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Evaluation of factors associated with surgical site infection in equine proximal interphalangeal joint arthrodesis: 54 cases (2010–2019)

Abstract Background The frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered. Objectives To determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols. Methods Records were evaluated (2010–2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence. Results Fifty‐four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1–3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1–3 vs. > 3 days), pre‐operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time (< or > 3 h) and SSI; however, modelling was complicated by quasi‐complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post‐operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall. Conclusions The prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1–3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.


INTRODUCTION
Surgical site infection (SSI) represents the primary cause of mortality after equine orthopaedic procedures including internal fixation (Stockle et al., 2018). Curtiss et al. reported that horses that developed SSI were 12 times less likely to survive hospital dismissal than horses without SSI (Curtiss et al., 2019). Treatment of infection increases the cost of care and can result in reduced functional and cosmetic concerns in the operated limb (Weese, 2008). The prevalence of SSI in equine orthopaedic procedures has been reported to occur in 10-28% of cases (Ahern et al., 2010;Curtiss et al., 2019;Knox & Watkins, 2006;Macdonald et al., 1994;McCormick & Watkins, 2017;Sakai et al. 2018). Factors previously associated with an increased risk of development of infection in equine musculoskeletal procedures include placement of implants, surgical duration (procedures > 3 h [Ahern et al., 2010] or 90 min [Macdonald et al., 1994], fracture configuration (open vs. closed), method of repair (open reduction), female sex and operated locations distal on the limb (Ahern et al., 2010;Curtiss et al., 2019;Macdonald et al., 1994;Richardson & Ahern, 2011). Increased risk of SSI was associated with internal fixation for carpal arthrodesis, fetlock arthrodesis, radial fracture, humeral fracture and femoral fracture when compared to other locations (Curtiss et al., 2019). A protective role for local antibiotic administration by regional limb perfusion (RLP) or prolonged systemic antibiotic administration has not been reported (Curtiss et al., 2019).
other causes (Herthel et al. 2016). The type of fixation did not affect the return to the intended level of performance, although the duration of casting was reduced in horses where a plate and screw combination was placed compared to screws alone (Herthel et al., 2016;Schaer et al., 2001). However, factors associated with the development of infection have not been investigated specifically and compared between perioperative techniques, specifically with regard to antibiotic protocols for PIPJ arthrodesis.
While infection rates are moderately high in surgeries involving orthopaedic implants compared to other commonly performed procedures, the use of antibiotics locally or for extended periods of time postoperatively has not been demonstrated to have a direct beneficial effect on reducing SSI risk and furthermore may precipitate negative side effects such as imbalance of intestinal microflora. However, the selection of specific antibiotic regimens and duration of administration have not been compared with respect to complications such as SSI. The increasing incidence of antibiotic resistance in equine practice (Herdan et al., 2012;Loncarac et al., 2014;Theelin et al., 2014;, Malardo et al., 2013;van den Eede et al., 2009van den Eede et al., , 2012 and the desire to minimize risks associated with antibiotic administration have prompted the evaluation of antibiotic protocols in many aspects of equine practice. Therefore, the objective of this study was to examine factors associated with SSI in horses undergoing PIPJ arthrodesis. We hypothesized that the development of infection would not be affected by the perioperative antibiotic protocol administered and that prolonged administration of systemic intravenous antibiotics past 72 h postoperatively would provide no additional benefit in minimizing the risk of SSI.

