Journal of Hospital Infection (2008) 70(S2) 15–20

Available online at www.sciencedirect.com

www.elsevierhealth.com/journals/jhin

Antibiotic resistance in common pathogens

reinforces the need to minimise surgical site
infections
P.M. Dohmen*

Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany

KEYWORDS Summary Surgical site infections (SSIs) remain an important cause

Skin bacteria; of postoperative morbidity and mortality and generate considerable
Wound additional healthcare and societal costs. Most SSIs are caused by skin-
contamination; derived bacteria such as Staphylococcus aureus and coagulase-negative
Antibiotic staphylococci. Antimicrobial resistance among these and other clinically
prophylaxis;
important pathogens is an increasing problem. Thus, while the overall
Antibiotic
resistance;
risk of SSI is influenced by numerous patient- and procedure-specific
Microbial sealant characteristics, effective antibiotic prophylaxis and skin preparation are
important components of the polymodal approach to SSI prevention.
Published guidelines recommend that selection of antimicrobial agents for
prophylactic use should take into account the expected flora, the ability of
the agent to reach the target tissue at appropriate concentrations, bacterial
resistance patterns and drug pharmacokinetics. Consistent with proper
antimicrobial stewardship, antibiotic prophylaxis should use an appropriate
drug and optimise the dose and duration of treatment to minimise toxicity
and conditions for selection of resistant bacterial strains. Because the risk
of developing SSI depends in part on the extent of wound contamination
with virulent bacteria, efficient preoperative patient skin preparation is
essential to decrease the number of potential wound contaminants. A recent
development to reduce the risk of surgical site contamination by skin flora
is a cyanoacrylate-based microbial sealant that is applied before surgery
and dries to immobilise skin bacteria under a breathable film. This novel
mechanism of action is not compromised by, and does not promote, bacterial
resistance and, with minimal potential to cause skin reactions, the microbial
sealant is an innovative addition to available options for SSI prophylaxis.
© 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights
reserved.

* P.M. Dohmen MD PhD, Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Chariteplatz 1,
D-10117 Berlin. Tel.: +49 30 450 522092; fax: +49 30 450 522921. E-mail: pascal.dohmen@charite.de (P.M. Dohmen)

