CHAPTER

57

Antimicrobial Prophylaxis for Surgical Procedures

Daniel J. G. Thirion, B. Joseph Guglielmo
RISK FACTORS FOR INFECTION 57-1
CLASSIFICATION OF SURGICAL
WOUNDS 57-1
PRINCIPLES OF SURGICAL ANTIMICROBIAL
PROPHYLAXIS 57-3

Decision to Use Antimicrobial Prophylaxis 57-3

Timing of Antimicrobial Administration 57-3
Route of Administration 57-3
Duration of Administration 57-4
Signs of Wound Infection 57-5
Selection of an Antimicrobial Agent 57-5

Prophylactic antibiotics are widely used in surgical procedures and account for substantial antibiotic use in many hospitals.1 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.2
Such surgical site infections reportedly extend the duration of
hospitalization by at least 1 week, at an annual cost of more
than $1.5 billion nationwide.35 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, and prophylaxis is not justified for
some surgical procedures (e.g., urologic operations in patients
with sterile urine).6 Consequently, the inappropriate or indiscriminate use of prophylactic antibiotics can increase the risk
of drug toxicity, selection of resistant organisms, and costs.

RISK FACTORS FOR INFECTION

The development of postoperative site infection is related to
the degree of bacterial contamination during surgery, the
virulence of the infecting organism, and host defenses. Risk
factors for postoperative site infection can be classified according to operative and environmental factors, and patient
characteristics.7
Bacterial contamination may occur from exogenous
sources (e.g., the operative team, instruments, airborne organisms) or from endogenous sources (e.g., the patients microflora of the skin, respiratory, genitourinary, or gastrointestinal [GI] tract).7,8 Infection control procedures to minimize
all sources of bacterial contamination, including patient and
surgical team preparation, operative technique, and incision
care, are compiled in Centers for Disease Control and Prevention guidelines for surgical site infection.7
The risk of postoperative site infection is affected by host
factors such as extremes of age, obesity, cigarette smoking,
malnutrition, and comorbid states, including diabetes mellitus, remote infection, colonization with microorganisms, and

Risks of Indiscriminate Antimicrobial Use 57-6

OPTIMIZING SURGICAL ANTIMICROBIAL
PROPHYLAXIS 57-6

immunosuppressive therapy.8,9 In addition, the longer the preoperative hospital stay and the surgical procedure, the greater
the likelihood of developing a postoperative wound infection,
presumably as a result of nosocomial bacterial acquisition in
the former and the greater amount of bacterial contamination
occurring over time in the latter.8
Another major risk factor for infection is the skill of the
surgeon. In one study,10 postoperative wound infection rates
were related inversely to the frequency of performing a surgical procedure; thus, hospitals with the highest frequency of
surgical procedures have the lowest incidence of postoperative infection.
Based on these risk factors for infection, the decision as to
whether a given patient should receive antimicrobial prophylaxis is multifactorial. Many experts recommend that antimicrobial prophylaxis should be given for surgical procedures
with a high rate of infection, procedures involving the implantation of prosthetic materials, or procedures in which an
infection would have catastrophic consequences.9,11 A widely
used surgical wound classification system to assist in this decision-making process follows.

CLASSIFICATION OF SURGICAL WOUNDS

From 1960 to 1964, the National Academy of Sciences National
Research Council conducted a landmark study of surgical
wound infections and formulated a widely used standard classification of surgical wounds based on the risk of intraoperative
bacterial contamination (Table 57-1).8 Current recommendations for surgical prophylaxis pertain to clean surgeries involving implantation of prosthetic material, clean-contaminated
surgeries, and select contaminated wounds. Antimicrobial
therapy for most contaminated and all dirty surgeries in which
infection already is established is considered treatment instead of prophylaxis and is not discussed further in this chapter. Table 57-2 lists suspected pathogens and recommendations for site-specific prophylactic antimicrobial regimens; a
detailed examination of clinical trials supporting these recommendations is presented elsewhere.6

57-1

57-2

INFECTIOUS DISORDERS

Table 57-1

National Research Council Wound Classification

Classification

Criteria

Infection Rate (%)

Clean

No acute inflammation or entry into GI, respiratory, GU, or biliary tracts; no break in aseptic
technique occurs; wounds primarily closed

5

Clean-contaminated

Elective, controlled opening of GI, respiratory, biliary, or GU tracts without significant spillage;
clean wounds with major break in sterile technique

10

Contaminated

Penetrating trauma (4 hr old); major technique break or major spillage from GI tract; acute,
nonpurulent inflammation

1520

Dirty

Penetrating trauma (>4 hr old); purulence or abscess (active infectious process); preoperative
perforation of viscera

3040

GI, gastrointestinal; GU, genitourinary.

