Surgical Prophylaxis and

Surgical Site Infections

PHAR 839 | Infectious Diseases II
Marc Salvatus, PharmD, BCPS
West Coast University, School of Pharmacy
November 3, 2022
Learning Objectives
1. Identify patient-related risk factors for development of surgical site infections
2. List the most common pathogens associated with infections at various surgical sites
3. Assess appropriateness of timing and duration of prophylactic antibiotics for surgical
site infections
4. Recommend an appropriate antimicrobial prophylaxis regimen given the type of
surgery
5. Recognize situations where antimicrobial therapy is indicated for surgical site
infections

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Resources
• Kanji S. Antimicrobial Prophylaxis in Surgery. In: DiPiro JT, Yee GC, Posey L, Haines ST,
Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e.
McGraw-Hill.
• Ban KA, Minei JP, Laronga  C, et al. American College of Surgeons and Surgical
Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. Jan
2017;224(1):59–74. 10.1016/j.jamcollsurg.2016.10.029. 27915053. 
• Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and
Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious
Diseases Society of America. Clinical Infectious Diseases. July 2014;59(2):e10-e52.
• Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for
antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm. Feb 2013;70:195-283.

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Epidemiology
• 57 million outpatient and 51 million inpatient surgical procedures are
performed annually in the U.S.1
• Surgical site infections – most common complication of surgery
• Occur in 3% to 6% of patients
• Account for 20% of all hospital-acquired infections
• Prolong hospitalization by ~7 days  annual cost of $5 billion to $10
billion
• Involvement of resistant organism or prosthetic joint  >$90,000

1. National Center for Health Statistics and the National Hospital Discharge Survey 4
Introduction
• Prophylactic antibiotics – administered prior to the contamination of previously sterile tissues or
fluids with the goal of preventing infection
• Prophylactic antibiotics are distinct from antibiotics used for treatment of a pre-existing infection
• Differences in spectrum of coverage and timing
• Surgical site infections (SSIs)
• Occur within 30 days following surgery (within 1 year for prosthetic implantation)
• Involve at least one of the following:
• Purulent incisional drainage
• Positive culture of aseptically obtained fluid or tissue from the superficial wound
• Unless culture negative: Local signs and symptoms of pain or tenderness, swelling,
and erythema after the incision is opened by the surgeon
• Diagnosis by the attending surgeon or physician based on their experience and
expert opinion

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CDC Classifications of SSIs
• SSIs can be categorized as incisional (e.g. cellulitis of the incision site) or organ/space
(e.g. development of bacterial peritonitis after bowel surgery)

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 Intraoperative Risk Factors
National Research Council (NRC) Risk Classification System*
Classification Criteria Indication for Antibiotics
No acute inflammation or transection of GI, oropharyngeal, Not indicated unless procedure
Clean genitourinary, biliary, or respiratory tracts; elective case, no involves implantation of
technique break prosthetic materials
Controlled opening of aforementioned tracts with minimal Prophylactic antibiotics indicated
Clean-contaminated spillage/minor technique break; clean procedures
performed emergently or with major technical breaks
Acute, nonpurulent inflammation present; major Prophylactic antibiotics indicated
Contaminated spillage/technique break during clean-contaminated
procedure
Obvious preexisting infection present (abscess, pus, or Therapeutic antibiotics required
Dirty necrotic tissue present)

*Limitations: classification occurs intraoperatively; does not account for patient-specific factors
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Patient-Specific Risk Factors
Risk Factors Comments
Age -
Nutritional status Malnutrition contributes to impaired wound healing
(preoperative albumin <3.5 g/dL) and prolonged hospital stay
Diabetes and preoperative glycemic control -
Smoking and alcohol use Nicotine impairs wound healing
Obesity -
Coexisting infections at distal body sites Should be resolved prior to surgery whenever possible

