INVITED COMMENTARY
Who, What, When, Where, Why, and How?
The Unanswered Questions of Surgical
Antimicrobial Prophylaxis
Titus L. Daniels, MD, Thomas R. Talbot, MD, MPH, and William Schaffner, MD
Corresponding author
Titus L. Daniels, MD
Division of Infectious Diseases, Vanderbilt University School of
Medicine, A-2200 MCN, 1161 21st Avenue South,
Nashville, TN 37232, USA.
E-mail: titus.daniels@vanderbilt.edu
Current Infectious Disease Reports 2006, 8:83 – 85
Current Science Inc. ISSN 1523-3847
Copyright © 2006 by Current Science Inc.
Prevention of surgical site infections (SSIs) has long been
a quality measure of surgical practice, and a cornerstone of
SSI prevention is the appropriate and timely administration
of antimicrobial prophylaxis (AMP). Guidelines for prevention of SSI are available from multiple specialty groups,
as well as national agencies of various countries. These
guidelines contain extensive reviews of the literature that
support their recommendations. Even so, interpretation
of guidelines can seem arbitrary even among experienced
physicians. Due to inconclusive data, the evolution of
microorganisms, and the continuous advancement of surgical techniques, guidelines are unable to answer several
key questions regarding surgical AMP. The nuances of AMP
not addressed by current guidelines can be highlighted by
asking the basic questions of “Who, What, When, Where,
Why, and How?”
Who Should Receive AMP?
Patients undergoing Class I (clean) procedures in which
an SSI would be catastrophic (eg, coronary artery bypass
grafting, neurosurgery, vascular and orthopedic prosthetic
material implantation) as well as patients having Class II
(clean-contaminated) procedures should receive AMP.
Because contamination has already occurred, patients
undergoing Class III (contaminated) and Class IV (dirty)
procedures usually are receiving antibiotic treatment at the
time of surgery, and AMP is not indicated. The omission
of AMP recommendations for many lower risk procedures,
such as herniorrhaphy and mastectomy, has been a cause
of some confusion. Unfortunately, studies to address the
utility of AMP for lower risk procedures have had differing
conclusions [1,2]. Some state that AMP is relatively inexpensive, safe, and likely effective for all procedures, but
critics argue that the risks of adverse drug reactions, the
potential selection for bacterial resistance, and the cost of
administering AMP outweigh the benefits of AMP in these
lower risk procedures. Rigorous studies evaluating AMP in
patients undergoing lower risk procedures would require
extremely large study populations and are beyond the
capacity of single institutions. In addition, funding for such
studies is sparse; neither pharmaceutical companies nor
granting agencies have been enthusiastic in providing support. Even if a positive effect were observed, the resultant
number of patients needed to receive AMP to prevent one
SSI would be exceptionally large, thus further complicating
the risk-benefit cost debate.
What Antibiotic Should Be Used for AMP?
Cefazolin remains the agent of choice for AMP of most
procedures. An increasingly important issue, however, is
determining the role of vancomycin. Current guidelines
indicate that vancomycin should be considered if there
is an “outbreak” of methicillin-resistant Staphylococcus
aureus (MRSA) SSIs or if the local occurrence of MRSA
is elevated. Determining what constitutes an “outbreak”
and what level of “elevated” incidence must occur before
vancomycin ought to be used remains unclear. The lack
of enthusiasm for vancomycin AMP is due in large part to
its long infusion time, poor inherent bactericidal activity,
poor central nervous system penetration (of importance
when used for neurosurgical procedures) and concern for
selection of resistant organisms (ie, vancomycin-resistant
Enterococci and glycopeptide-intolerant or -resistant Staphylococci). Newer antimicrobials that possess potent activity
against MRSA have become available (eg, quinupristin/
dalfopristin, linezolid, daptomycin, and tigecycline) but
are not included in current guidelines. Drug manufacturers rarely pursue indications for surgical prophylaxis;
therefore, recommendations for using newer agents arrive
slowly, if at all.
In addition to systemic AMP, there is renewed interest
in the use of local antibiotic delivery systems for AMP, such
84
Invited Commentary
as antibiotic-impregnated sutures, dressings, cement, beads,
and irrigant solutions. Local delivery of high concentrations of antimicrobial agents to prevent SSIs seems logical;
however, key questions remain. What concentration of antibiotic is optimal, and what duration of antibiotic exposure is
necessary for the agent to be effective? Does local antibiotic
therapy add any benefit to optimal systemic prophylaxis or
could it replace systemic AMP altogether? Studies with SSI as
an outcome to evaluate local antibiotic delivery methods are
rare and generally evaluate the treatment of infections, not
prophylaxis. Investigators have used different methods of
preparing some local agents (eg, orthopedic cement) which
result in varying concentrations of the locally delivered antimicrobial agent, compounding the difficulties encountered
when comparing the effectiveness of local delivery systems.
