CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials
77
40. Lopes MAF, White NA. Parenteral nutrition for horses with
gastrointestinal disease: a retrospective study of 79 cases. Equine
Vet J. 2002;34:250.
41. Durham AE, Phillips TJ, Walmsley JP, et al. Study of the clinical
effects of postoperative parenteral nutrition in 15 horses. Vet Rec.
2003;153:493.
VetBooks.ir
Surgical Site Infection and the
Use of Antimicrobials
Suzanne Stewart and Dean W. Richardson
INTRODUCTION
The study of the epidemiology and prevention of surgical site
infection (SSI) dates back to the early 19th century when James
Young Hamilton first reported “surgical fever.”1 Antiseptic use
for the prevention of orthopedic SSI was pioneered in 1865 by
Joseph Lister2 and advances in infection control have continued
over the past 150 years. Antibiotics and other antiinfective drugs,
collectively referred to as antimicrobial agents, have been used to
treat infectious disease for approximately 70 years. Penicillin,
the first commercially available antibiotic, was discovered in
1928 by Alexander Fleming.
Despite efforts within the United States to reduce the incidence
of SSI, including introduction of the Joint Commissions Surgical
Care Improvement Project in 2006, infections at the surgical site
still constitute an enormous annual financial burden ranging
from 3.5 to 10 billion USD.3–5 The overall incidence of SSI for
human inpatient surgery is 2% to 5%4 and SSI account for
21.8% of the 800,000 hospital-associated infections acquired
annually in the United States.4–6 The importance of SSI cannot be
overestimated, as it is a leading cause of morbidity and mortality
in both human and equine patients.6–11 Patients who develop
SSI are between two and eleven times more likely to die, 60%
more likely to be admitted to the intensive care unit, and five
times more likely to be readmitted to a hospital.12,13 Between
2008 and 2014, there was a 17% decrease in SSI in the United
States, with the greatest decreases in abdominal hysterectomy
and colon surgery.14 In Europe, there are decreasing trends
in SSI associated with caesarean section, hip prostheses, and
laminectomy, suggesting that prevention and surveillance strate-
gies have been improving.15 SSI associated with antimicrobial-
resistant pathogens, such as methicillin-resistant Staphylococcus
aureus (MRSA), are associated with worse outcomes than when
other pathogens are involved.16,17 MRSA remains the most
commonly reported pathogen in SSI (30.4%), followed by
coagulase-negative staphylococci, Escherichia coli and Enterococcus
faecalis.18
In a recent review of equine fracture repair, the reported
infection rate was 27.6% and patients with SSI were 7.25 times
less likely to survive to hospital discharge.10 In a paper from the
same hospital over the subsequent 10 years, the incidence of
42. Durham AE, Phillips TJ, Walmsley JP, et al. Nutritional and clinico-
pathological effects of post operative parenteral nutrition following
small intestinal resection and anastomosis in the mature horse. Equine
Vet J. 2004;36:390.
43. Jeejeebhoy KN. Total parenteral nutrition: potion or poison? Am J
Clin Nutr. 2001;74:160.
CHAPTER
7  
infection was halved, but the consequences of SSI remained
similar.19 A 44% rate of SSI was reported in horses with radial
fracture repair,11 resulting in a 17 times greater risk of implant
failure and a trend toward nonsurvival. Incisional site infection
is the most common SSI reported in equine surgical procedures
and can occur in up to 43% of procedures.20 A repeat laparotomy
can double the odds of incisional drainage,21 and horses with
wound complications and repeat laparotomies are more likely
to develop ventral herniation.22 Minimization of SSI is critical
if we are to decrease patient morbidity and achieve successful
outcomes.
SURGICAL SITE INFECTION CLASSIFICATION
The most widely used definition of SSI is provided by the Center
for Disease Control and Prevention,4,6,23 which groups SSIs into
the following three categories according to depth and tissue spaces
involved23 (Table 7-1): superficial incisional, deep incisional, and
organ/space involvement. An alternate system, based on the level
of intraoperative contamination, was developed as part of the
National Research Council’s wound-classification criteria, and is
more commonly used in veterinary medicine. This system uses
four classification levels: clean, clean-contaminated, contami-
nated, and dirty (Table 7-2). Distant infections are considered
complications and are not classified as SSI because they are
not directly associated with the surgical incision.24 Correlation
of wound classification with the risk of developing SSI varies
greatly, as the latter is multifactorial and not directly related to
procedure (Table 7-3).
RISK FACTORS FOR SURGICAL SITE INFECTION
The likelihood that an SSI will occur is a complex relationship
between (1) microbial characteristics (e.g., virulence and pathogen
burden); (2) host characteristics (e.g., immune status, age); and
(3) wound characteristics (e.g., hemostasis), presence of foreign
material, and devitalized tissue. The greatest period of risk for
SSI is from the time of the incision until the time of closure
(i.e., the duration of surgery).25 The host’s innate immunity
combined with both the dose and virulence of the bacteria are
the most significant contributors to SSI.26–30
 78 SECTION I  Surgical Biology

TABLE 7-1.  Classification of Surgical Site Infections

Surgical Site Infection Qualification
Superficial incisional Within 30 days of operation
Involves only skin or subcutaneous
tissue of the incision
VetBooks.ir
Includes at Least One of the Following
Purulent drainage from the superficial incision
Organism isolated from aseptically obtained culture of
fluid or tissue from the superficial incision
At least one of the following signs or symptoms of

infection: pain or tenderness, localized swelling

Deep incisional Within 30 days after operation
Within 1 year if implant is in place and
infection appears to be related to the
operation and involves deep soft
tissue (fascial and muscle layers)
Organ/space Within 30 days after operation if no
implant
Within 1 year if implant is in place and
infection appears to be related to the
operation and involves any part of
the anatomy (organs and spaces)
other than the incision, which was
opened or manipulated during the
operation
redness, or heat and superficial incision is deliberately
opened by surgeon, unless incision is culture negative
Diagnosis of superficial incisional infection by surgeon
or attending clinician
Purulent drainage from the deep incision but not from
organ/space of the surgical site
Deep incision spontaneously dehisces or is deliberately
opened by surgeon when patient has one of the
following symptoms: fever, localized pain, or
tenderness, unless site is culture negative
An abscess or other evidence of infection involving the
deep incision is found on direct examination, during
reoperation, or by histopathologic or radiologic
examination
Diagnosis of deep incisional SSI by a surgeon or
attending clinician
Purulent drainage from a drain that is placed through a
stab wound into the organs/space
An abscess or other evidence of infection involving the
organ/space that is found on direct examination,
during reoperation, or by histopathologic or
radiologic examination
Diagnosis of an organ/space SSI by a surgeon or
attending clinician

TABLE 7-2.  Classification of Surgical Wounds

Classification Criteria
Clean Elective, primarily closed, and undrained
Nontraumatic, uninfected
No break in technique
No inflammation encountered
Respiratory, alimentary, genitourinary tracts not entered
Clean-contaminated Gastrointestinal or respiratory tracts entered without significant spillage
Oropharynx entered
Vagina entered
Genitourinary tract entered in absence of infected urine
Minor break in technique
Contaminated Major break in technique
Gross spillage from gastrointestinal tract
Traumatic wound, fresh (<4 hours after trauma)
Entrance of genitourinary tract or biliary tract in presence of infected urine or bile
Dirty Acute bacterial inflammation encountered
Transection of “clean” tissues for the purpose of surgical access to a collection of pus
Traumatic wound with retained devitalized tissues, foreign bodies, fecal contamination, and/or
delayed treatment (<4 hours after trauma)
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 79

TABLE 7-3.  Risk Factors for SSIs in Horses Pathogens leading to SSI are most commonly acquired from
the patient’s endogenous flora and less frequently from exogenous
Risk Factors Examples sources. Microbial contamination is universal despite advance-
Host-related factors Extremities of age ments in technology, surgical technique, and asepsis (Table 7-4).
Gender (female)
Immunocompromised (failure of Infection and Sources of Microorganisms
passive transfer, corticosteroid
VetBooks.ir

administration) Endogenous Sources

Weight (>250 to 300 kg)
Distant sites of infection
Hypoxia (systemic and local)
Foreign material (e.g., clay, dirt)
Surgery-related factors Emergency procedures
Patient and surgeon preparation-
shaving, scrubbing technique
Duration of surgery
Surgical skill
Foreign material (suture and
prostheses)
Bandage (incise drape reduces
SSI, stent >3 days increases SSI,
postcolic abdominal bandage
reduces SSI)
As mentioned earlier, pathogens causing SSI are often acquired
from the patient’s endogenous flora (skin, mucous membranes,
hollow viscera). Within 24 hours of closure, the surgical site is
resistant to microorganism entry.31 Therefore, the critical period
for risk of SSI development is the intraoperative surgical period.
Colonization of the surgical site by remote-site endogenous flora
as well as postsurgical contamination secondary to remote foci
of infection (e.g., pneumonia) are infrequent causes of SSI.32
Twenty percent of bacterial skin flora are present in sebaceous
glands, hair follicles, and sweat glands. Preoperative and periopera-
tive methods of antisepsis can reduce but not eliminate endog-
enous contamination, and as a result gram-positive cocci are the
leading causes of SSI.33 The most common musculoskeletal
pathogen in humans and animals is Staphylococcus aureus, which
is a commensal of the skin and nasopharynx. Enterobacter spp.
are commensals of the genitourinary and gastrointestinal tracts

TABLE 7-4.  Interventions to Decrease SSI in the Horse

Timing Interventions
Preoperative Minimize surgical duration with careful planning
Thorough preoperative exam and CBC/fibrinogen to detect underlying disease
Remove gross foreign material (bath) before induction
Remove hair using clippers, do not use razors
Perform emergency surgery only when necessary
Delay surgery to treat distant sites of infection
Pay strict attention to aseptic preparation/technique
Minimize movement and personnel in operating room
Ensure instrument availability, quality, and sterility for the procedure
Use appropriate perioperative antimicrobials
Intraoperative Double gloves during draping and use orthopedic gloves for fracture repairs
Open surgical instruments/implants as required during surgery
Administer antimicrobials as appropriate
Strictly adhere to aseptic scrubbing/technique
Drape appropriately – drape to isolate enterotomy
Adhere to Halsted’s principles
Place exit drain distant to surgical incision
Use close suction drains and remove before 48 to 72 hours postoperatively
Debride infected/devitalized tissues
Lavage contaminated surgical sites
Minimize foreign material incorporated into surgical site
Maintain patient’s body temperature
Use expedient surgical procedure as appropriate
Consider changing gowns and gloves for procedures longer than 2 hours
Ensure appropriate perfusion and tissue oxygenation
Select appropriate suture material and patterns
Follow appropriate surgical technique
Postoperative Protect surgical site with bandages – colic (incise or abdominal bandage)
Use therapeutic antimicrobials as appropriate
Minimize duration of hospital stay
Provide thorough discharge instructions on wound care and suture removal

CBC, Complete blood count.