Colonization with resistant microorganisms Decolonization of S. aureus using intranasal mupirocin

and chlorhexidine
Altered immune response E.g. corticosteroid use, HIV, hepatitis C
Length of preoperative stay -
Bacteriology
• Sources of organisms involved in SSIs:
• Endogenous – from the patient’s own flora
• Exogenous – From contamination during the procedure
• Appropriate antibiotics can be selected based on the procedure’s anatomic location and
the NRC classification
• Most common pathogens in surgical wound infections (NNIS):
• S. aureus (20% incidence)
• Coagulase-negative staphylococci (14%)
• Enterococci (12%)
• E. coli (8%)
• Pseudomonas aeruginosa (8%)
• Candida species and MRSA becoming more prevalent due to broad-spectrum antibiotics

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Scheduling Antibiotic Administration
• Considerations for antimicrobial surgical prophylaxis:
• Antibiotics should be distributed to the surgical site prior to the initial incision
• Bactericidal concentrations of antibiotics should be maintained at the surgical site
throughout the surgical procedure
• Antibiotic administration should be initiated within 60 minutes prior to the initial incision
• Drug distribution throughout the tissues involved in surgery
• Exception: vancomycin and fluoroquinolones (120 minutes prior to the initial incision)
• Re-dose prophylactic antibiotic when surgery lasts longer than two half-lives of the antibiotic
• 4 hours for cefazolin
• Duration of prophylactic antibiotics after surgery does not typically exceed 24 hours
• Increased risk for C. difficile infection and acute kidney injury

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Classen DC, Evans RS, Pestotnik SL, et al. "The Timing of Prophylactic Administration of Antibiotics and the Risk of Surgical-Wound Infection." N Engl J Med 1992; 326:281-286. 12
Choice of Antibiotic
Dependent on:
• Type of surgical procedure
• Most frequent pathogens associated with procedure
• Safety and efficacy of antibiotic
• Literature evidence
• Susceptibility patterns of nosocomial pathogens within the institution
• Cost

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Choice of Antibiotic
• Parenteral route preferred
• Gram-positive coverage
• Skin flora: S. aureus, S. epidermidis
• Gram-negative and anaerobic coverage if warranted
• Based on surgical site
• Operation involves transection of a hollow viscous/mucous membrane that may contain
resident flora
• Cephalosporins most commonly prescribed
• Cefazolin preferred
• Cefotetan or cefoxitin for broader gram-negative and anaerobic coverage
• Vancomycin or clindamycin for Type I penicillin allergy
• Vancomycin for prosthetic implantation and high MRSA risk

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Learning Check 1
During your shift in the hospital, you receive an order for cefoxitin 1 g IV “on call” for surgical
prophylaxis. Upon further investigation of the patient’s chart, you see that they are scheduled
to undergo an appendectomy at 1300. You look up the pharmacokinetics of cefoxitin and find
that the half-life is approximately 1 hour. You then call the operating room nurse to
recommend appropriate timing of cefoxitin administration.
1. When would you recommend the nurse to begin the cefoxitin infusion?
2. Under what circumstance would you recommend the nurse to give another dose of
cefoxitin 1 g?

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 Recommendations for Specific Types of Surgery
Hepatobiliary Surgery

Type of Likely Recommended Alternative for β-

Operation / Prophylaxis Comments
SSI Risk Pathogens Regimen lactam allergy
Cholecystectomy Enteric gram- Cefazolin 1 g x1 Clindamycin or High-risk patients only (open
negative bacilli vancomycin biliary tract procedures,
NRC: Clean/clean- (E. coli, -plus- acute cholecystitis, common
contaminated Klebsiella), aztreonam, AG, duct stones, previous biliary
enterococci or FQ surgery, jaundice, age >60
SSI risk <5% years, obesity, diabetes)
Not indicated in laparoscopic
procedures

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Laparoscopic Cholecystectomy

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Recommendations for Specific Types of Surgery
Gastrointestinal Surgery

Type of Recommended
Operation / Likely Prophylaxis Alternative for β- Comments
SSI Risk Pathogens Regimen lactam allergy