From references 3 and 8.

Table 57-2

Suggested Prophylactic Antimicrobial Regimens for Surgical Procedures

Procedure

Predominant Organism(s)

Antibiotic Regimen (Alternative)

Adult Preoperative IV Dose (Alternative)

Cardiac (all with

sternotomy, cardiopulmonary bypass)

Staphylococcus aureus, Staphylococcus epidermidis

Cefazolin (Vancomycin)

1 g (1 g)

Vascular (aortic resection,

groin incision,
prosthesis)

S. aureus, S. epidermidis, Gramnegative enterics

Cefazolin (Vancomycin)

1 g (1 g)

Orthopedic (total joint

replacement, internal
fixation of fractures)

S. aureus, S. epidermidis

Cefazolin (Vancomycin)

1 g (1 g)

Neurosurgery

S. aureus, S. epidermidis

Cefazolin (Vancomycin)

1 g (1 g)

Head and neck

S. aureus, oral anaerobes, streptococci

Cefazolin (Clindamycin 
gentamicin)

2 g (600 mg clindamycin 
1.5 mg/kg gentamicin)

Gastroduodenal (only
for procedures entering
stomach)

Gram-negative enterics, S. aureus,

mouth flora

Cefazolin

1g

Colorectal

Gram-negative enterics, anaerobes

(Bacteroides fragilis)

Oral neomycinerythromycin base

(IV Cefoxitin or cefotetan)

1 g each at 1 PM, 2 PM, and 11

PM day before surgery (1 g of
either)

Appendectomy
(uncomplicated)

Gram-negative enterics, anaerobes

(B. fragilis)

Cefoxitin or cefotetan

12 g

Biliary tract (only for

high-risk procedures)

Gram-negative enterics,
Enterococcus faecalis, Clostridia

Cefazolin

1g

Cesarean section

Group B streptococci, enterococci,

anaerobes, Gram-negative enterics

Cefazolin

2 g after umbilical cord clamped

Hysterectomy

Group B streptococci, enterococci,

anaerobes, Gram-negative enterics

Cefazolin, cefoxitin, or cefotetan

1g

Genitourinary (only for

high-risk procedures)

Gram-negative enterics, enterococci

Ciprofloxacin

400 mg

Clean

Clean-Contaminated

ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

PRINCIPLES OF SURGICAL ANTIMICROBIAL

PROPHYLAXIS
Decision to Use Antimicrobial Prophylaxis
1. M.R., a 72-year-old woman, is admitted to the hospital
with severe abdominal pain, nausea and vomiting, and temperature of 39.3C. A diagnosis of acute cholecystitis is made, and
M.R. is scheduled for biliary tract surgery (cholecystectomy).
Why is antimicrobial prophylaxis warranted for M.R.?

Biliary tract surgery is considered a clean-contaminated

procedure and therefore carries a risk of surgical wound infection approaching 10% (see Tables 57-1 and 57-2). Prophylaxis for biliary tract surgery is limited to high-risk procedures, which include obesity, age 70 years, diabetes
mellitus, acute cholecystitis, obstructive jaundice, or common
duct stones.6,9,12 Thus, prophylaxis is warranted in M.R., who
falls into at least two high risk categories (age 70 years and
acute cholecystitis).
2. An order for cefazolin 1 g IV on call to the operating room
(OR) is written for M.R. Why is this an appropriate (or inappropriate) antibiotic selection?

The selected prophylactic agent should be directed against

likely infecting organisms (see Table 57-2) but need not eradicate every potential pathogen. Cefazolin has been proven effective for most surgical procedures, including biliary tract
surgery, given that the goal of prophylaxis is to decrease bacterial counts below critical levels necessary to cause infection.
Broad-spectrum agents such as third-generation cephalosporins should be avoided for prophylaxis because they are no
more effective than cefazolin and may alter microbial flora,
increasing the emergence of microbial resistance to these otherwise valuable agents.

