Antibiotic Prophylaxis In Surgical Site Infection

Prevention
Lailil Indah Seftiani
Rumah Sakit Umum Daerah Kota Bekasi

lailil_chaofrogy@yahoo.co.id

Abstact- Surgical site infection (SSI) is one of the

most common complications of surgery in both
adults and children. The purpose of the present
review is to highlight the progress in the
understanding of SSIs and the role of
antimicrobial prophylaxis (AMP).
Keywords: Surgical site infection, antibiotic
prophylaxis
I.

INTRODUCTION

Surgical site infections (SSIs) are defined as

infections occurring up to 30 days after surgery (or
up to one year after surgery in patients receiving
implants) and affecting either the incision or deep
tissue at the operation site. Despite improvements in
prevention, SSIs remain a significant clinical problem
as they are associated with substantial mortality and
morbidity and impose severe demands on healthcare
resources. The incidence of SSIs may be as high as
20%, depending on the surgical procedure, the
surveillance criteria used, and the quality of data
collection. In many SSIs, the responsible pathogens
originate from the patient's endogenous flora. The
causative pathogens depend on the type of surgery;
the most commonly isolated organisms are
Staphylococcus
aureus,
coagulase-negative
staphylococci, Enterococcus spp. and Escherichia
coli. Numerous patient-related and procedure-related
factors influence the risk of SSI, and hence
prevention requires a 'bundle' approach, with
systematic attention to multiple risk factors, in order
to reduce the risk of bacterial contamination and
improve the patient's defences. The Centers for
Disease Control and Prevention guidelines for the
prevention of SSIs emphasise the importance of good
patient preparation, aseptic practice, and attention to

surgical technique; antimicrobial prophylaxis is also

indicated in specific circumstances.1
II. SURGICAL SITE INFECTION
Definition
A wound is defined by the Center for Disease
Control (CDC) as an interruption or break in the
continuity of the external surface of the body or the
surface of an internal organ, caused by surgical or
other forms of injury or trauma. Surgical site
infection is a type of healthcare-associated infection
in which a wound infection occurs after an invasive
(surgical) procedure. An SSI is diagnosed by a
constellation of clinical findings occurring within 30
days of surgery. A surgical site infection (SSI) is
clinically defined as presence of pain at a surgically
created wound, which is accompanied by erythema,
induration and local tenderness or presence of
purulent discharge at wound site.2
Surveillance
In 2010, an estimated 16 million operative
procedures were performed in acute care hospitals in
the United States. A recent prevalence study found
that SSIs were the most common healthcareassociated infection, accounting for 31% of all HAIs
among hospitalized patients. NHSN data for 20062008 (16,147 SSIs following 849,659 operative
procedures) showed an overall SSI rate of 1.9%. SSI
is associated with a mortality rate of 3%,and 75% of
SSI-associated deaths are directly attributable to the
SSI.3
Wound status
Wound characteristics which increase the risk of SSI
include, presence of foreign bodies, nonviable tissue
in wound, tissue ischemia and haematoma formation.
All of these characteristics provide a fruitful bacterial
growing environment. Other factors known to

promote SSIs are a prolonged preoperative hospital

stay (since there is a growing opportunity for the skin
to be colonized by pathogens), a long operation time
(as it probably increases the extent of both tissue
trauma and contamination), and poor surgical
techniques (see below).
The risk of SSI varies with the type of surgery.
Certain types of surgery carry a higher risk of
contamination than others and have led to the
classification of surgical wounds as clean, cleancontaminated,
contaminated,
or
dirty.4

