Synovial sepsis diagnostics and antimicrobial resistance: a one-health perspective.

This article, as part of the Currents in One Health series, reviews the current state of diagnostics for synovial sepsis. Synovial sepsis is a condition that affects veterinary and human medicine and requires coordinated efforts from both parties, as well as environmental considerations to accurately diagnose and preserve effective treatments. The article discusses best practices to identify the causative agent in septic synovitis, trends in bacterial identification and antimicrobial resistance patterns across common bacterial species, and a one-health perspective to optimize diagnostics across species. Antimicrobial resistance is a challenge facing both human and veterinary medicine and requires mindful and attentive prescribing to reduce the development of antimicrobial resistance and preserve antimicrobials for future application. The current standard of care for bacterial identification in veterinary practice is culture and antimicrobial susceptibility; however, positive culture rates from synovial sepsis cases often remain < 50%. Recent developments in advanced bacterial identification present opportunities for improved bacterial identification in synovial sepsis. Increased bacterial isolation will also help guide empirical antimicrobial therapy. Utilizing information and recommendations from both the human and veterinary literature will improve timely and accurate bacterial identification and therefore rapid and effective treatment of synovial sepsis across species and limit the development of antimicrobial resistance.

A scoping review of the current evidence on treatment and outcomes following synovial sepsis.

BACKGROUND: Synovial sepsis is a frequent cause of morbidity and mortality in horses. Despite advances in diagnostics and treatments, persistent infection or chronic lameness can occur. OBJECTIVES: To perform a scoping review to identify and evaluate the current evidence on the factors implicated in the success of treatment for synovial sepsis. STUDY DESIGN: Joanna Briggs Institute scoping review. METHODS: A protocol was registered, and a systematic literature search was performed on CAB abstracts, Medline, Scopus and Embase. Inclusion and exclusion criteria were developed and studies systematically reviewed against this. Studies relating to factors affecting treatment success following synovial sepsis were retained and data was extracted on study method, population characteristics and factors significantly associated with treatment outcome. RESULTS: In total, 2338 studies were identified, and 61 were included to full paper analysis. Eight papers reported significant factors, identifying 15 risk factors associated with two measurements of outcome, either survival and/or return to athletic function. The 15 factors were identified and categorised into pre-, intra- and post-operative factors. Risk factors that were identified included the number or type of synovial structures involved, the presence of pannus, tendon and bone pathology, and the use of systemic antimicrobials. There were many discrepancies in inclusion criteria of cases of synovial sepsis as well as measurement and description of outcome variables. MAIN LIMITATIONS: Non-English language studies or conference proceedings were not included. Only small numbers of papers had similar findings. CONCLUSIONS: Standardisation of inclusion criteria is essential to enable comparisons and analysis between studies on synovial sepsis. Future studies should use methodologies to reduce bias including multicentre and multinational studies, prospective study design and robust statistical modelling.

Comparison of equine synovial sepsis rate following intrasynovial injection in ambulatory versus hospital settings.

BACKGROUND: Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed. OBJECTIVES: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings. STUDY DESIGN: Retrospective cohort study. METHODS: Records from the Colorado State University were evaluated (2014-2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising service, medications injected, location (field/hospital), whether synovial sepsis resulted, and at what time sepsis was recognised were recorded. Logistic regression was used to estimate the contributions of covariates to the occurrence of synovial sepsis following injection. RESULTS: During the study period, 3866 intrasynovial injections were performed in 1112 horses during 1623 sessions, with 643/1623 sessions performed in the field. The most frequently used medications were hyaluronate (846/1623, 52.1%), triamcinolone acetonide (780 /1623, 48.1%) and amikacin sulfate (684/1623, 42.1%). Four horses developed synovial sepsis (0.2% sessions, 0.1% synovial structures); 3/4 were injected in the field, 2/4 received antibiotics with the injection. The frequency of septic synovitis was 10.4 cases per 10 000 injections, or 1 in 967 injections. All horses recovered following synovial lavage and antibiotic therapy. Performing injections in the field (P = .2) or without antibiotics (P = .7) did not alter the risk of synovial sepsis. MAIN LIMITATIONS: Limitations include the retrospective nature of data collection and low rate of infection overall, which prohibited evaluation of individual medication regimes as factors associated with resultant infection. CONCLUSIONS: The frequency of synovial sepsis in this population of horses was not higher when injections were performed in the field or without concurrent antibiotic administration. These data may help to inform practitioners and clients regarding the relative potential risk of complications following intrasynovial medication in different environmental settings.