 80 SECTION I  Surgical Biology
and are the most common isolate in a recent retrospective of
equine long bone fracture repair.10 Additional distal limb com-
mensals in horses include Bacillus and Micrococcus spp.34 Although
many factors contribute to the risk of SSI, intraoperative pathogen
burden is one of the most widely accepted. Even with appropriate
antimicrobial prophylaxis, contamination of a surgical wound
with greater than 105 microorganisms will lead to SSI,25,35 and
VetBooks.ir
lower colony-forming units (CFUs) result in SSI in the presence
of foreign material or a surgical implant.36,37 Surgical sutures,
polytetrafluoroethylene grafts, and dextran beads can reduce the
minimum inoculum of Staphylococcus aureus required to cause
SSI, to 1 to 10 CFUs.29,30
Virulence of the microorganism and the immunocompetence
of the patient are also contributing factors; a low number of S.
aureus will cause SSI while a higher number of less virulent
microorganisms will not. Certain bacteria possess virulence factors
that increase the risk of SSI, such as the ability to develop biofilm.
Biofilm functions as a partial physical barrier against antimicrobi-
als, antibodies, and the activity of granulocytic cell popula-
tions,38–40 allowing the microorganisms encased within to evade
the host immune response.
Exogenous Sources
Exogenous bacteria are primarily gram-positive aerobes (staphy-
lococci and streptococci)23 and sources include the air, the
operating room environment (including patient and personnel
exogenous sources), and surgical-related factors.
The degree of microbial contamination is directly proportional
to the number of people in the operating room (OR).41,42 Airborne
bacteria and debris are controlled by choosing a low-traffic
location within the hospital and minimizing personnel within
the OR.23 OR design, as well as patient, surgeon, and instrument
preparation, are designed to reduce the number of exogenous
sources of contamination. It is essential that the OR is thoroughly
cleaned on a daily basis and that proper mechanical ventilation
is in place to prevent contamination associated with unfiltered
air. For additional information, see Chapter 10. Conventional
ventilation systems pass air with a mixed or turbulent flow to
the OR. Laminar airflow ventilation is preferred for high-risk
procedures, for example, orthopedic implant surgery. The goal
is to pass fresh filtered air in a unidirectional flow down onto
the surgery field, driving the air present in the surgery room
aerosols and particles out through the periphery of the room.
Guidelines from the Centers of Disease Control and Prevention
(CDC) and the Healthcare Infection Control Practices Advisory
Committee (HICPAC) recommend (1) maintenance of positive
air pressure in the OR; (2) filtration of greater than 90% of the
air; (3) exchange of air 15 times/hour; and (4) that air is intro-
duced from the ceiling and is exhausted onto the floor.43 Sedi-
mentation plate placement in key zones has shown that laminar
airflow systems significantly decrease OR contamination.44 More
recent publications have questioned the measurable benefits of
laminar airflow and a systematic review published in 2012 found
laminar airflow to be a risk factor for prosthetic joint infections.45
It is, however, deemed premature to discontinue use of laminar
airflow systems and a new national surveillance system is proposed
to explore variables associated with increased risk of SSI in laminar
airflow systems.44 Other OR systems in place to limit contamina-
tion include ultraviolet-irradiated rooms and surgical team exhaust
suits. The use of ultraviolet light is no longer recommended to
reduce SSI.43
Grooming of the horse as part of the preoperative patient
preparation minimizes overall gross contamination. The presence
of hair is not associated with increased risk of SSI; however, it
can make aseptic preparation of the site more difficult.46,47 Hair
removal did not affect CFUs following antiseptic skin preparation
over the carpal and distal interphalangeal joint regions34; however,
hair removal did result in increased odds ratio of hair contamina-
tion in arthrocentesis and arthroscopy.48 One study showed a
20-times increased risk of septic arthritis following intraarticular
injection when hair was removed at the injection site.49 Preopera-
tive hair removal should be performed with clippers, as micro-
scopic skin damage caused by razor use increases the incidence
of SSI by 5.6%.47,50 Risk of SSI is further increased when hair is
removed too early (i.e., the night before surgery).47 Aseptic
preparation of the surgical site can be performed using a variety
of agents including iodophors, alcohol-based agents, and
chlorhexidine gluconate.51 Surgical site draping has not been
shown to decrease SSI, but in the equine patient it is highly
likely to reduce contamination.52 The risk of pathogen transmis-
sion increases if barrier materials become wet, therefore drapes
and gowns should be impervious to liquids. Adhesive incise
drapes, plain or iodophor impregnated, have been used after
surgical site preparation, but there is no evidence they reduce
SSI.52,53 The efficacy of surgical gloves in maintaining sterility
has been evaluated, and it was found that despite their use,
contamination is common, with positive culture results of gloves
within 15 minutes of surgical time.54,55 Double gloving during
draping and discarding the outer glove afterwards reduces
contamination and potential for developing SSI.55–57 It is recom-
mended that surgical instruments are opened after the patient
is draped,58 as there is potential for airborne microorganisms to
adhere to the surgical instruments and cause surgical site con-
tamination. It is common practice in human medicine and in
equine clean-contaminated and contaminated procedures to
change to new instruments prior to wound closure. Studies have
investigated interventions such as instrument change, rescrubbing,
and changing of drapes, gowns, and gloves prior to wound closure
in colorectal surgery, and showed no benefit for SSI prevention.59,60
Intraoperative glove change prior to implant insertion showed
an insignificant reduction in the rate of SSI.61 An increase in SSI
could be associated with the use of a single surgical blade to
create superficial and deep incisions, but the single blade tech-
nique appears to present negligible additional risk in healthy
patients.62-65 As with many specific practices within aseptic
technique, the logic and trivial cost of a fresh surgical blade for
deep incision in comparison to the cost of a deep surgical site
infection has made it standard.
Microbe-Related Risk Factors
There may be many types of microorganisms present at the
surgical site, and the pathogens’ intrinsic virulence factors or
characteristics contribute to their ability to cause SSI. The ability
of a microorganism to adhere to eukaryotic cell surfaces, multiply,
and evade host immune responses is variable. Some staphylococci
and streptococci strains can produce exotoxins (hemolysins and
leukotoxins) that can affect host defense mechanisms, interfere
with phagocytosis, and alter cellular metabolism.66–69 Antimi-
crobial resistance can be mediated by plasmids, secreted proteins,
and enzymes such as β-lactamases.70,71
Enterococci can produce an aggregation substance (AS) viru-
lence factor that mediates attachment and survival within
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 81
macrophages and polymorphic neutrophils.72 Gram-negative
organisms produce endotoxins to stimulate cytokine production
and systemic inflammatory response syndrome.73 Several gram-
positive organisms (S. aureus, coagulase-negative Staphylococcus,
and Enterococcus faecalis) have a specific virulence factor in relation
to bacterial adhesion molecules. They possess microbial surface
components recognizing adhesive matrix molecules (MSCRAMMs),
VetBooks.ir
which allow improved adhesion to collagen, fibrin, fibronectin,
and other extracellular matrix proteins, and play a key role in
their pathogenesis of infection.74–78 Fibronectin-binding genes
fnbA and fnbB were detected in 98% and 99% of S. aureus infec-
tions recovered from human orthopedic patients, respectively.78
An additional virulence factor associated with these bacteria is
their ability to develop biofilm. Biofilm refers to an organized
community of bacteria attached to a surface and enveloped within
a self-produced matrix.39 S. aureus forms a unique matrix of
fibrin and glycocalyx79 that anchors to the cell or inert device
and functions as a partial physical barrier against antibiotics,
antibodies, and granulocytic cell populations.38 Biofilm-producing
bacteria possess the unique characteristic of phenotypic hetero-
geneity, which allows them to survive and grow at a slow rate
in localized nutrient and oxygen depletion compared with other
planktonic organisms in the same niche.80 SarA is a regulatory
element that controls staphylococcal virulence factors and is
essential for polysaccharide intercellular adhesion (PIA) synthesis
and biofilm development.81 Once adherence has occurred, the
bacterium changes phenotype and excretes extracellular matrix.
As it develops and matures, it takes cues from cell-to-cell signaling,
for example, quorum-sensing molecules.82 The mature biofilm
releases “planktonic seeds” to stimulate the host immune response
and the biofilm derives nutrients from the host exudate to promote
survival. Antimicrobial recalcitrance is a result of penetration
failure of the biofilm and the protective mechanisms can only
be overcome if the appropriate antimicrobial can be delivered
to the site for a sufficient time and concentration. Cationic
antimicrobials and biocides, for example, gentamicin and
chlorhexidine, can bind to sites within the biofilm and limit it
temporarily.83 Implant removal is often necessary to eradicate
biofilm infection10 and novel techniques to reduce biofilm-
associated infection are being developed continuously, including
surfactant surface modifications,84 sol gel coatings,85 covalent
antimicrobial tethering,86 hydrophobic polycationic coatings,87,88
and quorum-sensing inhibitor RIP (RNAIII-inhibiting peptide)
coatings.89
Host-Related Risk Factors
Systemic Risk Factors
AGE
The relationship of age to increased risk of SSI may be secondary
to comorbidities or immunosenescence.90–92 Increasing age has
previously been cited as a risk factor for horses undergoing elective
arthroscopy.93 In a more recent retrospective study, horses that
developed septic arthritis after arthroscopy tended to be younger,
but this result was not statistically significant.94 In a retrospective