0195-6701/$ - see front matter © 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
16
Introduction
Despite improvements in prophylaxis and infection
control measures, surgical site infections (SSIs)
remain an important cause of nosocomial morbidity
and mortality. With approximately 15% of elective
surgery patients and 30% of patients undergoing
contaminated or dirty surgery estimated to develop
post-operative wound infections, SSIs are the
most commonly encountered form of nosocomial
infection in surgical patients. 1,2
Patients with SSIs require a longer time in hospi-
tal, more nursing care, additional dressings and, in
some cases, readmission to the hospital and further
surgery. Treating SSIs has substantial demand on
healthcare resources and the associated cost may
be extremely high; retrospective data estimate
that SSIs contribute 1.47 19.1 billion Euros to the
economic costs of surgical procedures in Europe. 3
Studies reporting the costs generated by SSIs have
generally focused on the impact of additional
healthcare costs resulting from prolonged hospital
stays. SSIs have direct and indirect consequences,
however, and comprehensive assessment of the
costs to society and to the individual patient
attributable to SSIs indicates that the total
healthcare costs represent only a tenth of the
overall cost burden. 4
The risk of SSI developing is influenced by a
large number of patient- and procedure-specific
characteristics. Patients aged over 65 years, who
smoke or abuse alcohol, or with concurrent
disorders including cardiogenic shock, chronic
obstructive pulmonary disease, congestive heart
failure, diabetes mellitus, poor cardiac output
(ejection fraction <40%), hypertension, hyper-
cholesterolaemia, obesity, peripheral or cerebral
vascular disease, or renal impairment, or who
are receiving immunosuppressive therapy are at
higher risk of SSI, while emergency surgery or
reoperations are also associated with higher risk
of SSI. 5 21
The trend for increasing use of minimally
invasive surgical techniques, such as endoscopic
vessel harvesting for CABG, has several benefits
and often leads to shorter ambulation and recovery
times, shorter hospital stays and significantly
lower postoperative infection rates. 22,23 Such
improvements in healthcare have had to contend
with increasing numbers of elderly, debilitated,
chronically ill, or immunocompromised patients
in the surgical population, who are typically at
increased risk of SSI. This brief review focuses
on two methods that remain mainstays of the
polymodal approach to SSI prevention, antibiotic
prophylaxis and skin preparation.
P.M. Dohmen
Antibiotic prophylaxis
The introduction of routine prophylactic antibiotic
use has reduced postoperative infection rates
dramatically. Antibiotic prophylaxis increases the
threshold for bacterial infection and reduces but
does not eliminate the risk arising from bacterial
contamination of the surgical wound (Figure 1).
Selection of antimicrobial agents for prophylactic
use should be based on knowledge of expected
flora, ability of the antimicrobial to reach the
target tissue at appropriate concentrations, bacte-
rial resistance patterns and drug pharmacokinetics.
Guidelines addressing these issues have been
published. 24 26 Failure of antimicrobial therapy to
prevent or treat infection in the surgical patient
may result from poor antimicrobial selection,
inappropriate dosage or frequency, poor timing
of administration or inappropriate duration of
therapy.
0.80
0.70
0.60 Prophylaxis not given
0.50
0.40
0.30
0.20 Prophylaxis given
0.10
0.00
1 2 3 4 5 6
Total bacterial count (log10 scale)
Figure 1. In patients undergoing abdominal hysterectomy,
the risk of developing postoperative infection was related
to the degree of bacterial contamination of the surgical
wound by the end of surgery. Antibiotic prophylaxis reduces
the infection risk by increasing the theshold for infection
following contamination [Figure reproduced from Houang
and Ahmet (1991) 27 with permission].
Prophylactic antibiotics are indicated for most
clean-contaminated procedures, but for fewer and
more selected clean operations. This generally
includes those involving foreign body implanta-
tions, such as prosthetic cardiac valves, prosthetic
vascular grafts, and orthopaedic devices. Patients
with high-risk host factors, such as abdominal
incision, anticipated procedural length of more
than 2 hours, or 3 or more comorbidities, should
also be considered for antibiotic prophylaxis
for clean surgery. Some authors have advocated
routine prophylaxis for clean procedures, such as
breast surgery, which do not involve implantation
of foreign bodies, but this is more difficult to justify
unless patients are at high risk of infection because
of host factors.
Antibiotic resistance in common pathogens reinforces the need to minimise surgical site infections
Sources of organisms causing SSI
The microbiology of SSI depends on the type of
operation being performed, with inoculation of the
surgical site occurring either inward from the skin
or outward from the internal organ being operated
on. Most SSIs are caused by skin-derived Gram-
positive cocci including Staphylococcus aureus,
coagulase-negative staphylococci (usually S. epi-
dermidis), streptococci and Enterococcus species.
With gastrointestinal surgery or surgery of the head
and neck, in which pharyngoesophageal tissues are
incised, there is an increased likelihood of infection
due to enteric aerobic (e.g. Escherichia coli)
and anaerobic (e.g. Bacteroides fragilis) Gram-
negative bacilli. 28
Choice of agent
Reflecting the microbiology of SSI, a first- or
second-generation cephalosporin with high anti-
staphylococcal activity, such as cefazolin, is the
most often used drug for antibiotic prophylaxis
for clean surgery and high-risk clean-contaminated
elective surgery. Clindamycin and vancomycin are
preferred alternatives for patients with b-lactam
allergy. Vancomycin or teichoplanin are appro-
priate first choice agents for prophylaxis where
the risk of meticillin-resistant S. aureus (MRSA)
infection is high, although what threshold should
be used to define a high incidence has not been
set. 26 Guidelines for specific prophylaxis for MRSA
are not clear, and newer agents such as linezolid,
daptomycin or quinupristin/dalfopristin have also
been recommended. 29 Widespread or prolonged
use of antibiotics fosters the development of
resistant bacteria; it is therefore important that
overuse of later generation cephalosporins and
glycopeptides, the latter important therapeutic
options for established post-sternotomy infections,
should be restricted. 26
Timing and duration of prophylactic treatment
It seems rational that parenteral antibiotics
should be administered so that a bactericidal
concentration of antibiotic is established in serum
and tissues by the time the skin is incised.
Thus, cephalosporin prophylaxis should be infused