Epidural administration of opioid analgesics improves quality of recovery in horses anaesthetised for treatment of hindlimb synovial sepsis.

BACKGROUND: Opioid epidural analgesia has been shown to provide effective analgesia in horses. There is a lack of evidence regarding the effect of opioid epidural analgesia on quality of recovery in horses. OBJECTIVES: Identify whether opioid epidural analgesia influences quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis. STUDY DESIGN: Single-centre retrospective cross-sectional study. METHODS: Data were obtained from the clinical records of horses which had undergone arthroscopic or tenoscopic surgery for management of hindlimb synovial sepsis over a 9-year period in a referral hospital population. Multivariable logistic regression analysis was used to identify the perioperative factors that impact on quality of recovery. RESULTS: Records from 149 horses, undergoing 170 general anaesthetics were included. Multivariable logistic regression analysis showed that opioid epidural analgesia (OR 3.0, 95% CI 1.2 to 7.2, P = .02) was associated with good quality of recovery, whereas Cob breeds (OR 0.16, 95% CI 0.06 to 0.46, P = .001), age (in years) (OR 0.90, 95% CI 0.83 to 0.97, P = .004) increasing intraoperative dosages (in mg/kg) of thiopental (OR 0.64, 95% CI 0.46 to 0.90, P = .01) or ketamine (OR 0.42, 95% CI 0.18 to 0.98, P = .04) were associated with poor quality of recovery. MAIN LIMITATIONS: Certain variables that may influence quality of recovery, such as patient temperament and hindlimb orthopaedic co-morbidities were not recorded. The clinical prediction model obtained is only applicable to the specific facilities, population and perianaesthetic management practiced at our institution. CONCLUSIONS: Opioid epidural analgesia is significantly associated with good quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis. Other risk factors, such as increasing age, cob breed, use of higher intraoperative dosages (in mg/kg) of ketamine and/or thiopental, were associated with poor quality of recovery.

The synovial fluid proteome differentiates between septic and nonseptic articular pathologies.

Articular conditions are common in horses and can result in loss of function, chronic pain and/or inability to work. Common conditions include osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, but despite the high clinical prevalence of these conditions, rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. Synovial fluid from a range of arthropathies was enriched for low abundance proteins using combinatorial peptide ligand ProteoMiner™ beads and analysed via liquid chromatography-tandem mass spectrometry. Changes in protein abundances were analysed using label-free quantification. Principle component analysis of differentially expressed proteins identified groupings associated with joint pathology. Findings were validated using ELISA. Lactotransferrin (LTF) abundance was increased in sepsis compared to all other groups and insulin-like growth factor-binding protein 6 (IGFBP6) abundance decreased in sepsis compared to other disease groups. Pathway analysis identified upregulation of the complement system in synovial joint sepsis and the downregulation of eukaryotic translation initiation factors and mTOR signalling pathways in both OA and OC compared to the healthy group. Overall, we have identified a catalogue of proteins which we propose to be involved in osteoarthritis, osteochondrosis and synovial sepsis pathogenesis. SIGNIFICANCE: Osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, are common articular conditions in which rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. This study has identified that the equine synovial fluid proteome exhibits distinctive profile changes between osteoarthritis, osteochondrosis, synovial sepsis and healthy joints. Elevated synovial abundance of lactotransferrin and decreased insulin-like growth factor-binding protein 6 were both found to distinguish synovial sepsis from all other study groups. Thus, these protein markers may have a future role in clinical practice to enable an earlier and reliable diagnosis of synovial sepsis.