Timing of Antimicrobial Administration

3. Why is the administration time for this antimicrobial appropriate (or inappropriate) for M.R.?

Classic animal studies conducted by Burke13 and others14

clearly demonstrated the need for therapeutic antibiotic concentrations in the bloodstream and in vulnerable tissue at the
time of wound contamination. Bacteria were most likely to
enter the tissue beginning with the initial surgical incision and
continuing until the wound was closed; antibiotics administered 3 hours after bacterial contamination were ineffective
in minimizing the development of wound infection.13,14 This
2- to 3-hour period after the surgical incision was deemed the
effective or decisive period for prophylaxis, when the animal wound was most susceptible to the beneficial effects of
the antibiotic. This decisive period for administration of prophylactic antibiotics has been confirmed in humans.15,16
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. Because an antibiotic administered postoperatively cannot achieve therapeutic concentrations during the
decisive period, such timing of surgical prophylaxis is of no
benefit in preventing postoperative wound infections, and in-

57-3

fection rates are similar to those in patients who receive no antibiotics.16 An exception in which post-incision administration
sometimes is justified is in cesarean sections, because the incidence of post-cesarean endometritis is decreased significantly by postoperative administration of antibiotics.6
Based on these study results, prophylactic antibiotics
should be administered before the surgical procedure in the
OR before the induction of anesthesia.7 Prophylactic antibiotics are most effective when given during the 2-hour period
before the surgical incision is made, and rates of infection increase significantly if antibiotics are administered 2 hours
preoperatively or any time postoperatively.17
The on call prescribing practice for surgical prophylaxis,
as with M.R., has fallen into disfavor because the time between antibiotic administration and the actual incision may
exceed 2 hours and therefore may result in subtherapeutic antibiotic concentrations during the decisive period.18,19 M.R.s
cefazolin should be ordered preoperatively and should be administered in the operating room no earlier than 2 hours before the operative procedure.
4. Will M.R. require a second dose of cefazolin during the
surgical procedure?

The duration of the surgical procedure and the half-life of

the administered antibiotic should be considered when determining whether an additional dose is necessary to maintain adequate antibiotic concentrations at the operative site. Studies
have indicated an inverse relationship between the efficacy of
short-acting antibiotics and the duration of the surgical procedure; as operative time increases, so does the incidence of postoperative infection.20,21 Cefazolin, with a half-life of approximately 1.8 hours, is effective in a single preoperative dose for
most surgical procedures. For procedures lasting 3 hours, additional intraoperative doses should be administered every 3 to
8 hours during the procedure,9,22 especially if an antibiotic with
a short half-life, such as cefoxitin, has been administered. M.R.
should require an additional intraoperative cefazolin dose only
if the surgical procedure is prolonged (>3 hours).

Route of Administration
5. G.B., a 55-year-old woman recently diagnosed with carcinoma of the large bowel, is admitted to the hospital for an elective
colorectal surgical resection; the surgery is expected to last 5
hours. Physical examination reveals a cachectic woman with a 9kg weight loss over the previous 3 months (current weight, 60 kg).
Increased frequency of bowel movements and chronic fatigue are
noted; all other systems are normal. Laboratory data include hemoglobin (Hgb), 10.4 g/dL (normal, 11.5 to 15.5); hematocrit
(Hct), 29.7% (normal, 33% to 43%); and prothrombin time (PT),
15 seconds (normal, 11 to 13). Stool guaiac is positive. Vital signs
are within normal limits. G.B. is taking no medications and has
no history of drug allergies. The following orders are written to
begin at home on the day before surgery: (1) Clear liquid diet; (2)
Mechanical bowel cleansing with polyethylene glycol-electrolyte
lavage solution (CoLYTE, GoLYTELY); (3) Neomycin sulfate 1 g
and erythromycin 1 g PO at 1 PM, 2 PM, and 11 PM. Comment
on the appropriateness of the oral route of administration of antibiotic prophylaxis for G.B.
[SI units: Hgb, 104 g/L; Hct, 0.297]