The impact of local antimicrobial delivery methods on the
selection for antibiotic-resistant organisms is also unclear.
Further, removal of a local delivery system may prove difficult in the event of a local or systemic adverse reaction to
the antibiotic. Finally, local delivery modalities are often
expensive and may de-emphasize the proven roles of strict
adherence to antiseptic techniques and appropriate administration of AMP. Rigorous clinical trials to evaluate the
effectiveness of local delivery methods must be completed
before their routine use can be recommended.
When Should AMP Be Administered?
Recommendations state that the antibiotic infusion
should begin within 60 minutes before incision in order
to reach target tissue antibiotic concentrations but is there
a “point-of-no-return” prior to incision when administration of antibiotic does not result in adequate tissue
concentrations at the time of incision (eg, will a dose
given 5 minutes before incision yield adequate tissue concentrations of AMP at the time of incision?). Some argue
that it is critical to have adequate tissue concentrations
of the drug at the time of incision whereas others believe
that it is more important to have the highest antibiotic
concentrations during and at the end of the procedure.
Both arguments have theoretical merit; however, evidence
to fully substantiate or refute either is lacking. Until more
evidence is available, it is best to ensure adequate serum
and tissue concentrations of the antibiotic at the time of
incision, throughout the procedure, and for a short time
after the operation is complete.
Intraoperative redosing may be necessary to provide
adequate concentrations of AMP throughout the procedure. Typically recommended after an interval equivalent
to two half-lives of the AMP agent, redosing depends on
the duration of surgery and the specific agent used. Further complicating the issue of redosing is the use of AMP
in select populations. For example, it has been shown that
morbidly obese patients undergoing gastric bypass surgery
had rapidly declining tissue concentrations of cefazolin
during the surgical procedure and suboptimal tissue levels
well before the indicated redosing time [3]. Continuous
infusion of cefazolin for AMP has also been proposed [4]
to ensure adequate antibiotic levels throughout the procedure, though additional studies are needed before this
practice can be recommended.
Where Should AMP Be Administered and
How Can Delivery Be Improved?
These issues become difficult when considering the
complexity of modern health care systems. Designing
facility-specific processes to improve adherence to AMP
is essential for effective SSI prevention. A variety of
options are available for assisting providers in adhering
to surgical AMP administration. Computer-aided systems
for reminding providers to administer and/or redose
AMP have been successful in increasing the appropriate
redosing of AMP [5,6]. A preprinted checklist that accompanies the patient as they travel through the preoperative
process and surgery can serve to remind clinicians to
perform the essential tasks necessary to optimize AMP
administration. Using a multidisciplinary approach,
institutions must consider their unique facility characteristics to guide an AMP delivery process that best meets
the needs of each system. The most important principles
are to develop a system to improve AMP adherence and
to ensure its use.
Why Is AMP Important?
SSIs are estimated to occur in up to 5% of all surgical procedures [7] causing substantial morbidity and mortality,
are associated with prolonged hospitalizations, and lead
to increased health care costs. Surgical AMP is a critical
measure that has been proven effective in preventing SSI
in multiple studies. With the national movement to provide patients with facility-specific nosocomial infection
data, adherence to surgical AMP recommendations has
been proposed as a publicly-reported process measure.
The universal applicability of the basic tenets of surgical
AMP and AMP’s proven benefits makes AMP adherence
for major surgical procedures a rational quality metric for
public reporting.
Clinicians are entering a new era of SSI prevention.
Novel methods of surgical AMP are available, but their
effect on SSI prevention is unknown. Current AMP methods have a proven role in reducing SSIs, but several key
questions remain in our understanding of surgical AMP.
More effective strategies are welcomed, but one must first
ensure that current processes have been optimized before
venturing into unproven modalities. Funding such studies
is a major hurdle but might be overcome if the evaluation
of surgical AMP is also included as a component of studies
evaluating surgical procedures. Furthermore, investigations into new surgical procedures should also address the
question of surgical AMP as prevention of SSIs is a critical
Invited Commentary
element of any new surgical procedure. Current surgical
AMP guidelines provide an important foundation for the
prevention of SSIs. However, investigations to advance our
knowledge of surgical AMP are urgently needed, lest an era
of reliance on “the traditions of surgical AMP” be entered
and evidence-based practice be forlorn.
3.
4.
5.
References
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Mahatharadol V: A reevaluation of antibiotic prophylaxis
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