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‫بسم هللا الرحمن الرحيم‬

Surgical Site Infection

Prof. Dr. Hadia H. Bassim


Microbiology Unit
Ain Shams University
Surgical Site Infection

 CDC term for infections associated


with surgical procedures was changed
from surgical wound infection (SWI)
to surgical site infection (SSI) in 1992

 The term surgical site infection is used to include


the surgical wound and other tissues infection
involved in the operation ( the body cavity,
bones, joints, meninges) and the implants.
IMPACT OFInfected
SSI Un-infected
Mortality 7.8% 3,5%

ICU
29% 18%
admission
Length of Stay 11 days 6 days
Median direct
$7,531 $3,844
cost
Readmission 41% 7%

Kirkland. Infect Control Hosp Epidemiol. 1999;20:725.


Surgical Site Infection
SSI Can be classified
according to:

I- The type of operation & whether the


wound is drained or not: clean,
clean/contaminated, contaminated,
dirty/infected
II- Degree of severity: incisional SSI,
orgtan/space SSI
Surgical Site Infection
(cont.)
The type of operation & whether the wound is
drained or not

Clean Clean-contaminated

1.5-3% 3-4%

Contaminated Dirty/infected

8.5% 28-40%
Classification of operations
(WHO)

 Clean: An operative wound where an


organ space is not entered or a wound
that undergoes primary closure.

 Clean contaminated: An operative


wound in which an organ space is
entered under controlled conditions
without unusual contamination.
Classification of
operations (WHO)cont
 Contaminated: Open, fresh, accidental
wounds or operative wounds with
spillage and microbial contamination
from the gastrointestinal tract <4
houres.
 Dirty/infected: Old traumatic wounds
with existing clinical infection or
following operations on perforated
viscera.
SSI CLASSIFICATION
Degree of severity
A- incisional
-

Superficial Deep
incisional SSI
incisional SSI

Organ/space SSI
B_ Organ/space SSI
Global strategy for
hospital hygiene -
Cairo
The ASA physical status classification
system
  is a system for assessing the fitness of patients before surgery.
In 1963 the American Society of Anesthesiologists (ASA)
adopted the five-category physical status classification system; a
sixth category was later added. These are:
1. Healthy person.
2. Mild systemic disease.
3. Severe systemic disease.
4. Severe systemic disease that is a constant threat to life.
5. A moribund person who is not expected to survive without the 
operation for 24 h.
6. A declared brain-dead person whose organs are being removed
for donor purposes.
 If the surgery is an emergency, the physical status
classification is followed by “E” (for emergency) .
Class 5 is usually an emergency and is therefore
usually "5E". The class "6E" does not exist and is
simply recorded as class "6", as all organ retrieval in
brain-dead patients is done urgently.
 The emergency is now defined as "when delay in
treatment would significantly increase the threat to
the patient's life or body part.
NNIS Stratification

Contamination class
III or IV

+1 Duration
ASA score  3
>2h

+1
+1
NNIS index
from 0 to 3
NNIS Stratification
 NNIS risk index: 0 to 3 points
(1) American Society of Anesthesiologists (ASA)
Physical Status Classification of  3 + 1
(2) Contaminated or dirty/infected wound
classification + 1
(3) length of operation >T hours, where T depends
upon the operative procedure being performed
+1
to 3 po in ts
r is k i nd ex:0
NNIS

Index 1 (0 points): 1.5%


Index 2 (one point): 2.9%
Index 3 (two points): 6.8%
Index 4 (three points): 13%
Pathogenesis
:
Dose of bacterial contamination x virulence
= Risk of surgical site
Resistance of the host patient
infection
 Surgical site: >105 microorganisms/gram of tissue
 Endotoxin: gram-negative bacteria
 stimulates cytokine production
 systemic inflammatory response syndrome
 Exotoxin: certain strains of clostridia and streptococci
 disrupt cell membranes
 Despite the fact that
every surgical site
could be
contaminated by the
end of the surgery,
luckily enough, only
few become infected.
Sources of contamination
Skin flora +++
(if disinfection is insufficient)
Endogenou Colonised skin (dermatitis)
Gastro-intestinal tract
s Respiratory tract
From patient’s own Genital tract
flora Urinary tract

