) after primary total hip and knee arthroplasty. Our aim was to investigate whether a prior diagnosis of IBD was associated with a higher risk of PJI following primary total hip and knee arthroplasty. Method. A matched cohort study was designed. Primary endpoint was the occurrence of PJI at 2-year. Secondary endpoints were aseptic revisions, as well as discharge to rehab facility, complications up to 30 days, and readmission up to 90 days after TJA. ICD-9 and −10 codes were used to identify patients with IBD and the control cohort. A chart review was performed to confirm diagnosis of IBD. Using our institutional database, 154 patients with IBD were identified and matched (3 to 1) for age, sex, body mass index (BMI), year of surgery, and joint affected with 462 individuals without IBD undergoing TJA. Results. The cumulative incidence of PJI was 4.55% among patients with IBD versus 1.32% among the control cohort (p=0.024). When bivariate logistic regression was performed, a diagnosis of IBD was found to be an independent risk factor for PJI (OR 3.56 95% C.I. 1.17 – 11.23; p=0.024) and aseptic revisions (OR 3.47, 95% C.I. 1.30 – 3.47; p=0.012). The rate of postoperative complications was also higher in patients with IBD. Conclusions. Based on the findings of this study, it appears that patients with IBD are at higher risk for failure due to PJI or aseptic loosening after TJA. The exact reason for this finding is not known but could be related to the bacterial translocation from the inflamed intestinal mucosa, the dysregulated inflammatory status of these patients, malnutrition, and potentially other factors. Some of the so-called aseptic failures maybe also as a result of infection that may have escaped detection and/or recognition

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.