study evaluating risk factors associated with long bone fracture
repair, younger mares had a significantly increased rate of SSI
development with no effect on survival or hospital discharge.10
In a study evaluating radial fracture repair, age was significantly
associated with survival but had no effect on SSI development.11
Horses younger than 1 year that underwent colic surgery showed
reduced SSI (15%) compared with adults (~43%).95 Another
study found no increased risk of short-term complications caused
by age in horses recovering from colic surgery.96 However, a more
recent study demonstrated that horses older than 20 years of
age had a 17-times greater risk of developing incisional site
complications.97
CONCOMITANT INFECTION
Identification and treatment of all remote infections should be
performed prior to elective surgical procedures.23 In humans,
the presence of remote infections can double or triple the likeli-
hood of SSI development.98 Preoperative MRSA surveillance
screening allows for improved prophylactic antimicrobial selection
and extended use of decolonization protocols in MRSA-positive
patients.99 The current World Health Organization (WHO) recom-
mendation is that nasal carriers of S. aureus are pretreated with
mupirocin ointment with or without a combined chlorhexidine
body wash prior to undergoing cardiothoracic or orthopedic
surgery. Because of the increase in S. aureus resistance to mupi-
rocin, decolonization is limited to high-risk populations and
the aforementioned procedures.100–102 Where possible, concomitant
infection (e.g., pneumonia) or a separate site of infection (e.g.,
umbilical infection) should be managed prior to surgery to reduce
secondary SSI associated with bacteremia.23,103
GENDER
Female horses appear to be at greater risk of developing SSI
after arthroscopic and orthopedic surgery compared with intact
males and geldings.10,93 This can probably be explained by the
increased economic and breeding value of females and the greater
likelihood they will undergo more risky procedures than their
male counterparts.
OBESITY
One study reported rates of SSI of 8.9% and 4.1% in morbidly
obese and obese human patients compared with 1.4% in normal
weight patients.104 As it may not be possible to encourage weight
loss prior to surgical interventions, aggressive administration
and redosing of antibiotics is warranted in obese and morbidly
obese individuals. Obese patients may additionally benefit from
the use of subcutaneous sutures, talc application, and wound
vacuum application postoperatively.105,106 In horses, there is no
direct relationship between weight and SSI in orthopedic pro-
cedures. A study showed that horses greater than 300 kg were
more likely to have incisional complications compared with
lighter horses, but this is more likely a result of reduced tissue
perfusion and anesthesia-related hypotension than weight.95
NUTRITIONAL STATUS
Malnourished patients have a significantly increased incidence of
complications, longer hospital stay, higher risk of mortality, and
increased total health care costs compared with well-nourished
patients.107,108 Initiation of intensive glycemic control in patients
with diabetes mellitus and in nondiabetic patients with postopera-
tive hyperglycemia reduces SSI by 35% compared with patients
with unregulated glucose indices.109,110 The effect of nutritional
status on horses undergoing surgery has not been determined, but
severe metabolic derangements should be monitored and adequate
nutrition plans maintained for the best possible outcome.
IMMUNE FUNCTION
Neonates are more susceptible to infection and subsequent
septicemia compared with adults because of their immature
 82 SECTION I  Surgical Biology
immune system. Partial (IgG 400 to 800 mg/dL) or complete
(IgG <400 mg/dL) failure of passive transfer can result in further
reduction of the immune function. Therefore, IgG levels should
be evaluated and corrected in neonates prior to surgery. The
immune system can also be suppressed by the use of local or
systemic corticosteroids6,111 and their use can potentially increase
risk of SSI. The effects of endocrine disease on SSI in the horse
VetBooks.ir
have not been evaluated.
HYPOTHERMIA
Maintenance of normothermia has been shown in randomized
controlled trials to reduce the risk of SSI. Development of
hypothermia (temperature <36°C/96.8°F) or a reduction in body
temperature by 2°C intraoperatively can triple the risk of SSI.112,113
It is postulated that hypothermia impairs neutrophil function
either directly through vasoconstriction or indirectly through
tissue hypoxia.114,115 Additionally, hypothermia can affect platelet
function, resulting in increased blood loss and hematoma forma-
tion, and subsequently in an increasing risk of SSI. Prewarming
of the operating room is recommended, although during the
surgical procedure this can become uncomfortable for the surgeon.
Body core temperature can be maintained sufficiently by the use
of heating pads and warmers should be used in neonatal surgery
and long surgical procedures.116,117 Core temperature of the patient
can also be lowered in open abdominal procedures with prolonged
bowel exposure and abdominal lavage with room temperature
fluids.
Local Risk Factors
SURGICAL TRAUMA
Surgical trauma has been shown to affect immune function.
Neutrophils harvested in the postoperative period have 25% less
microbicidal activity compared with the preoperative period118
and there is a reduced T-cell proliferation and response.119
HYPOXIA
Randomized controlled trials in humans show lower SSI risk
with supplemental 80% FiO2 compared with 30% FiO2,120 and
wound infection rates decrease as tissue oxygen tension increases
to 100 mm Hg.121 This suggests that hypoxia increases the risk
of SSI and perioperative oxygen supplementation is warranted.120–123
The effects of supplemental oxygen on reduction of SSI in horses
have not been evaluated and the use of hyperbaric oxygen therapy
was not shown to have any adjunctive effect on wound healing.124
A low intraoperative PaO2 (<80 mm Hg) increases the risk of
horses developing ventral midline incisional site infection.125
Therefore, it can be assumed that supplemental oxygen may
help to avoid hypoxia at the surgery site, especially in the distal
extremities of the horse, which are more likely to be affected by
regional hypoxia because of lack of surrounding soft tissue and
muscle.
SKIN CONDITIONS/SKIN PENETRATION
Disruption of the skin at the surgical site as a result of a wound,
dermatitis, or inappropriate surgical preparation can increase
the rate of SSI.126 According to the CDC, hair should only be
removed if it interferes with surgery, because shaving results in
microscopic cuts and abrasions impairing the skin’s barrier defense
against microorganisms.50 Razors are no longer recommended
in human surgical fields and clippers should be used to remove
hair.6,23 Equine fractures that are open prior to presentation are
4.2 times more likely to become infected after surgical repair
compared with closed fractures because of the physical disruption
of the epidermis and direct inoculation.10
FOREIGN MATERIAL AND PROSTHETIC IMPLANTS
The presence of foreign material (organic debris, prosthetic device,
suture material) can alter the local immune response and result
in SSI with low levels of contamination.36 The surgical site should
be carefully débrided of contamination in cases of penetrating
wounds and lacerations. Some soils, such as montmorillonite
clay, are especially potent potentiators of infection.127 Removing
and minimizing foreign material will reduce the risk of SSI by
allowing efficient function of the immune system. Silk suture
material is 3.4 times more likely to be associated with SSI com-
pared with polyglactin 910 (Vicryl)27 and a single strand of silk
can reduce the number of S. aureus required to cause infection
by a factor of 10.26,128 Low vascularity at the site of the new
implant, adhesion of serum proteins, and formation of a fibrous
coating provides a protected environment for bacterial growth.
The implant surface has a potential effect on the development
of implant-associated infection (IAI). Stainless steel, titanium,
and titanium alloys are the most commonly used implant
materials. Stainless-steel implants have been associated with
a higher rate of infection owing to development of a fibrous,
fluid-filled capsule at the implant-bone surface that creates an
ideal medium for bacterial proliferation.129 These implants have
an increased risk of latent infection development at a mean of 70
months after the procedure and an SSI rate of 4.6% compared
with 1.3% for titanium implants.130 Titanium alloys decrease
fibroblastic adhesion properties and commercially pure titanium
implants have increased biocompatibility and increased soft tissue
adherence compared with stainless steel.129 More recently, 874
human patients receiving a variety of metallurgical implants
showed an overall infection rate of 6.1% with no difference in
infection rate between stainless steel (5.9%), titanium (6.7%),
and cobalt chrome (6%).131 Similar results were seen in another
study.132 Careful surgical technique and adherence to Halsted’s
principles (see Chapter 12) to reduce blood clots, dead space,
and fluid pockets will minimize the risk of SSI development.
Traditional teaching supports primary wound closure for clean
and clean-contaminated wounds, and delayed primary closure
for contaminated and dirty wounds due to increased risk of SSI.
Surgical Risk Factors
Surgical Procedure
Rates of SSI in commonly performed equine surgical proce-
dures range from 0% to 39%, with the lowest incidence of SSI
occurring in minimally invasive procedures (laparoscopy 0%,
arthroscopy 0.5% to 1%).93,94,133,134 Table 7-5 outlines SSI rates for
common surgical procedures. Use of laparoscopy is also associ-
ated with reduced SSI in humans compared with conventional
approaches,135,136 and initial studies on the use of laparoscopy
in horses report a similarly low risk of SSI.133,134 One study of
minimally invasive fracture repair in horses reported reduced SSI
rates, however, results were not statistically significant because of
the low study power.137 Closed reduction and internal fixation
have a 2.5 times lower risk for SSI compared with open reduc-
tion and internal fixation,10 and extensive long bone fractures
are 5.1 times more likely to develop an SSI than fractures only
involving the articular surface.138 Repair of distal phalanx fractures
have a reported SSI rate of 37.5%.139 SSI infection in acute cases
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 83