Personnel
WOUND
Exogenous Hands (operative team)
From physical and Hair & scalp
human environment Head & neck
Nares & oro pharynge
Environment & air
Probable Location of SSI
Infection
Operating
theatre Ward

Post-Discharge
infection
Infection Acquired in O.R.
 Deep infection in a clean, un drained wound
 Infection occurring within 3 days of the operation,
or prior to the first dressing in a clean wound

 Supporting evidence :
- Organisms Of the same type isolated in different
wards from patients operated on in the same O.R.
- Organisms Of the same type isolated in different
wards from patients operated on by same members
of the operating staff
Infections Acquired in the
Ward
 This is indicated by superficial infection in a
wound (usually drained), occurring after first
dressing. Culture of discharge may initially be
negative, & deep infection may develop later in
a drained wound

 Supporting evidence : Organism Of


the same type isolated from other patients
or members of the staff in the ward
Post-Discharge Infections (cont.)

 21-70% of SSI become


apparent after leaving hospital
Microbiology of Surgical Site
Infections

According to data from the NNIS system


 The distribution of pathogens isolated from

SSIs has not changed markedly during the last


years.  The causative pathogens depend on the type
of surgery
 Staphylococcus aureus, coagulase-negative

staphylococci, Enterococcus spp., and


Escherichia coli remain the most frequently
isolated pathogens.
Microbiology of Surgical Site
Infections

 An increasing antimicrobial-
resistant pathogens, such as
(MRSA), or by Candida albicans.

 The incidence of fungal SSIs


increased . This increased may
reflect increasing numbers of
severely ill and
immunocompromised surgical
patients.
Microbiology of Surgical Site
Infections

Outbreaks of SSIs have also been caused by unusual pathogens

such as Clostridium perfringens, and Legionella pneumophila ,

: These rare outbreaks have been traced to


contaminated adhesive dressings*
elastic bandages*
colonized surgical personnel*
tap water*
.contaminated disinfectant solutions*
.A formal epidemiologic investigation should be conducted
CDC_Recommendation for
prevention SSI

 RANKINGS
 Category I A. Strongly recommended for implementation
and supported by well-designed experimental,

 Category I B. Strongly recommended for implementation


and supported by some experimental, clinical, or
epidemiological studies

 Category II. Suggested for implementation and supported


by suggestive clinical or epidemiological studies or
theoretical rationale.

 No recommendation; unresolved issue. Practices for


which insufficient evidence or no consensus
SSI Prevention

prevention and control of SSI


Indication for preoperative
preparation
 Surgery
 labor (C.S)
 Cardiac catheterization
 Diagnostic venous investigation
 Spinal / epidural anesthesia
 C.V. catheterization
Recommendation for prevention
SSI
1-Preoperative

A. Preparation of the patient


 1. Identify and treat all infection and postpone elective
operations on patients with remote site infections until the
infection has resolved. Category IA

 2. Do not remove hair preoperatively unless the hair


at or around the incision site will interfere with the
operation.Category IA

 3. If hair is removed, remove immediately before the


operation, preferably with electric clippers Category IA
PRE-OPERATIVE SHAVING
 Shaving the surgical site with a razor induces
small skin lacerations

potential sites for infection

disturbs hair follicles which are often colonized with
S. aureus

Risk greatest when done the night before.
 Patient education

 be sure patients know that they should not do you a


favor and shave before they come to the hospital
CLIPPERS

 Recommendation: No hair
removal
If performed: clipping when
needed or depilatories,
 immediately before intervention

 Disposable heads

 Disinfection after use

 Puncture-resistant container
MOUTH HYGIENE
 Dental brushing for all patients.

 Add antiseptic mouth wash


 Pre and post cardiac surgery and
stomatology s.

 The night before and day of surgery.


A. Preparation of the patient
cont
 4. Adequately control serum blood glucose levels in
all diabetic patients less than 200mg . Category IB

 5. Encourage tobacco cessation at least 30 days any form


of tobacco consumption (e.g.chewing/dipping). Category
IB

 6. Do not withhold necessary blood products . Category IB


A. Preparation of the patient

 7. Keep preoperative hospital stay as short as


possible Category I preoperative hospital stay
Cause increased colonisation by nosocomial
pathogens.
 Ambulatory pre-surgical investigations to be
organised, when possible admission in the morning
or the day before.
B. Preparation of the patient skin
 1-Require patients to shower or bathe with an
antiseptic agent on the morning before intervention
Or at least the night before the operative day.
Category IB
antiseptic showering decreases colony counts
Conflicting evidence in term of SSI
 Remove all jewellery
 Brush teeth
 Clean sheets
 Clean gown prior surgery hair covered
B. Preparation of the patient skin
cont.

