Transcript ANTIBIOTIC USE - University of Nairobi

ANTIBIOTIC USE
PRESENTOR: DR HASSAN
FACILITATOR: DR MUASYA
OUTLINE
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Introduction
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Overview of antibiotics mechanism of action
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Rationale use and choice of antibiotics.
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Combination therapy.
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Resistance to antibiotics
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Summary
Introduction
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Antibiotics are substances produced by various microorganisms ( or synthetic
agents ) that suppress growth of other microorganisms.
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Among the most prescribed drugs.
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Proper use can be life saving
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Indiscriminate use: more cost of h/care, side effects, drug interactions and foster
emergence of drug resistance.
Bacteriostatic vs bacteriocidal
Bacteriocidal
Aminoglycosides
B-lactam antibiotics
Vancomycin
Quinolones
Isoniazid
Pyrazinamide
Rifampicin
Bacteriostatic
Chloramphenical
Clindamycin
Macrolides
Sulfonamides
Tetracycline
Ethambutol
Rationale use of antibiotics
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Is an antimicrobial agent indicated on the basis of clinical finding?
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Have appropriate clinical specimens been obtained?
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What are the likely etiologic agents for the patients illness?
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What measures should be taken to protect individuals exposed to the index case to
prevent secondary cases?
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Is there clinical evidence that antimicrobial therapy will confer clinical benefit for
the patient?
Choice of an antibiotic
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To choose the appropriate antibiotic to use, one needs to consider:
1.
Infectious agent.
2.
Antimicrobial agent to use.
3.
Host factors.
Factors affecting choice of an antibiotic
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Host factors
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Concomitant disease states (e.g immune status)
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Prior adverse drug effects
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Impaired elimination of the drugs
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Age of the patient
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Pregnancy status
Factors affecting choice of an antibiotics
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Pharmacologic factors
 Pharmacodynamics of the drug (concentration dependent vs. time dependent
killing)
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Site of infection (BBB, vegetations in IE)
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Toxicity of the agent
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Interactions with other drugs
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Bactericidal or bacteriostatic
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Resistance patterns
Antibiotic therapy
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Empirical therapy.
-Based on best guess guided by knowledge of likely pathogen in that site or clinical
setting.
-appropriate in life threatening infections, justified for by the hope that early
intervention will improve the outcome
Rx comm. Acquired infections e.g. CAP, UTI
-Once MCS results out change to specific agent
-Adv: immediate. Rx, short hosp. stay
-Disadv: use of many drugs, unnecessary S/E, good clinical acumen needed.
Empirical therapy: Approach
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Formulate a clinical diagnosis of microbial infection
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Obtain specimen for laboratory examination
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Formulate a microbiologic diagnosis
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Determine the necessity for empirical therapy
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Institute treatment
Examples of empiric antibiotic therapy based on
microbiological aetiology
Suspected org.
1st choice
Alternative drug
N. Gonorrhea
Ceftriaxone
Spectinomycin
N.Meningitidis
Pen G
Ceftriaxone
E.coli, klebsiella
Septirin, Ceph,
Quinolone, AG
Pseudomonas
Antips+AG
Antips+QN,CPH
S. Pneu
Pen
Cphl,macrldes,qnlns
V.Strep
Pen
Cphl, vanco
Enterococcus
Pen+AG
Vanc+AG
Clostrdm
Metrndzle
Vanc, bacitracin
Definitive therapy
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-depend on susceptibility & sensitivity tests.
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-requires isolation of the pathogen.
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-requires knowledge of the MIC and MBC.
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-Advantage: accuracy, cheaper
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-Disadvantage: delay treatment, specimen may be difficult to get, varying
sensitivity patterns in different hospitals.
Methods of susceptibility tests
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Broth microdilution
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Microdilution
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Agar dilution method
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Disk diffusion test (Bauer Kurby procedure)
 Susceptible
 Intermediate
 Resistant
Duration of therapy
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Depends on:
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the pathogen;
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site of infection and
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host factors.
Duration of Therapy for Bacterial Infections
Duration of
therapy
Infections
Single dose
GU, Strep pharyngitis, prim and secondary syphilis
3 days
Cystitis in young women, community/travel acquired dirrhea
3-10 days
CAP(3-5days);CAM(pnemo or meningo);Antbtc assctd
diarrhea(10 days);cellulitis ;epididymitis
2 weeks
H.Pylori assctd PUD; neurosyphilis; disseminated gon infctns;
acute pyelonephritis; Pen-suscptble VSE
3 weeks
Lyme disease; septic arthritis (NG)
4 weeks
Acut and chronic prostitis; IE (Pen resistant)
>4 weeks
A and C ostemyltis; S.aureaus endocarditis; FB infections
Combination of antibiotics
USED
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Provide broad-spectrum empiric therapy in seriously ill patients.
