Pharmacotherapy of surgical prophylaxis in detail

1. Zenebe k (B.Pharm., MSc,Rph)
Antimicrobial Prophylaxis for Surgical
Procedures

2. • Introduction
• Epidemiology and etiology
• Pathophysiology
• Treatment
• Patient care and monitoring
Outline

3. Learning Objectives

4. Learning Objectives
 By the end of the session you should be able to:
 Discuss the epidemiological data and impact of SSI
 Identify patient-specific risk factors for surgical site infections.
 Identify operation-specific risk factors for surgical site infections
 List common pathogens responsible for surgical site infections.
 Discuss the importance of timing, duration, and re-dosing in relation to
antimicrobial prophylaxis in surgery.
 Discuss selection and administration of antibiotic therapy for surgical
procedures.
 Identify non-antimicrobial methods that can reduce the risk of SSI

5. Introduction

6.  Surgical site infections (SSIs) are classified as either incisional or
organ/space (CDC)
 Incisional SSIs are further divided into
-superficial incisional SSI (skin or subcutaneous tissue) and
-deep incisional SSI (deeper soft tissues of the incision).
 Organ/space SSIs involve any anatomic site other than the
incised areas.
o For example, a patient who develops meningitis after removal of a brain
tumor could be classified as having an organ/space SSI.
 An infection is considered an SSI if any of the above criteria is met and
the infection occurs within 30 days of the operation.
o If a prosthetic is implanted, the timeline extends out to 1 year.

7.  Prophylactic antibiotics are widely used in surgical procedures
and account for substantial antibiotic use in many hospitals.
 The purpose of surgical antibiotic prophylaxis is to reduce
the prevalence of postoperative wound infection (about 5%
of surgical cases overall) at or around the surgical site.
 By preventing surgical site infections, prophylactic
antimicrobial agents have the potential to decrease patient
morbidity and hospitalization costs for many surgical
procedures that pose significant risk of infection.(e.g., appendectomy)

8.  However, the benefits of prophylaxis are controversial,
prophylaxis is not justified for some surgical
procedures (e.g., urologic operations in patients with
sterile urine).
Consequently, the inappropriate or indiscriminate use
of prophylactic antibiotics can increase the risk of :
drug toxicity,selection of resistant organisms,and
costs.

9. Epidemiology and etiology

10.  In U.S., >40 million inpatient surgical procedures
each year; 2-5% complicated by surgical site infection
 SSIs second most common nosocomial infection (24% of
all nosocomial infections)
Prolong hospital stay by 7.4 days
Cost $400-$2,600 per infection (TOTAL: $130-$845
million/year)

11. What are the risk factor for surgical site
infection???
a) Patient related factor
b) Operation related factor

12. Table-1: Factors Affecting the Incidence
of Surgical Site Infection

13. Source: Scottish National guideline

14.  Many experts recommend that antimicrobial
prophylaxis should be given for surgical procedures
(a) with a high rate of infection,
(b) involving the implantation of prosthetic
materials, or
(c) those in which an infection would have
catastrophic consequences.

15. Pathophysiology

16. Prophylaxis versus Treatment
 The distinction between prophylaxis and treatment influences
the choice of antimicrobial and duration of therapy.
 Appropriate antimicrobial selection, dosing, and duration of
therapy differ significantly between these two situations.
 A regimen for antimicrobial prophylaxis ideally involves
one agent and lasts less than 24 hours.
 Treatment regimens can involve multiple antimicrobials with
durations lasting weeks to months depending on desired
antimicrobial coverage and the surgical site.

17. Types of Surgical Operations
 Surgical operations are classified as
 clean,
 clean-contaminated,
 contaminated, or
 dirty.
 Antimicrobial prophylaxis is appropriate for clean, clean-
contaminated, and contaminated operations.
 Dirty operations take place in situations of existing infection and
antimicrobials are used for treatment, not prophylaxis

18. Table-2 : National Research CouncilWound Classification (* & **) +National Red Cross
Wound Classification (* &***)
Classification* Criteria*
Infection
Rate (%)**SSI Risk***
Antibiotic
Prophylaxis***
Clean No acute inflammation or entry
into GI, respiratory, GU, or biliary
tracts; no break in aseptic
technique occurs; wounds
primarily closed
<5 low indicated
Clean-
contaminated
Elective, controlled opening of GI,
respiratory, biliary, or GU tracts
without significant spillage; clean
wounds with major break in sterile
technique
<10 medium indicated
ContaminatedPenetrating trauma (<4-hr old);
major technique break or major
spillage from GI tract; acute,
nonpurulent inflammation
15–20 high indicated
Dirty Penetrating trauma (>4-hr old);
purulence or abscess (active
infectious process); preoperative
perforation of viscera
30–40 ___ Not indicated;
antibiotics
used for
treatment
Source: Koda-Kimble . Applied Therapeutics:

