Antimicrobial Prophylaxis for Surgical

Procedures

Zenebe k (B.Pharm., MSc,Rph)

Outline
• Introduction

• Epidemiology and etiology

• Pathophysiology

• Treatment

• Patient care and monitoring

Learning Objectives
 Learning Objectives
 By the end of the session you should be able to:
 Discuss the epidemiological data and impact of SSI

 Identify patient-specific risk factors for surgical site infections.

 Identify operation-specific risk factors for surgical site infections

 List common pathogens responsible for surgical site infections.

 Discuss the importance of timing, duration, and re-dosing in relation to

antimicrobial prophylaxis in surgery.

 Discuss selection and administration of antibiotic therapy for surgical

procedures.

 Identify non-antimicrobial methods that can reduce the risk of SSI

Introduction
 Surgical site infections (SSIs) are classified as either incisional or
organ/space (CDC)
 Incisional SSIs are further divided into
-superficial incisional SSI (skin or subcutaneous tissue) and
-deep incisional SSI (deeper soft tissues of the incision).
 Organ/space SSIs involve any anatomic site other than the
incised areas.
o For example, a patient who develops meningitis after removal of a brain
tumor could be classified as having an organ/space SSI.
 An infection is considered an SSI if any of the above criteria is met and
the infection occurs within 30 days of the operation.
o If a prosthetic is implanted, the timeline extends out to 1 year.
 Prophylactic antibiotics are widely used in surgical procedures

and account for substantial antibiotic use in many hospitals.

 The purpose of surgical antibiotic prophylaxis is to reduce

the prevalence of postoperative wound infection (about 5%

of surgical cases overall) at or around the surgical site.

 By preventing surgical site infections, prophylactic

antimicrobial agents have the potential to decrease patient

morbidity and hospitalization costs for many surgical

procedures that pose significant risk of infection.(e.g., appendectomy)

 However, the benefits of prophylaxis are controversial,

prophylaxis is not justified for some surgical

procedures (e.g., urologic operations in patients with

sterile urine).

Consequently, the inappropriate or indiscriminate use

of prophylactic antibiotics can increase the risk of :

drug toxicity, selection of resistant organisms, and

costs.
Epidemiology and etiology
 In U.S., >40 million inpatient surgical procedures

each year; 2-5% complicated by surgical site infection

 SSIs second most common nosocomial infection (24% of

all nosocomial infections)

Prolong hospital stay by 7.4 days

Cost $400-$2,600 per infection (TOTAL: $130-$845

million/year)
What are the risk factor for surgical site
infection???
a) Patient related factor
b) Operation related factor
Table-1: Factors Affecting the Incidence
of Surgical Site Infection
Source: Scottish National guideline
 Many experts recommend that antimicrobial

prophylaxis should be given for surgical procedures

(a) with a high rate of infection,
(b) involving the implantation of prosthetic
materials, or
(c) those in which an infection would have
catastrophic consequences.
Pathophysiology
 Prophylaxis versus Treatment
 The distinction between prophylaxis and treatment influences

the choice of antimicrobial and duration of therapy.

 Appropriate antimicrobial selection, dosing, and duration of

therapy differ significantly between these two situations.

 A regimen for antimicrobial prophylaxis ideally involves

one agent and lasts less than 24 hours.

 Treatment regimens can involve multiple antimicrobials with

durations lasting weeks to months depending on desired

antimicrobial coverage and the surgical site.
 Types of Surgical Operations
 Surgical operations are classified as

 clean,

 clean-contaminated,

 contaminated, or

 dirty.

 Antimicrobial prophylaxis is appropriate for clean, clean-

contaminated, and contaminated operations.

 Dirty operations take place in situations of existing infection and

antimicrobials are used for treatment, not prophylaxis

 Table-2 : National Research Council Wound Classification (* & **) +National Red Cross
Wound Classification (* &***)

Infection Antibiotic
Classification* Criteria* Rate (%)**SSI Risk*** Prophylaxis***
Clean No acute inflammation or entry <5 low indicated
into GI, respiratory, GU, or biliary
tracts; no break in aseptic
technique occurs; wounds
primarily closed
Clean- Elective, controlled opening of GI, <10 medium indicated
contaminated respiratory, biliary, or GU tracts
without significant spillage; clean
wounds with major break in sterile
technique
ContaminatedPenetrating trauma (<4-hr old); 15–20 high indicated
major technique break or major
spillage from GI tract; acute,
nonpurulent inflammation
Dirty Penetrating trauma (>4-hr old); 30–40 ___ Not indicated;
purulence or abscess (active antibiotics
infectious process); preoperative used for
perforation of viscera treatment
Source: Koda-Kimble . Applied Therapeutics:
 Microbiology/bacteriology
 Choosing the appropriate prophylactic antimicrobial relies on

anticipating which organisms will be encountered during the

operation.