57-4

INFECTIOUS DISORDERS

In general, oral administration of surgical antimicrobial

prophylaxis is not recommended because of unreliable or
poor absorption of oral agents in the anesthetized bowel. Oral
agents, however, function effectively as GI decontaminants
because high intraluminal drug concentrations are sufficient
to decrease bacterial counts.23 The concentration of bacteria in
the colon may approach 1013 bacteria/mm3 and colorectal procedures, such as the one G.B. will undergo, carry a relatively
high risk of postoperative infection. Antimicrobial regimens
with activity against the mixture of aerobic and anaerobic
bacteria that make up the fecal flora (Escherichia coli and
other Enterobacteriaceae and Bacteroides fragilis) are effective in preventing postoperative wound infections.24,25
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 for G.B.16,25 Mechanical bowel cleansing,
such as with polyethylene glycol-electrolyte lavage solution,
must precede this regimen; the purpose of such bowel purging
is to evacuate the colonic contents as completely as possible
to decrease colonic bacterial counts. Effective oral alternatives to neomycin plus erythromycin include metronidazole
with or without neomycin or with kanamycin, or kanamycin
plus erythromycin24,26; however, clinical situations warranting
the use of such alternatives over the well-established
neomycinerythromycin regimen are practically nonexistent.
Thus, the regimen selected for G.B. is highly appropriate.
6. The surgical resident has canceled the oral neomycin
erythromycin bowel regimen for G.B. Instead, he orders cefoxitin (Mefoxin) 1 g IV preoperatively. Why is (or is not) this
change in therapy an effective and rational choice for G.B.?

Numerous parenteral regimens, specifically with agents

that possess both aerobic and anaerobic activity, are effective
as surgical prophylaxis in colorectal procedures.24 The
second-generation cephalosporins with significant anaerobic
activity (e.g., cefoxitin, cefotetan) are superior to firstgeneration cephalosporins, which lack sufficient anaerobic
activity.27,28 At present, it is not clear whether oral antimicrobial prophylaxis is superior to parenteral therapy in the prevention of infection after colorectal surgery.29
Thus, although both intravenous (IV) and oral regimens
are effective for prophylaxis before colorectal surgery, the
parenteral route of administration, selected because of physician preference, may be less effective.9 Furthermore, the cefoxitin order for G.B. would be unacceptable if the surgery
lasts 3.5 hours (the relatively short half-life of cefoxitin
could render G.B. antibiotic-free and predispose her to infection).30 For prolonged procedures (>3 hours) such as anticipated for G.B., an alternative agent with a longer half-life
(e.g., cefotetan) or a second dose of cefoxitin should be administered. However, cefotetan may be a poor choice for G.B.
because of its propensity to cause hypoprothrombinemia with
or without associated bleeding episodes. This effect is attributed in part to the N-methylthiotetrazole side chain in the
chemical structure of cefotetan. G.B. currently has an increased prothrombin time, so it would be prudent to avoid cefotetan. Thus, for G.B., the importance and efficacy of established oral prophylactic regimens (plus bowel cleansing)
should be stressed to the resident.

7. The surgical resident has reconsidered the cefoxitin order

and decided to prescribe both the oral and parenteral prophylactic regimens for G.B. Will the combination significantly reduce the rate of postoperative wound infection compared with
either regimen administered singly?

Although the coadministration of both oral and parenteral

prophylactic regimens occurs commonly in practice (88% of
one surveys respondents),31 data in support of this practice
are inadequate,29 presumably because a study of large numbers of patients would be required to document a further decrease in already low infection rates (approximately 5% to
10%).32 Colorectal surgical procedures, however, are associated with a higher infection rate (than colonic procedures),
and an oral plus parenteral antimicrobial prophylaxis combination is superior to orally administered regimens alone in reducing infection rates.30 As a result, a combination of oral and
parenteral antimicrobial prophylaxis is recommended for colorectal surgery.9
Thus, evidence is conflicting for combination oral plus
parenteral therapy for colon surgery prophylaxis in G.B., although the standard of practice often dictates its use.31

Duration of Administration
8. L.G., a 28-year-old man with a history of rheumatic heart
disease, has a 12-year history of a heart murmur consistent with
mild mitral stenosis and mitral regurgitation. Over the past 4
months his murmur has become much more prominent. In addition, he has developed severe dyspnea with light physical activity and 3 pitting edema over both lower legs. Physical examination is notable for coarse rales and an S3 gallop. For the
past 6 weeks he has been maintained on digoxin and diuretics
without significant relief of his shortness of breath (SOB). The
cardiothoracic surgeon recommends mitral valve replacement
and orders the following surgical antibiotic prophylaxis regimen: cefazolin 1 g IV preoperatively, then Q 8 hr for 48 hours.
Why is cefazolin the most appropriate antimicrobial for L.G.?
Why was prophylaxis ordered for only 48 hours?

