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ANTIBIOTIC USE IN SURGERY
Dr. O O Afuye
OUTLINE
• Introduction
• Historical perspective
• Classification of antibiotics
• Antibiotic combinations
• Indications for antibiotic combinations
• General Principles of antibiotic use
• Uses of antibiotics
• Principles of chemoprophylaxis
• Indications for prophylaxis
• Administration
• Principles
• Mechanism of resistance
• Drug toxicity
• Treatment failure
• Current trends
• Conclusion
INTRODUCTION
•Antibiotics are antibacterial substances
derived from fungi or bacteria which are
active against a wide range of pathogenic
organisms.
•Most A/B presently are synthesized
derivatives of original naturally occurring
product.
•All exhibit selective toxicity
•The goal of therapy is to achieve levels of
antibiotic at site of infection that exceed the
minimum inhibitory concentration for the
pathogens present.
•Mild infection can be treated at the
outpatient with oral antibiotics.
•For severe infection intravenous antibiotics
will be most appropriate.
•For most surgical infection there is no specific
duration of antibiotic know to be ideal.
•Antibiotics are generally believed to support
local host defenses.
Historical Perspective
› Early 19th century – Louis Pasteur
discovered that certain saprophytic bacteria
can kill anthrax bacilli.
› 1928 – Alexander Fleming derived penicillin
from Penicillium notatum.
› 1939 – Tyrothricin was isolated from certain
soil bacteria by Rene Dubos.
› 1944 – Selman Waksman derived
streptomycin from Actinomycetes.
Classification of Antibiotics
› Cell wall synthesis inhibitors – Penicillins, cephalosporins,
vancomycin.
› Competitive antagonists/ Inhibition of nucleic acid synthesis –
Sulphonamides, quinolones, trimethoprim.
› Protein Synthesis inhibitors – Tetracyclines, aminoglycosides,
chloramphenicol, macrolides
› DNA synthesis inhibitors – mitomycins
› RNA synthesis inhibitors – rifamycins
CLASSIFICATION
•BACTERIOSTATIC :Drugs that inhibit growth and
replication of microorganism. The therapeutic
success of these agents depends upon
participation of the host immune system. Effect
is reversible.
•BACTERIOCIDAL : Drugs that cause death of
microorganisms.
BACTERICIDAL
•PENICILLINS
•CEPHALOSPORINS
•VANCOMYCIN
•AMINOGLYCOSIDE
•MACROLIDE
•LINEZOID
•FLUROQUINOLONES
•CHLORAMPHENICOL
BACTERIOSTATIC
•TETRACYCLINES
•MACROLIDES
•LINEZOID
•SULFONAMIDES
•TRIMETHOPRIM
•NITROFURANTOIN
•CHLORAMPHENICOL
Antibiotic combinations
Jawetz law
•Bactericidal + Bactericidal = Synergism
•Bacteriostatic + Bacteriostatic = Additive
•Bactericidal + Bacteriostatic =
Antagonistic
Indications for Antibiotic combinations
•Mixed bacterial infections in which the
organisms are not susceptible to a common
agent.
•To achieve synergistic antimicrobial activity
against a single organism.
•To overcome bacterial tolerance.
•To prevent development of bacterial antibiotic
resistance
•To decrease toxicity of the most effective
agent.
THERAPEUTIC SPECTRA
•NARROW SPECTRUM –act on only a
single or limited group of microorganism
e.g. isoniacid
•EXTENDED SPECTRUM- refers to
antibiotic that are effective against gram
–ve and significant no of gram +ve
bacteria e.g. ampicillin.
•BROAD SPECTRUM-these act on a wide
variety of microbial species .Their use
can alter the nature of normal bacteria
flora and precipitate super infection by
Candida e.g. tetracycline.
General Principles of A/B use
›Select an A/B to which the known or presumed
pathogen is likely to be fully sensitive.
›Spectrum of A/B should be known accurately.
Broad spectrum avoided if suitable narrow
spectrum A/B is available.
›Restrict use of A/B to which resistance is
developing or has developed.
› Systemic antibiotic should not be used
topically.
›Drug use must be indicated
PRINCIPLES( Contd)
•A/B should be given in full dose by appropriate
route & @ correct intervals.