 SSIs associated with extra-abdominal operations are the result

of skin flora organisms in nearly all cases.

 These organisms include gram-positive cocci,

 S. aureus and S.epidermidis being among the most frequently isolated SSI

pathogens according to the National Nosocomial Infections Surveillance System

(NNIS)

 Thus, for extra-abdominal operations an antimicrobial with strong gram-

positive coverage is useful.

 Intra-abdominal operations involve a diverse flora with the

potential for polymicrobial SSIs.

 Escherichia coli make up a large portion of bowel flora

 Other enteric gram-negative bacteria, as well as anaerobes

(especially Bacteroides spp.)

 Candida albicans is being implicated as the cause of a growing

number of SSIs.
 May be associated with increased use of broad spectrum antibiotics and rising

prevalence of immunocompromised and HIV–infected individuals

 Despite this fact, antifungal prophylaxis for surgery is not

currently recommended.
TABLE-3. Major Pathogens in Surgical Wound Infections
Table-4:profiles of bacterial isolates identified in postoperative wound infection
Gondar University Hospital, November 2010 - February 2011
Principles of Surgical
Antimicrobial Prophylaxis
 scheduling antibiotic administration
 Always consider the following principles in prophylaxis
(a) the agents should be delivered to the surgical site prior
to the initial incision, and
(b) bactericidal antibiotic concentrations should be
maintained at the surgical site throughout the surgical
procedure. so
 pre-operative …admn..30-60min
 Intra-operative(based on half life of antibiotics)—redosing
 Post-operative(based on setting cleans…go upto 72hrs
NB: Administration too early result in concentrations below the MIC
toward the end of the operation, and administration too late leaves
the patient unprotected at the time of initial incision.
 Choosing an Antibiotic
 Criteria

 covers expected pathogens (very crucial)

 should be inexpensive,

 available in a parenteral formulation, and easy to use.

 Adverse event potential should be minimal.

 Choosing an agent with a longer half-life reduces the

likely need to redose

 Table-5: Half-Lives, Dosage form, microorganisms coverage and Price of Selected
Antibiotics Commonly Used for Prophylaxis
antibiotic ½ m.o coverage Cost
life D.F /d
Cefazolin 1g 1.8 IV Staphylococci (except MRSA), Streptococci (not $10
Enterococci), E coli, Proteus & Klebsiella *
3 to 9
Vancomycin 1g IV Staphylococcus aureus, Staphylococ- $60
cus epidermidis including MRSA
0.6 to 1
Cefoxitin 1g IV m.o coverage of cefazolin plus bacteroides $30

3 to 4.6
Cefotetan IV m.o coverage of cefazolin plus bacteroides $30
2
Aminoglycosides IV aerobic Gram-negative bacilli, including $5
(gantamycin 80mg) pseudomonas
8
Metronidazole 0.5g IV Bacteroides fragilis and against several intestinal $10
protozoa
2.4 to 3
Clindamycin 600mg IV G+ bacteria (staphylococci, pneumococci, $10
Streptococcus pyogenes) and against most anaerobes

3 to 5 IV Enterobacteriacea, Pseudomonas, Chlamydia $10

Ciprofloxacin 400mg
Mycoplasma & Legionella
 Cefazolin is the preferred & mainstay for surgical

prophylaxis of extra-abdominal procedures b/c

 benign adverse-event profile, simple dosing, and low cost.

 Suitable for most clean procedures, including cardiac,

vascular, and orthopedic procedures.

 its risk of cross-allergenicity to B-lactam penicillin,

clindamycin or vancomycin is minimal and can be

used as an alternative.
 Vancomycin should be given within 2 hours prior to

surgical incision.
If duration of surgical procedure is >4 hours, patient

should receive a second prophylactic dose

intraoperatively….redosing
Total duration must be 24 hours for non-cardiothoracic

surgery and 48 hours for cardiothoracic surgery.