b) airborne dispersal surrounding air contaminated

with micro-organisms that deposit onto the wound;
and c) self-contamination (also known as endogenous
infection) physical migration of the patients own
normal flora which are present on the skin, mucous
membranes or gastrointestinal tract to the surgical
site. Most surgical infection is due to bacterial and,
more rarely, fungal infection.
Two broad qualities of pathogenic bacteria underlie
the means by which they cause disease:
1. Invasiveness is the ability to invade tissues. It
encompasses
mechanisms
for
colonization
(adherence and initial multiplication), production of
extracellular substances which facilitate invasion
(invasins) and ability to bypass or overcome host
defense mechanisms.
2. Toxigenesis is the ability to produce toxins.
Bacteria may produce two types of toxins called
exotoxins and endotoxins. Exotoxins are released
from bacterial cells and may act at tissue sites
removed from the site of bacterial growth.
Endotoxins are cell-associated substance. (In a
classic sense, the term endotoxin refers to the
lipopolysaccharide component of the outer membrane
of Gram-negative bacteria). However, endotoxins
may be released from growing bacterial cells and
cells that are lysed as a result of effective host
defense (e.g. lysozyme) or the activities of certain
antibiotics (e.g. penicillins and cephalosporins).
Hence, bacterial toxins, both soluble and cellassociated, may be transported by blood and lymph
and cause cytotoxic effects at tissue sites remote from
the original point of invasion or growth. Some
bacterial toxins may also act at the site of
colonization and play a role in invasion.

Table 1. Wound class and Classification of the risk of

SSI
III. THE MECHANISMS OF BACTERIAL
PATHOGENICITY
SSIs are caused by the deposition and multiplication
of microorganisms in the surgical site of a susceptible
host. There are a number of ways microorganisms
colonize and cause infection, including: a) direct
contact either from another patient, transfer from
surgical equipment or the hands of the hospital staff;

Picure 1. Bacterial structure

Typical Structure of a Bacterial Cell (from inside to
outside)
DNA bacterial genetic material
Ribosomes (protein-making factories), energygenerating systems, digestive system, and everything
else are located in the cytoplasm.
Cytoplasmic Membrane or Inner Membrane
a. Consists of phospholipids and other membrane
proteins
b. Semi-permeable
c. Regulates pH, osmotic pressure and availability of
essential nutrients
Bacterial Cell Wall or Peptidoglycan
a. Cross-linked mesh that gives a cell its shape,
strength and osmotic stability, a protective suit of
armour
b. Porous up to 100,000 Da.
The outer layer of lipopolysaccharide (LPS) and
phospholipid material helps protect bacteria from
bacteriophages, pH, enzymes, phagocytosis.
To multiply, the bacteria must be able to synthesize
peptidoglycan,
proteins and DNA
The cell wall, the ribosomes and DNA are all
potential antibiotic targets5

Depending on the particular strain, there are several

kinds of toxins attributed to S. aureus virulence.
Exotoxins can include toxic shock syndrome toxin-1
(TSST-1), exfoliatins, and enterotoxins. Others may
include alpha-toxin, beta-toxin, delta-toxin, and
bicomponent toxins such as Panton-Valentine
leukocidin.
Factors
including
protein
A,
Staphyloxanthin pigment, clumping factor, coagulase,
hyaluronidase, leukocidin, and biofilm production
can also affect the virulence (Forbes et al., 2007).
Exotoxin TSST-1 causes toxic shock syndrome by
stimulating the release of large amounts of
interleukin-1 (IL-1) by human monocytes,
interleukin-2 (IL-2), and tumour necrosis factor.
Similarly, it induces the expression of IL-2 receptors
and the proliferation of human T lymphocytes. It
does this by binding to MHC class II molecules and
the exotonin is produced by most strains of S. aureus
(Scholl et al., 1989). In general, the toxin is not
produced by bacteria growing in the blood; rather, it
is produced at the local site of an infection, and then
enters the bloodstream.
IV. ANTIBIOTICS
Antibiotics Work

The commonest organism causing SSI is

Staphylococcus aureus. Other common causative
organisms include other Gram-negative aerobes,
Streptococcus spp. and anaerobes. Overall, 144 of the
618 patients studied developed SSIs, with the most
common isolates being S. aureus (37%), E. coli
(11%), and Enterococcus spp. (5%).

Picture 3. The bacterial cell

Picture 2. Scanning electron micrograph of

Staphylococcus aureus bacteria.