Although the incidence of postoperative wound infection

for cardiothoracic procedures is low (5%), the devastating
consequences of a postoperative endocarditis (following valve
replacement) and mediastinitis or sternal osteomyelitis (following sternotomy) warrant careful antimicrobial prophylaxis.3346 Organisms of concern for cardiothoracic surgery include Staphylococcus aureus and Staphylococcus epidermidis
(see Table 57-2); based on these potential pathogens, successful prophylactic regimens include cefazolin (Ancef),
cefamandole (Mandol), and cefuroxime (Zinacef). When cefazolin has been compared with cefuroxime or cefamandole,
a statistical trend in favor of the second-generation cephalosporins has been noted, and collective wound infection rates
were slightly higher in the cefazolin group.3537 In contrast, a
comparison of prophylactic cefazolin and cefuroxime in patients undergoing open heart surgery noted a significantly
greater incidence of sternal wound infection and mediastinitis
in the cefuroxime group.38 Furthermore, equal efficacy between the two agents was noted in yet another study.39 In conclusion, cefazolin probably is at least as effective as secondgeneration cephalosporins; therefore, the choice of agent
should be based on an institutions antimicrobial susceptibil-

ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

ity and cost data. Hospital-specific antimicrobial resistance

patterns are especially important in determining the incidence
of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE); vancomycin is the drug of
choice for prophylaxis of such organisms.
Meta-analyses of the use of prophylactic antibiotics in
cardiac surgery demonstrated no significant differences in
the rate of surgical site infection between first- and secondgeneration cephalosporins.40,46 Thus, the cefazolin prophylaxis selected for L.G. is acceptable, provided MRSA and
MRSE are not of concern in this institution.
With regard to duration, 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).45 Single-dose prophylaxis, a viable option for
many surgical procedures (see Question 9), is controversial
for cardiac procedures.33 In practice, cardiothoracic antimicrobial prophylaxis often is continued 48 hours after surgery,9
as in L.G. There is no benefit to prolonging prophylaxis to
48 hours, and such use should be discouraged. The duration
of antimicrobial prophylaxis ordered for L.G. is appropriate.
9. G.J., a 27-year-old woman, is admitted to the obstetrics
unit at term with her first pregnancy. She is scheduled for a cesarean section because the baby is breech. Cefazolin 1 g IV to be
administered after the cord is clamped and Q 8 hr for 24 hours
is ordered. Why is this surgical prophylaxis inappropriate?

As noted previously, the shortest effective duration of prophylaxis is desired. In the past, 5- or 6-day antimicrobial regimens were used for cesarean section, but 24-hour regimens
have since been proven as effective as these longer regimens.47,48 Faro and colleagues demonstrated that a single 2-g
dose of cefazolin was superior to either a single 1-g dose or to
a three-dose, 1-g prophylactic regimen.48 Others have noted
similar results (i.e., a single cefazolin dose administered after
the umbilical cord is clamped seems to be sufficient in preventing postoperative wound infections in cesarean section).4951 Single-dose prophylaxis is less costly52 and minimizes the development of bacterial resistance.53 Thus, G.J.
should receive a single 2-g dose of cefazolin after the cord has
been clamped, without the three additional doses.
Single-dose prophylaxis also is effective in a variety of GI
tract, orthopedic, and gynecologic procedures.21 A single dose
of an antibiotic with a short half-life, however, may provide
insufficient antimicrobial coverage during a prolonged surgical procedure, and repeated intraoperative dosing or selection
of an agent with a longer half-life is recommended when the
duration of surgery is long.

Signs of Wound Infection

10. G.J. is discharged on the fifth hospital day and instructed
to observe her incision site carefully for signs of infection. What
are the typical signs of site infection? What is the typical time
course for signs of site infection to become manifest?