Consider 2 grams in patients >100 kg.
 Intra-abdominal operations necessitate broad-spectrum coverage of

gram-negative organisms and anaerobes.

 Anti-anaerobic cephalosporins (cefoxitin and cefotetan) are useful

but suffer from limited availability.

 Fluoroquinolones or aminoglycosides, paired with clindamycin

or metronidazole, should provide adequate coverage for intra-

abdominal operations.

 The Hospital Infection Control Practices Advisory Committee

allows for the use of vancomycin for surgical prophylaxis when

MRSA rates at an institution are “high.”
N.B patients who received cefazolin were more likely to develop an SSI due to MRSA.
Decision to Use Antimicrobial Prophylaxis

 The selected prophylactic agent should be directed against

likely infecting organisms, but need not eradicate every

potential pathogen.

 It should be bear in mind that, the goal of prophylaxis is

to decrease bacterial counts below critical levels necessary

to cause infection.
 Newer antimicrobials have not demonstrated superiority in the

prevention of SSI and should be reserved for treatment only.

 Broad-spectrum agents, such as Carbapenems

(antipseudomonal penicillins), 3rd & 4th generation

cephalosporins, should be avoided for prophylaxis, because
they are no more effective than cefazolin,
may alter microbial flora, and
increasing the emergence of microbial resistance
 Route of Administration
 In general, oral administration of surgical antimicrobial prophylaxis is not

recommended, because
unreliable or poor absorption of oral agents in the anesthetized bowel.
however, oral agents function effectively as GI decontaminants

 The concentration of bacteria in the colon may approach 1016

bacteria/mm3
 colorectal procedures, carry a relatively high risk of postoperative

infection.

 Antimicrobial regimens with activity against the mixture of aerobic and

anaerobic bacteria are effective in preventing postoperative SSIs in

these area
 The most widely used oral antimicrobial regimen directed

against the fecal flora is

 1 g each of the nonabsorbable antibiotics neomycin sulfate (for

gram-negative aerobes) and erythromycin base (for anaerobes),

 given 1 day before surgery at the times indicated.

 Mechanical bowel cleansing, such as with polyethylene glycol-

electrolyte or sodium phosphate lavage solution, should

precede the above regimen

 Effective oral alternatives to the above regimen include

 Metronidazole ± neomycin/kanamycin, or kanamycin +

erythromycin; but no clinical warranty

 Timing of Antimicrobial Administration
 For maximal efficacy, an antibiotic should be present in therapeutic

concentrations at the incision site as early as possible during

the decisive period and continuing until the wound is closed.

 However, an antibiotic administered postoperatively cannot

achieve therapeutic concentrations during the decisive period,

and infection rates are similar to those in patients who receive no
antibiotics.
 But some studies showed that the incidence of endometritis after

C/S is decreased significantly by postoperative administration of

antibiotics.
 Therefore, prophylactic antibiotics should be

administered before the surgical procedure in the OR

before or during the induction of anesthesia.

 Prophylactic antibiotics are most effective when given

 during the 30 min-1hour period before the surgical incision is made,

and
 rates of infection increase significantly if antibiotics are administered

>1 hour preoperatively or

any time postoperatively.

 Dosing and Redosing
 The goal of antimicrobial dosing for surgical prophylaxis is to

maintain antibiotic concentrations above the MIC of

suspected organisms for the duration of the operation.

 Dosing recommendations can vary between institutions and

guidelines.

 Clinical judgment should be exercised regarding dose modifications

for renal function, age, and especially weight.

 Obese patients often require higher doses than do non-obese

patients.
 Guidelines suggest that if an operation exceeds two half-

lives of the selected antimicrobial, then another dose

should be administered…redosing

 Repeat dosing has been shown to lower rates of SSI.

 The clinician should have extra doses of antibiotic ready

in case an operation lasts longer than planned.

 Redosing: administration of an additional dose of

antibiotics if the 1st dose half-life finished and operation

was take longer then expected time.
 Duration of Administration
 The shortest effective prophylactic course of antibiotics should be

used; i.e.,
 single dose preoperatively or not more than 24 hours postoperatively

for most procedures…if the setting is clean

 Postoperative doses after wound closure may continued for 72hrs if

the setting is not clean

 Single-dose prophylaxis, a viable option for many surgical

procedures, is controversial for cardiac procedures.