19. Microbiology/bacteriology
 Choosing the appropriate prophylactic antimicrobial relies on
anticipating which organisms will be encountered during the
operation.
 SSIs associated with extra-abdominal operations are the result
of skin flora organisms in nearly all cases.
 These organisms include gram-positive cocci,
 S. aureus and S.epidermidis being among the most frequently isolated SSI
pathogens according to the National Nosocomial Infections Surveillance System
(NNIS)
 Thus, for extra-abdominal operations an antimicrobial with strong gram-
positive coverage is useful.

20.  Intra-abdominal operations involve a diverse flora with the
potential for polymicrobial SSIs.
 Escherichia coli make up a large portion of bowel flora
 Other enteric gram-negative bacteria, as well as anaerobes
(especially Bacteroides spp.)
 Candida albicans is being implicated as the cause of a growing
number of SSIs.
 May be associated with increased use of broad spectrum antibiotics and rising
prevalence of immunocompromised and HIV–infected individuals
 Despite this fact, antifungal prophylaxis for surgery is not
currently recommended.

21. TABLE-3. Major Pathogens in Surgical Wound Infections

22. Table-4:profiles of bacterial isolates identified in postoperative wound infection
Gondar University Hospital, November 2010 - February 2011

23. Principles of Surgical
Antimicrobial Prophylaxis

24. scheduling antibiotic administration
Always consider the following principles in prophylaxis
(a) the agents should be delivered to the surgical site prior
to the initial incision, and
(b) bactericidal antibiotic concentrations should be
maintained at the surgical site throughout the surgical
procedure. so
 pre-operative …admn..30-60min
 Intra-operative(based on half life of antibiotics)—redosing
 Post-operative(based on setting cleans…go upto 72hrs
NB: Administration too early result in concentrations below the MIC
toward the end of the operation, and administration too late leaves
the patient unprotected at the time of initial incision.

25. Choosing an Antibiotic
 Criteria
 covers expected pathogens (very crucial)
 should be inexpensive,
 available in a parenteral formulation, and easy to use.
 Adverse event potential should be minimal.
 Choosing an agent with a longer half-life reduces the
likely need to redose

26. antibiotic ½
life D.F
m.o coverage Cost
/d
Cefazolin 1g 1.8 IV Staphylococci (except MRSA), Streptococci (not
Enterococci), E coli, Proteus & Klebsiella *
$10
Vancomycin 1g 3 to 9
IV Staphylococcus aureus, Staphylococ-
cus epidermidis including MRSA
$60
Cefoxitin 1g
0.6 to 1
IV m.o coverage of cefazolin plus bacteroides $30
Cefotetan 3 to 4.6
IV m.o coverage of cefazolin plus bacteroides $30
Aminoglycosides
(gantamycin 80mg)
2
IV aerobic Gram-negative bacilli, including
pseudomonas
$5
Metronidazole 0.5g
8
IV Bacteroides fragilis and against several intestinal
protozoa
$10
Clindamycin 600mg 2.4 to 3
IV G+ bacteria (staphylococci, pneumococci,
Streptococcus pyogenes) and against most anaerobes
$10
Ciprofloxacin 400mg 3 to 5 IV Enterobacteriacea, Pseudomonas, Chlamydia
Mycoplasma & Legionella
$10
Table-5: Half-Lives, Dosage form, microorganisms coverage and Price of Selected
Antibiotics Commonly Used for Prophylaxis

27.  Cefazolin is the preferred & mainstay for surgical
prophylaxis of extra-abdominal procedures b/c
 benign adverse-event profile, simple dosing, and low cost.
 Suitable for most clean procedures, including cardiac,
vascular, and orthopedic procedures.
 its risk of cross-allergenicity to B-lactam penicillin,
clindamycin or vancomycin is minimal and can be
used as an alternative.

28.  Vancomycin should be given within 2 hours prior to
surgical incision.
If duration of surgical procedure is >4 hours, patient
should receive a second prophylactic dose
intraoperatively….redosing
Total duration must be 24 hours for non-cardiothoracic
surgery and 48 hours for cardiothoracic surgery.
Consider 2 grams in patients >100 kg.

