A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study

Abstract

Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck.

Introduction

Orthopedic infections can lead to increased patient morbidity, delayed healing, increased cost of treatment, and negatively impact success of the surgery (1). Removal of surgical implants is often needed to resolve a deep tissue infection due to bacterial adherence to the implant and formation of a biofilm (2–5).

Implant removal may be augmented with antimicrobial therapy. Systemic antimicrobial therapy has several potential disadvantages, including insufficient concentration at the infection site, systemic side effects, and owner non-compliance (4,6). Local antimicrobial therapy has the advantages of high local antimicrobial concentrations and reduced systemic side effects (6–8). An ideal local antimicrobial vehicle is sterile, stable in storage, biocompatible, biodegradable, and delivers a consistent elution profile for the antimicrobial(s) it carries (4,9,10).

A fully biodegradable, cross-linked dextran polymer matrix product [polymer hydrogel (Vetrigel; Royer Animal Health, Frederick, Maryland, USA)] has been developed as an antimicrobial delivery vehicle. The matrix forms a hydrazone with an in vivo residence time of 4 to 5 wk before it is degraded by hydrolysis (4). The product is packaged as a dihydrazide cross-linking reagent that is mixed with a solution of oxidized dextran, forming a gel in 2 min (4). This polymer hydrogel is easy to apply, can conform to the wound, and is not susceptible to proteolytic degradation (4). Clinical testing in horses showed no increased inflammatory reaction at the implantation site (11). The authors are unaware of any in vivo studies reported in the peer-reviewed literature regarding the use or tolerance of this product in small animal patients (12).

At the time of manuscript preparation, the polymer hydrogel was available only as an individual device (Vetrigel; Royer Animal Health). The product used in this study was formulated and commercially available with both amikacin and clindamycin (R-Gel; Royer Animal Health). Aminoglycosides are effective against aerobic Gram-negative bacteria and have a concentration- dependent bactericidal effect (13). Clindamycin provides complementary antimicrobial coverage, being effective against most aerobic Gram-positive cocci as well as anaerobic bacteria (13). Amikacin and clindamycin in combination elute from the polymer hydrogel matrix effectively and maintain bioavailability at concentrations above the breakpoint minimum inhibitory concentration for 9 d and at least 10 d, respectively (4).

In the absence of clinical data on the use of this dextran polymer, we sought a pilot study to assess tolerance of this device in clinical patients. A cohort of patients having orthopedic implants removed was deemed an appropriate population for consistent application. The tibial plateau leveling osteotomy (TPLO) is a standard procedure for stabilizing the canine stifle joint with cranial cruciate ligament deficiency (14). Being an elective procedure, the TPLO avoids such confounding factors as trauma, open fractures, or other co-morbidities. The postoperative infection rate for the TPLO is reported to be 3% to 13.3% and implant removal rate is 2% to 7.4% (1,15–23). Given this high explantation rate on a commonly performed procedure, investigation of new methods of infection control is warranted and provides a reasonable cohort for a pilot study.

The purpose of this pilot study was to determine if this dextran polymer product is well-tolerated by dogs so that further safety and efficacy studies may be performed. The primary objective was to identify adverse events associated with local application of the polymer hydrogel impregnated with amikacin and clindamycin in dogs having TPLO implants removed due to suspicion of surgical site infection (SSI). This was assessed based on physical, laboratory, and radiographic evaluation. Our hypothesis was that no abnormalities would be identified in parameters evaluated after local polymer hydrogel application.

Materials and methods

Patients were identified for potential inclusion if TPLO implant removal was recommended due to suspected SSI, as defined by the United States Centers for Disease Control (Table 1) (24). The owners of study candidates provided informed consent for participation in the study. Procedures were compliant with our institution’s guidelines for research animals and were consistent with the American College of Veterinary Surgeons statement for the humane use and care of animals, as well as the United States animal welfare acts [animal welfare acts (United States Public Laws: 89–544; 91–579; 94–279)] and the Canadian Council on Animal Care.

Table 1.

