Читать книгу Complications in Canine Cranial Cruciate Ligament Surgery - Ron Ben-Amotz - Страница 45

The vast majority of SSIs occur secondary to contamination of the surgical site by commensal or pathogenic organisms arising from the patient's own microbiome [8]. The most common microorganism identified in SSIs is Staphylococcus pseudintermedius. Other common microorganisms identified include Streptococcus spp., Pseudomonas aeruginosa, and Escherichia coli. Staphylococcus pseudintermedius is an opportunistic pathogen with an ability to create a biofilm, leading to its increased virulence [9]. The ability to create a biofilm is important as it makes eradication of these SSIs more challenging. Additionally, resistance of S. pseudintermedius is on the rise, creating an even greater challenge for management of patients with SSIs [9].

Following the diagnosis of a SSI, several factors must be considered prior to determining a treatment protocol. These include the patient's overall clinical status, category of SSI (superficial, deep, organ/space), susceptibility of inciting microorganisms, presence of biofilm formation, stage of healing, availability of treatment options, and client considerations such as emotional and financial strain associated with treatment.

The vast majority of SSIs reported by category in the veterinary literature are limited to superficial or deep tissue layers, with an organ/space SSI occurring in <1% of infections [4, 10].

For superficial incisional SSIs, topical or systemic antimicrobial therapy may be sufficient. Topical therapies may include antiseptic agents such as chlorhexidine or povidone‐iodine or antimicrobial therapies such as medical‐grade honey or silver compounds. When the SSI is relatively focal or has minimal purulent discharge, topical antiseptic solutions may be used to clean the site several times daily and may result in resolution of the SSI. However, when a large portion of the wound appears to be affected or when there are large volumes of purulent discharge, topical antimicrobial therapies are best employed if the wound is reopened and explored. This allows for greater source control by lavaging the wound and removing the large microbial burden and allows topical therapies to be in direct contact with the affected tissues. Medical‐grade honey and silver ointments are often used in these scenarios. There is no evidence for antimicrobial resistance for honey, but resistance may exist for silver compounds [11]. This resistance has been demonstrated in vitro and may not be clinically applicable.

Regardless of the potential for resistance, response to topical therapy should be monitored and treatments altered if there is a lack of response. Ideally, a bacterial culture should be submitted from the onset of clinical signs, so that an appropriate systemic antimicrobial can be added to the treatment regime, should topical therapy fail to resolve the SSI.

Systemic antimicrobial therapies should be employed in the face of an intact incision and direct identification of microorganisms. Initially, systemic antimicrobials will be chosen empirically until the results of culture and susceptibility testing are available to guide specific therapy. It is important to collect and submit a bacterial culture when an SSI is suspected, to ensure appropriate antimicrobial stewardship is followed and reduce the risk of potentiating antimicrobial resistance.

Initial empirical recommendations will vary based on hospital known infectious agents and their resistance patterns. Appropriate duration of therapy is a topic of debate and varies between prescribers, with reported treatment lengths ranging from 1 to 6 weeks of antimicrobial therapy [12, 13]. While extended durations of antimicrobial therapy are reported, these prolonged courses of antimicrobials are not likely required unless implanted materials are involved. Most uncomplicated, superficial SSIs will resolve with a systemic course of antimicrobials for 3–5 days. Ultimately, when antimicrobial therapy is discontinued and there is recurrence of clinical signs, involvement of implanted materials should be considered and prolonged antimicrobial therapy based on culture and susceptibility results will be required until implanted materials can be removed or local therapies can be employed [12].

Deep SSIs involving implanted materials can be more challenging to manage, due to the risk for biofilm formation. A biofilm is a community of sessile bacteria embedded in a self‐produced matrix that has adhered to a surface (Figure 3.4) [14]. The most commonly implicated bacterium in veterinary SSIs is S. pseudintermedius which has a propensity for biofilm formation and multidrug resistance [9, 15, 16]. The self‐produced matrix protects the bacteria from antimicrobial penetration and makes treatment more complex as minimum inhibitory concentrations are much higher for bacteria in a biofilm than planktonic bacteria [17].