 2. Thoroughly wash and clean gross contamination before


performing antiseptic skin preparation. Category IB
Reduce number of microorganisms on intact skin
Just before incision
 3. Use an appropriate antiseptic agent for skin preparation
Category IB

 antiseptic product with a broad spectrum


(iodine, or chlorhexidine ),
 fast active and persistent
 Non inflammable
 4. Apply in concentric circles
moving toward the periphery.
The prepared area must be large
enough to extend the incision .
Category II
 Sterile gloves
 Sterile technique
 Concentric circles
 Final application (no touch technique)
Steps of skin antisepsis
 Clean (to remove supserficial bacteria)

 Rinse (sterile water)

 Dry

 Use antiseptic (to reduce deep resident

flora) by application of iodine, or


chlorhexidine (broad spectrum)
 Let dry before drapping
Cleansing
Rinse
Skin antisepsis
5-DRAPING
 Barrier measures
 Covering with sterile barrier materials
the nonsterile area immediate to and
surrounding the operative site
 Consider as a standard in OR
 100% cotton textiles should not be
used
 Adhesive drapes
C. Hand/forearm antisepsis for surgical
team members

 1. Keep nails short and do not wear artificial nails .Category IB

 2. Perform a preoperative surgical scrub for at least 2 to 5


minutes using an appropriate antiseptic Scrub the hands and
forearms up to the elbows. Category IB

 3. After performing the surgical scrub, keep hands up and away


from the body (elbows in flexed position) so that water runs
from the tips of the fingers toward the elbows. Dry hands with a
sterile towel and don a sterile gown and gloves. Category IB

 4. Clean underneath each fingernail prior to performing the first


surgical scrub of the day. Category II

 5. Do not wear hand or arm jewelry. Category II


 6. No recommendation on wearing nail polish. Unresolved Issue
D. Management of infected or colonized
surgical personnel

 1. Educate and encourage surgical personnel


to report infectious illness conditions
promptly . Category IB

 2. Develop well-defined policies , which


should govern
 (a) personnel responsibility in using the
health service and reporting illness,
 (b) work restrictions, and
 (c) clearance to resume work after an illness
 The policies also should identify persons who
have the authority to remove personnel from
duty. Category IB
D. Management of infected or colonized
surgical personnel
cont.

 3. Obtain appropriate cultures , and exclude from


duty surgical personnel who have draining skin
lesions until infection has resolved. Category IB

 4. Do not routinely exclude surgical personnel who


are colonized with organisms such as S. aureus
(nose, hands, or other body site) or group A
Streptococcus, unless such personnel have been
linked epidemiologically to dissemination of the
organism in the healthcare setting.
Category IB
E. Antimicrobial prophylaxis

 1. Administer a prophylactic antimicrobial agent only when


indicated, and select it based on its efficacy against the most
common pathogens causing SSI for a specific operation (and
published recommendations).
Category IA

 2. Administer by the IV route the initial dose of prophylactic


antimicrobial agent, timed such that a bactericidal concentration
of the drug is established in serum and tissues when the incision
is made. Maintain therapeutic levels of the agent in serum and
tissues throughout the operation and until, at most, a few hours
after the incision is closed in the operating room. Category IA
E- Administer antimicrobial prophylaxis in
accordance with evidence based standards
and guidelines
 Administer within 1 hour prior to incision*
 2hr for vancomycin and fluoroquinolones

 Select appropriate agents on basis of


 Surgical procedure

 Most common SSI pathogens for the procedure

 Published recommendations

*Fry DE. Surgical Site Infections and the Surgical Care Improvement Project (SCIP): Evolution of National
Quality Measures. Surg Infect 2008;9(6):579-84.
E. Antimicrobial prophylaxis
 3. Before elective colorectal operations
mechanically prepare the colon by use of
enemas and cathartic agents. Administer non
absorbable oral antimicrobial agents in divided
doses on the day before the operation. Category
IA
 4. For high-risk cesarean section, administer the
pro-phylactic antimicrobial agent immediately
after the umbilical cord is clamped. Category IA

