Download Management of culture-negative surgical site infections

J Med Allied Sci 2012; 2 (1): 02-06
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Print ISSN: 2231 1696 Online ISSN: 2231 170X
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Management of culture-negative surgical site infections
B. Ravinder Reddy
Consultant Surgeon, Division of General Surgery and Surgical Gastroenterology,
Care Hospital–The Institute of Medical Sciences, Banjara Hills, Hyderabad, Andhra Pradesh, India.
Sunshine Hospital, Paradise Circle, Secunderabad, Andhra Pradesh, India
Article history:
Received 28 April 2011
Revised 08 June 2011
Accepted 23 August 2011
Early online 01 September 2011
Print 31 January 2012
Corresponding author
B. Ravinder Reddy
Division of General Surgery & Surgical
Gastroenterology,
Care Hospital,
Banjara Hills, Hyderabad,
Andhra Pradesh, India.
Phone: +91 9849001345
E-mail: [email protected]
Abstract
Infections at the surgical site delays wound healing, prolongs hospitalization, increases morbidity and the overall costs. These issues
are compounded when the postoperative infection is culturenegative. This article outlines the general principles of managing
postoperative surgical site infections, with an emphasis on culturenegative infections. Practical issues, in the absence of positive culture are discussed, together with practice points to minimize the
incidence of culture-negative surgical site infections.
Key words: surgical site infections, Gram positive, Gram negative,
bacterial culture, culture negative SSIs
urgical site infections (SSIs) are defined as
infections of skin or underlying soft tissues at
the surgical site, following an operation. These
are common postoperative complications. Their incidence varies, but is more common following emergency surgical procedures. SSIs are associated with
tissue destruction up to varying depths, delay or
even failure in wound healing, disfiguring or disabling scars, persistent or recurrent pain at the operated site, bacteremia, pyrexia, and incisional hernias.
S
In addition, they also prolong the hospital stay and
increase the costs.
This article is an overview of the management of
surgical site infections with emphasis on culture
negative SSIs. For a detailed review, please refer to
1-3
the published literature and to the articles listed in
the further reading* section.
Management of SSIs is based on structured protocols, which are as follows:
i. Appropriate preoperative management, which
include assessment and optimization of various
© 2012 Deccan College of Medical Sciences. All rights reserved.
risk factors (Table 1).
ii. Initiation of antibiotic prophylaxis to cover the
common pathogens causing SSIs (Table 2).
iii. Control of operating theater environment and
avoidance of hypothermia.
iv. Appropriate intra-operative management of the
tissues and incision.
v. Appropriate postoperative management which
include optimization of hyperglycemia, supplemental oxygenation, judicious use of blood
transfusion, nutritional support with emphasis on
early enteral nutrition.
The incidence of SSIs can be reduced significantly
1, 2
with these evidence-based protocols . Despite the
efforts, 2 to 10% of all elective surgical cases do
develop SSI. Further management of such infected
wounds is simplified to a certain extent by the culture and sensitivity reports, by remaining updated
with the current hospital microbiological data and by
administration of nutrition supplements which facilitate wound healing. Such attempts may limit the pro3
longed hospital stay and will also reduce the costs .
2
Reddy BR
Culture negative surgical site infections
Table 1: Risk factors for the development of SSIs
4
Table 3: Micro-organisms causing Culture Negative
5
SSIs
Patient factors:
Diabetes
Malnutrition (undernutrition & obesity)
Extremes of age
Skin disease at operation site
Irradiation at operation site
Peripheral vascular disease (for lower limb surgeries)
Hypoxemia
Postoperative anemia
Steroid therapy
Chronic inflammatory conditions
Infection at remote sites
Staphylococcal carriers
Mycobacterium chelonae
Mycobacterium fortuitum
Mycobacterium abscessus
Ureaplasma urealyticum
Mycoplasma hominis
Staphylococcus aureus (small colony variant)
Coagulase-negative staphylococci
Legionella species
Actinomyces
Coxiella burnetti
Cornybacteria
Table 4: Non-Infectious causes
5
Treatment factors:
Emergency procedures
Inadequate and inappropriate antibiotic prophylaxis
Prolonged preoperative hospitalization
Prolonged operative time
Hypothermia
Surgical drains
Environmental factors:
Inadequate skin antisepsis
Inadequate sterilization of instruments
Inadequate ventilation
Contaminated medications
Table 2: Microbiology of surgical site infection
Pathogen
Pyoderma gangrenosum
Factitious inoculation
Culture negative SSIs
A common problem is managing a patient with all
the clinical signs of surgical site infection, but with
“no bacterial growth” on the culture report! The incidence of such ‘culture negative SSIs’, based on pub5,6
lished studies can be up to 30% .