Picture 4. Major target for antibacterial action

Picture 5. Sites of antibacterial action

Antibiotics for prophylaxis of SSIs
The goals of antibiotic prophylaxis are to achieve
inhibitory antibiotic levels at incision and throughout
the procedure in an effort to decrease the likelihood
of developing a SSI. Antibiotics can also play an
important role in the treatment of SSIs.
Animal studies have shown that antibiotic
prophylaxis is most effective in preventing postsurgical infections when administered before the start
of surgery, and pharmacokinetic data suggest
administration as near the time of incision as

possible. Classen et al., in a prospective

observational study, monitored the timing of
antibiotic prophylaxis in 2847 patients in clean or
clean contaminated surgery. Using a step-wise
logistic regression model, they found that
preoperative antibiotics within two hours of incision
had the lowest rate of infection as compared to
antibiotics given after incision or earlier than two
hours prior.6
In addition to being given preoperatively,
prophylactic antibiotics should not be continued
postoperatively. A five-month prospective survey of
surgical-site infections (SSI) conducted in the
department of general surgery at Kilimanjaro
Christian Medical Center, Tanzania by Eriksen et al.,
showed that 77 (19.4%) of the 397 patients studied
developed SSI. Twenty-eight (36.4%) of these
infections were apparent only after discharge from
hospital. A surprising eighty-seven percent of the
patients who developed SSI had received antibiotics,
the majority having received the antibiotics for
several days. Such a practice is contrary to the
current recommendation of a single preoperative
dose, and prolonged inappropriate use of broadspectrum antibiotics may contribute to increased
emergence of resistance. 7
The type of surgery (clean, clean/contaminated,
contaminated, or dirty) also impacts the role of
antibiotic prophylaxis. An understanding of this
classification, as well as knowledge
of
recommendations for specific procedures, is
invaluable in making an appropriate choice regarding
antibiotic prophylaxis. Antibiotic administration in
dirty cases is not considered prophylactic as these
cases represent treatment of infection rather than
prophylaxis.

Controversy exists regarding the use of antibiotic

prophylaxis for clean cases. When antibiotic
prophylaxis is given, the agent should target S.
aureus, the most common organism causing SSIs in
clean cases; cefazolin is a good choice. When bone is
incised, the use of prophylactic antibiotics is clearly
recommended. A good choice in this situation, or for
cardiothoracic or vascular surgery, is cefazolin or
cefuroxime (or clindamycin or vancomycin for
penicillin allergic). For general surgical clean cases,
the decision is less clear. A Cochrane Database of
Systematic Reviews examined the use of
prophylactic antibiotics prior to hernia surgery, and
found that infection rates were lower with use of
antibiotics (2.9% versus 3.9%) but concluded that
antibiotic prophylaxis for elective inguinal hernia
repair cannot be universally recommended because of
overall low infection rates, a high number needed to
treat, and a lack of a large, randomized controlled
trial to prove efficacy.
For clean-contaminated and contaminated cases,
antibiotic prophylaxis is recommended. Colorectal
surgery is the most thoroughly studied type of
procedure in this category, and as such most
recommendations are based on studies involving
colorectal surgery. The most commonly encountered
organism in clean-contaminated and contaminated
SSIs is still S. aureus, though other aerobic as well as
anaerobic bacteria are also culprits. As such,
prophylaxis should be broader than that used for
clean cases. Song et al. reviewed all randomized
controlled trials of antibiotic prophylaxis in
colorectal surgery. Four of these studies compared
antibiotic regimens to no antibiotics and showed a
convincing benefit of prophylactic antibiotics (odds
ratio 0.24, 95% confidence interval 0.13 to 0.43).
Further analysis revealed that the most efficacious
regimens include coverage against both aerobic and
anaerobic organisms (such as a 2nd or 3rd generation
cephalosporin, or gentamicin in combination with
metronidazole), and cited certain regimens
inadequate (metronidazole alone, doxycycline alone,
piperacillin alone). Though data from Africa is
limited, differences in efficacy between various 2nd
and 3rd generation cephalosporins appear negligible,
and choice prophylaxis with a single-agent 2nd or 3rd
generation cephalosporin can probably be dictated by
availability or cost. For penicillin-allergic patients,
clindamycin combined with gentamicin, aztreonam,
or ciprofloxacin, or metronidazole combined with
gentamicin or ciprofloxacin are adequate choices.8,9