5. Do not routinely use vancomycin
for antimicrobial prophylaxis. Category IB
2. Intraoperative
2. Intraoperative
a. Ventilation

 1. Maintain positive-pressure ventilation in the operating room


with respect to the corridors Category IB

 2. Maintain a minimum of 15 air changes per hour, of which at


least 3 should be fresh air. Category IB

 3. Filter all air, recirculated and fresh, through the appropriate


filters Category IB

 4. Introduce all air at the ceiling, and exhaust near the floor.
Category IB
a. Ventilation
cont.
 5. Do not use UV radiation in the operating room to
prevent SSI. Category IB

 6. Keep operating room doors closed .


Category IB

 7. Consider performing orthopedic implant operations in


operating rooms supplied with ultraclean air.
 Category II

 8. Limit the number of personnel entering the operating


room to necessary personnel. Category II
b. Cleaning and disinfection of
environmental
surfaces
1. When visible soiling or contamination with blood or other
body fluids of surfaces or equipment occurs during an
operation, use an EPA-approved hospital disinfectant to
clean the affected areas before the next operation.
Category IB*
2. Do not perform special cleaning or closing of operating
rooms after contaminated or dirty operations. Category IB
3. Do not use tacky mats at the entrance to the operating
room suite or individual operating rooms for infection
control. Category IB
4. Wet vacuum the operating room floor after the last
operation of the day or night with an EPA-approved
hospital disinfectant. Category II
5. No recommendation on disinfecting environmental
surfaces or equipment used in operating rooms between
operations in the absence of visible soiling. Unresolved
issue
c. Microbiologic sampling

Do not perform routine


environmental sampling of
the operating room.
Perform microbiologic sampling
of operating room
environmental surfaces or air
only as part of an
epidemiologic investigation.
Category IB
d. Sterilization of surgical
instruments
 1. Sterilize all surgical instruments
according to published guidelines Category
IB

 2. Perform flash sterilization only for patient


care items that will be used immediately
(e.g., to reprocess an inadvertently
dropped instrument).
Do not use flash sterilization for reasons of
convenience, as an alternative to purchasing
additional instrument sets, or to save time.
Category IB
d. Sterilization of surgical
instruments

 1. Sterilize all surgical instruments according to


published guidelines Category IB

 2. Perform flash sterilization only for patient care


items that will be used immediately (e.g., to
reprocess an inadvertently dropped instrument).
Do not use flash sterilization for reasons of
convenience, as an alternative to purchasing
additional instrument sets, or to save time.
Category IB
E. Surgical attire and drapes

 1. Wear a surgical mask that fully covers the mouth and nose
when entering the operating room if an operation is about
to begin or already under way, or if sterile instruments are
exposed. Wear the mask throughout the operation.
CategoryIB*

 2. Wear a cap or hood to fully cover hair on the head and


face when entering the operating room. Category IB*

 3. Do not wear shoe covers for the prevention of SSI.


Category IB*
Protection of surgical team members when splashes or spills with
blood and body fluids may occur

 4. Wear sterile gloves if a scrubbed surgical team member


Put on gloves after donning a sterile gown. Category IB*
e. Surgical attire and
drapes cont.

 5. Use surgical gowns and drapes that are effective


barriers when wet (i.e., materials that resist liquid
penetration).
Category IB

 6. Change scrub suits that are visibly soiled,


contaminated,and/or penetrated by blood or other
potentially infectious materials. Category IB*

 7. No recommendations on how or where to launder


scrub suits, on restricting use of scrub suits to the
operatin suite, or for covering scrub suits when out
of the operatin suite. Unresolved issue
f. Asepsis and surgical technique

 1. Adhere to principles of asepsis when


placing intravascular devices spinal or
epidural anesthesia catheters, or when
dispensing and administering intravenous
drugs. Category IA

 2. Assemble sterile equipment and solutions


immediately prior to use. Category II
Protection of
the
instruments
during the
preparation
f. Asepsis and surgical technique
cont.
 3. Handle tissue gently, maintain effective
homeostasis,
minimize devitalized tissue and foreign bodies and
eradicate dead space at the surgical site. Category IB

 4. Use delayed primary skin closure or leave an incisi


open to heal by second intention if the surgeon
consider the surgical site to be heavily contaminated
Category IB