29.  Intra-abdominal operations necessitate broad-spectrum coverage of
gram-negative organisms and anaerobes.
 Anti-anaerobic cephalosporins (cefoxitin and cefotetan) are useful
but suffer from limited availability.
 Fluoroquinolones or aminoglycosides, paired with clindamycin
or metronidazole, should provide adequate coverage for intra-
abdominal operations.
 The Hospital Infection Control Practices Advisory Committee
allows for the use of vancomycin for surgical prophylaxis when
MRSA rates at an institution are “high.”
N.B patients who received cefazolin were more likely to develop an SSI due to MRSA.

30. Decision to Use Antimicrobial Prophylaxis
 The selected prophylactic agent should be directed against
likely infecting organisms, but need not eradicate every
potential pathogen.
 It should be bear in mind that,the goal of prophylaxis is
to decrease bacterial counts below critical levels necessary
to cause infection.

31.  Newer antimicrobials have not demonstrated superiority in the
prevention of SSI and should be reserved for treatment only.
 Broad-spectrum agents,such as Carbapenems
(antipseudomonal penicillins), 3rd & 4th generation
cephalosporins,should be avoided for prophylaxis, because
they are no more effective than cefazolin,
may alter microbial flora,and
increasing the emergence of microbial resistance

32. Route of Administration
 In general, oral administration of surgical antimicrobial prophylaxis is not
recommended, because
unreliable or poor absorption of oral agents in the anesthetized bowel.
however, oral agents function effectively as GI decontaminants
 The concentration of bacteria in the colon may approach 1016
bacteria/mm3
 colorectal procedures, carry a relatively high risk of postoperative
infection.
 Antimicrobial regimens with activity against the mixture of aerobic and
anaerobic bacteria are effective in preventing postoperative SSIs in
these area

33.  The most widely used oral antimicrobial regimen directed
against the fecal flora is
 1 g each of the nonabsorbable antibiotics neomycin sulfate (for
gram-negative aerobes) and erythromycin base (for anaerobes),
 given 1 day before surgery at the times indicated.
 Mechanical bowel cleansing,such as with polyethylene glycol-
electrolyte or sodium phosphate lavage solution,should
precede the above regimen
 Effective oral alternatives to the above regimen include
Metronidazole ± neomycin/kanamycin, or kanamycin +
erythromycin; but no clinical warranty

34. Timing of Antimicrobial Administration
 For maximal efficacy, an antibiotic should be present in therapeutic
concentrations at the incision site as early as possible during
the decisive period and continuing until the wound is closed.
 However, an antibiotic administered postoperatively cannot
achieve therapeutic concentrations during the decisive period,
and infection rates are similar to those in patients who receive no
antibiotics.
But some studies showed that the incidence of endometritis after
C/S is decreased significantly by postoperative administration of
antibiotics.

35.  Therefore, prophylactic antibiotics should be
administered before the surgical procedure in the OR
before or during the induction of anesthesia.
 Prophylactic antibiotics are most effective when given
during the 30 min-1hour period before the surgical incision is made,
and
rates of infection increase significantly if antibiotics are administered
>1 hour preoperatively or
any time postoperatively.

36. Dosing and Redosing
 The goal of antimicrobial dosing for surgical prophylaxis is to
maintain antibiotic concentrations above the MIC of
suspected organisms for the duration of the operation.
 Dosing recommendations can vary between institutions and
guidelines.
 Clinical judgment should be exercised regarding dose modifications
for renal function, age, and especially weight.
 Obese patients often require higher doses than do non-obese
patients.

37.  Guidelines suggest that if an operation exceeds two half-
lives of the selected antimicrobial, then another dose
should be administered…redosing
 Repeat dosing has been shown to lower rates of SSI.
 The clinician should have extra doses of antibiotic ready
in case an operation lasts longer than planned.
 Redosing: administration of an additional dose of
antibiotics if the 1st dose half-life finished and operation
was take longer then expected time.