Many micro-organisms (Table 3) and non-infective
factors (Table 4) are responsible for causing culture
negative surgical site infections.
Modes of inoculation of microbes causing culture negative SSIs
4
Incidence (%)
There are three ways by which surgical sites can get
infected.
Staphylococcus
19
Coagulase-negative Staphylococcus
14
Enterococcus
12
Escherichia coli
8
Pseudomonas
8
Miscellaneous aerobic gram-ve bacilli
8
Enterobacter sp.
7
Streptococcus
6
Klebsiella sp
4
Causes of culture negative SSIs
Miscellaneous anaerobic bacteria
3
Miscellaneous aerobic gram+ve bacteria
2
Various agents have been hypothesized as causes
for culture negative infection at surgical sites:
J Med Allied Sci 2012; 2(1)
1. Intraoperative inoculation of the surgical wound
from non-sterile instruments and contaminated
prosthetics and even surgical solutions. Clinical
examples are Legionella species and rapidly
growing mycobacteria, etc.
2. Improper cleaning of surgical site by an inappropriate surgical solution. Clinical examples are
Staphylococcus epidermidis, Mycoplasma species, etc.
3. By blood-spread, in the postoperative period.
Clinical examples are Mycoplasma species.
3
Reddy BR
1. The most frequent cause is thought to be due to
culturing the infected site after commencement
of antibiotics.
2. Atypical organisms do not grow on standard
culture media. Also they may grow rather slowly
and the culture plates are discarded before the
growth becomes apparent.
3. Common contaminant like Staph. epidermidis)
are generally ignored as contaminants, but may
actually be the cause of postoperative infection.
Role of microbiologist in detecting SSIs
The standard practice is to incubate the culture material (from infected surgical sites) for 48 hours . If no
growth is seen, these plates are discarded and the
result is reported as ‘no growth’ or ‘culture negative’.
In such instances, the microbiologist should be
aware of some organisms might be missed, especially if the culture plates are discarded soon after 48
hours. Alternately, some of the colonies are quite
small and might be missed, if not looked for.
Hence communication with the microbiologist should
be a standard clinical practice to ensure optimal
identification of the microbes. Also, relevant information, like previous antibiotics used, co-morbid
conditions and depth and extent of SSI should be
provided to the microbiologist, thereby minimizing
the chance of overlooking or missing the presence
of atypical organisms. The microbiologist will then
incubate the cultures for a longer period of 5 or more
days and also by utilizing specific media (Table 5).
Microbes which can be ‘missed’ on routine culture, but can cause SSI
There are many pathogenic microorganisms which
cause SSI, but do not exhibit a positive growth on
standard culture plates within 48 hours. Some examples are::
1. Atypical Mycobacteria
2. Mycoplasma and Ureaplasma
3. Legionella
4. “Small-colony variant” Staphylococcus aureus
5. Anaerobic pathogens
Atypical Mycobacteria:
These organisms grow more rapidly (compared to
the typical mycobacteria species) within 5 days on
standard blood agar plates. Common organisms are
Mycobacteria abscessus, M. chelonae and M.
fortuitum. Common clinical procedures where these
organisms can cause postoperative infections are:
i. Permanent cardiac pacemaker implantation.
ii. Laparoscopic procedures
iii. Breast operations
J Med Allied Sci 2012; 2(1)
Culture negative surgical site infections
iv. Liposuction
v. Facial surgery and body piercing
vi. Arthroplasty
Atypical mycobacteria are susceptible to a wide
range of antibiotics, especially fluoroquinolones.
Sensitivity of each isolate is recommended.
Mycoplasma and Ureaplasma
Mycoplasma hominis and Ureaplasma urealyticum
are the common Mycoplasmas that can cause SSI.
These are common in immunosuppressed patients.
Commonest source is the persons own endogenous
flora. These require special culture methods for optimum identification, as these are not included in
routine culture protocols and must be requested by
the surgeon, in all immunosuppressed patients with
SSI. These are generally susceptible to tetracyclines
and macrolides. Some of the common clinical procedures where these organisms can cause postoperative infections are:
i.
ii.
iii.
iv.
v.
vi.