A recent meta-analysis of meta-analyses involving

250 clinical trials and 4809 patients has provided an
estimation of the relative benefit of systematic
prophylactic antibiotics to reduce infection for 23
different types of surgery. The type of antibiotic,
timing, dosing, and type of procedure varied widely
in this analysis, but the relative risk of developing
infection for all types of operations with prophylactic
systemic antibiotics versus no prophylactic
antibiotics varied from 0.19 to 0.82, suggesting a
generalized benefit regardless of the degree of
contamination. Taken as a whole, the use of
prophylactic systemic antibiotics decreased the
incidence of wound infections by about one half. This
does not mean that prophylactic antibiotics should be
used for every case, in as much as there are
significant costs involved with their administration,
they can have serious adverse effects and there is a
risk of the development of antibiotic resistant
pathogens or C. difficele colitis. Because of this, there
has been reluctance to use prophylactic antibiotics in
clean cases.However, prospective randomized studies
have shown a clear benefit in clean elective
operations such as hernia and breast procedures
(SDC-137-141). Recent reports have also shown
significant protection against infections in patients
with a cesarean section (SDC-142-143). A review of
the use of antimicrobial prophylaxis in colorectal
surgery, including 182 trials with 3880 participants
and 50 different antibiotics, showed a definite benefit
of prophylactic antibiotics compared to a placebo or
no treatment (RR = 0.30). In that same study,
combined therapy against both aerobic and anerobic
organisms and combined oral and intravenous
antibiotic prophylaxis compared to intravenous alone
had significant benefits (RR, 0.41 and 0.74,
respectively). 10
General principles in surgical prophylaxis
1.Duration of prophylaxis:The duration of
antimicrobial prophylaxis should not routinely
exceed 24 hours (1 dose at induction and 2 more
doses postoperatively, i.e. 3 doses in total). There is
wide consensus that only a single dose of intravenous
antimicrobial agent is needed for surgical prophylaxis
in the great majority of cases. Published evidence
shows that antimicrobial prophylaxis after wound
closure is unnecessary and could lead to emergence
of resistant bacteria. Most studies comparing singlewith multiple-dose prophylaxis have not shown
benefit of additional doses.
2.Timing: For many prophylactic antimicrobial
agents, the administration of an initial dose should be
given within 30 minutes before incision (coinciding
with the induction of anesthesia) to achieve an
adequate tissue concentration at the time of initial

incision. This can be facilitated by having the

anesthesiologist administer the drug in the operating
room at induction.
3.Antimicrobial dosing: The dose should be adequate
based on the patients body weight. An additional
dose of antimicrobial agent should be given
(intraoperatively) if the operation is still continuing
after two half-lives of the initial dose or massive
intraoperative blood losses occur. Suggested initial
dose and time to re-dose for selected antimicrobial
agents used for surgical prophylaxis.11

Table 2. Antimicrobial agent

V.

CONCLUSION

A wound is defined by the Center for Disease Control

(CDC) as an interruption or break in the continuity of
the external surface of the body or the surface of an
internal organ, caused by surgical or other forms of
injury or trauma. Surgical site infection is a type of
healthcare-associated infection in which a wound
infection occurs after an invasive (surgical)
procedure. Surgical site infections (SSIs) are defined
as infections occurring up to 30 days after surgery (or
up to one year after surgery in patients receiving
implants) and affecting either the incision or deep
tissue at the operation site. The causative pathogens
depend on the type of surgery; the most commonly
isolated organisms are Staphylococcus aureus,
coagulase-negative staphylococci, Enterococcus spp.
and Escherichia coli. The Centers for Disease Control
and Prevention guidelines for the prevention of SSIs
emphasise the importance of good patient
preparation, aseptic practice, and attention to surgical
technique; antimicrobial prophylaxis is also indicated
in specific circumstances. The goals of antibiotic
prophylaxis are to achieve inhibitory antibiotic levels
at incision and throughout the procedure in an effort
to decrease the likelihood of developing a SSI.
Antibiotics can also play an important role in the
treatment of SSIs.
VI.
1.

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