38. Duration of Administration
 The shortest effective prophylactic course of antibiotics should be
used; i.e.,
single dose preoperatively or not more than 24 hours postoperatively
for most procedures…if the setting is clean
Postoperative doses after wound closure may continued for 72hrs if
the setting is not clean
 Single-dose prophylaxis, a viable option for many surgical
procedures, is controversial for cardiac procedures.
In practice, cardiothoracic antimicrobial prophylaxis often is
continued 48 hours after surgery.(but>48hrs emergence of resistance)

39. Signs of Surgical Site Infection
 Typically, an infected incision site wound is red, inflamed, and purulent.
 The purulent drainage should be cultured
 Empiric therapy directed against the most likely pathogens should be
instituted while awaiting culture and sensitivity test results.
 Although most incision site infections are clinically apparent shortly after
surgery (within 30 days), some deep-seated infections present
indolently over weeks to months…..may extended to 90 days
 When implants/prosthetic are involved, infections occurring up to a year
after surgery may be related to the operation.

40. Risks of Indiscriminate Antimicrobial Use
 The risks of indiscriminate use of antimicrobials to a given patient
include the potential for adverse effects and superinfection.
 The administration of any β-lactam agent poses the risk of a
hypersensitivity reaction, and many antibiotics, including
cefoxitin, are known to predispose patients to Clostridium
difficile-associated disease (pseudomembranous colitis).
 In addition, widespread or prolonged use of antimicrobial agents
increases the potential for the development or selection of
resistant organisms in a given patient or other patients who may
acquire a pathogen nosocomially.

41. What are the “Emerging Pathogens”?
-due to Indiscriminate Antimicrobial Use
 Multi-Drug Resistant Gram Negative Bacilli (MDR)
 ESBLs* (E. coli, Klebsiella)
 P. aeruginosa
 Acinetobacter spp.
 Vancomycin-Resistant Enterococci (VRE)
 Enterococcus faecium
 Methicillin-Resistant S. aureus (MRSA)
 Clostridium difficile-Associated Disease
*Extended Spectum Beta-Lactmase

42. Optimizing Surgical Antimicrobial
Prophylaxis
 Antibiotic control strategies have improved the appropriate use of
antimicrobial agents for surgical prophylaxis.
 The implementation of an automatic stop-order policy for
surgical prophylaxis has reduced the duration of antimicrobial
prophylaxis dramatically.
 These stop-order policies can be printed directly onto an antibiotic
order form.
 The process can help improve antibiotic appropriateness and timing
of administration.

43.  In collaboration with other health care providers, the
pharmacy department of health care organizations is
responsible for optimizing the timing, choice, and
duration of antimicrobial surgical prophylaxis.
 Education of surgical, anesthesia, and nursing staff, supported by
hospital policy changes initiated by pharmacists improved
appropriate timing from 68% to 97% and resulted in significant
cost avoidance.

44. Treatment/goals of prophylaxis

45. Goals of Surgical Prophylaxis
 Ideally, an anti-infective drug for surgical prophylaxis should
achieve the following goals:
(1) prevent postoperative infection of the surgical site,
(2) prevent postoperative infectious morbidity and mortality,
(3) reduce the duration and cost of health care,
(4) produce no adverse effects, and
(5) have no adverse consequences for the microbial flora of the
patient or the hospital.

46. Table-6: Suggested Prophylactic Antimicrobial Regimens for
Surgical Procedures in Adults
Procedure
Predominant
Organism(s)
Antibiotic
Regimen
(Alternative)
Adult
Preoperative IV
Dose
(Alternative)a
Cardiac (all with sternotomy,
cardio-pulmonary bypass)
Staphylococcus aureus,Staphylococcus
epidermidis
Cefazolin
(Vancomycin)
1 g (1 g)
Thoracic S.aureus, S.epidermidis, gram-negative
enterics
Cefazolin
(Vancomycin)
1 g (1 g)
Vascular (aortic resection,
groin incision, prosthesis)
S.aureus,S.epidermidis, gram-negative
enterics
Cefazolin
(Vancomycin)
1 g (1 g)
Orthopedic (total joint
replacement, internal
fixation of fractures)
S.aureus,S.epidermidis Cefazolin
(Vancomycin)
1 g (1 g)
Neurosurgery S.aureus,S.epidermidis Cefazolin
(Vancomycin)
1 g (1 g)

47. Table-6: cont’d
Head and neck S.aureus, oral anaerobes,
streptococci
Cefazolin
(clindamycin/
gentamicin)
2 g (600 mg
clindamycin/
1.5 mg/kg
gentamicin)
Gastroduodenal (only for
procedures entering
stomach)
Gram-negative enterics, S.aureus,
mouth flora
Cefazolin 1 g
Colorectal Gram-negative enterics, anaerobes
(Bacteroides fragilis), enterococci
Oral
neomycin-
erythromycin
base
(Cefoxitin)
1 g each at 1 PM,
2 PM, and 11 PM
day before
surgery (1 g)
Appendectomy
(uncomplicated)
Gram-negative enterics, anaerobes (B.
fragilis)
Cefoxitin 1–2 g
Biliary tract (only for high-
risk procedures)
Gram-negative enterics, Enterococcus
faecalis,Clostridia
Cefazolin 1 g