Because of this increased challenge of eradicating a biofilm‐associated infection, implant removal is often recommended. However, if the SSI is identified early postoperatively and insufficient healing has occurred, methods other than implant removal must be considered. Antimicrobials are often used in situations like this to try to control the SSI, with a realization that the goal is most likely to allow for bone healing, at which point implant removal would be indicated. In the face of a completely healed osteotomy or adequately stabilized extracapsular repair, implant removal, and thus biofilm eradication, are often recommended. Several studies have reported implant removal rates for TPLO, tibial tuberosity advancement (TTA), cranial closing wedge osteotomy, triple tibial osteotomy, and lateral fabellar suture extracapsular repairs [12, 13,18–23]. Explant rates for management of an SSI ranged from 1.3% to 71%, with TPLO and lateral fabellar sutures being the highest rate of explanted materials [12, 13,18–20, 22, 23].

Figure 3.4 Scanning electron microscopy image of a biofilm.

Source: Adapted from Singh et al. [9].

Additional approaches to biofilm infections are currently limited. Two enzymes have been identified as being able to prevent biofilm formation; deoxyribonuclease I and dispersin B. While both are capable of inhibiting biofilm formation, only dispersin B has been proven to be able to disrupt an established biofilm [24]. A recent in vitro study has identified that the combination of dispersin B and amikacin in a biodegradable gel allows for rapid elution of dispersin B with a gradual reduction in concentrations over a period of 10 days [25]. While this is a promising avenue, clinical application has not yet been assessed.

When implant removal cannot yet be performed, local antimicrobial therapies (Table 3.3) may be employed. The main goal of these therapies is to allow higher antimicrobial concentrations to be achieved locally than could be tolerated systemically, with limited systemic exposure [26]. Alternative local therapies may include antimicrobial‐eluting bone cement, gel polymer, or collagen sponges, with the most common antimicrobials used being gentamicin, amikacin, and clindamycin.

Table 3.3 Pros and cons of implantable antimicrobial elution products.

Product	Pros	Cons
PMMA beads	Readily available (especially if used for other orthopedic procedures in your facility)	Nonbiodegradable Must be removed Surgical implantation
Calcium‐based beads	Biodegradable – no removal required	Surgical implantation
Polymer gel	Can combine with dispersin B to break down biofilm Minimally invasive application – injectable Biodegradable – no removal required	Cannot flush surgical site to dilute microbial burden Location of application less precise
Collagen sponge	Biodegradable – no removal required	Surgical implantation Incites inflammation Causes lameness with IA application Causes renal impairment

IA, intraarticular; PMMA, polymethylmethacrylate.

Bone cement consisting of a calcium base or polymethylmethacrylate (PMMA) may be formed into beads containing various antimicrobials and may be placed locally at the surgical site (Figure 3.5). The antimicrobial powder or liquid solution is added to the PMMA powder before the addition of the methylmethacrylate liquid. It is important that the antimicrobial of choice will remain stable during the exothermic reaction that takes place when the PMMA powder and methylmethacrylate liquid are combined [26]. Once combined, beads can be formed around a small gauge cerclage wire, to create a string of beads. In vitro evaluation identified that gentamicin‐susceptible methicillin‐resistant S. pseudintermedius (MRSP) was effectively treated with gentamicin‐impregnated beads, whereas gentamicin‐resistant MRSP was not effectively treated and silver‐impregnated beads had no effect on MRSP biofilms [11]. PMMA beads, however, are not biodegradable and require removal at a later date, whereas calcium‐based beads can be degraded locally, thus not requiring removal [27]. Therefore, when considering antimicrobial‐impregnated beads, one must determine the susceptibility of the microorganisms to effectively choose an antimicrobial and take into consideration the potential requirement for removal of beads if PMMA is chosen.

Figure 3.5 In this craniocaudal view of the antebrachium, two discontinuous strands of antimicrobial‐impregnated PMMA beads can be seen on the lateral and medial aspects of the bone.

Antimicrobial‐impregnated dextran polymer gel has been proven in vitro to elute high concentrations of antimicrobials that maintain their bioactivity after elution [28]. Gels can be injected locally, without requiring a surgical approach, and do not require removal as they are naturally resorbed [28]. A single case series of an amikacin and clindamycin‐impregnated dextran polymer gel used in combination with explantation of TPLO plates resulted in excellent clinical outcomes after 12 weeks [29]. Despite limited data existing at this time, this may be a promising option for the future and application without implant removal should be further evaluated.