Most surgical site infections involve the incision site. Typically, an infected incision site wound is red, inflamed, and purulent. The purulent drainage should be cultured to identify
the causative pathogen and to direct antimicrobial therapy.
Empiric therapy directed against the most likely pathogens

57-5

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 deepseated infections present indolently over weeks to months, by
which time an abscess may have developed.8 When implants
are involved, infections occurring up to a year after surgery
may be related to the operation.54

Selection of an Antimicrobial Agent

11. L.T., a 46-year-old woman, has a recent history of abnormal uterine bleeding and vaginal discharge. Endometrial biopsy
is positive for squamous cell carcinoma. Invasive disease is not
evident. The diagnosis is carcinoma in situ, and a vaginal hysterectomy is scheduled. What would be a good surgical prophylaxis antimicrobial regimen for L.T.?

The selection of a prophylactic regimen should incorporate

such factors as the agents microbiologic activity against the
most likely potential pathogens encountered during the surgical procedure (see Table 57-2), pharmacokinetic characteristics (e.g., half-life), inherent toxicity, potential to promote the
emergence of resistant strains of bacteria, and cost.
The usefulness of antimicrobial prophylaxis in vaginal hysterectomies is well established and is directed against vaginal
microflora, including Gram-positive and Gram-negative aerobes and anaerobes (see Table 57-2). The narrowest-spectrum
agent that is efficacious is desired, given that the goal of prophylaxis is not to eradicate every potential pathogen, but to reduce bacterial counts below a critical level necessary to cause
infection. Cefazolin has been proven to be an effective prophylactic agent for vaginal hysterectomy when compared with
broad-spectrum agents such as ceftriaxone (Rocephin).55 This
indicates that a broader-spectrum agent with anaerobic activity (which cefazolin lacks) is unwarranted.
Similar to vaginal hysterectomy, cefazolin and numerous
agents have been documented to reduce the incidence of postoperative surgical infection via the abdominal approach.56,57
However, as with vaginal hysterectomy, most trials have not
documented significant differences between first- and secondgeneration cephalosporins.56 In contrast, Hemsell and associates observed a significantly higher incidence of major postoperative surgical infection in patients receiving the
first-generation agent cefazolin when compared with cefotetan.58 As a result of this controversy, the American College of
Obstetricians and Gynecologists has recommended first-, second-, or third-generation cephalosporins for prophylaxis in
these procedures.59 Cefazolin exhibits a favorable toxicity profile and has a relatively long half-life (approximately 1.8
hours) such that a single dose has proven prophylactic efficacy.55 Cefazolin also is considerably less expensive than
broader-spectrum agents. Although it has a broader spectrum
of coverage, a single dose of cefotetan would also be an appropriate choice for this patient.
12. Because cefotetan has an increased spectrum of activity
against the anaerobe B. fragilis, it is being considered as an alternative to cefazolin prophylaxis for L.T. Comment on the appropriateness of this proposed change in prophylaxis.

The second- and third-generation cephalosporins generally

are not more effective than the first-generation cephalosporins
for surgical prophylaxis in vaginal hysterectomy or gastro-

57-6

INFECTIOUS DISORDERS

duodenal, biliary, and clean surgical procedures.6 One clear

exception to these findings is in the prevention of infection after colorectal procedures and perhaps hysterectomy. Several
investigations have documented the failure of first-generation
agents when used as prophylaxis in colorectal procedures,
probably a consequence of their weak anaerobic coverage.27,28
As stated previously, second- and third-generation agents generally are no more efficacious than cefazolin and should not
be used for surgical prophylaxis in most procedures. However,
cefotetan would be a reasonable choice in colorectal surgery
or hysterectomy. Considering that this patient is undergoing a
hysterectomy, either cefazolin or cefotetan is appropriate.
13. S.N., a 57-year-old woman with rheumatoid arthritis and
degenerative joint disease, has been admitted for total hip
arthroplasty. She has an allergy to penicillin. What should be
prescribed for S.N. for surgical prophylaxis?