 5. If drainage is necessary, use a closed suction


drain. Place a drain through a separate incision
distant from the operative incision Category IB
3. Postoperative incision
care
3. Postoperative incision care

 a. Protect with a sterile dressing for 24 to 48 hours


postoperatively an incision that has been closed primarily
Category IB

 b. Wash hands before and after dressing changes and any


contact with the surgical site. Category IB

 c. When an incision dressing must be changed, use


sterile technique. Category II

 d. Educate the patient and family regarding proper incision


care, symptoms of SSI, and the need to report such
symptoms. Category II
What should the duration be for
antibiotic prophylaxis?
Prophylactic antibiotic administration
should not exceed the 24-hour post-
operative period
 – No evidence that continuing
antibiotics until all drains and catheters
removed will reduce infection rates
 Antimicrobial prophylaxis (AMP)
 Reduce the microbial burden
 Not pertain to prevention of SSI caused by
postoperative contamination
 Antimicrobial prophylaxis is Indicated for :
@ All Clean-contaminated operation
@ Some clean operation:
(1) Intravascular prosthetic material or a prosthetic
joint will be inserted,
(2) An incisional or organ/space SSI would pose
catastrophic risk.
 Not indicated: contaminated or dirty operations
MRSE, MRSA & glycopeptide
prophylaxis
 CDC guideline group strongly supports
recommendations against the use of
Vancomycin in prophylaxis.
 The major reason for not recommending
glycopeptides is fear that overuse of
these drugs will increase the prevalence
of VRE and may lead to the development
of VISA (GISA)&VRSA .
Dosage of antibiotic
administration.
-Dose amount should be proportional to
patient weight
- Additional intraoperative doses of
antibiotic are advised if:
1. The duration of the procedure exceeds one to
two times the antibiotic's half-life.
2. There is significant blood loss during the
procedure greater than two liters
Bundle Approach for SSI Prevention

• Bundle is a structured way of improving


processes of care and patient outcome.
• It is a small (usually three to five) but
critical set of procedures, all evidence-
based, which when taken together create
much improved outcome.
• Knowing the risk determinants of SSI, a
bundle could be formulated in order to
prevent and control this type of HCAIs.
SSI Bundle approach
 Preoperative Screening
1-Preoperative Screening for
MRSA
 Screening for MRSA does not prevent
infection.
 Screening only has the potential for
benefit if something is done in response
to the information.
 Altered antimicrobial prophylaxis
 “Decolonization” therapy

89
1-Altered Antimicrobial
Prophylaxis

Use of vancomycin for patients with


 Documented MRSA colonization
 Institutions with high prevalence of MRSA

 Patients with at high-risk of MRSA colonization

 Neurosurgery

 cardiac surgery patients

 patients undergoing orthopedic surgery involving

metal prostheses and/or fixation


1
Akins PT. J Neurosurg 2010;112:354-61
90
2- MRSA “Decolonization”
 Eradication or suppression of the MRSA
bioburden by administration of topical agents
with activity against MRSA.
 Decolonization therapy in the perioperative
period may reduce the risk of MRSA SSI .
 Preoperative decolonization protocols typically
include
- Intranasal treatment with or without
- cutaneous and/or oropharyngeal treatment.
91
Decolonization Therapy
 Intranasal therapy
 Mupirocin (2%) ointment
 Usually used two or three times daily / 5 days
 Emergence of resistance during therapy has been

described (relatively low frequency)


 Mupirocin resistance has been associated with

treatment failure
 Other agents that have been used include
povidone-iodine, “triple antibiotic” ointment, tea
tree oil, retapamulin

92
Decolonization Therapy
 Topical treatment
 Skin antiseptics
 Chlorhexidine: used during bathing or showering

 Other antiseptics (e.g., triclosan,

hexochlorophane)
 Mucous membrane (e.g., oropharynx) antiseptics
 Chlorhexidine, others

93
Logistics
 Select the population to be screened
 All?

 Specific surgical procedures in which S. aureus is a

common pathogen?
 e.g., neurological, cardiac, orthopedic surgery

 Populations in which MRSA is prevalent?

 Determine how screening will be performed


 Method: culture versus PCR

 Considerations: complexity, cost, turn-around-time,

sensitivity
 Timing and location of specimen collection

 MD office, pre-op testing, upon admission

94
SCREENING
Screening patient for:

- Virus: HCV – HBV – HIV?