•Antibiotics are not used to Rx abscess without
ensuring effective surgical drainage.
•Side-effects of A/B should be known &
monitored.
•Expensive A/B are not used if equally effective &
cheaper alternatives are suitable.
•Consideration for toxicity and drug-drug
interaction
•Monitoring
•Compliance
Uses of Antibiotics
•Prophylaxis – preventive use of A/B where
contamination might occur, but is not yet present.
•Therapeutic – use of A/B to treat established
infection.
•Empiric – A/B Rx based on familiarity with microbes
likely to cause infection.
•Definitive – A/B Rx based on m/c/s result.
However careful aseptic theatre routine should be
maintain.
Thorough wound toileting.
Make sure there are no foreign bodies, dead tissues,
excessive blood clot or faeces in the wound.
Principles of chemoprophylaxis
•Specificity – must be directed @ org. most
likely to infect @ surgery.
•Short course – usu. 24hrs. is sufficient.
•High dose – to achieve adequate blood
levels.
•Timed dose – 1st dose given @ induction or
premed.
Principles of chemoprophylaxis
•Not a substitute to aseptic practice & good
surgical technique
•Necessary only in high-risk cases of bact.
Contamination.
•Route of administration should be I.V.
•Should be employed only when scientific
evidence shows it has advantages.
Antibiotics used for Surgical Prophylaxis
Commonly used surgical prophylactic
antibiotics include:
•intravenous 'first generation' cephalosporins
– cephazolin or cephalothin
•intravenous gentamycin
•intravenous or rectal metronidazole (if
anaerobic infection is likely)
•Oral tinidazole (if anaerobic infection is likely)
•Intravenous flucloxacillin (if methicillin-
susceptible staphylococcal infection is likely)
•Intravenous vancomycin (if methicillin-
resistant staphylococcal infection is likely).
Indications for prophylaxis
•Prevention of Surgical Site Infection (SSI)
•Prevention of other HealthCare Associated
Infections (HCAIs)
•Prevention of specific infections in
susceptible patients E.g. Urinary tract
infection
Goals of Antibiotic Prophylaxis
• Reduce the incidence of surgical site
infection (SSI)
• Minimize the effect on the patient’s normal
bacterial flora.
• Minimize adverse side effects of antibiotics.
• Minimize the emergence of antibiotics
resistant strains of bacteria.
• Cost effectiveness.
Indications for prophylaxis
•Clean surgery – prosthetic joint
replacement/ heart valves
- neurosurgical shunts
- insertion of mesh (hernia
repair), pacemakers (heart block)
-surgical procedures &
instrumentations in rheumatic & valvular
heart dx pts & pts with pacemakers.
•- Host immune system suppression e.g. DM,
CRF, e.t.c.
•- Vascular surgeries
Indications for prophylaxis
›Clean contaminated surgery
– GI surgeries with minimal spillage
›- Upper Resp. Tract procedures
›- Genitourinary procedures
›- Limb amputations
›- Dental procedures
Therapeutic Use of Antibiotics
Indications
›Clinical evidence of established infection
›Laboratory (microbiological) evidence of
infection
›Suspected infection
Empirical Use
No culture result
• Based on:
Knowledge of common pathogens known to cause
infection in that organ/region
Local bacterial profile and antibiotic sensitivity
Broad-spectrum activity
• Specimens should be taken before commencing
antibiotics (if
possible/feasible)
• Culture/sensitivity results should be obtained as soon
as possible
• If patient is responding well:
No need to change to antibiotic of sensitivity
When to start ?
• Risk of surgical infection is high - based on the
underlying disease process (e.g. perforated
appendicitis) [prophylaxis empiric]
• Significant contamination during surgery has
occurred (e.g.
considerable spillage of colon contents)
• In critically ill patients – potential site of infection
has been identified
• Severe sepsis or septic shock
• Short course (3-5 days)
• Stop if the presence of a local site or systemic
infection is not revealed
Definitive
•Culture results and antibiotic sensitivity known
Administration
•Route – I.V preferred in seriously ill surgical pts.
With improvement, can be changed to oral.
•Other routes – I.M, intrathecal, subcut.,
intraosseous.
•Duration – most surgical infections can be Rx in 5-7
days, however Rx can be much longer based on
clinical response.