 In practice, cardiothoracic antimicrobial prophylaxis often is

continued 48 hours after surgery.(but>48hrs emergence of resistance)

 Signs of Surgical Site Infection
 Typically, an infected incision site wound is red, inflamed, and purulent.

 The purulent drainage should be cultured

 Empiric therapy directed against the most likely pathogens should be

instituted while awaiting culture and sensitivity test results.

 Although most incision site infections are clinically apparent shortly after

surgery (within 30 days), some deep-seated infections present

indolently over weeks to months…..may extended to 90 days

 When implants/prosthetic are involved, infections occurring up to a year

after surgery may be related to the operation.

Risks of Indiscriminate Antimicrobial Use
 The risks of indiscriminate use of antimicrobials to a given patient
include the potential for adverse effects and superinfection.

 The administration of any β-lactam agent poses the risk of a

hypersensitivity reaction, and many antibiotics, including
cefoxitin, are known to predispose patients to Clostridium
difficile-associated disease (pseudomembranous colitis).

 In addition, widespread or prolonged use of antimicrobial agents

increases the potential for the development or selection of
resistant organisms in a given patient or other patients who may
acquire a pathogen nosocomially.
 What are the “Emerging Pathogens”?
-due to Indiscriminate Antimicrobial Use

 Multi-Drug Resistant Gram Negative Bacilli (MDR)

 ESBLs* (E. coli, Klebsiella)

 P. aeruginosa

 Acinetobacter spp.

 Vancomycin-Resistant Enterococci (VRE)

 Enterococcus faecium

 Methicillin-Resistant S. aureus (MRSA)

 Clostridium difficile-Associated Disease

*Extended Spectum Beta-Lactmase
 Optimizing Surgical Antimicrobial
Prophylaxis
 Antibiotic control strategies have improved the appropriate use of

antimicrobial agents for surgical prophylaxis.

 The implementation of an automatic stop-order policy for

surgical prophylaxis has reduced the duration of antimicrobial

prophylaxis dramatically.
 These stop-order policies can be printed directly onto an antibiotic

order form.

 The process can help improve antibiotic appropriateness and timing

of administration.
 In collaboration with other health care providers, the

pharmacy department of health care organizations is

responsible for optimizing the timing, choice, and
duration of antimicrobial surgical prophylaxis.

 Education of surgical, anesthesia, and nursing staff, supported by

hospital policy changes initiated by pharmacists improved

appropriate timing from 68% to 97% and resulted in significant
cost avoidance.
Treatment/goals of prophylaxis
Goals of Surgical Prophylaxis
 Ideally, an anti-infective drug for surgical prophylaxis should

achieve the following goals:

(1) prevent postoperative infection of the surgical site,
(2) prevent postoperative infectious morbidity and mortality,
(3) reduce the duration and cost of health care,
(4) produce no adverse effects, and
(5) have no adverse consequences for the microbial flora of the
patient or the hospital.
 Table-6: Suggested Prophylactic Antimicrobial Regimens for
Surgical Procedures in Adults
Adult
Antibiotic Preoperative IV
Predominant Regimen Dose
Procedure Organism(s) (Alternative) (Alternative)a
Cardiac (all with sternotomy, Staphylococcus aureus, Staphylococcus Cefazolin 1 g (1 g)
cardio-pulmonary bypass) epidermidis (Vancomycin)

Thoracic S. aureus, S. epidermidis, gram-negative Cefazolin 1 g (1 g)

enterics (Vancomycin)

Vascular (aortic resection, S. aureus, S. epidermidis, gram-negative Cefazolin 1 g (1 g)

groin incision, prosthesis) enterics (Vancomycin)

Orthopedic (total joint S. aureus, S. epidermidis Cefazolin 1 g (1 g)

replacement, internal (Vancomycin)
fixation of fractures)
Neurosurgery S. aureus, S. epidermidis Cefazolin 1 g (1 g)
(Vancomycin)
 Table-6: cont’d
Head and neck S. aureus, oral anaerobes, Cefazolin 2 g (600 mg
streptococci (clindamycin/ clindamycin/
gentamicin) 1.5 mg/kg
gentamicin)

Gastroduodenal (only for Gram-negative enterics, S. aureus, Cefazolin 1g

procedures entering mouth flora
stomach)