2-SCREENING VIRUSES
 controversial
 A protocol for action in case of
exposure accident
 Consent of patients
THANK
YOU
Methods of infection
control of MRSA outbreak

 There are many theories on the best way to


control MRSA outbreak, resistant bacteria
often requiring expensive antibiotics and
costly isolation and screening.

 Despite this, basic measures for the control


of infection such as hand hygiene, ward
cleaning and high standards of aseptic
techniques are essential.
Methods of infection control of MRSA
outbreak
(Ayliffe, 1996)

a) Isolate all known cases of


MRSA in a single room with
contact isolation precautions
or cohort the patients into a
suitable area of ward or unit.
b) The number of stuff caring for
the patient should be kept to
a minimum .
Methods of infection control of
MRSA outbreak

* Single use disposal latex gloves must be worn for


handling contaminated tissue, dressings or linen.
Hands must be washed after removing gloves.

** Aprons must be worn for activities involving contact


with the patient or their environment. Used plastic
aprons should be discarded into a red clinical waste bag
before leaving the room.

** Goggles should be worn for procedures that may


generate staphylococcus aerosols, e.g., sputum suction
and when performing dressings on patients with
extensive burns or lesion.
Methods of infection control of
MRSA outbreak

**. Clinical waste bags must be sealed before leaving the


room.

** Any reusable items must be processed in accordance


with the local disinfection policy.

** All bed linen and clothing must be changed daily. Linen


must be processed as infected linen according to the
local policy. The linen bags must be sealed at the
bedside and removed directly to the dirty utility area or
to the collection point.
Methods of infection control
of MRSA outbreak .
 Hand hygiene is thought to be the
cornerstone of the prevention of MRSA
infection and an alcohol-based hand
rub has frequently been shown to be
effective against hospital-acquired
MRSA infection. Despite this
compliance is estimated to be low.
Many personnel don’t realize when they
have germs on their hands

 Nurses, doctors and other healthcare


workers can get 100s or 1000s of
bacteria on their hands by doing simple
tasks, like
 pulling patients up in bed
 taking a blood pressure or pulse
 touching a patient’s hand
 rolling patients over in bed
 touching the patient’s gown or bed
sheets
 touching equipment like bedside rails,
over-bed tables, IV pumps Culture plate showing
growth of bacteria 24
hours after a nurse
placed her hand on the
plate
**Hands must be washed before and
after patient contact or their immediate
environment. They should be washed
thoroughly using an antiseptic
chlorhexidine or alternatively, physically
clean hands can be treated with an
alcoholic hand rub.
The room should be cleaned after all
other areas of the ward. A freshly
prepared hypochlorite disinfectant
should be used.
Staphylococci has been shown to survive
after 56 and 90 days on polyester and
polyethylene plastic respectively.
The Inanimate Environment Can
Facilitate Transmission

X represents VRE culture positive sites

~ Contaminated surfaces increase cross-transmission ~


Abstract: The Risk of Hand and Glove Contamination after Contact with a
VRE (+) Patient Environment. Hayden M, ICAAC, 2001, Chicago, IL.
MRSA Prevention Bundle
• Screen high risk or all patients.
• Pre-operative screening of surgical implant patients;
if MRSA-positive decolonize with intranasal mupiricin,
CHG baths, and use vancomycin prophylaxis.
• Barrier precautions for MRSA positive patients.
• Hand hygiene
• Environmental cleaning.
TREATMENT
 vancomycin should be reserved for the treatment of
serious infection with ß-lactam-resistant organisms
 Trimethoprim-sulfamethoxazole TMP-SMX has been
used successfully in the treatment of MRSA infections
  All of the VISA isolates identified in the United States
have been susceptible to (TMP-SMX) and tetracycline,
and these agents have been used in various combinations
.
TREATMENT
Linezolid
 Linezolid, was approved for clinical use in the
UK in 2001. It is a synthetic antibiotic with
antibacterial activity against MRSA.

 One of the advantages of linezolid is that it is


available in an oral formulation therefore
potentially allowing an earlier discharge of
patients.

 However, resistant isolates have already been


described , and the cost of linezolid is nearly
10 times greater than the cost of vancomycin
THANK
YOU

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