Gastroduodenal Enteric gram- Cefazolin 1 g x1 Clindamycin or High-risk patients

NRC: Clean / negative vancomycin only (obstruction,
clean- bacilli, gram- -plus- hemorrhage,
contaminated positive cocci aztreonam, AG, malignancy, acid
or FQ suppression therapy,
SSI risk <5% morbid obesity)

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Recommendations for Specific Types of Surgery
Type of Likely Recommended Alternative for β-
Operation / Prophylaxis Comments
SSI Risk Pathogens Regimen lactam allergy

Appendectomy Enteric gram- Cefotetan or Clindamycin Re-dose cefoxitin if

negative cefoxitin 1 g x1 -plus- procedure lasts >2
NRC: bacilli, -or- aztreonam, AG, hours
Contaminated anaerobes Cefazolin 1 g x1 or FQ
-plus-
SSI rate 15-30% Metronidazole 1 g -or-
x1
Metronidazole
-plus-
AG or FQ

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Recommendations for Specific Types of Surgery
Type of Likely Recommended Alternative for
Operation / Comments
SSI Risk Pathogens Prophylaxis Regimen β-lactam allergy

Colorectal Enteric gram- Cefotetan or cefoxitin Clindamycin Role of mechanical

negative 1 g x1 -plus- bowel preparation
NRC: bacilli, aztreonam, AG, is controversial, but
Contaminated anaerobes PO: neomycin 1 g + or FQ still widely used
erythromycin base 1 g
SSI rate 15-30% + mechanical bowel -or-
preparation (e.g.
polyethylene glycol or Metronidazole
sodium phosphate -plus-
solutions) AG or FQ

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Recommendations for Specific Types of Surgery
Type of Likely Recommended Alternative for
Operation / Comments
SSI Risk Pathogens Prophylaxis Regimen β-lactam allergy

Gastrointestinal Enteric gram- Cefazolin 1 g x1 or Clindamycin or High-risk patients*

Endoscopy negative ampicillin 2 g x1 vancomycin undergoing high-
bacilli, gram- -plus- risk procedures^
Low positive cocci, aztreonam, AG,
oral anaerobes or FQ

*High-risk patients: prosthetic heart valves, history of endocarditis, systemic-pulmonary shunt,

synthetic vascular graft <1 year old, complex cyanotic congenital heart disease, obstructed bile duct,
liver cirrhosis, immunocompromised
^High-risk procedures: stricture dilation, variceal sclerotherapy, endoscopic retrograde
cholangiopancreatography (ERCP)

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Learning Check 2
Cefazolin monotherapy is an inadequate antimicrobial prophylaxis regimen for the following
types of surgery (select all that apply):
A. Cholecystectomy
B. Gastroduodenal
C. Appendectomy
D. Colorectal
E. Gastrointestinal endoscopy

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 Recommendations for Specific Types of Surgery
Urologic Surgery

Type of Operation / Likely Recommended

Alternative Comments
SSI Risk Pathogens Prophylaxis Regimen
Prostate resection, shock- E. coli Aminoglycoside All patients with positive
wave lithotripsy, ureteroscopy with or without preoperative urine
Ciprofloxacin 500 mg PO clindamycin cultures should receive a
Unknown (catheters -or- course of antibiotic
commonly used Bactrim DS 1 tablet PO treatment
postoperatively)

Removal of external urinary E. coli Clindamycin or Consider only in patients

catheters, cystography, vancomycin with risk factors*
urodynamic studies, simple
cystourethroscopy Cefazolin 1 g x1
Low

*Elderly, anatomic anomalies present, poor nutrition, external catheter, colonized endogenous/exogenous material,
coexisting infection, smoker, immunocompromised, prolonged hospital stay 23
 Recommendations for Specific Types of Surgery
Gynecological Surgery

Recommended
Type of Operation / Likely Prophylaxis Alternative for β-lactam Comments
SSI Risk Pathogens Regimen allergy