Adverse Effects of A/B
•Penicillins – mostly hypersensitivity
reactions.
•Cephalosporins – similar to penicillins
•Quinolones – nausea, vomiting, diarrhea
•Aminoglycosides – nephrotoxity & 8th CN
toxicity.
Adverse Effects of A/B
›Tetracyclines – stains teeth of children, may
cause growth deformity/inhibition.
›Macrolides – acute cholestatic hepatitis
›Metronidazole – disulfiram-like reaction,
peripheral neuropathy (prolonged use)
›Chloramphenicol – bone marrow
suppression, gray baby syndrome
›Carbapenems – nausea, vomiting, diarrhea,
skin rashes
Rx Failure
› Wrong choice of antibiotic
› Inadequate dose
› Inappropriate route
› Clinical condition not susceptible to A/B Rx
-undrained abscess
-infxn not responsive to A/B
-super infection with A/B resistant org
› Devt. of resistance
› Antagonistic A/B combination
› Inadequate duration of Rx
Mechanism of Resistance
•Inactivation of the antibiotic – penicillins
•Mutational change of bacterial enzyme
affected by antibiotic – tetracyclines
•Transmission of resistance genes via
plasmids.
Current Trends
•Antibodies to bacterial toxins and mediators
of sepsis are currently being evaluated.
CONCLUSION
›Prophylactic antibiotic should be given in clean
surgery which involves prosthetic implants, in
clean-contaminated and contaminated
surgeries
›Prophylactic antibiotics should be
administered within 1 hour prior to incision
›Therapeutic antibiotic should be started for
dirty wound
›Empirical therapy should be altered according
to the sensitivity of the culture
•Therapeutic drug monitoring is done in
antibiotics with narrow therapeutic range
(Amikacin, Gentamycin, Vancomycin)
•Allergic reactions include anaphylaxis, fever,
rashes, nephritis, granulocytopenia &
hemolytic anemia are possible side effects of
Penicillins and Cephalosporins
•Appropriate choice of antibiotics, dosage,
compliance should be ensured to avoid
emergence of resistance
References
•Medscape
•National Antibiotic Guideline 2008
•Schwartz’s Principles of Surgery
•Enterococcal Resistance – An Overview (YA
Marothi, H Agnihotri, D Dubey) Indian
Journal of Medical Microbiology, (2005) 23
(4):214-9
•Niederman MS. Principles of appropriate
antibiotic use
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Antibiotic use in surgery

  • 1. ANTIBIOTIC USE IN SURGERY Dr. O O Afuye
  • 2. OUTLINE • Introduction • Historical perspective • Classification of antibiotics • Antibiotic combinations • Indications for antibiotic combinations • General Principles of antibiotic use • Uses of antibiotics • Principles of chemoprophylaxis • Indications for prophylaxis • Administration • Principles • Mechanism of resistance • Drug toxicity • Treatment failure • Current trends • Conclusion
  • 3. INTRODUCTION •Antibiotics are antibacterial substances derived from fungi or bacteria which are active against a wide range of pathogenic organisms. •Most A/B presently are synthesized derivatives of original naturally occurring product. •All exhibit selective toxicity
  • 4. •The goal of therapy is to achieve levels of antibiotic at site of infection that exceed the minimum inhibitory concentration for the pathogens present. •Mild infection can be treated at the outpatient with oral antibiotics. •For severe infection intravenous antibiotics will be most appropriate. •For most surgical infection there is no specific duration of antibiotic know to be ideal. •Antibiotics are generally believed to support local host defenses.
  • 5. Historical Perspective › Early 19th century – Louis Pasteur discovered that certain saprophytic bacteria can kill anthrax bacilli. › 1928 – Alexander Fleming derived penicillin from Penicillium notatum. › 1939 – Tyrothricin was isolated from certain soil bacteria by Rene Dubos. › 1944 – Selman Waksman derived streptomycin from Actinomycetes.
  • 6.
  • 7. Classification of Antibiotics › Cell wall synthesis inhibitors – Penicillins, cephalosporins, vancomycin. › Competitive antagonists/ Inhibition of nucleic acid synthesis – Sulphonamides, quinolones, trimethoprim. › Protein Synthesis inhibitors – Tetracyclines, aminoglycosides, chloramphenicol, macrolides › DNA synthesis inhibitors – mitomycins › RNA synthesis inhibitors – rifamycins
  • 8.