Cesarean section wounds
Sternotomy wounds
Vascular grafts
Post-transplant surgery
Orthopedic procedures
Maxillofacial surgery
Legionella
Legionella species commonly cause lung infections.
Rarely, they can gain access to surgical site by
hematogenous route and result in SSI. They also
spread by nosocomial route. They are thin gramnegative bacilli and are poorly visible on gram stain.
They do not grow on ordinary culture media and
need addition of special substances like cysteine
and iron salts for optimal growth. Published case
reports of SSIs caused by Legionella species include:
i. Hemodialysis fistula
ii. Hip surgery wounds
iii. Sternotomy wounds
Legionella species are generally susceptible to
fluoroquinolones or macrolides.
Small-colony variant-Staphylococcus aureus (SCV)
These species can be commonly be mistaken for
coagulase-negative staphylococci, as their coagulase test can be delayed. Also, they tend to grow
rather slowly, and take more than 3 days to be identified (seen as small pinpoint colonies). Infection with
these organisms tends to be less pathogenic, but
they have the capacity to develop resistance to antibiotics, perhaps due to the fact that they persist
intracellularly, and hence result in chronic infections.
4
Reddy BR
Culture negative surgical site infections
Table 5: Duration and types of media used in Identification of microbes
Medium
Incubation Period
7
Microbes Isolated
Sheep blood agar
MacConkey agar
Aerobic for 3 days
Deep tissues: 7 days
Staphylococcus aureus and CNS
Streptococci, Enterococci, Gram –ve rods,
Corynebacteria
Chocolate agar
Aerobic 4 – 7 days
Most RGM, Nocardia species
SCV Staphylococcus aureus
Occasional: Legionella and Mycoplasma
Buffered charcoal-yeast Aerobic 4 -14 days
extract agar (BCYE)
Legionella, Mycoplasma and Nocardia
RGM. Fungi, SCV Staphylococcus aureus
CDC-anaerobic agar,
CAN, LKV,
Anaerobic 14 – 28 days
Anaerobes, Nocardia species
SCV Staphylococcus aureus, Brucella,
A7 & A8 agar
Aerobic 3 – 4 days
Mycoplasma, Ureaplasma
Thioglycolate broth
(Blood culture bottles)
Aerobic 7 – 14 days
Growth for all routine microbes
Atypical remain alive for subculture
10B Arginine broth
Aerobic 3 – 4days
Special broth for recovery of Mycoplasma
and Ureaplasma
7h9 broth with
TM
PANTA
Aerobic up to 14 days
Antibiotic supplements broth for recovery
of Mycobacterium species
RGM: Rapidly growing mycobacteria, SCV: Small colony variant
A classic example is the persistent discharging infection, following a hernia repair with a synthetic
mesh. They can also be the causative organisms of
SSI in patients who received aminoglycosides as
prophylactic antibiotic. These are generally susceptible to clindamycin and also medications that are
effective against MRSA.
Anaerobic Bacteria:
The surgical site infections caused by these tend to
be rare, but can result in a fulminant course. Common organisms are Clostridium, Bacteroides and
Prevotella species. They cannot be cultured on routine aerobic media and need special anaerobic me7
dia . Appearance of dirty-water like exudates, which
is culture negative, is a clue to the presence of these
bacteria (C. perfringens). Infections caused by such
organisms have a high mortality rate and debridement should be done early. They are susceptible to
clindamycin and penicillins.
Organisms causing SSI which can be mistaken
for contaminants
Coagulase-negative staphylococci (CNS) or even
Corynebacterium species can cause postoperative
wound infections, and yet diagnosed as ‘contamiJ Med Allied Sci 2012; 2(1)
nants’! If these organisms are present in exudates at
5
or more than 10 colony-forming units/ml then they
should be assumed as the cause of SSI. Some of
the common clinical situations where these organisms cause SSI are:
i.
ii.
iii.
iv.
Vascular grafts
Prosthetic joints
Prosthetic shunts
Other implanted devices
Other assorted organisms causing SSI
These are comprised of a mixture of microorganisms
can be difficult to culture and yet cause SSIs. They
might need special culture media and PCR analysis
7
to diagnose . They cause infections at various surgical sites. Some of these organisms are:
i.
ii.
iii.
iv.