Cesarean section Cefazolin 2 g x1 and Clindamycin plus AG Antimicrobial

azithromycin 500 mg administration should be
High IV x1 prior to the initial
Enteric gram- incision; decreases
negative bacilli, antibiotic exposure to
anaerobes, neonate
group B
Hysterectomy streptococci, Vaginal or Clindamycin or vancomycin
enterococci abdominal: cefazolin -plus-
High 1 g x1 or cefotetan 1 aztreonam, AG, or FQ -
g x1 -or-
Metronidazole + AG or FQ
 Recommendations for Specific Types of Surgery
Head and Neck Surgery
• Prophylaxis necessary if incision is made through a mucosal layer

Type of Operation / Likely Recommended Alternative for β-

Comments
SSI Risk Pathogens Prophylaxis Regimen lactam allergy

Maxillofacial surgery Cefazolin 2 g x1 Clindamycin

-or-
NRC: Clean to clean- clindamycin 600 mg x1 -
contaminated S. aureus,
streptococci
spp., oral
Head and neck anaerobes Clindamycin 600 mg at Add gentamicin for
cancer resection induction and every 8 clean-contaminated
NRC: Clean to clean- hours for 2 more doses - procedures
contaminated

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Learning Check 3
Cefazolin monotherapy is an inadequate antimicrobial prophylaxis regimen for the following
types of surgery (select all that apply):
A. Urologic surgery involving kidney stones
B. Cesarean section
C. Hysterectomy
D. Maxillofacial surgery
E. Head and neck cancer resection

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Recommendations for Specific Types of Surgery
Cardiothoracic Surgery
• Coronary artery bypass graft (CABG) surgery: 22% mortality rate at 1 year if SSI is developed
after surgery (0.6% mortality if no SSI develops)
• Risk factors for developing a SSI after cardiac surgery
• Obesity
• Renal insufficiency
• Connective tissue disease
• Re-exploration for bleeding
• Poorly timed antibiotic administration
• Cefazolin usually drug of choice for cardiac surgeries
• Vancomycin for hospitals with high MRSA incidence or when sternal wounds require surgical
exploration for possible mediastinitis
• Cefuroxime superior to cefazolin for pulmonary surgeries

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 Recommendations for Specific Types of Surgery
Cardiothoracic Surgery

Type of Operation / Recommended Prophylaxis Alternative

Likely Pathogens for β-lactam Comments
SSI Risk Regimen allergy
Cardiac surgery S. aureus, S. Cefazolin 1 g Q8H for 48 hours Patients >80 kg should
epidermidis, receive 2 g of cefazolin
NRC: Clean Corynebacterium Intranasal mupirocin BID for 5 instead; consider
days preoperatively for vancomycin in areas with
patients colonized with S. high prevalence of S.
aureus aureus resistance
Clindamycin,
vancomycin
Thoracic surgery S. aureus, S. Cefuroxime 750 mg IV Q8H for First-generation
epidermidis, 48 hours cephalosporins are
NRC: Clean Corynebacterium, inadequate
enteric gram-
negative bacilli

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Recommendations for Specific Types of Surgery
Orthopedic Surgery
• Most orthopedic surgery is clean
• Prophylactic antibiotics indicated only when prosthetic materials are implanted
(e.g. pins, plates, artificial joints)
• Infection can result in significant morbidity  prosthesis failure and subsequent removal
• Drug of choice is cefazolin
• Vancomycin for penicillin allergy or high MRSA prevalence
• Recommended duration of prophylaxis is 24 hours
• Exception: hip fracture repair
• Data behind efficacy of antibiotic-impregnated cement and beads is lacking

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 Recommendations for Specific Types of Surgery
Orthopedic Surgery
Alternative
Type of Operation / Likely Pathogens Recommended Prophylaxis for β-lactam Comments
SSI Risk Regimen allergy
Joint replacement Cefazolin 1 g x1 preoperatively, Intranasal mupirocin BID
then every 8 hours x2 more for 5 days preoperatively
NRC: Clean doses for patients colonized
S. aureus, S. with S. aureus
epidermidis
Hip fracture repair Cefazolin 1 g x1 preoperatively,
then every 8 hours for 48 hours Clindamycin, -
NRC: Clean vancomycin
Open/compound S. aureus, S. Cefazolin 1 g x1 preoperatively, Gram-negative coverage
fractures epidermidis, then every 8 hours for a course (i.e. gentamicin) often
gram-negative of presumed infection indicated for severe open
Infection presumed bacilli, fractures
polymicrobial