TABLE 7-5.  SSI Rates for Common Surgical Procedures

Procedure Rate of SSI Risk Factor Protective Factors
CELIOTOMY
Emergency 7.4% to 39% Reoperation, inexperienced surgeon, Lavage of linea alba, topical antibiotics
Elective 9% near-far-far-near suture pattern, to surgical site closure, incise drape
staples, polyglactin 910 for recovery, minimize surgical
VetBooks.ir

ORTHOPEDIC PROCEDURES
Clean
Clean-contaminated
Long bone fractures
Arthroscopy
duration
8.1% Procedure classification, long bone
52.6% affected, surgical duration >90
minutes, female patients
28% to 32% Open fracture configuration, surgical Minimally invasive reduction
duration >180 minutes
0.5% to 1.5% Draft breed, tibiotarsal joint

Castration-Routine 2% to 3.2% Lack of drainage, lack of antibiotics, Laparoscopic technique, recumbent,

prophylaxis, standing unsutured sutured technique
technique
Laparoscopic cryptorchid 0%
Laryngoplasty 0% to 4% Laryngotomy, draft breed

was associated with early disruption of the hoof plug in the
immediate postoperative period and delayed infections were
presumed to be a result of ascending infection through disrupted
laminae. Emergency surgical procedures are at increased risk of
SSI development compared with elective procedures140,141 and
this is reflected in equine gastrointestinal surgery. Incisional site
infection is reported to occur in up to 39% of equids undergo-
ing emergency ventral midline celiotomy compared with a 9%
incisional infection rate in elective celiotomies.95 Stabilization of
the patient to improve physical status reduces SSI in humans142
and is likely to be associated with a reduced risk in horses. A
score greater than 2 in the American Society of Anesthesiologists
(ASA) Physical Status Classification System was significantly associ-
ated with SSI development.143 Therefore, in situations where a
concurrent infectious or inflammatory process is present, elective
surgical procedures should be delayed to improve outcome.143,144
PATIENT AND SURGEON PREPARATION
Basic grooming of the equine patient to reduce debris can reduce
bacterial contamination. It is recommended to pick out the feet;
clean the coat, mane, and tail; and cover the feet and tail prior
to entering the OR.144 Initial patient preparation should be
performed in a designated area, separate to the OR to reduce
potential contaminants. Preoperative hair removal is often
performed to reduce anesthetic time and is acceptable only when
removal occurs immediately before surgery (see earlier in the
chapter and Chapter 10). Antisepsis of the surgical site prior to
initiation of surgery is a critical step in preventing SSI. Preoperative
bathing with a chlorhexidine gluconate, povidone-iodine, or
triclocarban medicated soap decreases the amount of endogenous
skin microflora,145,146 but in clinical trials this has not been shown
to reduce risk in SSI development. Trimming and soaking the
hoof prior to surgery is recommended to reduce bacterial con-
tamination,147 but even with earlier preparation and povidone-
iodine soaking, hoof samples still contained more than 105
bacteria per gram of tissue. There is a high incidence of SSI
associated with distal phalanx fracture repair;139 however, a
significant number are delayed infections likely associated with
ascending infection from the hoof wall to the screw head and
not with surgical aseptic technique.
To date, no single antiseptic has been identified as the most
effective at preventing SSI.148 Many randomized trials have
compared chlorhexidine- to iodine-based antiseptics, unfortu-
nately most are underpowered, making it difficult to draw a
decisive conclusion.149–152 Alcohol-based solutions have a rapid
bactericidal effect but limited persistent antimicrobial effect.
Addition of chlorhexidine- or iodine-based solutions prolongs
bactericidal activity in alcohol-based solutions. Overall, there is
evidence that alcohol-based preparations (Avagard, Sterillium,
Manorapid) are more effective than aqueous preparations.151,153,154
One standard aseptic agent is not likely to be optimal for every
case and surgical procedure. Therefore, the surgeon should select
the most appropriate agent based on the potential infective
microorganism and the action of the antiseptic agent. The use
of various scrub types and methods is covered extensively in
Chapter 10.
SURGICAL ATTIRE
Scrubs, surgical masks, caps, and shoe covers are traditionally
worn surgical attire. The Association of periOperative Registered
Nurses (AORN) guidelines dictate that clean, facility-laundered
scrubs should be worn, and these should be changed daily or
when they become soiled.155,156 There are no data to support
increased SSI with exposure of hair and skin, but it is documented
that bacterial loads in laminar flow theaters can be traced to the
skin of exposed ears.157 A sterile barrier gown should be worn in
combination with the use of disposable impervious drapes where
possible, although the effects on SSI are largely unknown.23,158
The use of impervious drapes on the distal limbs of dogs reduced
bacterial contamination compared with traditional techniques,159
and it is recommended that any method to reduce contamination
in high-risk procedures (e.g., equine orthopedic surgery) should
 84 SECTION I  Surgical Biology
be actively utilized. Surgical gloves contain and can easily develop
a large number of defects, with one glove becoming defective in
26.2% of small animal surgical procedures.160 Skin pathogens
can be transmitted from the surgeon to the patient, but there
is no evidence to support increased risk of SSI. The practice
of double gloving reduces the risk of holes in the inner glove,
and routine double gloving is now a recommended guideline
VetBooks.ir
to reduce SSI in human surgery.57,161 Surgical attire and draping
techniques are extensively covered in Chapter 10.
SURGICAL TECHNIQUE AND DURATION OF SURGERY
Adherence to Halsted’s principles and focus on careful tissue
handling, appropriate débridement of devitalized tissue, effective
hemostasis, reduction of dead space, and appropriate use of
drains and suture materials are essential to minimize SSI (see
Chapter 12).23,144,162,163 Regardless of the host’s immune status,
a poor surgical technique will result in increased SSI. Careful
attention to surgical detail and strict adherence to aseptic tech-
nique have a direct effect on reducing surgical site contamination.
The odds of ventral midline celiotomy SSI increased twofold
when less experienced surgeons (first-year or second-year resident)
closed the abdomen.164 Surgical débridement and copious lavage,
combined with appropriate selection and use of suture materials,
drains, and implants, will decrease SSI incidence.144,162,164 Skin
incisions can be made using conventional scalpels, lasers, or
electrosurgical devices. There are numerous electrosurgical devices
on the market including monopolar and bipolar cautery, harmonic
scalpel, and LigaSure units.165–168 Although lasers and electrosurgi-
cal devices have the benefit of improved hemostasis, there is a
resultant collateral tissue damage and eschar formation.169,170
Both the LigaSure and harmonic scalpel are associated with
reduced thermal damage and are less likely to produce necrotic
tissue, which can serve as a nidus for infection. Skin incisions
made using steel scalpels heal more rapidly than incisions made
with other devices, therefore steel scalpels should be used in
every possible circumstance.165,167,170,171
Increased surgical duration results in increased tissue trauma
and reduced tissue perfusion, and is associated with SSI in
horses.10,95,98,125,138,162,172 Infection rates of clean wounds can double
with every hour of surgery.173 Postoperative incisional complica-
tions are more likely in abdominal surgeries exceeding 2 hours,
with reported SSI incidence of up to 47%.95,125,172 Equine
orthopedic procedures (e.g., long bone fracture and surgical
arthrodesis) also have increased risk of SSI associated with
increased surgical time10 and procedures greater than 90 minutes
are 3.6 times more likely to develop SSI.138
SUTURE MATERIALS AND SURGICAL IMPLANTS
The presence of any foreign material or prosthetic implant
increases the likelihood of SSI. Suture pattern and type have
been shown to affect SSI. Near-far-far-near suture patterns have
increased rates of SSI compared with simple interrupted suture
patterns.174 The use of polyglactin 910 to close the linea alba
and polyglycolic acid to close the subcutaneous space have
been associated with an increased risk of SSI development.125,175
Multifilament, nonabsorbable suture materials, such as silk, are
prone to contamination with multidrug-resistant bacteria and
can promote SSI development.125,176 There are several studies to
support the use of triclosan antibiotic-coated suture for prevention
of SSI.177–180 Therefore, it is currently recommended for wound
closure in clean and clean-contaminated human abdominal
surgeries.161 Paradoxically, use of triclosan-coated polyglactin
910 for equine linea alba181 or subcutaneous182 closure had no
beneficial effect on incisional complication rate and was associated
with increased incisional edema.181 There was no difference in
the rate of SSIs in two-layer, ventral midline celiotomy closure
(linea alba and skin), versus conventional three-layer closure
techniques.183 However, a modified two-layer closure (linea alba
and subcuticular pattern) resulted in a significantly lower incidence
of postoperative incisional infection.184 Use of surgical-steel staples
for skin closure almost quadruples the risk of SSI development164
and the incidence of incisional drainage is 1.3 times greater
than when using a subcuticular pattern alone.184 Some studies
have shown reduced SSI associated with cyanoacrylate tissue
glue compared with suture or staple closure,185,186 however a
large-scale review of the current literature failed to demonstrate a
difference between the various closure methods.187 SSI associated
with orthopedic implants and subsequent biofilm development
necessitating implant removal is a devastating complication
for equine orthopedic patients and surgeons. New, emerging
technologies modifying implant coatings to reduce or prevent
bacterial adherence are currently being evaluated,86,88 and their
introduction to the veterinary market will likely play a large
role in SSI reduction.
TOPICAL ANTIMICROBIAL THERAPY
Available intraoperative therapies to potentially reduce SSI
include the use of antimicrobial irrigation fluids, topical antimi-
crobial agents, antimicrobial-impregnated dressings, and wound
sealants.188–190 A metaanalysis on the use of topical vancomycin
to reduce SSI in spine surgery showed a reduction in SSI risk.191
One study reported a 26.4% reduction in celiotomy incisional
complications with topical application of benzyl penicillins.21
While topical antimicrobial use is supported in small studies,
a metaanalysis of topical antimicrobial therapy for prevention
of SSI found insufficient evidence for their use in clean and
contaminated procedures.192 Incisional irrigation allows for
removal of superficial and deep incisional contamination with
reduction of the bioburden, and has been highly effective
for reduction in SSI risk.193,194 The efficacy of irrigation with
vancomycin and polymyxin was evaluated in 1990 patients
receiving total joint arthroplasty and no patient developed a
primary SSI.193 For this reason, tissues should be regularly rinsed
with antibiotic-containing sterile fluids. Drugs not commonly
used systemically are most often chosen for the lavage solutions
in equine orthopedic surgeries (e.g., bacitracin, polymyxin B,
neomycin). Incisional lavage with sterile saline prior to skin
closure has been shown to have a protective effect against SSI
development in exploratory celiotomies164 and a pulsed lavage
technique was reported to be significantly more effective for
reducing bacterial contaminants compared with low-pressure bulb
syringe use.195
BANDAGES AND DRAINS
Despite efforts to maintain a clean surgical site, horses are returned
to dusty and dirty housing environments immediately postop-
eratively. Incisional contamination during anesthetic recovery154
can be a risk factor for SSI development and application of an
incise drape (Steri-Drape) for recovery reduced the risk significantly
in colic cases.174 In another report of horses undergoing abdominal
surgery, a sterile antiadhesive combined with an absorbent wound
dressing applied as a stent bandage and a protective adhesive
drape (Opsite) had an incisional site infection rate of 2.7%
compared with a 21.8% infection rate in those with no stent.196
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 85
Conversely, a previously mentioned study showed an increased
rate of incisional complication with stent application for 3 days
postoperatively.21 A potential difference is the addition of an
Opsite dressing for recovery only, which may have prevented
additional stent contamination during recovery. Horses with an
abdominal bandage applied postoperatively had a reduced risk
in the incidence and severity of incisional complications.197
VetBooks.ir
Conversely, occurrence of incisional complications in paramedian
celiotomies increased significantly when abdominal bandages
were applied postoperatively.198 Postoperative abdominal bandage
use is controversial and there is evidence to show that they can
become a source of contamination if soiled or if they remain
in place for too long.174,199 Therefore the beneficial effects of
bandage application on SSIs are unclear based on current studies.
There are mixed results in the literature on the use of silver-based
dressings, with insufficient evidence to support their use rou-
tinely.200 Several small studies show a decreased risk of SSI in
some orthopedic and spinal procedures, which may be extrapo-
lated for use in the horse with increased risk of SSI.200 If it is
necessary to use a drain, it is important to place the exit site at
a distance from the primary surgical incision. The use of a closed
suction drain is preferable and early drain removal is recom-
mended to reduce the risk of ascending infection.23 The use of
a negative pressure–wound therapy system (see Chapter 17) in
the postoperative period to decrease SSI has been supported in
the literature, although these studies had a small sample size
and were surgical site specific (e.g., ventral hernia repair, vascular
groin incisions).201–203
NOSOCOMIAL INFECTION
A surveillance study of equine critical care patients found that
at least one nosocomial event (surgical site infection, catheter
site inflammation, fever of unknown origin, gastrointestinal and
respiratory disorders) occurred in almost 20% of admissions.204
The financial burden associated with nosocomial outbreaks (e.g.,
salmonellosis) has led to the development of infection control
programs (ICP) in most veterinary teaching hospitals and large
private practices.205
The consequences of nosocomial salmonellosis are severe
and result in increased patient morbidity and mortality, loss of
case load, loss of revenue, and incurrence of high disinfection
costs.206,207 Risk factors identified for Salmonella infection in
hospitalized horses include hospital admission for colic,208,209
nasogastric intubation, and treatment with antimicrobials. Horses
undergoing exploratory celiotomy can be 2 to 8 times more
likely to develop nosocomial Salmonella infections,210,211 and
clinical indicators associated with acute salmonellosis include
a fever greater than 103°F, abnormal leukocyte counts, or acute
colitis. Horses presenting with acute colic that become lethargic
and inappetent are almost 17 times more likely to shed Salmonella,
and a number of these horses develop reflux alone in the absence
of diarrhea.211
Clostridium difficile can be found in the gastrointestinal tract
of healthy foals and horses. Stress of hospitalization, concurrent
gastrointestinal disease, and antimicrobial therapy are recognized
risk factors that allow C. difficile to overwhelm the microbiome
and cause acute enteric disease.212–214 Pathogenic environmental
reservoirs can develop as clostridial spores that resist disinfection
and can persist in cracks and pores within the floors.214,215 C.
difficile has been isolated from 3% to 17% of veterinary hospital
samples.213,216–218 Methods to reduce possible outbreaks of C.
difficile include antimicrobial restriction (especially macrolides
and lincosamides), reduction of environmental spores, isolation
of contagious horses, and conduction of routine surveillance for
pathogen detection.
Catheter site inflammation and infection occurs in approxi-
mately 9% of horses admitted for treatment of gastrointestinal
disease, and commonly isolated pathogens include Staphylococcus,
Corynebacterium, Bacillus, Enterobacter, and Pseudomonas spp.205
Catheter-related complications are higher in instances of pro-
longed catheterization (>3.5 days)219 and in foals receiving
parenteral nutrition.220
MRSA infections have been reported in equine clinics in North
America,221-223 Europe,224,225 and Australia,226 however currently
the infection rate is low.227 Emerging MRSA strains in the equine
population can be of human hospital origin or evolutionary