Commercially available gentamicin‐impregnated collagen sponges have been placed intraarticularly in a study population of dogs with sterilely induced synovitis. A rapid elution rate was identified, resulting in a rapid rise of intraarticular gentamicin concentrations, but a rapid decline was also observed. This rapid decline may not be clinically relevant, as gentamicin is a concentration‐dependent antimicrobial and thus the high concentrations achieved may be sufficient to result in bactericidal activity.

The gentamicin‐impregnated sponge was found to incite joint inflammation, lameness, and renal impairment and was thus not recommended for clinical use [30]. However, one case report exists of its use in a clinical incidence of septic arthritis following an extracapsular stifle stabilization procedure. This case reports clinical resolution of the septic arthritis but systemic gentamicin was administered simultaneously, making it hard to determine the role of the intraarticular gentamicin [31]. A separate case series combined implant removal with an amikacin‐impregnated collagen sponge being placed at the site of implant removal for treatment of TPLO SSI, which resulted in a 96.8% long‐term resolution rate [32]. The benefit of an antimicrobial collagen sponge is its absorbable nature, thus precluding the requirement for retrieval following SSI resolution.

While all of these local antimicrobial‐eluting options provide increased levels of local therapy, differences in biodegradability may play a role in clinical decision making. If these local therapies are being employed in the face of an incompletely healed osteotomy or incomplete stabilization of an extracapsular repair, implant removal cannot be performed concurrently. Two sides of the coin can therefore be considered following complete healing of the osteotomy or adequate stifle stabilization. On the one hand, a biodegradable option does not require further surgical extraction and if the SSI is clinically resolved, the implant may not require removal. However, on the other hand, a nonbiodegradable option must be surgically removed and allows the opportunity for concurrent implant removal. With the major concern of biofilm formation on implanted materials, locally applied antimicrobial therapy may not be sufficient to eradicate the SSI and recurrence may result in further treatment and possible implant removal at a later date.

In the case of implant removal, the major microorganism burden is removed with the implant, assuming that most of these SSIs are biofilm related and as such systemic or local therapies may not be required (Figure 3.6). Of the various studies reporting treatment of SSIs with implant removal, few indicate whether postoperative systemic antimicrobial therapy was continued empirically and/or altered pending culture and susceptibility testing results. While all these studies encourage culture and susceptibility testing of implants that are removed, how this information is applied clinically is unknown. As such, evidence‐based recommendations for postoperative systemic antimicrobial use following implant removal for management of an SSI remain unclear. Logically, if the major burden of disease has been removed, monitoring for clinical recurrence of SSI signs is recommended. Thus, patients without active evidence of an SSI at the time of implant removal do not require systemic antimicrobial therapy and results of culture and susceptibility testing should be employed only in the face of recurrent signs of SSI.

Though few studies exist, when local antimicrobial therapy is combined with implant removal, such as implantation of an amikacin‐impregnated collagen sponge or amikacin and clindamycin polymer gel, SSI resolution rates ranged from 95% to 96.8%, without the concurrent use of systemic antimicrobials [29, 32].

Figure 3.6 (a) Exposed TPLO plate. (b) Screw removed. When removing screws to submit for culture, use a pair of forceps that have not touched the skin to stabilize the screw while it is being removed. Do not allow the screw to contact the skin to avoid growth of skin contaminants on your bacterial culture. (c) Screw placed in broth medium for bacterial culture submission. (d) Surgical site following implant removal.

Regardless of local or systemic therapies used in conjunction with implant removal, bacterial culture and susceptibility testing is recommended following implant removal. While a positive culture may not indicate the need for antimicrobial treatment, it allows for proper selection of the antimicrobial if treatment is determined to be clinically indicated. A positive culture result has been reported following implant removal in 72–80% of cases [18, 23]. However, sonication of implants may aid in improved bacterial recovery when considering culture and susceptibility testing [33]. As sonication is not likely to be performed routinely for culture and susceptibility testing, this may play a role in identification of negative culture results following implant removal for SSI. Alternatively, preoperative treatment with antimicrobial therapy targeted at the known microorganisms may be sufficient to eradicate or significantly reduce the microbial burden, such that a negative culture result is achieved post implant removal [13, 18, 23].