Synovial sepsis is rare following intrasynovial medication in equine ambulatory practice.

BACKGROUND: There are few observational studies regarding the potentially serious complication of synovial sepsis following intrasynovial medication in general equine practice. Quantification of risk is fundamental to fully inform decision-making and owner consent prior to undertaking procedures. OBJECTIVES: To describe the occurrence of synovial sepsis following intrasynovial injections in a large ambulatory equine practice between 2006-2011. STUDY DESIGN: Retrospective cohort study. METHODS: Medication records were cross-referenced against synovial cytology submissions and hospital admissions for synovial sepsis. The occurrence of synovial sepsis within strata of interest, including horse age, sex and product used were described as proportions with corresponding 95% confidence intervals, and measures of attributable risks. RESULTS: In the study period, 9456 intrasynovial medications were performed in 4331 sessions. The most frequently used medications were: corticosteroids (3869/4331, 89.3% [95% CI 88.4, 90.3%]), hyaluronate (3617/4331, 83.5% [95% CI 82.4, 84.6%]) and amikacin sulphate (4044/4331, 93.4% [95% CI 92.6, 94.1%]). Overall four horses developed post medication synovial sepsis (0.04% [95% CI 0.0, 0.08%] of all medications), two of these cases were given polysulphated glycosaminoglycans and hyaluronate (2/14, 14.3% [95% CI 0.0, 32.6%]), two were given triamcinolone acetonide (2/3592, 0.1% [95% CI 0.0, 0.1%]), and hyaluronate (2/3617, 0.06% [95% CI 0.0, 0.1%]). One of these cases had received concurrent medication with amikacin sulphate (1/4044, 0.02% [95% CI 0.0, 0.1%]). All four cases returned to racing following joint lavage. MAIN LIMITATIONS: Due to the low frequency of cases multivariable statistical analysis was not performed. Although the study was conducted in an ambulatory setting, the population included a high number of racehorses, limiting application to the general horse population. CONCLUSIONS: The frequency of synovial sepsis in this population of horses was 0.04%. These data may be helpful in informing clients regarding the potential risks of adverse complications resulting from intrasynovial medication.

Are serum amyloid A or D-lactate useful to diagnose synovial contamination or sepsis in horses?

Synovial sepsis in horses is life threatening and accurate diagnosis allowing prompt treatment is warranted. This study assessed the diagnostic value of serum amyloid A (SAA) and D-lactate in blood and synovial fluid (SF) as diagnostic markers of synovial sepsis in horses and correlated them with total nucleated cell count (TNCC), percentage of neutrophils (%N) and total protein (TP) in SF. Blood and SF SAA and D-lactate concentrations were determined in a case-control observational study including 112 horses (38 with synovial contamination or sepsis (SCS), 66 with non-septic intra-synovial pathology (NSISP) and 8 controls). Blood and SF SAA were significantly higher in SCS than in NSISP and control horses. SAA values were similar in NSISP and control horses. SF SAA was moderately correlated with synovial TNCC, TP and blood SAA. Blood and SF SAA were 82.4 per cent and 80 per cent sensitive and 88.9 per cent and 73 per cent specific for diagnosis of SCS, with cut-off values of 60.7 and 1.14 µg/ml, respectively. Blood and SF D-lactate concentrations were not significantly different between groups. This study shows that blood and SF SAA concentrations can aid to distinguish SCS from non-septic synovial pathology; however, D-lactate was not useful.

Antimicrobial selection and dosing in the treatment of wounds in the United Kingdom.