from livestock strains.228 Nasal colonization is reportedly between
9.4% and 22.2% in veterinarians and veterinary personnel,228
and although MRSA colonization is frequent, human infection
is infrequently reported.
PREVENTION AND MANAGEMENT OF
SURGICAL SITE INFECTION
SSI can be one of the most catastrophic and costly complications
of surgery, and accounts for 20% of all hospital-acquired infections
(HAI). On average, SSI extends the length of hospital stay by 9.7
days and increases the cost by $10,000 to $43,000/human patient/
SSI.161 Although the majority of patients will recover without
long-term effects, it is reported that up to 77% of mortalities can
be attributed to the development of SSI.6,229,230 Approximately
60% of SSIs are estimated to be preventable complications.
Consequently, SSI has become a target for improvement in
prevention efforts.6
In horses undergoing complicated orthopedic procedures, SSI
significantly increased the length of hospital stay by 32.1 days
and increased the duration of antimicrobial therapy by 17.3
days.10 The financial cost of SSI in horses has not been determined.
Surgeons must be aware of the risk factors of SSI and be vigilant
in its diagnosis, as early interventions will improve outcomes.
It is more cost effective to investigate suspected infections than
to wait for overwhelming sepsis to occur before commencing
aggressive prolonged therapies.
Diagnosis
Clinical Signs
Clinical diagnosis of an SSI in the early stages can be challeng-
ing and often there are several mild, nonspecific signs present.
Potential clinical indicators include, but are not limited to,
the development of a low-grade fever (>38.6°C or >101.5°F),
swelling or edema of the surgical site that can be persistent or
recurring, pain on palpation of the surgical site, reduced appetite,
and development of drainage. Development of a fever in the
immediate postoperative period of horses undergoing explor-
atory laparotomy was not uniformly indicative of an infectious
process,20 and therefore antimicrobial therapy should not be
initiated on the basis of a fever alone. However, the presence
of a persistent mild elevation in rectal temperature in horses
receiving nonsteroidal antiinflammatory drugs (NSAIDs) should
be considered an important indicator of SSI when it cannot be
attributed to another cause. Incisional drainage is more likely
to occur 6 to 10 days postoperatively and at this point SSI has
 86 SECTION I  Surgical Biology
already been established.182 Persistent swelling in combination
with painful palpation should be thoroughly investigated with
radiographs and ultrasonography for the presence of subcutaneous
fluid. Horses maintained in distal limb casts should be evaluated
daily for comfort, degree of heat, presence of drainage, and odor.
The horse should be asked to stand on the cast by picking up
the contralateral limb and should be walked briefly to assess
VetBooks.ir
comfort levels. Any change in the degree of comfort is suspi-
cious of a developing SSI or cast sore. The degree of lameness
present in postoperative orthopedic patients should be carefully
monitored as increasing lameness can correlate with the develop-
ment of SSI. Horses postarthrodesis or fracture repair should be
comfortable within 36 to 48 hours of surgery and fully weight
bearing if the primary repair was considered stable. Suspicion
of SSI should be present if they remain lame despite NSAID
therapy.
Clinical Pathology
Complete blood counts are unreliable in the horse for specifically
identifying an infection. Both neutrophil and lymphocyte counts
can be normal in horses with known infectious processes.231
Concentrations of acute phase proteins (APP) such as serum
amyloid A (SAA), haptoglobin (Hp), and fibrinogen increase in
plasma of horses in response to inflammation232–237 and although
they are not specific for SSI, they can be used to detect and
monitor inflammation associated with infection. Fibrinogen is
synthesized by the liver and has a wide reference interval (200
to 400 mg/dL) that peaks within 7 to 10 days of injury. A plasma
fibrinogen of 900 mg/dL has been a consistent and reliable
indicator of osteomyelitis.238 Plasma clearance occurs over time,
making the use of fibrinogen to determine treatment efficacy
difficult. SAA concentrations range from 0.5 to 20 mg/L. In
contrast to fibrinogen, this response begins within 6 to 8 hours
of the stimulus and peaks at 36 to 48 hours. Serum clearance
is rapid and concentration will decrease to baseline within 1 to
2 weeks in the absence of new stimuli, making it a good indicator
of real-time inflammation.239 SAA concentration analysis may
be a more reliable indicator of inflammation and infection, and
more reliable in determining response to treatment compared
with total WBC count or plasma fibrinogen.240,241 There is no
association between SAA concentration at admission and survival
outcome.242,243 Serial analysis of APP is more beneficial than
analysis of a single time point, and an increasing SAA concentra-
tion over time is significantly associated with development of
complications or to result in euthanasia.243
Cytologic evaluation of fluid samples from the surgical site,
adjacent synovial site, or the abdominal or pleural space can
be useful indicators of SSI. Normal synovial fluid has less than
1000 cells/µL, less than 10% neutrophils, and a total protein
of less than 2 g/dL.244 Fluid color in septic joints may range
from normal yellow to dark orange or red and is usually turbid
and nonviscous. A nucleated cell count (NCC) >20,000 cells/µL
should be suspected as infectious, especially when combined
with an elevation in total protein >4 g/dL. Cytologic evaluation
with 90% degenerate neutrophils, with or without the presence
of intracellular bacteria, is specific for infection.244 The lack
of such degenerate changes does not rule out septic synovitis.
A NCC of greater than 75,000 cells/µL is pathognomonic for
infection.245 Lower cell counts do not preclude infection and
the presence of fibrin within joints can produce false readings
as the cells aggregate within the fibrin clot.246 SAA will increase
in serum and synovial fluid in cases of infectious and noninfec-
tious arthritis247,248; however, a more significant increase (1000
to 2000 mg/L) will be seen in horses with acute infectious
synovitis compared with noninfectious synovitis.248,249 Synovial
fluid analysis will be altered because of inflammation associ-
ated with repeat lavage and repeated intraarticular medications.
Intraarticular total protein (TP) concentrations have been shown
to increase within 4 hours of arthrocentesis and values can
remain elevated with repeated arthrocentesis.249 Unlike total
NCC and TP, SAA is unaffected by repeated arthrocentesis249
or repeated intraarticular medication with aminoglycosides.250
Repeated through-and-through lavage251 and endoscopic lavage252
had no effect on synovial SAA concentration, but this has yet
to be evaluated in cases of septic arthritis. Another nonspecific
marker of synovial infection is synovial fluid lactate concentra-
tion. Synovial fluid lactate is normally less than 3.9 mmol/L
and will increase to greater than 4.9 mmol/L during infec-
tion.253 Monitoring trends of lactate concentrations in the
synovial fluid may be more useful than relying on the absolute
numbers.
Evaluation of peritoneal fluid pH, glucose concentration, and
lactate can be used to assess postoperative septic peritonitis. The
NCC and TP of peritoneal fluid increase in response to abdominal
surgery, castration, and parturition, and their use in diagnosis of
a septic process is limited.254–257 A difference in peritoneal and
peripheral serum glucose of greater than 50 mg/dL has been
shown to be indicative of septic peritonitis,258 especially when
combined with a peritoneal fluid pH of less than 7.3 and a glucose
concentration of less than 30 mg/dL. SAA elevations within
peritoneal fluid is a nonspecific indicator of a disease process
in the abdomen (simple obstruction, strangulating obstruction,
septic inflammation).259 Peritoneal D-lactate concentrations are
a useful marker in people for septic peritonitis260,261 and are
increased in horses with septic peritonitis and gastrointestinal
rupture. However, larger studies are required to determine its
use as a diagnostic tool in horses.262
Microbiology
Microbial culture is regarded as the gold standard for diagnosis
of SSI, and both culture and susceptibility testing should be
submitted prior to initiating antimicrobial therapy. Obtain-
ing a positive culture is dependent on the method of culture,
the number and virulence of the organism, and the defense
mechanism of the organism. It is important to submit samples
for fungal culture, especially if there is a preexisting wound
or history of intraarticular medication. There are a variety of
culture techniques currently in use, including tissue sampling,
swab culture, fluid aspiration, and implant sonication. It has
been proven that a negative culture can be attributed to the
ability of bacteria to form matrix-enclosed biofilms, which allows
evasion of traditional culture methods and therefore a negative
culture does not confirm the absence of SSI.39,263 Swab culture
has largely fallen out of favor in human medicine because of
increased risks of contamination, decreased volume for culture,
and potential for inhibition of growth.264 One study found that
tissue culture had increased specificity (93%) and sensitivity
(98%), compared with swab culture (70% specificity, 89%
sensitivity), and recommended against the use of swab culture
over tissue culture or percutaneous fluid aspiration.264 Positive
culture from synovial fluid ranges from 64% to 89%244,245,265–267
and use of a blood culture medium is associated with improved
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 87
results of bacterial culture (79%) when compared with other
methods.268,269 Typical blood culture vials (Septi-Chek) require 8
to 10 mL of fluid and an effort should be made to obtain as much
fluid as possible to increase chances of a positive culture. There
is no advantage to obtaining synovial membrane for culture, as
bacterial isolation is similar or higher for synovial fluid.265,269 If
intraarticular antimicrobials have already been administered, it is
VetBooks.ir
still recommended to obtain a sample for culture and sensitivity
even though the chance of a positive culture is decreased.245
Biochemical markers, for example, C-reactive protein (CRP) and
erythrocyte sedimentation rate (ESR), have been evaluated in
synovial fluid and are found to have a high sensitivity to detect
infection but a low specificity, especially when additional causes
of inflammation are present.270 Use of reverse transcription–
quantitative polymerase chain reaction (RT-PCR) to detect
bacterial 16S ribosomal RNA has a high sensitivity of bacterial
detection and has shown promise in cases of false-negative culture
results.271,272 Positive bacterial detection by PCR has been reported
in 100% of cultured equine synovial fluid samples, and increased
rates of bacterial isolation may be associated with greater preva-
lence of false-positive results.273
Implant sonication in cases where implant removal is necessary
serves to dislodge the adherent biofilm and increase the diagnostic
yield of culture.274 Briefly, implants are placed in sterile sealed
containers partially filled with either Ringer solution or Tween.
They are subsequently sonicated in a water bath for 5 to 10
minutes and the fluid is gram stained and cultured. Sonicate is
highly sensitive for diagnosis of SSI; however, a negative result
does not rule out infection. Evaluation of intraoperative culture
results as a predictor for development of postoperative incisional
infection in exploratory celiotomy did not provide evidence to
support routine use,275 similar to findings in elective hip and
knee arthroplasty in humans.276
Imaging Techniques
Radiographic changes can be subtle or absent in the early course
of SSI and often underestimate the severity of disease. Infection
must cause greater than 50% bone demineralization before bone
lysis is seen radiographically, and detection of this amount of
bone loss may take up to 21 days.277 Computed tomography
(CT) is a superior diagnostic modality in these cases as it provides
excellent sensitivity and can accurately define the extent of the
lesions through multiplanar reconstruction.278 The addition of
contrast material can be useful to delineate abscesses within
necrotic tissue. Magnetic resonance imaging (MRI) has been
successfully utilized to detect osteomyelitis in a foal279 and enables
improved imaging of synovial proliferation, cartilage lesions,
and changes in periarticular soft tissues. A combination of
T1-weighted, T2-weighted, and short tau inversion recovery
sequences is recommended for suspected cases of SSI.280 MRI
provides excellent definition of the medullary cavity. Although
it facilitates early detection of intramedullary lysis, detection of
cortical bone involvement is limited. MRI has very limited use
for imaging bones with metal implants. Both CT and MRI have
the disadvantage of additional cost, but this may be negligible
when compared with repeated radiographic studies and a delay
in onset of treatment. If standing units for CT and MRI are
unavailable, the additional risk and cost of general anesthesia
should also be considered.
Ultrasonography can identify fluid pockets that may be sampled
for culture and susceptibility, allowing more rapid diagnosis of
the causative agent(s) of SSI. It is also useful to help guide
synoviocentesis, and to detect effusion and hypercellularity in
anatomic locations that are more difficult to palpate (e.g., coxo-
femoral, scapulohumeral joints, bicipital bursa).281 Typical
sonographic findings indicative of a septic process include marked
effusion with hyperechoic particles, cellular-appearing fluid, and
synovial thickening.282 The use of ultrasonography to detect
osteomyelitis has been evaluated,283,284 but its value is limited
to the surface of any infected bone.
Nuclear scintigraphy, a useful whole-body screening tool, is
excellent for localization of lesions within the axial and proximal
appendicular skeleton. Limitations of its use include a lack of
differentiation between septic osteomyelitis, fracture, and normal
growth plate modelling. When used in combination with other
imaging modalities, it may help identify or rule out a septic
process. It is important to note that decreased uptake (photopenia)
rather than increased uptake may be an indicator of septic
osteitis.285 99m Tc-hexamethylpropylene amine oxime (HMPAO)
labeled leukocytes have successfully diagnosed orthopedic infec-
tion in 85% of adult horses.286
Pathogenic Bacteria Associated With Equine
Surgical Site Infection
To select appropriate prophylactic and therapeutic antimicrobial
therapy, clinicians must determine the likely identity of the
pathogen, have knowledge of their typical in vitro susceptibility
pattern, and be aware of the reported clinical responses. Monitor-
ing and surveillance of commonly isolated pathogens at your
surgical facility will provide an evidence-based approach to
antimicrobial prophylaxis. SSI surveillance and surgeon feedback
has reportedly reduced the rate of SSI for numerous procedure
types.287,288 The most common musculoskeletal pathogen in
humans and animals is Staphylococcus aureus, which causes between
19% and 21% of equine orthopedic infections and is associated
with up to 60% of equine cellulitis cases.10,162,289 S. aureus is also
the most common isolate (34.3%–52%) in postoperative synovial
structure infections,267,289 followed by hemolytic Staphylococcus
spp. (22%), and gram-negative bacteria (25%).267 Positive cultures
from joints of septic foals revealed gram-negative bacteria in
62.5% and gram-positive bacteria in 37.5% of cases.266 Escherichia
coli, Actinobacillus spp., and Klebsiella spp. are the most commonly
isolated pathogens in neonates.266,290 SSI in long bone fracture
repair and arthrodesis are typically polymicrobial in origin
(19%–60%),10,245,291 while the remainder of monomicrobial
isolates are gram positive or gram negative in equal measure.10
Enterobacter cloacae is the most commonly isolated gram-negative
organism (24.5%) that is similar to other musculoskeletal infec-
tion rates (23%–28%).162,292 Other bacteria associated with
orthopedic SSI include Pseudomonas, Streptococcus spp., and
anerobes.10,245,291 Penetrating wounds are likely to be infected by
a mixed bacterial population, including Staphylococcus, Pseudo-
monas, Proteus, Enterobacteriaceae, yeast, and other fungi,245 and
culture of foot wounds most commonly isolate Enterobacteriaceae
or Streptococcus zooepidemicus.293–295 Deep punctures within the
foot are excellent sites for anaerobic growth.293 Gastrointestinal,
urogenital, and respiratory tract SSIs are usually associated with
a mixed bacterial infection and a representative culture and
sensitivity is important for appropriate antimicrobial selection.
Postoperative peritonitis is associated with Streptococci, Entero-
bacteriaceae, Actinobacillus spp., and anaerobes,296,297 which is
reflective of the equine endogenous flora (Table 7-6).
 88 SECTION I  Surgical Biology