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Treat polymicrobial infection such as intraabdominal abscess.
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To decrease emergence of resistance strains.
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To enhance antibacterial activity (synergy)
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To use lower doses of a toxic drug
Antibiotic prophylaxis
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Risk of infection must be greater than S/E of drugs
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Shortest time possible
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Primary or secondary prophylaxis
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Surgical or nonsurgical prophylaxis
Antibiotic prophylaxis
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Surgical
 Contaminated and clean contaminated procedures
 Operations in which postop infections may be catastrophic eg open heart
surgery
 Placement of prosthetic materials
 Procedures in imunocompromised pts.
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Nonsurgical
 Individuals at high risk for temporary exposure to selected virulant org.
 Patients at increased risk for developing infection because of underlying
disease e.g immunocompromised pts
MISUSE OF ANTIBIOTICS
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Treating FUO
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Improper dosing
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Inappropriate reliance on chemotherapy alone
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Lack of adequate bacteriological information
Resistance to antibiotics
RESISTANCE TO ANTIBIOTICS
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Genetic determinants of resistance
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Biochemical mechanisms of resistance
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Current status of antibiotic resistance
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Limiting resistance to antibiotics
Genetic determinant of Resistance
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Chromosomal determinant
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Spontaneous mutation rate in bacteria popn. For any particular gene very low
(1: 1000000)
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In most org., resistance from chromosomal mutation not of great significance
coz mutants have decreased pathogenecity
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Impo. in MRSA and mycobacterium infections - TB
Genetic determinant of Resistance
Extrachromosomal determinants
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Plasmids: extra chromosomal genetic elements called plasmids that exist
free in the cytoplasm. These genetic elements can replicate on their own.
They are closed loops of DNA that consist of single gene or many genes.
Plasmids that carry genes for resistance for antibiotics (r genes) are called
R plasmids. Much drug resistance in clinical medicine is plasmid
mediated.
Transfer of r genes between bacteria take place in one of these form:
1.
2.
3.
Transposons: stretches of DNA that can be transferred (transposed) from
one plasmid to another or plasmid to chromosome.
Conjugation: conjugate plasmids which cause bacteria to make a
connecting tube btn bacteria through which the plasmid or other plasmids
can pass.
Transduction: transmission of r gene-carrying plasmid by bacteriophage
(bacteria virus)
BIOCHEMICAL MECHANISM OF RESISTANCE
TO ANTIBOITICS
1.
2.
3.
4.
Production of enzymes that inactivate the drug:B lactamase –penicillins,
cephalosporins, acetyltransferase –CAF
Alteration of drug sensitive site or binding site
-plasmid mediated alt 50s binding site-erythromycin
- alt of 30s subunit- amino glycoside (xsomal mutation)
Decreased drug accumulation in the bacteria
-active efflux of the drug: resistance to B lactams, amino glycosides, quinolones.
-plasmid mediated resistance to TCs through efflux of the TCs
Alteration of enzyme pathways
-plasmid mediated synthesis of DHFR with low affinity for trimethoprim.
Examples of antibiotic resistance
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Enteroccocci:
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B-lactam: b-lactamse enzyme
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AG: enzymes that modify the drugs
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Clindamycin:gene that effluxes the drug
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Vancomycin: modified targets of vanco (low level and high level resistance)
Examples..ctd
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MRSA
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Many strains of staph now resistant to all currently available antibiotics.
Produce B-latamase –resist to B-lactams
-B-lactam binding protein –resist to methicillin
-staph also show resistance to other antibiotics:
streptomycic(alt of target site)
-CAF & macrolides, (change enzymes
-trim/sulfo,(DHFR, incr PABA)
-amino glycosides (alt target site)
-quinolones( decr uptake.
Summary
1.
2.
3.
4.
5.
6.
7.
Make a diagnosis
as precisely as possible
state org. responsible and site of infection
Decide if chemotherapy is necessary: if no symptomatic rx. If yes:
Select best drug
Administer drug: best route, optimum dose , freq & duration.
Continue therapy until cured/improvement.
Test for cure/improvement. (clinical & lab.)
? Prophylaxis & how long
EXAMPLE: IE
Referances:
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Katzung pharmacology
Harrisons internal med 17th ed
Uptodate.com
Hopkins-abxguide.com
Idsociety.org
YA MUNGU NI
MENGI!!!!