Perioperative protocols
Preoperatively, all horses underwent preoperative radiographic imag- plate with two trans-articular screws placed in lag fashion, two LCP plates or two trans-articular screws were used as previously described (Herthel et al., 2016;Hicks et al., 2021;Sakai et al., 2018). All plates were contoured to provide plate-to-bone contact as needed.
The transected ends of the extensor tendon were opposed with absorbable sutures using a combination of simple interrupted and continuous patterns. The skin was closed using a combination of simple Postoperatively, all horses were administered nonsteroidal antiinflammatories (phenylbutazone 2.2 mg/kg IV or PO, every 12 h) for at least 5 days following surgery with duration depending on patient discomfort and at the discretion of the senior surgeon. Intravenous antibiotics (either cefazolin or potassium penicillin in combination with gentamicin as described above) were continued postoperatively for a total of 3-7 days, followed by oral antibiotics in some cases, as described above.
Postoperative radiographs were typically performed 24 h following surgery, at the time of first cast change or removal, and at approx-

Statistical analysis
The following variables were coded as binary predictors (Y or N) for  in an attempt to model the data more efficiently.
Further analysis of the models was performed using Bayesian logistic regression (stan-glm) via the R package rstanarm (Goodrich et al, 2020). The final model was arrived at by omitting individual predictors from the model containing all predictors and examining the change in expected log predictive density via leave-one-out sampling (elpdloo) (R package loo) (Vehtari et al, 2017(Vehtari et al, , 2020). The final model included the use of antibiotics for less than or equal to 3 days, the use of postoperative regional antibiotic perfusion and the duration of anaesthesia (classified as less than or greater than 3 h). Diagnostics and summary statistics for the final model are summarized in Table 1. Statistical analysis was performed using R version 4.1.2 ("Bird Hippie") (R Core Team, 2021).
Reasons for performing surgery were primarily osteoarthritis (n = 33), followed by fracture (n = 11), subluxation (n = 5), osseous cystlike lesion (n = 2), osteoarthritis with osseous cyst-like lesion (n = 2) and severed lateral collateral ligament (n = 1). The distribution of limbs operated on was relatively even between the fore-and hindlimbs and left to right (LF n = 13, RF n = 14, LH n = 13, RH n = 14). Only a single limb was operated on in every case. The data are summarized in Table 2.
The three most common protocols prescribed included intravenous administration for 3 days (n = 19), intravenous administration for 5 days (n = 4) and intravenous administration for 5 days followed by oral administration for 5 days (n = 4). Drugs and durations of administration varied from intravenous use alone for 2-8 days, oral (PO) antibiotic administration (duration unrecorded in a single case) or intravenous administration for 1-7 days followed by oral antibiotic administration for 5-104 days.

Surgical site infection rate
SSI was diagnosed in 2/54 (3.7%) cases, which were identified at days 15 and 30 postoperatively. Bayesian analysis indicated that a short course of antibiotics (< 3 days) and a longer duration of anaesthesia (> 3 h) could be associated with a decrease in the incidence of SSI