48. Cesarean section Group B streptococci,
enterococci, anaerobes, gram-
negative enterics
Cefazolin 2 g after
umbilical cord
clamped
Hysterectomy Group B streptococci, enterococci,
anaerobes, gram-negative enterics
Cefazolin or
cefoxitin
1 g
Genitourinary (only for high-
risk procedures)
Gram-negative enterics, enterococci Ciprofloxacin 400 mg
 Cefazolin should be dosed at 2 g in patients >80 kg.
Source: Koda-Kimble . Applied Therapeutics:
Table-6: cont’d

49. Outcome Evaluation

50.  The clinician should consistently follow-up post-operative
patients and screen for any sign of SSI.
According to CDC criteria, SSI may appear up to 30 days after an
operation and up to 1 year if a prosthesis is implanted.
This period often extends beyond hospitalization so patients should
be educated on warning signs of SSI and be encouraged to contact a
clinician immediately if necessary.
 The presence of fever or leukocytosis in the immediate post-
operative period does not constitute SSI and should resolve with
proper patient care.

51.  Distal infections, such as pneumonia, are not considered SSIs
even if these infections occur in the 30-day period.
 The appearance of the surgical site should be checked regularly
and any changes documented (e.g., erythema,drainage,or pus).
The presence of pus or other signs suggestive of SSI must
be treated accordingly.
 Any wound requiring incision and drainage is considered an SSI
regardless of appearance.
 Prompt cultures should be collected and appropriate
antimicrobial therapy initiated to reduce any chance of
morbidity and mortality.

52. Alternative Methods to Decrease SSI
 Several non-antimicrobial methods have been studied for
reducing the risk of SSI.
providing supplemental warming(normothermia) to patients
(36.6°C -38°C) during the intraoperative period reduced
infection rates
use of warming blankets and IV fluid warmers
intensive glucose control [80 to 110 mg/dL (4.44 to 6.1
mmol/L)] versus conventional control [glucose less than 210
mg/dL (less than 11.7 mmol/L)] in reducing infections in
critically ill patients.

53. Provision of supplemental oxygen in the perioperative period.
 Administration of high concentrations of oxygen (80% via ventilator
or 12 L/min via a nonrebreather mask)
Antibiotic-impregnated bone cement is being used as an
adjunct or alternative to traditional antimicrobial prophylaxis.
 A study by Chiu and associates found cefuroxime/gentamycin-
impregnated cement lowered the risk of deep infection after
primary total knee arthoplasty.
Problem:The long-term durability is unknown,

54. Literatures & Guidelines Review

55.  Several studies have been performed investigating the utility of
prophylactic antibiotics in surgery.
 With regards to surgical prophylaxis, the data from these studies
support several recurring themes:
 Plenty of articles & guidelines found that‘a single preoperative dose
of antibiotic is as effective as a 5-day course of postoperative
therapy assuming an uncomplicated procedure’&
 Almost all articles & guidelines are complimentary in that
‘Prophylactic antibiotics should target the anticipated organisms’

56.  Most guidelines & literatures still agreed on:-
complicated,contaminated,or dirty procedures should receive
additional postoperative antimicrobial coverage
 During prolonged procedures,antibiotic prophylaxis should be
readministered every 3-4 hours…redosing
 Prophylactic antibiotics should be administered within 1 hour
prior to incision

57. Patient Care and Monitoring

58.  Conduct a thorough medication history including prescription
and non-prescription medications as well as herbals and vitamins.
 Verify the patient’s allergy history and the type of reaction
experienced.
 β-Lactam–allergic patients may receive clindamycin,
vancomycin, or other antimicrobials.
 The patient should be monitored for signs of an allergic reaction
during the operation.
 The patient should be monitored for signs and symptoms of
infection post-operatively.
 Patients being discharged should be counseled on recognizing
signs and symptoms of SSI.
 Food matters……protein, carbohydrate
 Drugs for comorbidity….mostly missed…becareful!

59. QUESTIONS?

60. ThankYou!!!