Antibiotics are used against a wide range of pathogens and are very important in preventing and treating infections. The use of appropriate choice of antibiotics, dose and enforcing compliance is important in patient's care and preventing drug resistance.
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
â˘Antibiotics are antibacterial substances
derived from fungi or bacteria which are
active against a wide range of pathogenic
organisms.
â˘Most A/B presently are synthesized
derivatives of original naturally occurring
product.
â˘All exhibit selective toxicity
4. â˘The goal of therapy is to achieve levels of
antibiotic at site of infection that exceed the
minimum inhibitory concentration for the
pathogens present.
â˘Mild infection can be treated at the
outpatient with oral antibiotics.
â˘For severe infection intravenous antibiotics
will be most appropriate.
â˘For most surgical infection there is no specific
duration of antibiotic know to be ideal.
â˘Antibiotics are generally believed to support
local host defenses.
5. Historical Perspective
âş Early 19th century â Louis Pasteur
discovered that certain saprophytic bacteria
can kill anthrax bacilli.
âş 1928 â Alexander Fleming derived penicillin
from Penicillium notatum.
âş 1939 â Tyrothricin was isolated from certain
soil bacteria by Rene Dubos.
âş 1944 â Selman Waksman derived
streptomycin from Actinomycetes.
9. CLASSIFICATION
â˘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.
â˘BACTERIOCIDAL : Drugs that cause death of
microorganisms.
12. Indications for Antibiotic combinations
â˘Mixed bacterial infections in which the
organisms are not susceptible to a common
agent.
â˘To achieve synergistic antimicrobial activity
against a single organism.
â˘To overcome bacterial tolerance.
â˘To prevent development of bacterial antibiotic
resistance
â˘To decrease toxicity of the most effective
agent.
13. THERAPEUTIC SPECTRA
â˘NARROW SPECTRUM âact on only a
single or limited group of microorganism
e.g. isoniacid
â˘EXTENDED SPECTRUM- refers to
antibiotic that are effective against gram
âve and significant no of gram +ve
bacteria e.g. ampicillin.
14. â˘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
âşSelect an A/B to which the known or presumed
pathogen is likely to be fully sensitive.
âşSpectrum of A/B should be known accurately.
Broad spectrum avoided if suitable narrow
spectrum A/B is available.
âşRestrict use of A/B to which resistance is
developing or has developed.
âş Systemic antibiotic should not be used
topically.
âşDrug use must be indicated
16. PRINCIPLES( Contd)
â˘A/B should be given in full dose by appropriate
route & @ correct intervals.
â˘Antibiotics are not used to Rx abscess without
ensuring effective surgical drainage.
â˘Side-effects of A/B should be known &
monitored.
â˘Expensive A/B are not used if equally effective &
cheaper alternatives are suitable.
â˘Consideration for toxicity and drug-drug
interaction
â˘Monitoring
â˘Compliance
17. Uses of Antibiotics
â˘Prophylaxis â preventive use of A/B where
contamination might occur, but is not yet present.
â˘Therapeutic â use of A/B to treat established
infection.
â˘Empiric â A/B Rx based on familiarity with microbes
likely to cause infection.
â˘Definitive â A/B Rx based on m/c/s result.
ďHowever careful aseptic theatre routine should be
maintain.
ďThorough wound toileting.
ďMake sure there are no foreign bodies, dead tissues,
excessive blood clot or faeces in the wound.
18. Principles of chemoprophylaxis
â˘Specificity â must be directed @ org. most
likely to infect @ surgery.
â˘Short course â usu. 24hrs. is sufficient.
â˘High dose â to achieve adequate blood
levels.
â˘Timed dose â 1st dose given @ induction or
premed.
19. Principles of chemoprophylaxis
â˘Not a substitute to aseptic practice & good
surgical technique
â˘Necessary only in high-risk cases of bact.
Contamination.
â˘Route of administration should be I.V.
â˘Should be employed only when scientific
evidence shows it has advantages.