Definitions for surgical site infection (21,22,24)

Category	Criteria
Superficial SSI	— Within 30 days — Skin and/or subcutaneous tissues — 1 or more of: Pus Bacteria Heat, redness, pain OR localized swelling AND incision reopened by surgeon UNLESS culture negative
Deep SSI	— Within 30 days, 1 year if implant present — Deep soft tissues of the incision — 1 or more of: Pus Spontaneous dehiscence of deeper incision OR incision is deliberately opened when patient has fever, localized pain OR tenderness UNLESS culture negative Abscess or other evidence of infection on imaging or histology
Organ/Space SSI	— Within 30 days, 1 year if implant present — Involves any part of the body, excluding the skin incision, fascia, or muscle layers, that is opened or manipulated during the operative procedure — 1 or more of Pus Bacteria Abscess or other evidence of infection examination, re-operation, histology, or imaging

Data recorded included: signalment; date of initial TPLO surgery; date of explantation surgery; surgeon performing each surgery; intervening surgeries or co-morbidities; clinical signs that lead to implant removal (e.g., presence or absence of suspected SSI); pre- and post-explantation clinicopathologic data; radiographic findings; aerobic bacterial culture and sensitivity results; volume of polymer hydrogel administered; postoperative medications, and any intra- or post-operative complications. Follow-up was obtained through serial re-examinations and included surgical site evaluation for SSI (Table 1) as well as lameness score (on a scale of 1 to 5) at the 2, 6, and 12-week recheck examinations.

Prior to general anesthesia, all patients had a physical examination and orthogonal radiographs of the affected stifle. Clinicopathologic data included serum biochemistry, hematology, and urinalysis. Anesthetic protocols varied depending on the attending surgeon and the individual patient’s level of anesthetic risk. The affected limb was suspended, clipped, and prepared for aseptic surgery using 4% chlorhexidine (Dermachlor 4% Surgical Scrub; Henry Schein Animal Health, Dublin, Ohio, USA) and 70% isopropanol (Buffered Alcohol 70%; Henry Schein Animal Health). The skin was incised through the previous scar over the TPLO plate and any fistulous tracts were removed. The plate and screws were identified and removed. Proliferative bone and tissue at the site, as well as the screw holes, were debrided. A sample for aerobic bacterial culture of the implant and/or deep tissue was collected and a single injection of cefazolin (Cefazolin For Injection, USP; West-Ward, Eatontown, New Jersey, USA), 22 mg/kg body weight (BW), IV, was subsequently administered. The surgical site was lavaged with sterile saline. The polymer hydrogel (R-Gel) was loaded with 100 mg amikacin sulfate and 50 mg clindamycin HCl per 2 mL aliquot. This product was mixed per package directions, allowed to partially congeal, and applied to the surgical site. Wound closure was routine. Mediolateral and caudocranial radiographs were acquired immediately thereafter. No other perioperative antimicrobials were used and systemic antimicrobials were not dispensed.

If hospitalized, analgesia was managed overnight using hydromorphone (Hydromorphone HCL Injection, USP; WestWard), 0.1 mg/kg BW, IV, q8h, buprenorphine (Buprenorphine Hydrochloride Injection; Hospira, Lake Forest, Illinois, USA), 0.016 mg/kg BW, IV, q6h, or tramadol (Tramadol Hydrochloride Tablets; Amneal Pharmaceuticals, Glasgow, Kentucky, USA), 2 to 2.5 mg/kg BW, PO, q8h. Patients were discharged from the hospital 8 to 24 h following surgery. Analgesics dispensed for home-care included tramadol, 2 to 2.5 mg/kg BW, PO, q8-12h and a non-steroidal anti-inflammatory drug (NSAID) such as carprofen (Carpaquin Caplets; Nutramax Pharmaceuticals, Lancaster, South Carolina, USA), 2.2 mg/kg BW, PO, q12h, meloxicam (Metacam; Boehringer Ingelheim Vetmedica, St. Joseph, Missouri, USA), 0.1 mg/kg BW, PO, q24h, deracoxib (Deramaxx; Novartis Animal Health US, Greensboro, North Carolina, USA), 1 to 1.5 mg/kg BW, PO, q24h, or firocoxib (Previcox; Merial, Duluth, Georgia, USA), 5 to 6 mg/kg BW, PO, q24h.