DISCUSSION
This study described the rate of SSI in equine PIPJ arthrodesis and the relative risk for development of infection with various systemic and local antibiotic protocols. The prevalence of SSI in this population (3.7%) was lower than previous reports in equine orthopaedic internal fixation (10-28%; Ahern et al., 2010;Curtiss et al., 2019;Macdonald et al., 1994) or PIPJ arthrodesis specifically (6.6-17.2%; Hicks et al., 2021;Knox & Watkins, 2006;McCormick and Watkins, 2017;Sakai et al., 2018). There was no difference in SSI rate in cases administered systemic antibiotics for 1-3 days or > 3 days, or for those horses that did or did not receive regional antibiotic perfusion in this population, although Bayesian odds ratios indicate that a shorter course (< 3 days) of antibiotics may be associated with a decrease in the odds of a postoperative SSI. The interpretation of this decrease may be made in sev-eral ways. One is that a shorter course of antibiotic administration (< 3 days) is as good or better than a longer course of antibiotic administration at preventing SSI. Another is that cases that were deemed 'at risk' for post-operative SSI were routinely treated for a longer period of time and that some of these cases did indeed develop an SSI. As there is no way to retrospectively determine the basis for decisions made at the time of surgery, both of these remain valid, with the former supporting the initial hypothesis that an extended duration of antibiotic treatment would not provide any additional benefit in the prevention of SSI.
There was no association found in either analysis between the antibiotic protocol selected, sex, anaesthetic duration or surgeon with the development of infection. These findings differ from previous reports where females and prolonged anaesthetic duration > 90 min or 3 h were identified as risk factors for the development of infection (Ahern et al., 2010;Curtiss et al., 2019;Macdonald et al., 1994;Richardson & Ahern, 2011). As this study was performed in a single referral clinic, other factors that may affect the risk of SSI such as intraoperative protocols for asepsis were maintained relatively consistently between clinicians and surgeries and may play a role in the overall low rate of SSI observed.
The perioperative antibiotic protocols used were highly variable between cases and clinicians, illustrating the lack of therapeutic guidelines available to equine surgeons performing orthopaedic implant procedures. The most commonly used protocols prescribed included parenteral administration alone for 3 or 5 days, or parenteral administration for 5 days followed by an additional 5 days of oral antibiotics.
Antibiotic protocols reported previously for PIPJ arthrodesis also var- factors, such as intraoperative practices including the presence of additional personnel in the operating room to perform radiographs, as has been previously described (Sakai et al., 2018). These data may be useful to equine surgeons in examining their own practice's complications rates, intraoperative protocols and medication administration practices.
The implementation of local antimicrobial therapy via RLP preoperatively prior to the placement of orthopaedic implants was not identified as a factor associated with reduced risk for the development of SSI in this study. However, the use of regional perfusions postoperatively was observed in both cases where SSI developed and was therefore associated with increased odds of SSI, presumably due to increased frequency of the use in cases perceived to have a higher risk of SSI development or following the development of SSI, similar to previous reports (Curtiss et al., 2019). The extremely large confidence interval for the odds ratio (3.039-6392.058) indicates some degree of model misspecification, and these numbers should be interpreted with caution, but the model was significantly degraded in its ability to predict outcomes without this factor and so it was included in the final model.
Despite the increased frequency of use of antimicrobial regional limb perfusion (A-RLP) in equine practice and a large number of studies investigating side effects and drug pharmacokinetics indicating relative safety with its use, there remains a lack of evidence that A-RLP makes a difference in prophylaxis or treatment of equine orthopaedic infections (Rubio-Martinez, 2021). However, greater evidence for efficacy in human medicine has reported improved outcomes in people treated for diabetic and ischaemic nonhealing pedal ulcers (Agarwal et al., 2005;Seidel et al., 1994), infected total knee arthroplasty (Lazzarini et al., 2003) and chronic osteomyelitis (Finsterbush & Weinberg, 1972). The clinical benefits of A-RLP may be difficult to confirm in equine practice due to the lack of standardization or determination of the optimal methods for the A-RLP technique in equine practice in terms of drugs used, volume and concentration of perfusate, dosing interval, type, method and duration of application of the tourniquet and whether the procedure should be performed standing or under general anaesthesia (Biasutti et al., 2021). This was supported by the findings of this study where six different drug selection and dosing protocols were used for A-RLP in cases where data were available. Future studies to standardize the technique are indicated to fully investigate the potential benefit of RLP in equine orthopaedic procedures (Biasutti et al., 2021).