TABLE 7-6.  Common Bacterial Isolates in the Horse antimicrobial therapy. In addition to reducing systemic toxicity,
local dosing is more economically feasible. Subsequently, a wider
Disease Process Bacterial Isolates variety of antimicrobials (carbapenems, vancomycin) are available
Orthopedic surgery Enterobacteriaceae, to combat resistant infections.
Staphylococcus, Streptococcus,
Pseudomonas
Antimicrobial Prophylaxis Against
Cellulitis Staphylococcus, Streptococcus
VetBooks.ir

Surgical Site Infection

Chronic wounds Pseudomonas, Staphylococcus, Burke’s 1961 demonstration that administration of antibiotics
Serratia, Enterococcus, prior to surgical incision significantly reduced surgical site infec-
Providencia tion is the foundation of antimicrobial prophylaxis. However,
Enterocolitis Salmonella, Clostridium routine prophylactic antimicrobial use remains controversial in
Iatrogenic septic arthritis Staphylococcus aureus both human and veterinary medicine.31,303–305 Antimicrobials
should be selected judiciously, should achieve appropriate
Wounds Streptococcus, Staphylococcus,
minimum inhibitory concentrations (MICs) at the site of infection,
Enterobacteriaceae,
and be active against likely pathogens. Optimal antimicrobial
Pseudomonas, and anaerobes
usage is essential for reducing SSI and reducing the risk of
Peritonitis after Streptococcus, developing antimicrobial resistance.
abdominal surgery Enterobacteriaceae,
Actinobacillus, anaerobes
Penetrating wounds to Enterobacteriaceae, anaerobes Antibiotic Classification
synovial structures Antibiotics can be classified by their mechanism of action or
Septic physitis/arthritis Escherichia coli, Rhodococcus according to their bactericidal or bacteriostatic mechanism of
(foals) equi action.306 They are further categorized by their pharmacokinetics
as being either concentration or time dependent. The efficacy
Paranasal sinus and Streptococcus equi ssp. equi,
of time-dependent antimicrobials (β-lactams, trimethoprim
guttural pouch Streptococcus zooepidermicus,
sulphonamides, macrolides, tetracyclines, and chloramphenicol)
Aspergillus, Cryptococcus
is dependent on the duration tissue drug concentration exceeds
the MIC of the pathogen.307 The rate of killing is dictated by the
length of time bacteria are exposed to the antimicrobial concentra-
tion above MIC. Increasing the concentration of a time-dependent
drug above MIC does not increase its rate of killing.31 Such drugs
therefore may require frequent administration for optimal effects.
Treatment of Surgical Site Infection On the other hand, the efficacy of concentration-dependent
A prompt diagnosis of SSI is vital to achieve the best possible antimicrobials (aminoglycosides, fluoroquinolones, and metro-
outcome. Once the SSI has been identified, a treatment course nidazole) increases as the drug concentration rises above MIC
must be determined according to the surgical location, the for the pathogen and it is not necessary to maintain drug con-
procedure performed, and whether implants were used. Initial centrations above MIC between doses. A ratio of 10:1 or 12:1
treatment includes (1) establishing drainage of infected tissue (peak concentration:MIC) is optimum for concentration-
and abscess cavities; (2) débridement of infected and necrotic dependent antimicrobial effect.31 Optimal drug dose and dose
tissue; and (3) initiation of appropriate systemic antimicrobial interval can be confirmed by monitoring the peak and trough
therapy and targeted local therapy based on culture and sensitivity drug concentrations. Serum samples for peak drug concentration
results.162,172,298,299 Studies evaluating human superficial soft tissue are obtained 60 minutes after intravenous drug administration
injuries have found limited benefit of prophylactic antimicrobial and 60 to 90 minutes after intramuscular drug administration.
use,300–302 rather, meticulous débridement was critical for favorable Samples for trough concentrations are collected 30 minutes prior
outcomes. to the next dose administration. A peak MIC ratio of 8 to 10 or
Biofilm was first recognized as an important cause of implant- >10 increases the odds of a positive response to aminoglycosides
associated infection in the early 1990s. Typically, these infections by 6.49% to 8.41%.308 Dosage can be increased if the desired
require extensive local tissue débridement and prolonged local peak concentration is not achieved, and dosing intervals must
and systemic antimicrobial therapy. Despite treatment, implant be increased if the trough concentration is not suitably low as
removal is frequently required to fully eliminate the problem. trough concentrations generally correspond to toxicity. Mainte-
Rapid adhesion of serum proteins to implanted prosthetic material nance of trough levels of amikacin <1 µg/mL significantly reduce
creates the ideal environment for bacterial growth. A complex the incidence of nephrotoxicity.309
extracellular matrix within biofilm protects bacteria from the
host immune response and antimicrobial therapy.10,38,298 Therefore,
an important consideration in treatment is timing of implant Prophylactic Antibiotic Use
removal. There has been a marked improvement in outcome of Improvement in the rate of SSI and subsequent improvement
SSIs over the past 10 years, primarily as a result of improvement in outcome has been associated with the use of prophylactic
in and increased utilization of local antimicrobial therapies. antibiotic therapy.300 Prophylactic antibiotics are administered
Local antimicrobial therapies deliver a high concentration of to reduce the bacterial load at the surgical site and therefore
antimicrobial to the region of interest while concurrently minimiz- decrease the incidence of SSI. To choose the most appropriate
ing the risk of toxic side effects associated with prolonged systemic antimicrobial agent, several key factors must be considered.
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 89
Clinicians must determine the likely identity of the infecting
microorganism(s), their typical in vitro sensitivity pattern or the
reported clinical response of previous equine patients, the
pharmacokinetics of the antimicrobial (bioavailability, tissue
distribution, and rate of elimination), the pharmacodynamics
of the antimicrobial, and the cost and safety of its use. Antimi-
crobials should only be used in cases where the development
VetBooks.ir
of an SSI has previously resulted in a catastrophic outcome and
in those surgical procedures that are at high risk of developing
SSI.23,144 Once it is decided that antimicrobial prophylaxis is
indicated, the most appropriate drug, dosing regimen, and
duration of use should be determined. Timing of administration
to achieve effective tissue levels at the time of surgery is a factor
that is often overlooked. Correct timing will increase the con-
centration and duration of the antimicrobial at the surgical site
when it is most likely to be inoculated. Underdosing a drug
should always be avoided not only because it is ineffective but
also because the practice encourages antimicrobial drug resistance.
Additional intraoperative doses of antibiotics are recommended
if the surgical procedure exceeds 1 to 2 times the half-life of the
antibiotic. Hospitals that are compliant with appropriate anti-
microbial prophylaxis guidelines in regard to timing and duration
of administration have decreased rates of SSI. Operating room
“checklists” can be valuable to ensure correct timing of antimi-
crobial drugs. A metaanalysis of 34,133 procedures at 56 hospitals
showed the impact of improved antimicrobial prophylaxis
methods with a 27% reduction in SSI.310
SELECTION OF PROPHYLACTIC ANTIMICROBIALS
Prophylactic antibiotic use is recommended when the occurrence
of infection is greater than 5% without their use, or when the
development of an SSI would be life threatening.31 Therefore, pro-
phylactic antimicrobial therapy is indicated in clean-contaminated
and contaminated procedures. Current infection rates in equine
arthroscopy are between 0.5% and 1%,93,94,311 and therefore the
use of antibiotics is not clearly indicated according to current
guidelines. Clean orthopedic procedures have a reported SSI
rate of 8% and clean-contaminated procedures have a rate of
52% to 57%, warranting prophylactic antimicrobial use.10,11,138
As mentioned earlier, critically ill patients are predisposed to
SSI. Horses undergoing emergency celiotomy had an SSI of
39% compared with an SSI of 7% in elective celiotomy cases,
suggesting antimicrobial prophylaxis is indicated.95 Addition-
ally, fluid therapy and endotoxemia have been shown to affect
gentamicin pharmacokinetics,312 therefore it is important that these
critically ill patients receive appropriate doses. In the authors’
experience, a gentamicin dose of 6.6 mg/kg IV does not result in
peak concentrations 10 times the MIC of common pathogens,
so the current hospital dose used is 8.8 mg/kg IV. Antimicrobial
use can be considered directly therapeutic in dirty or infected
surgical wounds and empiric broad-spectrum drugs should be
used initially, followed by an appropriate selection based on
culture and sensitivity. Recognition that contamination is not
infection is an important concept and prolonged antimicrobial
therapy is only warranted in therapeutic circumstances.313
TIMING AND DURATION OF ANTIBIOTIC ADMINISTRATION
The Surgical Care Improvement Project makes recommendations
on antibiotic selection, redosing, and discontinuation of pro-
phylactic antimicrobial therapy.300,314 Antibiotic selection should
be based on the type of surgery, the likelihood of infection, and
the potential risk factors. The prophylactic regimen should be
effective against the most likely infective organisms. A large
multicenter human study315 showed that an overall incidence of
SSI was 4.7% when a cephalosporin was administered more
than 120 minutes prior to a surgical incision. The SSI incidence
dropped to 1.6% when the cephalosporin was administered 0
to 30 minutes prior to incision. Therefore, current reports and
guidelines recommend antibiotics to be administered within 1
hour of surgical incision.300,314,316–319 The risk of SSI increases
from 6.3% to 28% for procedures lasting longer than 2 hours.320
Therefore additional intraoperative doses of antibiotics should
be administered during extended procedures. Failure to redose
antibiotic prophylaxis during long surgeries increased the risk
of SSI 4.51 times.321 A general rule is that antibiotics should be
redosed at one to two times the half-life of the drug from the
time the preoperative dose is administered.317,322–325 Reports on
hospital compliance with these guidelines have shown improve-
ment from 56% in 2005323 to 73% in 2013.326 As with initiation
of antimicrobials, the practice of a checklist in the OR can help
ensure correct dosing of prophylactic drugs.
In an equine retrospective study on the use of perioperative
antimicrobials in arthroscopic surgery, only 6.3% of horses
received penicillin within the first hour of surgery, and on
average, antibiotic administration occurred 142 minutes prior
to surgery.305 A more recent retrospective on antimicrobial use
in horses undergoing colic surgery found that 67.2% of horses
received inappropriate antimicrobial prophylaxis and only
1.8% of horses were redosed appropriately.327 Improvements
in compliance with antimicrobial prophylaxis guidelines during
equine surgeries will likely reduce SSI and other postoperative
complications associated with prolonged postoperative antimi-
crobial use. Prolonged administration of prophylactic antibiotics
(>24 hours) has no additional benefit.317,325,328–331 The surgical
site is sealed and resistant to microorganism entry within 24
hours of a surgical procedure, rendering technically prophylactic
antibiotic use beyond this time redundant.31 Antibiotics should
only be continued when there are clear medical indications
to do so.31,138,322–324 Development of a fever in the immediate
postoperative period is not necessarily indicative of a bacterial
infectious process, so therapeutic antimicrobial therapy should
be reserved for patients with a convincing diagnosis of bacterial
infection.20 Research has shown that continued antimicrobial
prophylaxis is associated with antibiotic-related morbidity,
increased antimicrobial resistance, and increased health care
costs.332 In human medicine, prophylactic antimicrobial therapy
has been reduced from multiple days to 24 hours328,331,333 as a
single, correctly timed dose of an antibiotic is just as effective
as multiple doses over a 48-hour period. One study showed no
difference in SSI in horses undergoing exploratory celiotomy
when horses were administered antimicrobials for less than 36
hours compared with greater than 36 hours, further emphasizing
that routine prophylactic antimicrobial therapy for more than 24
hours is unnecessary in colic patients.20 Comparison of incisional
infection rates after colic surgery in horses receiving antimicrobials
for 72 hours versus 120 hours showed no benefit in prolonged
antimicrobial use.334 Evaluation of antibiotic regimens in dogs
undergoing orthopedic implant surgeries showed no difference
in the rate of SSI when antimicrobial therapy was prolonged
beyond 24 hours.335
POSTANTIBIOTIC EFFECT
The postantibiotic effect (PAE) occurs when the growth of
target bacteria remains suppressed for a period of time after
 90 SECTION I  Surgical Biology

TABLE 7-7.  Antibiotics Commonly Used in the Horse

Antimicrobial Mechanism of Action Adverse Effects
BACTERICIDAL
Penicillin Inhibit cell wall synthesis by binding to penicillin- Autoimmune hemolytic anemia anaphylaxis,
binding proteins, leading to cell lysis transient hypotension, increased large
intestinal motility, cardiac arrhythmia
VetBooks.ir

Cephalosporins As for penicillin Enterocolitis

Aminoglycosides Inhibit protein synthesis by binding to 30S ribosomal Nephrotoxicity, neuromuscular blockade,
subunit ototoxicity
Fluoroquinolones Inhibit bacterial DNA gyrase Cartilage disorders in young (<3-year-old)
horses, oral ulceration
Metronidazole Disrupt bacterial DNA by free radicals and unstable Enterocolitis, inappetence
intermediate compounds after structural change once
in target organism
Trimethoprim/ Synergistic action to inhibit folic acid synthesis Idiosyncratic reactions
sulfonamide (sulfonamides block first step and trimethoprim the
second step in folic acid synthesis pathway)
BACTERIOSTATIC
Tetracyclines Inhibit protein synthesis by reversibly binding to 30S Nephrotoxicity, discoloration of urine and
ribosomal subunit erupting teeth
Chloramphenicol Inhibit protein synthesis by reversibly binding to 50S Reversible aplastic anemia (use carefully, it
ribosomal subunit may cause idiosyncratic anemia in humans)
Macrolides Inhibit protein synthesis by reversibly binding to 50S Intestinal prokinetic
ribosomal subunit