Patients were rechecked 10 to 14 d following surgery for incision site and lameness evaluation. Skin staples were removed and samples were collected for serum biochemistry, hematology, and urinalysis to evaluate for signs of possible side effects from the polymer hydrogel. At 6 and 12 wk after surgery, physical examinations, including lameness assessment and surgical site inspection, were performed and orthogonal radiographs were acquired to evaluate bone healing and any periosteal changes.

Paired, non-parametric data from preoperative and 2-week postoperative serum biochemistry, hematology, and urinalysis were analyzed by Wilcoxon signed-rank test. McNemar’s test was used to evaluate for changes in frequency and type of nominal urinalysis data (presence of casts and crystals). Statistical significance was defined as P < 0.05. Summary statistics were calculated to describe the patient population, clinical signs, perioperative treatments, postoperative examination and radiographic findings, frequency of complications or side-effects and overall success rate.

Results

A total of 813 TPLO procedures were performed at our clinics between September 2008 and April 2011. Forty-nine TPLO implants were removed during that time. Twenty-eight of these 49 cases were enrolled in the study. Eight cases were excluded due to incomplete records or inadequate follow-up. Of the 20 dogs included for data analysis, the average age was 5.8 y (range: 2 to 13 y). Average body weight was 36.4 kg (range: 8.6 to 80.2 kg). Additional descriptive statistics of these cases are listed in Table 2. The mean time between original TPLO surgery and explantation was 22.1 mo (range: 2.5 to 91.5 mo), median 14.4 mo.

Table 2.

Descriptive statistics of cases with TPLO implants removed for suspected SSI in the present study

	Number (%)
Gender
Male	1 (5)
Castrated male	5 (25)
Female	1 (5)
Spayed female	13 (65)
Breed
Labrador retriever	6 (30)
Mixed breed dog	3 (15)
German shepherd dog	2 (10)
Mastiff	2 (10)
Doberman pinscher	2 (10)
Giant schnauzer	1 (5)
Golden retriever	1 (5)
Lhasa apso	1 (5)
English bulldog	1 (5)
American pit bull terrier	1 (5)
Side of TPLO plate removed
Right	12 (60)
Left	8 (40)

The original TPLO procedures were performed by 6 American College of Veterinary Surgeons board-certified surgeons, or a resident under their supervision. The explantation procedures were performed by the same surgeon as the TPLO (or a resident under supervision). There were no perioperative complications during explantation procedures. Eight of the patients were discharged with postoperative antimicrobial therapy following the original TPLO procedure at the discretion of the surgeon; medical records did not indicate breaks in aseptic technique or other specific reasons for these medications. The antimicrobials included cephalexin (n = 6), cefpodoxime proxetil (n = 1), and ciprofloxacin (n = 1). At the time of suture removal from the original TPLO surgery, 11 dogs were reported to have had a grossly healthy and normally healed incision site. The remaining 9 dogs had abnormalities including swelling or seroma (n = 7), erythema (n = 1), and a lick granuloma (n = 1).

Clinical signs at the time of presentation of cases that ultimately resulted in implant removal included draining tracts (n = 12), lameness (n = 11), pain on palpation (n = 1), and self-mutilation (n = 1). Treatment initiated at our clinic or by the referring veterinarian included systemic antimicrobial therapy (n = 6), NSAID (n = 4), and surgical debridement (n = 1). Systemic antimicrobials used prior to plate removal included cephalexin (n = 2), ciprofloxacin (n = 2), cefpodoxime proxetil (n = 1), chloramphenicol (n = 1), and doxycycline (n = 1). No preoperative treatment was initiated in 7 patients.

At the time of skin staple removal from explantation surgery, incisions were considered grossly healthy or healed in 15 dogs (75%). Abnormalities noted in the other 5 dogs included erythema (n = 2), swelling or seroma (n = 2), and purulent discharge (n = 1). The patient with purulent discharge from the incision was treated with ciprofloxacin (prescription provided for alternative pharmacy, drug information unavailable), 12.6 mg/kg BW, PO, q12h for 21 d and clinical abnormalities had resolved by the 6-week recheck examination. One patient with swelling was treated with doxycycline (Doxycycline Tablets; Par Pharmaceutical Companies, Spring Valley, New York, USA), 3.75 mg/kg BW, PO, q12h for 21 d, and had persistent but improved swelling noted at the 6-week re-check that resolved by the 12-week re-check.