Aerobic/anaerobic bacterial culture and sensitivity were submitted in one case of SSI in this series, which yielded positive results for Pseudomonas, Cronobacter and Aerococcus spp. Previous studies reporting on equine SSI rates have frequently identified Staphylococcus spp. (Ahern et al., 2010;Hicks et al., 2021;Knox & Watkins, 2006;Sakai et al. 2018) associated with infections following orthopaedic implant placement, as well as Enterobacter (Ahern et al. 2010;Knox & Watkins, 2006), Streptococcus (Knox & Watkins, 2006), Pseudomonas (Ahern et al., 2010;Hicks et al., 2021;Knox and & Watkins, 2006) and Corynebacterium (Sakai et al., 2018). Ahern et al. reported a relatively equal distribution of Gram-positive and negative bacterial isolates with Enterobacter and Staphylococcus being the most commonly cultured Gram-negative and positive isolates, respectively (Ahern et al., 2010). Positive bacterial culture was previously associated with a lower rate of survival to hospital dismissal when compared to horses without infection (Ahern et al., 2010). However, there was no significant difference in the rate of dismissal between horses with different bacterial culture types (Gram-positive vs. negative) or horses with mixed bacterial cultures (Ahern et al. 2010 The surgical removal of all implants under general anaesthesia was performed on day 144 postoperatively. Lameness improved rapidly following the removal, and therefore soft tissue impingement was thought to be the more likely cause; however, delayed SSI could not be ruled out as culture and sensitivity were not performed. Radiographic images of both cases in which implant-associated discomfort occurred are presented in Figure 3. These findings are similar to one previous study examining outcomes following LCP placement for PIPJ arthrodesis, where implant removal was performed in 2/30 cases due to infection, although no incidences of implant failure were reported (Hicks et al., 2021).
The duration of postoperative coaptation until the first cast change was similar in this study (median 21 days, mean 24 days) to previous reports of a median of 14 days (Hicks et al., 2021;Knox & Watkins, 2006), 20 days (McCormick & Watkins, 2017), 20 days until first change with a second cast placed in 10/29 cases (Sakai et al., 2018), 27 days (Maclellan et al., 2001), and 35 days (Schaer et al., 2001 ity of the plate-screw construct and greater resistance to cyclic failure associated with unprotected weight-bearing in the early postoperative period, which may further reduce the incidence of complications such as cast sores in the early postoperative period (Hicks et al., 2021). The observation that both SSI events occurred following placement of an LCP construct should not be over-interpreted and was attributed to the increased frequency of use of LCP over DCP or LC-DCP temporally at that stage of the study time period.
Limitations of this study include the retrospective nature of data retrieval, a limited number of cases meeting inclusion criteria to enroll, and a low rate of SSI overall. It is possible that additional follow-up with owners would have allowed the detection of more complete information regarding the development of infection postoperatively. Outcomes for return to the previous level of athleticism long-term were not assessed in this study. The definition of SSI varies between studies and may represent a limitation in that some cases that resolved with conservative therapy under the care of referring veterinarians may not have been recorded. In the one case in this study where implants were removed due to persistent lameness and subsequently rapidly improved, the cause of lameness was thought more likely to be due to implant impingement on adjacent soft tissues; however, delayed SSI cannot be ruled out definitively as culture and sensitivity were not performed. The criteria used here to define 'SSI' have been previously reported and used for retrospective designation of synovial infection, and all cases defined as SSI in this study met those criteria (Ahern et al., 2010;Curtiss et al., 2019). Finally, it is acknowledged that the relatively rare occurrence of infection necessitates caution in the extrapolation of conclusions to populations. These findings add to the body of the literature regarding the risk of SSI in equine patients undergoing internal fixation with orthopaedic implants, specifically with regard to perioperative antibiotic protocols.
In conclusion, the frequency of SSI in this population of horses undergoing PIPJ arthrodesis was lower than that in previous reports of internal fixation in equine patients and was not affected by the antibiotic protocol administered. There was no additional benefit to the administration of parenteral antibiotics for longer than 72 h postoperatively or the preoperative use of RLP in preventing SSI. These data may be useful to surgeons in evaluating their own postoperative infection rate with musculoskeletal procedures and in assessing factors associated with increased risk for SSI. Further evaluation of prophylactic local antibiotic administration is indicated.
ical approval was required as this manuscript represents a retrospective analysis of medical records.

DATA AVAILABILITY STATEMENT
The data that support these findings are available from the authors upon reasonable request.

PEER REVIEW
The peer review history for this article is available at https://publons. com/publon/10.1002/vms3.839