Colorectal Gram-negative enterics, anaerobes Oral 1 g each at 1 PM,

(Bacteroides fragilis), enterococci neomycin- 2 PM, and 11 PM
erythromycin day before
base surgery (1 g)
(Cefoxitin)
Appendectomy Gram-negative enterics, anaerobes (B.Cefoxitin 1–2 g
(uncomplicated) fragilis)

Biliary tract (only for high- Gram-negative enterics, Enterococcus Cefazolin 1g

risk procedures) faecalis, Clostridia
 Table-6: cont’d

Cesarean section Group B streptococci, Cefazolin 2 g after

enterococci, anaerobes, gram- umbilical cord
negative enterics clamped

Hysterectomy Group B streptococci, enterococci, Cefazolin or 1g

anaerobes, gram-negative enterics cefoxitin

Genitourinary (only for high-Gram-negative enterics, enterococci Ciprofloxacin 400 mg

risk procedures)

 Cefazolin should be dosed at 2 g in patients >80 kg.

Source: Koda-Kimble . Applied Therapeutics:

Outcome Evaluation
 The clinician should consistently follow-up post-operative

patients and screen for any sign of SSI.

 According to CDC criteria, SSI may appear up to 30 days after an

operation and up to 1 year if a prosthesis is implanted.

 This period often extends beyond hospitalization so patients should

be educated on warning signs of SSI and be encouraged to contact a

clinician immediately if necessary.

 The presence of fever or leukocytosis in the immediate post-

operative period does not constitute SSI and should resolve with
proper patient care.
 Distal infections, such as pneumonia, are not considered SSIs

even if these infections occur in the 30-day period.

 The appearance of the surgical site should be checked regularly

and any changes documented (e.g., erythema, drainage, or pus).

 The presence of pus or other signs suggestive of SSI must

be treated accordingly.

 Any wound requiring incision and drainage is considered an SSI

regardless of appearance.

 Prompt cultures should be collected and appropriate

antimicrobial therapy initiated to reduce any chance of

morbidity and mortality.
 Alternative Methods to Decrease SSI
 Several non-antimicrobial methods have been studied for

reducing the risk of SSI.

providing supplemental warming(normothermia) to patients

(36.6°C -38°C) during the intraoperative period reduced

infection rates
 use of warming blankets and IV fluid warmers

intensive glucose control [80 to 110 mg/dL (4.44 to 6.1

mmol/L)] versus conventional control [glucose less than 210

mg/dL (less than 11.7 mmol/L)] in reducing infections in
critically ill patients.
 Provision of supplemental oxygen in the perioperative period.

 Administration of high concentrations of oxygen (80% via ventilator

or 12 L/min via a nonrebreather mask)

 Antibiotic-impregnated bone cement is being used as an

adjunct or alternative to traditional antimicrobial prophylaxis.

 A study by Chiu and associates found cefuroxime/gentamycin-

impregnated cement lowered the risk of deep infection after

primary total knee arthoplasty.

 Problem: The long-term durability is unknown,

Literatures & Guidelines Review
 Several studies have been performed investigating the utility of
prophylactic antibiotics in surgery.

 With regards to surgical prophylaxis, the data from these studies

support several recurring themes:
 Plenty of articles & guidelines found that ‘a single preoperative dose
of antibiotic is as effective as a 5-day course of postoperative
therapy assuming an uncomplicated procedure’ &
 Almost all articles & guidelines are complimentary in that
‘Prophylactic antibiotics should target the anticipated organisms’
 Most guidelines & literatures still agreed on:-

complicated, contaminated, or dirty procedures should receive

additional postoperative antimicrobial coverage

 During prolonged procedures, antibiotic prophylaxis should be

readministered every 3-4 hours…redosing

 Prophylactic antibiotics should be administered within 1 hour

prior to incision
Patient Care and Monitoring
 Conduct a thorough medication history including prescription
and non-prescription medications as well as herbals and vitamins.
 Verify the patient’s allergy history and the type of reaction
experienced.
 β-Lactam–allergic patients may receive clindamycin,
vancomycin, or other antimicrobials.
 The patient should be monitored for signs of an allergic reaction
during the operation.
 The patient should be monitored for signs and symptoms of
infection post-operatively.
 Patients being discharged should be counseled on recognizing
signs and symptoms of SSI.
 Food matters……protein, carbohydrate
 Drugs for comorbidity….mostly missed…becareful!
QUESTIONS?
Thank You!!!