  • 9. CLASSIFICATION •BACTERIOSTATIC :Drugs that inhibit growth and replication of microorganism. The therapeutic success of these agents depends upon participation of the host immune system. Effect is reversible. •BACTERIOCIDAL : Drugs that cause death of microorganisms.
  • 11. Antibiotic combinations Jawetz law •Bactericidal + Bactericidal = Synergism •Bacteriostatic + Bacteriostatic = Additive •Bactericidal + Bacteriostatic = Antagonistic
  • 12. Indications for Antibiotic combinations •Mixed bacterial infections in which the organisms are not susceptible to a common agent. •To achieve synergistic antimicrobial activity against a single organism. •To overcome bacterial tolerance. •To prevent development of bacterial antibiotic resistance •To decrease toxicity of the most effective agent.
  • 13. THERAPEUTIC SPECTRA •NARROW SPECTRUM –act on only a single or limited group of microorganism e.g. isoniacid •EXTENDED SPECTRUM- refers to antibiotic that are effective against gram –ve and significant no of gram +ve bacteria e.g. ampicillin.
  • 14. •BROAD SPECTRUM-these act on a wide variety of microbial species .Their use can alter the nature of normal bacteria flora and precipitate super infection by Candida e.g. tetracycline.
  • 15. General Principles of A/B use ›Select an A/B to which the known or presumed pathogen is likely to be fully sensitive. ›Spectrum of A/B should be known accurately. Broad spectrum avoided if suitable narrow spectrum A/B is available. ›Restrict use of A/B to which resistance is developing or has developed. › Systemic antibiotic should not be used topically. ›Drug use must be indicated
  • 16. PRINCIPLES( Contd) •A/B should be given in full dose by appropriate route & @ correct intervals. •Antibiotics are not used to Rx abscess without ensuring effective surgical drainage. •Side-effects of A/B should be known & monitored. •Expensive A/B are not used if equally effective & cheaper alternatives are suitable. •Consideration for toxicity and drug-drug interaction •Monitoring •Compliance
  • 17. Uses of Antibiotics •Prophylaxis – preventive use of A/B where contamination might occur, but is not yet present. •Therapeutic – use of A/B to treat established infection. •Empiric – A/B Rx based on familiarity with microbes likely to cause infection. •Definitive – A/B Rx based on m/c/s result. However careful aseptic theatre routine should be maintain. Thorough wound toileting. Make sure there are no foreign bodies, dead tissues, excessive blood clot or faeces in the wound.
  • 18. Principles of chemoprophylaxis •Specificity – must be directed @ org. most likely to infect @ surgery. •Short course – usu. 24hrs. is sufficient. •High dose – to achieve adequate blood levels. •Timed dose – 1st dose given @ induction or premed.
  • 19. Principles of chemoprophylaxis •Not a substitute to aseptic practice & good surgical technique •Necessary only in high-risk cases of bact. Contamination. •Route of administration should be I.V. •Should be employed only when scientific evidence shows it has advantages.
  • 20. Antibiotics used for Surgical Prophylaxis Commonly used surgical prophylactic antibiotics include: •intravenous 'first generation' cephalosporins – cephazolin or cephalothin •intravenous gentamycin •intravenous or rectal metronidazole (if anaerobic infection is likely)
  • 21. •Oral tinidazole (if anaerobic infection is likely) •Intravenous flucloxacillin (if methicillin- susceptible staphylococcal infection is likely) •Intravenous vancomycin (if methicillin- resistant staphylococcal infection is likely).
  • 22. Indications for prophylaxis •Prevention of Surgical Site Infection (SSI) •Prevention of other HealthCare Associated Infections (HCAIs) •Prevention of specific infections in susceptible patients E.g. Urinary tract infection
  • 23. Goals of Antibiotic Prophylaxis • Reduce the incidence of surgical site infection (SSI) • Minimize the effect on the patient’s normal bacterial flora. • Minimize adverse side effects of antibiotics. • Minimize the emergence of antibiotics resistant strains of bacteria. • Cost effectiveness.