20. Antibiotics used for Surgical Prophylaxis
Commonly used surgical prophylactic
antibiotics include:
â˘intravenous 'first generation' cephalosporins
â cephazolin or cephalothin
â˘intravenous gentamycin
â˘intravenous or rectal metronidazole (if
anaerobic infection is likely)
21. â˘Oral tinidazole (if anaerobic infection is likely)
â˘Intravenous flucloxacillin (if methicillin-
susceptible staphylococcal infection is likely)
â˘Intravenous vancomycin (if methicillin-
resistant staphylococcal infection is likely).
22. Indications for prophylaxis
â˘Prevention of Surgical Site Infection (SSI)
â˘Prevention of other HealthCare Associated
Infections (HCAIs)
â˘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 patientâs normal
bacterial flora.
⢠Minimize adverse side effects of antibiotics.
⢠Minimize the emergence of antibiotics
resistant strains of bacteria.
⢠Cost effectiveness.
24. Indications for prophylaxis
â˘Clean surgery â 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.
â˘- Host immune system suppression e.g. DM,
CRF, e.t.c.
â˘- Vascular surgeries
25. Indications for prophylaxis
âşClean contaminated surgery
â GI surgeries with minimal spillage
âş- Upper Resp. Tract procedures
âş- Genitourinary procedures
âş- Limb amputations
âş- Dental procedures
26.
27. Therapeutic Use of Antibiotics
Indications
âşClinical evidence of established infection
âşLaboratory (microbiological) evidence of
infection
âşSuspected 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 â 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
31. Administration
â˘Route â I.V preferred in seriously ill surgical pts.
With improvement, can be changed to oral.
â˘Other routes â I.M, intrathecal, subcut.,
intraosseous.
â˘Duration â 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
â˘Penicillins â mostly hypersensitivity
reactions.
â˘Cephalosporins â similar to penicillins
â˘Quinolones â nausea, vomiting, diarrhea
â˘Aminoglycosides â nephrotoxity & 8th CN
toxicity.
33. Adverse Effects of A/B
âşTetracyclines â stains teeth of children, may
cause growth deformity/inhibition.
âşMacrolides â acute cholestatic hepatitis
âşMetronidazole â disulfiram-like reaction,
peripheral neuropathy (prolonged use)
âşChloramphenicol â bone marrow
suppression, gray baby syndrome
âşCarbapenems â nausea, vomiting, diarrhea,
skin rashes
34. Rx Failure
âş Wrong choice of antibiotic
âş Inadequate dose
âş Inappropriate route
âş Clinical condition not susceptible to A/B Rx
-undrained abscess
-infxn not responsive to A/B
-super infection with A/B resistant org
âş Devt. of resistance
âş Antagonistic A/B combination
âş Inadequate duration of Rx
35. Mechanism of Resistance
â˘Inactivation of the antibiotic â penicillins
â˘Mutational change of bacterial enzyme
affected by antibiotic â tetracyclines
â˘Transmission of resistance genes via
plasmids.
37. CONCLUSION
âşProphylactic antibiotic should be given in clean
surgery which involves prosthetic implants, in
clean-contaminated and contaminated
surgeries
âşProphylactic antibiotics should be
administered within 1 hour prior to incision
âşTherapeutic antibiotic should be started for
dirty wound
âşEmpirical therapy should be altered according
to the sensitivity of the culture
38. â˘Therapeutic drug monitoring is done in
antibiotics with narrow therapeutic range
(Amikacin, Gentamycin, Vancomycin)
â˘Allergic reactions include anaphylaxis, fever,
rashes, nephritis, granulocytopenia &
hemolytic anemia are possible side effects of
Penicillins and Cephalosporins
â˘Appropriate choice of antibiotics, dosage,
compliance should be ensured to avoid
emergence of resistance
39. References
â˘Medscape
â˘National Antibiotic Guideline 2008
â˘Schwartzâs Principles of Surgery
â˘Enterococcal Resistance â An Overview (YA
Marothi, H Agnihotri, D Dubey) Indian
Journal of Medical Microbiology, (2005) 23
(4):214-9
â˘Niederman MS. Principles of appropriate
antibiotic use