Cefazolin is the preferred prophylactic agent for most

clean procedures, including cardiac, vascular, and orthopedic
procedures6 (see Table 57-2). Although the risk of cefazolin
cross-allergenicity to penicillin is minimal, S.N. experienced
a significant penicillin allergy (hives, SOB); therefore, an alternative prophylactic agent definitely is appropriate. The organisms most likely to cause postoperative infection after total hip replacement are S. aureus and S. epidermidis (see Table
57-2). Nafcillin, cefazolin, and vancomycin possess excellent
activity against S. aureus, however, the -lactams have only
marginal activity against S. epidermidis. Regardless, nafcillin
clearly must be avoided because of the penicillin allergy.
Thus, the preferred agent for S. N. is vancomycin.
Preoperative vancomycin 1 g should be administered IV
slowly, over at least 60 minutes. This slow rate of infusion is
necessary to reduce the risk of infusion-related hypotension,
which poses a particular danger during anesthesia induction
and has been reported to cause cardiac arrest.60
14. B.K., an 18-year-old woman, complains of severe acute abdominal pain and nausea; the pain is localized to the periumbilical region. B.K. has a temperature of 39.5C. After initial examination by her pediatrician, she is admitted to hospital with
presumed appendicitis and an exploratory laparotomy is scheduled. What surgical antimicrobial prophylaxis should be ordered
for B.K.?

As with colorectal surgery, the most likely infecting organisms in appendectomy are Bacteroides species and Gramnegative enterics (see Table 57-2). Upon surgical inspection,
if the appendix appears normal (uninflamed, without perforation), then antimicrobial prophylaxis is unnecessary.61 If the
appendix is inflamed without perforation, a single preoperative antibiotic dose is necessary. If the appendix is perforated
or gangrenous (complicated), infection is already established
and postoperative treatment is warranted. Unfortunately, the
status of the appendix cannot be determined before surgery;
therefore, all patients should receive at least one dose of an
appropriate antibiotic preoperatively. After surgical inspection

of the appendix, the need for postoperative antibiotic therapy

can be determined.
Based on the pathogens likely to be encountered, an antimicrobial agent with both aerobic and anaerobic activity is
desired for surgical prophylaxis in this situation. Consequently, cefoxitin (Mefoxin), cefotetan (Cefotan), ceftizoxime
(Cefizox), or cefotaxime (Claforan) are acceptable choices for
prophylaxis.62,63

Risks of Indiscriminate Antimicrobial Use

15. Upon surgical exploration, B.K. was found to have uncomplicated (nonperforated, nongangrenous) appendicitis; however,
cefoxitin therapy was continued for 3 days for unclear reasons.
What are the risks of indiscriminate use of antimicrobials for
surgical prophylaxis?

The risks of indiscriminate use of antimicrobials to a given

patient include the potential for adverse effects and superinfection. The administration of any -lactam agent poses the
risk of a hypersensitivity reaction, and many antibiotics, including cefoxitin, such as in B.K., are known to predispose
patients to Clostridium difficileassociated disease. 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.64

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.65,66 In one early
study, the creation of an antibiotic order form with an automatic stop order after 2 days of surgical prophylaxis reduced
the mean duration of surgical prophylaxis from 4.9 to 2.9
days.65 One study noted that the duration of surgical prophylaxis exceeded the recommended 24 hours in only 4% to 18%
of cases.66 Both examples demonstrate significant improvement in the use of antimicrobial prophylaxis.
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.6769 In one program, computer-assisted monitoring of the duration of surgical prophylaxis
helped identify and automatically discontinue inappropriately
long courses of surgical antimicrobial prophylaxis, significantly reduced the average number of antibiotic doses administered, and generated reduced costs without jeopardizing
clinical outcomes.68 Similar cost savings can be achieved by
orchestrating changes within an institution aimed at reducing
the duration and frequency of prophylactic surgical antibiotic
administration.67

ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

57-7

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2. Cruse PJE et al. The epidemiology of wound infection: a 10-year prospective study of 62,939 wounds.
Surg Clin North Am 1980;60:27.
3. Haley RW et al. Extra charges and prolongation of
stay attributable to nosocomial infections: a
prospective interhospital comparison. Am J Med
1981;70:51.
4. Wenzel RP. Preoperative antibiotic prophylaxis. N
Engl J Med 1992;326:337.
5. Kirkland KB 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.
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