REASONS FOR PERFORMING STUDY: Antimicrobial stewardship within the veterinary profession is recognised by governing and professional bodies as being important; the attitudes and behaviour of veterinary surgeons merit investigation. OBJECTIVES: To investigate levels of protected antimicrobial use and accuracy of antimicrobial dosing in a common clinical scenario in equine practice. STUDY DESIGN: Retrospective cohort study. METHODS: Antimicrobial use was evaluated retrospectively in 113 cases subsequently referred to a single referral hospital for the treatment of limb wounds over a 20-month period. Antimicrobial classification (first-line, alternative or protected) was made according to guidelines produced by the British Equine Veterinary Association. These guidelines also served as the reference for recommended dose rates. RESULTS: Systemic antimicrobials were administered prior to referral in 94/113 (83.2%) horses, of which 8 (8.5%) received the protected third or fourth generation cephalosporins or fluoroquinolones. Forty-eight of 87 (55.2%) horses for which complete dosing data were available received antimicrobials at ≤90% of the recommended dose. Practitioners who held a postgraduate clinical qualification or worked in purely equine practice were no more or less likely to use protected antimicrobials (P = 0.06 and P = 0.64, respectively) or administer inadequate doses (P = 0.75 and P = 0.85, respectively). Veterinary surgeons with more experience were less likely to use protected antimicrobials (P<0.001); however, with the small case numbers, this finding should be interpreted with caution. Heavier horses were more likely to be under-dosed (P<0.002). CONCLUSIONS: This study highlights the administration of certain classes of antimicrobials in situations where their use is unlikely to be justified. If these findings reflect more general attitudes and behaviour then greater awareness of, and compliance with, recommendations for responsible antimicrobial use are required among equine practitioners. Bodyweight ought to be measured or estimated using validated objective techniques prior to systemic medications being administered.

Factors associated with survival to hospital discharge following endoscopic treatment for synovial sepsis in 214 horses.

REASONS FOR PERFORMING STUDY: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. OBJECTIVES: Investigate pre-, intra- and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. STUDY DESIGN: Retrospective case series. METHODS: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra- and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. RESULTS: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. CONCLUSIONS: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

Outcome of horses with synovial structure involvement following solar foot penetrations in four UK veterinary hospitals: 95 cases.

REASONS FOR PERFORMING STUDY: The factors associated with outcome following solar foot penetration involving synovial structures treated using endoscopic lavage have not been described in the UK population. OBJECTIVES: To provide descriptive data on horses with synovial contamination or sepsis following solar penetration in 4 UK equine referral hospitals and to identify specific factors associated with the outcome. STUDY DESIGN: Retrospective case series. METHODS: Data were collected from 4 veterinary hospitals. Follow-up data were obtained via a telephone questionnaire. Two multivariable logistic regression models were generated. Model 1 included all horses with synovial contamination following foot penetration undergoing surgical treatment, with the outcome variable being euthanasia during hospitalisation. Model 2 included all horses surviving anaesthesia, with the outcome variable being failure to return to pre-injury athletic function. RESULTS: Ninety-five horses were included. Overall, 56% of horses survived to discharge and 36% of horses returned to pre-injury athletic function. Model 1 included penetration of the central frog sulcus (odds ratio [OR] 10, 95% confidence interval [CI] 1.9-51.8), concurrent distal phalanx involvement (OR 32, 95% CI 2.6-101.9), increasing days to presentation (OR 1.2, 95% CI 1.0-1.3) and hospital. Model 2 included increasing days to presentation (OR 1.1, 95% CI 1.1-1.6), breed (OR 32, 95% CI 2.2-135.4), more than one surgery (OR 5.6, 95% CI 1.0-32.7) and hospital. CONCLUSIONS AND POTENTIAL RELEVANCE: Synovial involvement following solar foot penetration has a guarded prognosis for survival to discharge and a poor prognosis for return to pre-injury athletic function. Penetration of the central sulcus of the frog and distal phalanx involvement are associated with euthanasia during hospitalisation. Delayed referral and hospitalisation are associated with both euthanasia and failure to return to pre-injury athletic function. Breed and more than one surgery are associated with failure to return to pre-injury athletic function. These data may assist veterinary surgeons and owners to make evidence-based decisions when managing cases with synovial involvement following solar foot penetration.