Actinomyces
Nocardia
Coxiella burnetti
Gordona species
Published literature on case reports include chronic
sternal infections and mediastinitis following cardiac
surgery, carotid artery rupture following resection of
oropharyngeal carcinoma, facial infections following
facial-cutaneous surgery.
5
Reddy BR
Culture negative surgical site infections
Role of clinician and microbiologist in management of culture negative SSIs
Practice Points to Minimize Incidence of Culture
Negative SSIs
Managing SSI needs a close cooperation between
the surgeon and microbiologist. The tenets of this
clinical partnership can be summarized as follows:
i.
ii.
i. Discuss with the microbiologist and provide all
the clinical details, including the antibiotics in
use (immediate past and present). The microbiologist in turn needs to do the following:
a) Review the gram stain. This includes
original smears as well as stains of broth
into which the specimen has been inoculated.
b) Review the original culture plate and hold
it up to 2 weeks to allow growth of slowgrowing’ microbes.
c) Can subculture on specialized media.
d) Request for a fresh specimen, which
should be sent to laboratory immediately,
which can then be cultured for acid-fast
bacteria and fungus.
ii. Consider empiric therapy (after vigorous attempts have been made to identify the responsible pathogen in concurrence with the
microbiologist) if SSI persists after routine
treatment with first-line antibacterial drugs
against common pathogens. The choice of antibiotics includes antistaphylococcal penicillins,
cephalosporins, vancomycin, and β-lactum /
β-lactumase inhibitor combination for suspected mixed infections.
iii. Consider additional diagnostic tests and special culture media and repeat cultures.
iv. Consider newer fluroquinolones like levofloxacin on long course basis, as these are active
against Mycoplasma, Legionella and other
atypical mycobacteria.
Conclusion
Managing surgical site infections in the absence of
positive culture can be difficult. In such situations, an
effective communication with the microbiologist and
infectious-disease specialist will enable a positive
clinical outcome. The steps can be summarized as
follows:
1) The standard plates to be incubated for an additional 5 to 7 days, which allows the ‘slowgrowers’ to be identified.
2) Subculture the broth even in the absence of visible growth.
3) Repeat surgical biopsies if diagnosis is doubtful,
with a request for special diagnostic studies.
J Med Allied Sci 2012; 2(1)
iii.
iv.
v.
vi.
vii.
Optimize preoperative morbidity.
Ensure adequacy of operation theatre environment.
Ensure adequate antisepsis at surgical sites.
Ensure appropriate tissue handling.
Prevent breakdown of infection control procedures.
a. Avoid rinsing instruments in contaminated
surgical solutions, tap water or contaminated ‘sterile water’.
b. Avoid contaminated gentian violet or methylene blue marking solutions.
Institute appropriate evidence-based prophylactic antibiotics.
Be aware of the recognized causes of culture
negative SSIs.
Conflict of interest: None
Acknowledgment: None
References
1.
2.
3.
4.
5.
6.
7.
Hospital Infection Control Practices Advisory Committee.
Guidelines for Prevention of Surgical Site Infections. January
1999.
Forbes SS, Stephen WJ, et al. Implementation of evidencebased practices for surgical site infection prophylaxis: Results of a pre- and postintervention study. J Am Coll Surg.
2008; 207(3):
Fry DE. The economic costs of surgical site infections. Surg
Infec (Larchmt). 2002; 3 (suppl 1): S37-43.
Barie PS, Eachempati SR. Surgical Site Infections. Surg Clin
N Am.2005; 85:1115-1135.
Giacometti A, Cirioni O. Epidemiology and microbiology of
surgical wound infections. J Clin Microbiol 2000;38:918-922.
Twum-Danso K, Grant C, et al. Microbiology of postoperative wound infections: A prospective study of 1770 wounds.
J Hosp Infect 1992; 21:29-37
Manual of Clinical Microbiology. Washington. D.C. ASM
Press, 1999.
Further reading*
Mandell GR, Bennett JE, Dolin R, eds. Principles and Practice of
Infectious Diseases. Seventh edition. Philadelphia. Churchill
Livingstone 2000.
Mishriki SF, Law DJ, Jeffery PJ. Factors affecting the incidence
of postoperative wound infection. Journal of Hospital Infection
1990.
Leaper D, Burman-Roy S, Palanca A, et al. Prevention and
treatment of surgical site infection: summary of NICE guidelines
BMJ 2008.
McHugh SM, Hill AD, Humphreys H. Preventing healthcareassociated infection through education: have surgeons been
overlooked? Surgeon 2010.
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