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 Recommendations for Specific Types of Surgery
Neurosurgery

Alternative
Type of Operation / Likely Pathogens Recommended Prophylaxis for β-lactam Comments
SSI Risk Regimen
allergy
CSF shunt procedures Cefazolin 1 g Q8H x3 doses No agents have been
-or- shown to be better than
High ceftriaxone 2 g x1 cefazolin in randomized
comparative trials
Spinal surgery Cefazolin 1 g x1 Limited number of clinical
S. aureus, S. Clindamycin, trials comparing different
Low epidermidis vancomycin treatment regimens

Craniotomy Cefazolin 1 g x1 or cefotaxime Vancomycin 1 g IV x1 for

1 g x1 penicillin allergy
Low

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CSF Shunt

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Learning Check 4
Cefazolin monotherapy is an inadequate antimicrobial prophylaxis regimen for the following
type of surgery:
A. Cardiac
B. Thoracic
C. Orthopedic
D. Neurosurgery

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Surgical Site Infections
IDSA Practice Guidelines for SSTIs (2014)
Signs of Significant
• All SSIs: suture removal plus incision and drainage Systemic Response
• Antibiotics not routinely indicated; may be beneficial in conjunction Erythema and induration
with I/D and signs of significant systemic response extending >5 cm from the
• wound edge
Short course (24-48 hours) of antibiotics
• Especially in operations on the trunk, head and neck, or extremities Temperature >38.5°C
• MSSA: 1st-generation cephalosporin, anti-staph penicillin Heart rate >110 beats/min
• MRSA: vancomycin, linezolid, daptomycin, telavancin, ceftaroline WBC >12K
• Gram-negatives + anaerobes: cephalosporin or FQ + metronidazole
• SSIs following operations on the axilla, GI tract, perineum, or
female genital tract

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Summary
• Antibiotic administration should be initiated within 60
minutes prior to the initial incision
• Exception: 120 minutes for vancomycin and FQs
• Re-dose prophylactic antibiotic when surgery lasts
longer than two half-lives of the antibiotic
• Common pathogens associated with anatomical sites
• Spectrum of coverage
• Cefazolin
• Cefotetan/cefoxitin
• Alternatives in β-lactam allergy
• Indications for treatment of surgical site infections

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References
1. Hollingsworth  JM, Krein  SL, Ye  Z,  et al. Opening of ambulatory surgery centers and procedure use in elderly
patients: Data from Florida. Arch Surg 2011;146:187–193. 
2. National Hospital Discharge Survey. Available at: 
ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Datset_Documentation/NHDS/NHDS_2010_Documentation.pdf.
3. Berríos-Torres  SI, Umscheid  CA, Bratzler  DW,  et al. Centers for Disease Control and Prevention Guideline for
the Prevention of Surgical Site Infection, 2017. JAMA Surg. Aug 1 , 2017;152(8):784–791.
4. Hendrick  TL, Anastacio  MM, Sawyer  RG. Prevention of surgical site infection. Expert Rev Anti Infect
Ther. 2006;4:223–233.
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ofultraviolet irradiation of the operating room and of various other factors. Ann Surg. 1964;160:32–135.
6. Cruse  PJE, Foord  R. A five-year prospective study of 23,649 surgical wounds. Arch Surg. 1973;107:206–210. 
7. Alexander  JW, Solomkin  JS, Edwards  MJ. Updated recommendations for control of surgical site infections. Ann
Surg. 2011;253:1082–1093.
8. NNIS.National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992
through June 2004 issued October 2004. Am J Infect Control. 2004;32:470–485.
9. Classen  DC, Evans  RS, Pestotnik  SL,  et al. The timing of prophylactic administration of antibiotics and the risk
of surgical wound infection. N Engl J Med. 1992;326:281–286. 

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Thank You
• Active learning due at 1:30 PM on Canvas

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