Six dogs were reported to have had a grade 1/5 lameness at the 6-week post-explantation re-check. By the 12-week re-check, only 1 (different) dog had a grade 1/5 lameness and no other dogs were reported to be lame. The dog with a lameness at the final study recheck was diagnosed with an iliopsoas strain. There was no pain or swelling at the level of the surgical site for any dog at the final re-check.

The results of serum biochemistry and hematology analysis are provided (Table 3). The Wilcoxon signed-rank test results indicate there was no statistically significant change in the values for renal or hepatic variables.

Table 3.

Selected results of serum biochemistry, hematology, and urinalysis

Laboratory variable (units)	P-value	Pre-op median	Pre-op 25th to 75th percentile	2-week post-op median	2-week post-op 25th to 75th percentile	Reference range
ALP (U/L)	0.54	44.5	34.8 to 61.5	45	33.8 to 67.8	10 to 150
ALT (U/L)	0.23	26.5	23.0 to 34.3	24.0	20.0 to 29.3	5 to 107
AST (U/L)	0.25	110.0	82.5 to 136.3	112.5	84.3 to 153.3	5 to 55
GGT (U/L)	0.78	4.5	3.0 to 5.0	4.0	2.8 to 4.3	0 to 14
Tbili (mg/dL)	0.77	0.1	0.1 to 0.1	0.1	0.1 to 0.1	0.0 to 0.4
Alb (g/dL)	0.86	3.2	3.0 to 3.5	3.4	3.0 to 3.6	2.5 to 4.0
BUN (mg/dL)	0.52	17.0	12.8 to 21.3	18.5	13.8 to 23.0	7 to 27
Creat (mg/dL)	0.89	1.1	0.9 to 1.2	1.1	1.0 to 1.2	0.4 to 1.8
WBC (103/uL)	0.72	9.1	7.5 to 10.3	8.9	7.9 to 9.5	5.7 to 16.3
Neuts (%)	0.18	70.5	66.0 to 75.3	69.5	63.5 to 73.3	60 to 77
Urine specific gravity	0.91	1.030	1.022 to 1.040	1.028	1.020 to 1.039	—
Urine pH	0.9	7.0	6.6 to 8.3	6.5	6.0 to 7.5	—
Urine protein	1.00	0	0	0	0	—

Pre-op — preoperative; post-op — postoperative; ALP — alkaline phosphatase; ALT — alanine aminotransferase; AST — aspartate aminotransferase; GGT — gama-glutamyl transpeptidase; Tbili — total bilirubin; Alb — albumin; BUN — blood urea nitrogen; Creat — creatinine; WBC — white blood cell count; Neuts — segmented neutrophils; — no specified reference range.

The results of urine sediment examination of casts and crystals are provided (Table 4). Here, the McNemar’s test indicates there was no statistically significant change in frequency or type of variables.

Table 4.

Results from urine sediment examination for casts and crystals

	Time = 0 wk
CASTS	None	Fine granular	Hyaline
Time = 2 wk
None	16	0	1
Fine granular	0	1	0
Hyaline	0	0	0
P = 0.80
	Time = 0 wk
CRYSTALS	None	Ammonium Mg Phos	Calcium oxalate
Time = 2 wk
None	17	1	0
Ammonium Mg Phos	1	0	0
Calcium oxalate	2	0	0
P = 0.57

Ammonium Mg Phos — ammonium-magnesium-phosphate or struvite.

Sixteen of the 20 dogs (80%) herein had a positive bacterial culture result. The most common bacterial species isolated was Staphylococcus (n = 13; 81%), others included Corynebacterium (n = 1; 6%), Enterococcus (n = 1), and Pseudomonas aeruginosa (n = 1). Of the Staphylococcus isolates, 7 (44% positive culture, 35% of all cases) were methicillin resistant, including strains of S. aureus (n = 3) and S. pseudintermedius (n = 4).

Bacterial culture and sensitivity results are listed in Table 5. Four isolates were resistant to clindamycin. Of these isolates, 1 was resistant to amikacin and 2 had an intermediate susceptibility to amikacin. No isolates were resistant to amikacin and susceptible to clindamycin. The local polymer hydrogel was still used in all cases. One of these patients (bacterial isolate resistant to clindamycin and intermediate to amikacin) was later treated with systemic trimethoprim sulfa (Sulfamethoxazole and Trimethoprim Tablets, USP; Qualitest Pharmaceuticals, Huntsville, Alabama, USA) due to the bacterial resistance profile. None of these patients developed clinical signs of SSI during the follow-up period.