  • 24. Indications for prophylaxis •Clean surgery – prosthetic joint replacement/ heart valves - neurosurgical shunts - insertion of mesh (hernia repair), pacemakers (heart block) -surgical procedures & instrumentations in rheumatic & valvular heart dx pts & pts with pacemakers. •- Host immune system suppression e.g. DM, CRF, e.t.c. •- Vascular surgeries
  • 25. Indications for prophylaxis ›Clean contaminated surgery – GI surgeries with minimal spillage ›- Upper Resp. Tract procedures ›- Genitourinary procedures ›- Limb amputations ›- Dental procedures
  • 26.
  • 27. Therapeutic Use of Antibiotics Indications ›Clinical evidence of established infection ›Laboratory (microbiological) evidence of infection ›Suspected infection
  • 28. Empirical Use No culture result • Based on: Knowledge of common pathogens known to cause infection in that organ/region Local bacterial profile and antibiotic sensitivity Broad-spectrum activity • Specimens should be taken before commencing antibiotics (if possible/feasible) • Culture/sensitivity results should be obtained as soon as possible • If patient is responding well: No need to change to antibiotic of sensitivity
  • 29. When to start ? • Risk of surgical infection is high - based on the underlying disease process (e.g. perforated appendicitis) [prophylaxis empiric] • Significant contamination during surgery has occurred (e.g. considerable spillage of colon contents) • In critically ill patients – potential site of infection has been identified • Severe sepsis or septic shock • Short course (3-5 days) • Stop if the presence of a local site or systemic infection is not revealed
  • 30. Definitive •Culture results and antibiotic sensitivity known
  • 31. Administration •Route – I.V preferred in seriously ill surgical pts. With improvement, can be changed to oral. •Other routes – I.M, intrathecal, subcut., intraosseous. •Duration – most surgical infections can be Rx in 5-7 days, however Rx can be much longer based on clinical response.
  • 32. Adverse Effects of A/B •Penicillins – mostly hypersensitivity reactions. •Cephalosporins – similar to penicillins •Quinolones – nausea, vomiting, diarrhea •Aminoglycosides – nephrotoxity & 8th CN toxicity.
  • 33. Adverse Effects of A/B ›Tetracyclines – stains teeth of children, may cause growth deformity/inhibition. ›Macrolides – acute cholestatic hepatitis ›Metronidazole – disulfiram-like reaction, peripheral neuropathy (prolonged use) ›Chloramphenicol – bone marrow suppression, gray baby syndrome ›Carbapenems – nausea, vomiting, diarrhea, skin rashes
  • 34. Rx Failure › Wrong choice of antibiotic › Inadequate dose › Inappropriate route › Clinical condition not susceptible to A/B Rx -undrained abscess -infxn not responsive to A/B -super infection with A/B resistant org › Devt. of resistance › Antagonistic A/B combination › Inadequate duration of Rx
  • 35. Mechanism of Resistance •Inactivation of the antibiotic – penicillins •Mutational change of bacterial enzyme affected by antibiotic – tetracyclines •Transmission of resistance genes via plasmids.
  • 36. Current Trends •Antibodies to bacterial toxins and mediators of sepsis are currently being evaluated.
  • 37. CONCLUSION ›Prophylactic antibiotic should be given in clean surgery which involves prosthetic implants, in clean-contaminated and contaminated surgeries ›Prophylactic antibiotics should be administered within 1 hour prior to incision ›Therapeutic antibiotic should be started for dirty wound ›Empirical therapy should be altered according to the sensitivity of the culture
  • 38. •Therapeutic drug monitoring is done in antibiotics with narrow therapeutic range (Amikacin, Gentamycin, Vancomycin) •Allergic reactions include anaphylaxis, fever, rashes, nephritis, granulocytopenia & hemolytic anemia are possible side effects of Penicillins and Cephalosporins •Appropriate choice of antibiotics, dosage, compliance should be ensured to avoid emergence of resistance
  • 39. References •Medscape •National Antibiotic Guideline 2008 •Schwartz’s Principles of Surgery •Enterococcal Resistance – An Overview (YA Marothi, H Agnihotri, D Dubey) Indian Journal of Medical Microbiology, (2005) 23 (4):214-9 •Niederman MS. Principles of appropriate antibiotic use
  • 40. THANK YOU FOR LISTENING!