the antimicrobial drug concentration falls below MIC. Factors
affecting the duration of PAE include the duration of antimicrobial
exposure, the bacterial species, and the antimicrobial used. PAE is
an attractive property of an antibiotic as it results in less frequent
administration. All antibiotics can produce a PAE against gram-
positive cocci. Aminoglycosides, fluoroquinolones, tetracyclines,
macrolides, and chloramphenicol produce the most profound
PAEs. β-lactam antibiotics produce no PAE against gram-negative
bacilli.336,337
PROPHYLACTIC ANTIBIOTICS USED IN HORSES
The most commonly administered antibiotics in the horse are
summarized in Table 7-7.
β-Lactam antibiotics
β-lactam antibiotics, such as penicillin and the cephalosporins,
are the most commonly used prophylactic, time-dependent
antimicrobials. Their mechanism of action is to inhibit cell wall
synthesis by binding to penicillin-binding proteins, resulting
in bacterial cell lysis. Time-dependent antimicrobials have a
saturable, concentration-dependent increase in bacterial killing.
This means that there is no additional benefit once a certain
concentration has been achieved (i.e., plasma concentrations 2
to 4 times above the MIC).31 The bactericidal activity is optimal
when drug concentration is greater than MIC for a percentage
of the dosing interval and should be administered at frequent
low doses or as a continuous rate infusion. The increase in
plasmid-mediated resistance and β-lactamase production has
reduced their spectrum of activity, but this can be improved
with the addition of a β-lactamase inhibitor: clavulanic acid,
sulbactam, or tazobactam.
Aminoglycoside antibiotics
Aminoglycosides are commonly used in conjunction with a
penicillin as part of a broad-spectrum antimicrobial prophylactic
regimen. They are bactericidal, concentration-dependent antibiot-
ics that inhibit protein synthesis by binding to the 30S ribosomal
subunit, resulting in disruption of mRNA function. Bacterial
resistance is plasmid mediated and results in downregulation
of influx pathways with subsequently decreased intracellular drug
concentrations and enzymatic degradation of the antibiotic.
Multiple in vivo and in vitro studies show that a ratio of Cmax
serum concentration to MIC between 8 and 12 to 1 increases
the bactericidal effect332,338–340 and the PAE is prolonged at higher
peak drug concentrations.341 Additionally, a Cmax:MIC ratio of
10:1 has been associated with decreased risk of antimicrobial
resistance development.308,342 Because of the PAE, once-daily
dosing regimens are effective. Aminoglycosides are distributed
within the extracellular fluid (ECF) space. As equine neonates
have increased ECF compared with adults, they require much
larger doses of aminoglycosides up to 4 to 6 weeks of age.343,344
In one study, optimal peak and trough concentrations of amikacin
were reached in 88% of neonates treated with 25 mg/kg IV once
daily.343 As previously mentioned, critically ill patients also have
altered gentamicin pharmacokinetics,345 therefore in neonates
and critically ill patients, serum peak and trough concentrations
of aminoglycosides should be analyzed. Therapeutic drug monitor-
ing is important in aminoglycoside use because of the risk of
nephrotoxicity. Nephrotoxicity occurs after sustained exposure
of renal tubular cells to the drug, rather than exposure to high
drug concentrations, further supporting once daily dosing. If
trough concentrations are not suitably low (amikacin 1 µg/mL,
gentamicin 2 µg/mL), the dose interval should be increased.
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 91
Horses with preexisting renal damage, hypovolemia, or severe
systemic illness are at increased risk of nephrotoxicity, especially
if concurrent nonsteroidal antiinflammatory therapy is used.
Trimethoprim sulphonamides
Trimethoprim combined with sulfadiazine or sulfamethoxazole
is commonly used in horses because of its broad spectrum of
VetBooks.ir
activity, good oral bioavailability,346 and low incidence of adverse
reactions.347,348 Trimethoprim sulphonamides act synergisti-
cally to inhibit folic acid synthesis, which is a requirement for
microbial DNA synthesis. Sulphonamides prevent conversion
of para-aminobenzoic acid (PABA) to dihydrofolic acid and are
bacteriostatic when used alone. The addition of trimethoprim
inhibits dihydrofolic acid reductase, which is necessary for the
conversion of dihydrofolic acid to tetrahydrofolic acid, so the com-
bined activity of the two results in a synergistic bactericidal effect.
A formulation at a ratio of 1:5 for potentiated sulphonamides
and trimethoprim is required. Bacterial resistance is plasmid
mediated and results in a reduced chromosomal susceptibility
to trimethoprim. They are less commonly used as prophylactic
antibiotics.
Special Routes of Administration and Dosages
Use of prophylactic antimicrobials combined with improvements
in the operating room management and surgical techniques have
helped greatly to reduce the incidence of SSI in equine patients.
However, deep wound infection remains a serious complication.
Systemic antimicrobial therapy may not be effective in deep
infections due to reduced vascular supply and low antimicrobial
concentration at the infection site.349 Local antimicrobial therapy
provides high concentrations of antibiotic at the site of infection
with reduced risk of systemic toxicity and side effects in an
economically feasible manner.350
ANTIBIOTIC-IMPREGNATED POLYMETHYL METHACRYLATE
(AIPMMA) OR PLASTER OF PARIS (AIPOP)
Antimicrobial-impregnated bone cements were pioneered in
1970350 and continue to be recognized as a reliable method for
delivering high concentrations of antibiotic to the site of
infection.351–353 Both polymethyl methacrylate (PMMA) and plaster
of Paris (POP) can be used as carriers for local drug delivery
and can significantly reduce deep infection rates in total knee,
hip, and shoulder arthroplasty in humans.354–356
PMMA is a high-density plastic that is formed when a powdered
polymer and fluid monomer are combined. Commonly utilized
brands include Surgical Simplex P, Palacos, Zimmer, and CMW
cement. Advantages of using PMMA includes high biocompatibil-
ity, documented elution profiles, as well as ease of use and ready
availability. Local concentrations of antibiotic released from
PMMA beads are reported to reach 200 times the level achieved
by systemic administration of the same antibiotic.357–359
POP is degraded and absorbed by the body, and so does not
require removal. However, bead manufacture is more time
consuming than with PMMA. The POP set-up time is very slow
and lengthy aerating and drying times are necessary, requiring
that beads be manufactured in advance (24 hours prior to surgery)
and maintained in sterile containers. Bactericidal activity is
maintained after ethylene oxide sterilization, and beads remain
active for up to 5 months when stored at room temperature.
However, the beads may become very brittle after prolonged
storage. POP drug elution occurs in an initial burst release. For
impregnated POP beads, 80% of the drug will be eluted in the
initial 48 hours, with slow secondary release at bactericidal
concentrations over 14 days.144
Antimicrobial elution from PMMA also occurs in a bimodal
pattern with rapid elution in the initial 24 hours and subsequent
slow release over weeks to months of implantation, depending
on the antimicrobial used.360 There are multiple factors affecting
drug elution rate, including type and porosity of the PMMA,
surface area and surface characteristics of the beads, concentration
of the antimicrobial used, and the diffusion properties of the
antimicrobial. The maximum concentration of antimicrobial
possible should be used. There is concern over “set-up” of
the cement, as high drug volumes may prolong or inhibit the
hardening process (>20% of antimicrobial)360 or weaken the
biomechanical properties of the cement (>10% of antimicro-
bial).361 Diminished mechanical strength is only a concern if the
PMMA is being used to cement a prosthesis. Some authors dose
the drug at 5% of the weight of the PMMA as a general rule of
thumb (i.e., 0.5 g amikacin for 10 g PMMA, but these authors
use 1 to 2 g of antibiotic for each 10 g of PMMA). Both liquid
and powdered antibiotics can be used. If a liquid is used, it is
important to reduce the volume of the PMMA fluid monomer by
half the volume of the added antibiotic. During the hardening
process, the cement should be formed into cylinders or beads.
The ambient temperature of the room will affect the process,
with rapid solidification to cement in warm rooms. For ease,
the cement can be placed into a 60-mL dose syringe while still
in liquid form and injected onto a nonadhesive, nonporous
surface (any sterile plastic) in long cylinders. The cylinders can
then be cut to size to form beads prior to complete hardening.
Alternatively, the dose syringe can be used to directly inject cement
into the underside of the plate or surrounding the screws, taking
care not to enter the fracture line or screw heads. Premade beads
should be sterilized using ethylene oxide gas sterilization, as
there is potential for loss of antimicrobial potency associated
with steam autoclaving.362,363 Culture and sensitivity profiles aid
antimicrobial selection, but in cases where AIPMMA is being
used prophylactically, an antibiotic with low tissue toxicity that
is heat stable up to 100°C should be chosen to prevent degrada-
tion during the exothermic hardening process.364,365 Antibiotics
such as polymyxin B, chloramphenicol, and tetracyclines are
not sufficiently heat stable and do not retain full activity after
incorporation into beads.366 Antibiotics that elute well from
PMMA include amikacin, gentamicin, tobramycin, amoxicillin,
ciprofloxacin, imipenem, ticarcillin, cefazolin, clindamycin,
vancomycin, erythromycin, metronidazole, and fluoroquinolones.
Combinations of antimicrobials such as vancomycin-amikacin,
cefazolin-amikacin, or gentamicin-metronidazole enhance elution,
whereas others (tobramycin-oxacillin) inhibit it.367–369
Possible disadvantages of using antimicrobial-impregnated
beads include an increased risk of developing antimicrobial
resistance and toxicity or reaction to the cements. Furthermore,
PMMAs are nonbiodegradable and heat-labile antimicrobials
cannot be incorporated. Removal of PMMA is not usually
necessary, unless it is proven to interfere with function. While
systemic toxicity is rare, local tissue toxicity as a result of the
initially high antimicrobial concentration can occur.370–374 In
addition, the release kinetics of elution technologies such as
methylmethacrylate cement are often unpredictable and may result
in large fluctuations in local drug concentrations.375–377 At some
point in the elution cycle, the level of eluted antimicrobial drops
below the MIC, raising concerns about the potential emergence of
 92 SECTION I  Surgical Biology
resistant organisms. All elution methods have first-order (linear)
release kinetics that result in a continuous decrease in the level
of the eluted drug. Therefore, during the elution period, there
comes a point when antimicrobials are released at sub-MIC level,
creating a potential environment for the emergence of resistant
organisms.378,379
VetBooks.ir
OTHER
Bovine collagen sponge (Ultrafoam) is a popular and frequently
used local drug delivery device. Advantages include ease of use,
rapid absorption, and availability of presterilized, “off-the-shelf”
packaged material. There are no reports of local reaction or allergic
response in the horse. It absorbs liquid forms of antimicrobial
easily. It should be placed at the surgery site prior to addition
of antimicrobial drug, as it can disintegrate very easily during
placement.
Other materials utilized as local drug delivery vehicles include
hydroxyapatite (HAP), β-tricalcium phosphate (β-TCP), polylactic
acid (PLA), polyglycolic acid (PGA), and polylactide-co-glycolide
(PLGA) and sol gels.378–382 Advantages include their biocompat-
ibility, promotion of new bone formation, and prolonged
antimicrobial elution for 4 to 6 weeks.330 The availability and
current cost of these materials have limited use in equine surgery.
Prevention of bacterial colonization of metal implants requires
a more permanent surface modification that provides a constant
therapeutic level of antimicrobial concentration.86 A modified
implant surface that prevents biofilm formation without cytotoxic
effects or risk of antimicrobial resistance development would
provide the desired protection against the development of
implant-associated infections. Long hydrophobic polymeric chains
that are physically deposited onto implant surfaces can kill bacteria
on contact by damaging the cell membrane or wall. Advantages
of polycation usage include a lack of toxicity to mammalian
cells and limited potential for antimicrobial resistance to
develop.383,384 A preclinical, in vivo ovine infection model of long
bone plate osteosynthesis385 was performed to evaluate the safety
and efficacy of the hydrophobic polycationic (HPC) device. The
results of this study demonstrated that intraoperative dip-coated
fracture plates significantly supported fracture healing in the
presence of active infection when compared with a control
cohort.88 The coating has been successfully used on a transfixation
pin in a case of distal phalanx osteitis where antimicrobial therapy
was not possible.
REGIONAL LIMB PERFUSION
Regional limb perfusion (RLP) was first introduced in the early
1900s to provide regional anesthesia to surgical sites386 and
was subsequently developed to administer antimicrobials and
cytostatic drugs to humans and horses.387–390 In experimental
rabbit models of orthopedic chronic infection, antimicrobial
perfusion of distal limbs resulted in a negative bacterial culture
in 70% of cases, compared with 35% of cases where systemic
antimicrobial therapy was used.387 Regional perfusion is pos-
sible in any situation where there is an accessible peripheral
vessel and an effective tourniquet can be applied to isolate the
infected region. If possible, a tourniquet should be placed above
and below the area to be treated, with venous access distal to
the proximal tourniquet. It is essential to use a wide elastic
tourniquet (Esmarch) or a pneumatic tourniquet, and movement
of the horse must be limited to prevent venous escape of the anti-
biotic.391,392 Tourniquets should remain in place for 30 minutes.
An evaluation of tourniquet time for RLP reported that there was
no difference in synovial amikacin concentration after 10-minute
versus 30-minute tourniquet application times using a 2-g dose
diluted to 60 mL,393 however therapeutic levels reached only 10
times the lower end of the MIC and may contribute to resistance
emergence. While general anesthesia is not usually justified for
RLP,394 horses should be well sedated prior to application of the
tourniquet. Additionally, perineural anesthesia can be performed
to reduce movement because of discomfort while tourniquets
remain in place. It is recommended to use a small-gauge (25- to
27-gauge) butterfly catheter to limit vascular trauma and to allow
for maximum vessel integrity in cases of infection that require
prolonged treatment. Placement of long-term indwelling catheters
have a reported complication rate of 27%395 compared with
only 12.26% when using 22-gauge butterfly catheters.396 In the
authors’ clinical experience, fewer complications occur when
even smaller catheters are used (25 gauge). After completion
of drug administration, a pressure bandage should be applied.
This should be removed at the time of tourniquet removal and a
support bandage is placed over the site to reduce limb swelling.
Application of topical antiinflammatories (e.g., 1% diclofenac
sodium [Surpass]) has been shown to decrease postinjection
swelling and reduce subcutaneous thickening at the injection
site,397 thereby prolonging vessel health and increasing ease of
repeated treatment. Addition of 2% mepivacaine hydrochloride to
RLP solution has been used to provide additional analgesia and
has been reported to have no effect on antimicrobial activity.398
Simultaneous joint lavage and RLP can safely be performed in
cases of synovial infection with negligible loss of amikacin in
egress lavage fluids.391 Concentration-dependent antimicrobials
are ideal for RLP, as the rate and extent of bacterial killing are
related to high maximum concentration (Cmax) in relation to the
MIC. In humans, RLP is sometimes performed twice daily if time-
dependent antimicrobials are being used. The pharmacokinetics
and pharmacodynamics of several commonly used antimicrobials