Table 5.

Results of antimicrobial sensitivity testing of positive culture results

Organism	Staph — C.P.	Staph — C.P.	Staph aureus	Enterococcus	Staph — C.P. BT1.	Staph aureus	Staph pseud	Staph intermedius	Staph — C.P.	Staph pseud	Staph aureus	Staph intermedius	Pseudomonas aeruginosa	Staph — C.P.	Staph — C.P.
Methicillin resistance	No	No	Yes	No	No	Yes	Yes	Yes	No	Yes	Yes	Yes	No	No	No
Amox/Clav acid	S	S	R	R	S	R	—	R	S	R	R	R	—	S	S
Amoxicillin	R	R	R	R	R	R	R	R	R	R	R	R	—	R	R
Ceftiofur	I	S	R	—	S	R	R	R	S	R	R	R	R	S	S
Cephalexin	S	S	R	—	S	R	R	R	S	R	R	R	—	S	S
Cefovecin	—	—	—	—	—	R	R	—	—	—	—	—	—	—	—
Cefpodoxime	—	—	—	—	—	R	R	—	—	—	—	—	—	—	—
Chloramphenicol	—	—	—	S	—	S	S	S	—	S	S	S	R	—	—
Ciprofloxacin	—	—	—	—	—	R	S	R	—	S	R	S	S	—	—
Clindamycin	S	—	R	—	S	R	S	R	S	—	R	—	—	S	S
Enrofloxacin	S	R	R	R	R	R	S	R	S	S	R	S	R	S	S
Erythromycin	S	R	R	S	S	R	S	R	S	R	R	R	—	S	S
Gentamicin	S	I	S	—	S	S	S	R	S	S	S	S	S	S	S
Imipenem	—	—	—	—	—	R	R	—	—	—	—	—	—	—	—
Marbofloxacin	—	—	—	—	—	R	S	R	—	S	R	S	—	—	—
Moxifloxacin	—	—	—	—	—	R	S	I	—	S	R	S	—	—	—
Oxacillin	S	S	R	—	S	R	R	R	S	R	R	R	—	S	S
Penicillin G	R	R	R	R	R	R	R	R	R	R	R	R	—	R	R
Tetracycline	S	R	S	—	S	S	R	R	S	S	S	S	—	S	S
Trimethoprim-Sulfa	S	—	—	—	—	S	S	—	—	R	—	—	—	—	S
Tribrissen	—	R	S	—	S	—	—	R	S	—	S	S	—	S	—
Amikacin	S	—	I	—	—	I	S	S	—	S	R	S	S	—	—
Azithromycin	—	—	—	S	—	R	S	—	—	—	—	—	—	—	—

Staph — Staphylococcus; C.P. — coagulase positive; BT1 — biotype 1; pseud — pseudintermedius; Amox/Clav acid — amoxicillin and clavulanic acid; S — sensitive; R — Resistant; I — intermediate; —, not tested.

All stifle radiographs were reviewed by board-certified veterinary radiologists. Healing of the osteotomy site progressed at a normal rate and there was no evidence of osteolysis or periosteal response to suggest osteomyelitis in the pre-explantation images. There was no evidence of implant failure or loosening of any screws. Given the lack of overt radiographic changes, a numerical grading scale could not be applied. Subjectively, the 6-week post-explantation radiographs revealed smooth continuous modeling of mineralized callus in each case. The 12-week post-explantation radiographs revealed progression of normal modeling. No dogs exhibited increased periosteal reaction or progressive soft tissue swelling to suggest local tissue response from the polymer hydrogel.

Discussion

Our results support the hypotheses that no adverse laboratory or radiographic findings occur after polymer hydrogel application. Of the 49 TPLO implants that were removed, 9 were removed at the time of arthrotomy for subsequent meniscal injury and the remaining 40 implants were removed for suspected SSI or sensitivity. There was a 4.9% implant removal rate for suspected SSI, similar to recently reported rates of 2.6% to 7.4% (5,19,23). Variation could be related to surgeon experience, operative technique, perioperative patient management, postoperative antimicrobial use, and implants used.