within 1 hour before incision, while infusion of
vancomycin should be started within 2 hours
before the incision is made. Antibiotics given
sooner (except possibly for longer half-life agents
such as metronidazole) are not effective, nor are
agents that are given after the incision is closed.
Antibiotics with short half-lives (<2 h), such as
17
cefazolin or cefoxitin, should be re-dosed every
3 to 4 hours during surgery if the operation is
prolonged or there is major blood loss. 28 Despite
the existence of published guidelines, timely
antibiotic administration relative to surgery is poor,
occurring in just over half of cases according to one
report. 30
In contrast, recommendations for the duration
of antibiotic prophylaxis are less clear. In cardiac
surgery, for example, the US Society of Thoracic
Surgeons conclude that antibiotic prophylaxis of
48 hours duration is effective, but note that
single-dose prophylaxis or 24-hour prophylaxis
may be as effective as 48-hour prophylaxis. 25
The consensus of the National Surgical Infection
Prevention Project is that prophylaxis should be
discontinued within 24h after the end of surgery. 31
Anecdotally, however, while recognising that the
likelihood that resistant organisms will emerge
appears to be related directly to the duration
of prophylaxis, some surgeons feel that a 48-
hour prophylaxis is justified for gastrointestinal
surgery. 32
Antibiotic resistance
In the hospital environment, particularly in ICUs,
antibiotic use is extensive, resulting in selec-
tive pressure for antibiotic-resistant pathogens.
Mobile genetic elements have facilitated the
rapid spread of antibiotic resistance within and
among species. 33 Antimicrobial resistance among
bacteria is an increasing threat. Clinically im-
portant drug-resistant bacteria that commonly
cause healthcare-associated infections include
MRSA and meticillin-resistant coagulase-negative
staphylococci, vancomycin-resistant enterococci,
and multidrug-resistant Gram-negative rods, in-
cluding strains of Pseudomonas aeruginosa and
E. coli. Antimicrobial resistance among nosocomial
pathogens often results in prolonged periods of
antimicrobial therapy and increased treatment
costs, prolonged hospital stays and higher mortal-
ity. 34
Antibiotic stewardship
With bacterial resistance appearing to grow
inexorably, in terms of both the rates of resistance
among prevalent pathogens and the number of
antibiotics encountering resistance, prescribing
habits have been forced to change. In the
past decade, an integrated process designed
to slow the emergence of resistance among
microorganisms has developed. Often referred to
as antimicrobial stewardship, this process involves
18
selecting an appropriate drug and optimising its
dose and duration to cure an infection while
minimising toxicity and conditions for selection
of resistant bacterial strains. This may involve
restriction and rotation of antibiotics in individual
centres. Awareness of the antibiotic susceptibility
pattern of pathogens isolated in their clinical
centre is clearly important for surgeons, and
close liaison with the microbiology department is
essential.
Preoperative skin preparation
With the predominant role of skin flora in
SSI, effective and efficient preoperative patient
skin preparation is an essential perioperative
intervention that decreases the number of wound
contaminants and reduces the risks for postopera-
tive SSI. Nevertheless, complete sterilisation of the
skin is not possible.
In some procedures, removal of body hair is
unnecessary. Where hair removal is required,
clipping is preferable to shaving and chemical
depilation more effective than either of these
methods in reducing the risk of SSI. 32
Careful preparation of the skin with an appro-
priate antiseptic is essential. Some studies have
shown that chlorhexidine alcohol was more effec-
tive than povidone iodine 35,36 while others have
shown no important difference. 32 Chlorhexidine-
based antiseptics may also be preferable, espe-
cially in reduction of residual skin flora microbes,
because occasional patients show an adverse
skin reaction to iodine preparations. Preoperative
showering or bathing with chlorhexidine does not
appear to provide any benefit over other wash
products in reducing SSI. 37
Similarly, some studies have shown less surgical
wound contamination by skin bacteria and a lower
risk of SSI by the use of iodine-impregnated adhe-
sive plastic drapes 38,39 but the overall data for this
tradition of surgery is not convincing. 28 In addition,
exposure of patients’ skin to materials with adhe-
sive substances has the potential to cause skin re-
actions that result in intraoperative and postoper-
ative skin complications. The recent development
of a non-irritating, cyanoacrylate-based microbial
sealant (InteguSeal*, Kimberly-Clark Health Care,
Roswell, USA) that, once dry, immobilises skin
bacteria under a breathable film is an innovative
and promising approach to reducing the risk of
surgical site contamination by skin flora that may
obviate the use of surgical drapes in future. 40,41
Adhesive plastic incision drapes remain tightly
adherent throughout the operative procedure, and
epidermal loss caused by drape removal may
P.M. Dohmen
follow, with high risk of subsequent infection.
The use of adhesive plastic incision drapes is a
particular risk in patients with skin atrophy, such
as the elderly, malnourished patients, and in those
receiving long-term steroid therapy. In others with
skin sensitivity to iodine-containing preparations,
impregnated drapes are contraindicated. In such
cases, it may be possible to use a ‘skin-friendly’
microbial sealant without incision drapes, thereby
minimising potential skin damage, as well as
creating substantial cost-saving by reducing or
avoiding the use of iodine-impregnated drapes.
Growing numbers of high-risk patients
In many countries, populations are becoming older,
and increasing numbers of elderly patients are be-
ing referred for surgery. Many have a wide variety
of chronic concurrent, often subclinical, diseases
that decrease immune defences and contribute to
increased risks of SSI, postoperative morbidity and
mortality. 20 Several perioperative interventions
have been shown to reduce the risk of SSI infection,
including maintaining normothermia, 42 provision
of supplemental perioperative oxygen, 43 and tight
glucose control (regardless of whether or not
patients have diabetes mellitus). 44 Prevention is
clearly preferable to treatment of SSI, particularly
given the increasing prevalence of antibiotic
resistance among common nosocomial pathogens.
Effective reduction of skin bacteria and wound
contamination, appropriate antibiotic prophylaxis
and improving host defences are all important
strategies that together will help achieve this
overall objective.
Funding: None
Conflict of Interest statement: The author has
no conflicts of interest to declare.
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