for RLP have been evaluated extensively. Dosage of the chosen
antimicrobial varies, but generally about one-third of the systemic
dose is used. The authors have additional experience of using
the entire systemic dose in the perfusion without additional
parenteral antibiotic use. Subjectively, the high dose seems to
improve clinical response. However, there is an increased risk of
phlebitis with increased concentration of antimicrobial. Use of
1 g of amikacin diluted to 10, 60, or 120 mL was found to reach
therapeutic concentrations (>32 µg/mL) for susceptible pathogens
in the radiocarpal joint and reached therapeutic concentrations
for resistant pathogens (>128 µg/mL) in the distal interphalangeal
joint.399 Evaluation of a 2-g versus a 3-g dose of amikacin in
the distal limb found that higher doses should be reserved for
bacterial isolates (Escherichia coli, Actinobacillus sp.), with an MIC
higher than that achievable with a 2-g dose.400 Use of 250 mg
of amikacin in RLP did not achieve concentrations above MIC,
and therefore doses less than 1 g are not recommended.401
Combining ticarcillin/clavulanic acid with amikacin reduced the
synovial concentration of amikacin and had a negative effect on
the antimicrobial activity of both amikacin and ticarcillin.402
Unfortunately, ticarcillin is no longer available for RLP use,
but an alternate carboxypenicillin in human medicine with
antipseudomonal activity is piperacillin-tazobactam (Zosyn).
RLP with amikacin and a carboxypenicillin can be performed
safely on alternate days. RLP with vancomycin achieves effective
synovial concentrations using a dose of 300 mg in 60 mL of
saline without adverse side effects and remains above MIC (4 µg/
mL) for approximately 20 hours.403,404 The use of enrofloxacin
 CHAPTER 7  Surgical Site Infection and the Use of Antimicrobials 93
(1.5 mg/kg) has been associated with an increased risk of
vasculitis401 and use of erythromycin405 has an added risk of
potential systemic side effects, therefore additional care should be
taken with their use. Although gentamicin can be used for both
intraarticular and RLP use under a tourniquet, the commercial
injectable solution of gentamicin is quite acidic and can be
much more irritating than amikacin. Typically, the total perfus-
VetBooks.ir
ate volume used for the distal limb is 30 mL or 60 mL if the
tourniquet is above the carpus or tarsus. The effect of perfusate
volume on antimicrobial concentrations were evaluated in two
different studies and no significant differences between volumes
of 10, 30, 60, or 120 mL were found.406,407 The prophylactic
use of RLP prior to orthopedic procedures has been effective in
human knee replacements.408 The authors typically perform an
RLP immediately after complex fracture repair and arthrodesis
while the incision is being sutured with the patient still on
the table.
Intraosseous (IORLP) or intraarticular (IARLP) antibiotic
regional perfusion will also provide a high concentration of
antibiotic at the site of infection. Tourniquets should be placed
above and below the joint or bone that is to be targeted and
remain in place for 30 minutes. Both commercial intraosseous
catheters (Cook) and cannulated screws can be safely inserted
for repeated treatments. One author (DR) drills a 4.0-mm hole
into the medullary cavity and inserts the male end of a Luer-tip
extension set into the hole to allow direct injection.
Severe complications including osteonecrosis and osteomyelitis
resulting in pathologic fracture after IORLP, with gentamicin in
the proximal phalanx, have been reported.409
Toxic Side Effects of Antibiotics
Antimicrobial therapy has been identified as a risk factor for
colitis associated with C. difficile infection and salmonellosis in
human and veterinary patients.217,410,411 Parenteral antimicrobial
treatment increases the risk of developing salmonellosis 6.4 times
and the risk is increased further to 40 times with the combined
use of parenteral and enteral antimicrobials.410 This supports the
clinical opinion that oral antimicrobial therapy is more likely
to result in antimicrobial-associated diarrhea. Horses with
gastrointestinal disease have a 4.2-times greater risk of developing
salmonellosis and in horses undergoing colic surgery, reinstitution
of antimicrobial therapy significantly increased the risk of shed-
ding Salmonella by 2.3 times.211 The reported rate of antimicrobial-
associated diarrhea in horses undergoing elective arthroscopy is
6.3%. C. difficile and Salmonella spp. have been associated with
high mortality rates between 20% and 50%.217,412
Nephrotoxicity is the most common side effect associated
with aminoglycoside use in horses and occurs as a result of
sustained exposure of renal tubular cells to the drug rather than
high drug concentrations.312,413 Horses with preexisting renal
damage, hypovolemia, or severe systemic illness are at increased
risk, especially if concurrent nonsteroidal antiinflammatory
therapy is used. Because of the concentration-dependent bacte-
ricidal effect combined with potential for toxicity over time,
once daily dosing regimens are recommended.31 Aminoglycoside
therapy is infrequently reported to cause neuromuscular block-
ade414 and gentamicin was shown to augment the neuromuscular
blockage of atracurium under general anesthesia.415 A single dose
of 6 mg/kg gentamicin administered to healthy horses undergoing
halothane anesthesia resulted in no significant neuromuscular
blockade.414 As mentioned, the authors routinely use a dose of
8.8 mg/kg gentamicin IV in horses undergoing emergency and
elective procedures without adverse effects.
Fluoroquinolones, notably enrofloxacin, have been reported
to have deleterious effects on tendons, bone, and cartilage416–419
in horses, with an increased detrimental effect in young
animals.419,420 They should be used with caution in younger horses.
Emergence of Bacterial Resistance to Antibiotics
When Fleming received the Nobel Prize for his discovery of
penicillin, he warned people of the hazard of antimicrobial
resistance (AMR) in his acceptance speech. Penicillin resistance
was first reported in 1940, methicillin-resistant Staphylococcus
(MRSA) in 1962, and vancomycin-resistant Staphylococcus in 2002.
Two million people become infected with bacteria resistant to
antimicrobials annually in the US and at least 23,000 die each
year as a direct result. Although the emergence of resistant strains
is a natural phenomenon that cannot be avoided, the transforma-
tion of resistant strains into resistant populations is favored by
irrational antibiotic therapy. Antimicrobials are the most com-
monly prescribed drugs; however, up to 50% of the time antibiot-
ics are either prescribed for conditions which they are not designed
to treat (e.g., human asthma, influenza virus, recurrent airway
obstruction in horses), are utilized unnecessarily, or are admin-
istered at an incorrect dose for a suboptimal duration.421–423
Subtherapeutic dosing provides an ideal environment for the
development of AMR, and there is evidence from both human
and veterinary medicine that it is important to take dosing into
consideration when dealing with critically ill patients. The useful-
ness of antimicrobial therapy is now counteracted by the ability
of bacteria to resist their effects, and the additional hurdle in
veterinary medicine includes the pressure to restrict access to
certain drug classes due to the potential effects on human-related
resistance patterns.
AMR is recognized in a wide range of equine pathogens
including Salmonella, Escherichia coli, Klebsiella, Pseudomonas, and
Staphylococcus spp. Increases in E. coli resistance of 75% to 90%
to tetracyclines, penicillins, and sulphonamides have been
reported.424 A recent study highlighted penicillin G resistance in
all gram-positive isolates obtained from septic joints (except
Streptococcus spp.).267 Penicillin G is considered a first-line
antimicrobial, and this study highlights that alternate, first-line
antimicrobial therapies may need to be selected in synovial sepsis.
Bacterial susceptibility to oxytetracycline, gentamicin, and
trimethoprim-sulfamethoxazole advocated their empiric use in
initial therapy and promotes the concept of antibiotic cycling.
High-profile bacteria, extended spectrum β-lactamase (ESBL)
Enterobacteriaceae, MRSA, and multidrug-resistant Salmonella
spp. have been identified in the equine population.227,425–431 These
discoveries have focused attention on antimicrobial use in horses
and the potential for public health implications. Clients expect
antimicrobials to be administered as part of the standard therapy
for many conditions and might put pressure on clinicians to
prescribe these drugs, even when their use may not be effective.
To reduce unnecessary antimicrobial use that may contribute to
the development of resistant pathogens, clinicians must set new
treatment standards by focusing on client education, evidence-
based medicine, and antimicrobial stewardship.
Several strategies have been developed in human medicine,
including hospital formulary restriction, development of anti-
microbial practice guidelines, and antimicrobial cycling.31
Although these methods may be effective in the human field,
 94 SECTION I  Surgical Biology
there are limitations associated with antimicrobial availability
and economics in veterinary medicine. Broad guidelines have
been instituted in statements by the American College of Veteri-
nary Internal Medicine432,433 to assist clinicians in effective
antimicrobial use for common clinical conditions in response
to World Health Organization (WHO) strategies. The British
Small Animal Veterinary Association (BSAVA) and British Equine
VetBooks.ir
Veterinary Association (BEVA) have developed detailed online
toolkits (<http://www.beva.org.uk/protectme>) to help practices
develop policies on antimicrobial use. Antimicrobial stewardship
guidelines relate to drugs that are important in human health,
for example, third- and fourth-generation cephalosporins, fluo-
roquinolones, and macrolides. Online recommendations include
use of antimicrobials in relation to the disease process, local
resistance patterns, and for the species being targeted. Additionally,
antimicrobials classified as critically important (CIA) are listed
and their use should be avoided without supporting culture and
susceptibility testing. Veterinary hospitals can form committees
to monitor antimicrobial use, infection rates, common pathogens
isolated, and their resistance patterns, as well as to monitor for
nosocomial disease. A combination of best practice, evidence-
based medicine, and reduction of inappropriate antimicrobial
use is vital to reduce AMR and ensure continued efficacy of
antimicrobials.
Summary of Antibiotic Prophylaxis
SSI is a devastating complication of surgery that can lead to
increased costs, as well as increased patient morbidity and
mortality. Improved adherence to evidence-based medicine and
appropriate antimicrobial prophylactic regimens can decrease
rates of SSI, reduce AMR, and maintain antimicrobial efficacy.
Aggressive surgical debridement and adequate drainage combined
with local, targeted antimicrobial therapy based on culture and
susceptibility results is required for optimal therapy.
REFERENCES
1. Selwyn S. Hospital infection: the first 2500 years. J Hosp Infect.
1991;18(suppl A):5–64.
2. Toledo-Pereyra L. Louis Pasteur surgical revolution. J Invest Surg.
2009;22:82–87.
3. Scott RD. The direct medical costs of healthcare-associated infec-
tions in U.S. hospitals and the benefits of prevention. 2009 (http://
www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf. Accessed May 1,
2016).
4. Anderson DJ. Surgical site infections. Infect Dis Clin North Am.
2011;25(1):135–153.
5. Zimlichman E, Henderson D, Tamir O, et al. Health care-associated
infections: a meta-analysis of costs and financial impact on the US
Health Care System. JAMA Intern Med. 2013;173(22):2039–2046.
6. Anderson DJ, Berrios-Torres SI, Bratzler DW, et al. Strategies to
prevent surgical site infections in acute care hospitals: 2014 update.
Infect Control Hosp Epidemiol. 2014;35(06):605–627.
7. Magill SS, Edwards JR, Bamberg W, et al. Multistate point-
prevalence survey of health care associated infections. N Engl J
Med. 2014;370(13):1198–1208.
8. Watanabe A, Kohnoe S, Shimabukuro R, et al. Risk factors associ-
ated with surgical site infection in upper and lower gastrointestinal
surgery. Surg Today. 2008;38:404–412.
9. Owens CD, Stoessel K. Surgical site infections: epidemiology,
microbiology and prevention. J Hosp Infect. 2008;70(suppl 2):3–10.
10. Ahern B, Richardson DW, Boston R, et  al. Orthopedic
infections in equine long bone fractures and arthrodesis treated
by internal fixation: 192 cases (1990-2006). Vet Surg. 2010;39(5):
588–593.
11. Stewart S, Richardson DW, Boston R, et al. Risk factors associated
with survival to hospital discharge of 54 horses with fractures of
the radius. Vet Surg. 2015;44:1036–1041.
12. Kirkland KB, Briggs JP, Trivette SL, et al. The impact of surgical-
site infections in the 1990s: attributable mortality, excess length
of hospitalization, and extra costs. Infect Control Hosp Epidemiol.
1999;20:725–730.
13. Hidron AI, Edwards JR, Patel J, et al. NHSN annual update:
antimicrobial-resistant pathogens associated with healthcare-
associated infections: annual summary of data reported to the
National Healthcare Safety Network at the Centers for Disease
Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol.
2008;29(11):996–1011.
14. National and state healthcare-associated infections progress report.
Atlanta (GA): National Center for Emerging and Zoonotic Infectious
Diseases, Centers for Disease Control and Prevention; 2016 (http://
www.cdc.gov/HAI/pdfs/progressreport/hai-progress-report.pdf,
accessed August 10, 2016).
15. Surveillance of surgical site infections in Europe 2010–2011.
Stockholm: European Centre for Disease Prevention and Control;
2013 (http://ecdc.europa.eu/en/publications/Publications/SSI-in-
europe-2010-2011.pdf, accessed August 10, 2016).
16. Cosgrove SE, Sakoulas G, Perencevich EN, et al. Comparison of
mortality associated with methicillin-resistant and methicillin-
susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin
Infect Dis. 2003;36(1):53–59.
17. Cosgrove SE, Qi Y, Kaye KS, et al. The impact of methicillin resistance
in Staphylococcus aureus bacteremia on patient outcomes: mortality,
length of stay, and hospital charges. Infect Control Hosp Epidemiol.
2005;26(2):166–174.
18. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial resistant
pathogens associated with health care associated infections: summary
of data reported to the National Healthcare Safety Network at the
Centers for Disease Control and Prevention, 2009-2010. Infect Control
Hosp Epidemiol. 2013;34(1):1–14.
19. Curtiss AL, Stefanovski D, Richardson DW. Post-operative infec-
tion associated with equine orthopedic internal fixation:155 cases
(2008-2016), Abstract, American College of Veterinary Surgeons
Symposium, Indianapolis, Indiana 2018.
20. Freeman KD, Southwood LL, Lane J, et al. Post-operative infection,
pyrexia and perioperative antimicrobial drug use in surgical colic
patients. Equine Vet J. 2012;44(4):476–481.
21. Mair TS, Smith LJ. Survival and complication rates in 300 horses
undergoing surgical treatment of colic. Part 2: short-term complica-
tions. Equine Vet J. 2005;37(4):303–309.
22. Mair TS, Smith LJ. Survival and complication rates in 300 horses
undergoing surgical treatment of colic. Part 3: long-term complica-
tions and survival. Equine Vet J. 2005;37(4):310–314.
23. Mangram A, Horan T, Pearson M, et al. Guideline for Prevention
of Surgical Site Infection, 1999. Centers for Disease Control and
Prevention(CDC) Hospital Infection Control Practices Advisory
Committee. Am J Infect Control. 1999;27:97–134.
24. Ahrenholz DH, Simmons RL. Mixed and synergistic infections
p119-133. In: Howard RJ, Simmons RL, eds. Surgical Infectious
Diseases. 3rd ed. Norwolk, Conn: Appleton and Lange; 1994.
25. Wong ES. Surgical site infections. In: Mayhall CG, ed. Hospital
Epidemiology and Infection Control. 3rd ed. Balitmore (MD): Lippincott,
Williams, and Wilkins; 2004:287–310.
26. Howard R. Surgical infections. In: Schwartz SI, ed. Principles of
Surgery. 7th ed. New York: McGraw-Hill; 1999:123–137.
27. Togo S, Kubota T, Takahashi T, et al. Usefulness of absorbable sutures
in preventing surgical site infection in hepatectomy. J Gastrointest
Surg. 2008;12:1041–1046.
28. Taylor G, McKenzie M, Kirkland T, et al. Effect of surgeon’s
diagnosis on surgical wound infection rates. Am J Infect Control.
1990;18:295–299.