Reported toxic effects of amikacin following systemic administration include nephrotoxicity, ototoxicity, neuromuscular blockade, peripheral neuropathy, pain/inflammation at the injection site, facial edema, hypersensitivity reactions, and rarely signs related to the gastrointestinal tract, liver, or bone marrow (25–27). Toxic effects from clindamycin administration are uncommon, but include gastroenteritis and pain at the site of intramuscular injection (28,29). Our primary concern was amikacin-induced nephrotoxicity, although this locally applied product is formulated with the systemic dose appropriate for a 5-kg dog (4). As expected, no dog in this study developed clinical signs related to either amikacin or clindamycin toxicity. Blood and urine were evaluated only at the 2-week re-check because a previous study indicated antimicrobials delivered by the polymer hydrogel were almost all eluted in the first 10 d, with a cumulative total elution of 86.4% of clindamycin and 73.0% of amikacin (4).

Physical examination abnormalities included 5 cases with erythema, seroma, or purulent discharge at the 2-wk re-check and all signs resolved by 12 wk. Only 1 dog had mild grade 1/5 lameness of the operated limb at the 12-week re-check and this dog was diagnosed with an iliopsoas strain. Recheck radiographs were evaluated for periosteal reaction, soft tissue swelling, and/or delayed healing that might indicate a reaction to the polymer hydrogel and no such signs were seen. All dogs had resolution of clinical signs of SSI and were comfortable on palpation over the surgical site by the 12-week re-check examination.

Signs of SSI at the 2-week re-check included erythema (n = 2), seroma (n = 2), and purulent discharge (n = 1). Two of these were started on systemic antimicrobials. Clinical signs resolved in both cases by the 6-week re-check. The causes of these signs are unknown and future studies should investigate such possible findings. Ultimately the clinical signs resolved, but it is not clear if this was due to the systemic antimicrobials that were administered, or if the signs would have resolved over time without further intervention. A recent report of SSIs of TPLO documented resolution of clinical signs in 94.9% of dogs treated by implant removal with or without postoperative antimicrobial therapy (20). In the human literature, post-implantation antimicrobial therapy is recommended as part of arthroplasty revision but may not be necessary for simple implant removal after complete bone healing (30,31). Bacterial culture in this study identified 4 isolates that were resistant to clindamycin, 3 of which also had some resistance to amikacin (2 intermediately susceptible, 1 resistant). None of these patients developed clinical signs of SSI during the follow-up period.

Many vehicles for local antimicrobial therapy are retained in situ and may cause a foreign body reaction or become a nidus for infection (4,9–11). In a study of gentamicin-impregnated polymethyl methacrylate beads placed at time of revision for total hip arthroplasty in humans, bacteria were isolated from implanted beads in 18 of 20 patients compared to no growth on culture of tissue in 12 of those 18 (9). Additionally, 19 of 28 bacterial isolates in that study were resistant to gentamicin (9). The use of this polymer hydrogel with amikacin provides an aminoglycoside alternative to gentamicin for bacteria suspected or confirmed to be resistant to gentamicin. The manufacturer indicates this polymer hydrogel is bioabsorbable in horses and dogs although histopathologic studies post-application are needed to confirm this claim.

This study has several important limitations. Since it was a pilot study, there was no control group to exclude the possibility that these were self-limiting infections. While data were collected prospectively, lack of sufficient follow-up and/or missing data reduced the number of included cases. Additionally, quantitative bacterial cultures were not performed and would have required additional invasive sampling. An additional concern is that bacteria in a biofilm may not grow in standard aerobic culture (32).

To our knowledge, this is the first report of clinical use of this novel bioabsorbable dextran polymer as a vehicle for local antimicrobial therapy with amikacin and clindamycin in dogs. This pilot study indicates this product is well-tolerated and further prospective, case-controlled, and possibly histopathologic studies to determine the safety and potential efficacy of this product are warranted. While TPLO explantation was used as the model of SSI here, the clinical consideration of this production should not be limited to this use nor should it be compounded only with amikacin and clindamycin together. Other potential uses could include application of orthopedic implants, soft tissue infections, septic arthritis, wound dressings, and local chemotherapy or other antimicrobial administration, with further elution studies as indicated.