Antibiotic use 09 revised Presentation.ppt
- 1. ANTIBIOTIC USE ANTIBIOTIC USE PRESENTOR: DR HASSAN PRESENTOR: DR HASSAN FACILITATOR: DR MUASYA FACILITATOR: DR MUASYA
- 2. OUTLINE OUTLINE Introduction Introduction Overview of antibiotics mechanism of action Overview of antibiotics mechanism of action Rationale use and choice of antibiotics. Rationale use and choice of antibiotics. Combination therapy. Combination therapy. Resistance to antibiotics Resistance to antibiotics Summary Summary
- 3. Introduction Introduction Antibiotics are substances produced by various microorganisms ( or synthetic Antibiotics are substances produced by various microorganisms ( or synthetic agents ) that suppress growth of other microorganisms. agents ) that suppress growth of other microorganisms. Among the most prescribed drugs. Among the most prescribed drugs. Proper use can be life saving Proper use can be life saving Indiscriminate use: more cost of h/care, side effects, drug interactions and foster Indiscriminate use: more cost of h/care, side effects, drug interactions and foster emergence of drug resistance. emergence of drug resistance.
- 5. Bacteriostatic vs bacteriocidal Bacteriostatic vs bacteriocidal Bacteriocidal Bacteriocidal Bacteriostatic Bacteriostatic Aminoglycosides Aminoglycosides Chloramphenical Chloramphenical B-lactam antibiotics B-lactam antibiotics Clindamycin Clindamycin Vancomycin Vancomycin Macrolides Macrolides Quinolones Quinolones Sulfonamides Sulfonamides Isoniazid Isoniazid Tetracycline Tetracycline Pyrazinamide Pyrazinamide Ethambutol Ethambutol Rifampicin Rifampicin
- 6. Rationale use of antibiotics Rationale use of antibiotics Is an antimicrobial agent indicated on the basis of clinical finding? Is an antimicrobial agent indicated on the basis of clinical finding? Have appropriate clinical specimens been obtained? Have appropriate clinical specimens been obtained? What are the likely etiologic agents for the patients illness? What are the likely etiologic agents for the patients illness? What measures should be taken to protect individuals exposed to the index case to What measures should be taken to protect individuals exposed to the index case to prevent secondary cases? prevent secondary cases? Is there clinical evidence that antimicrobial therapy will confer clinical benefit for Is there clinical evidence that antimicrobial therapy will confer clinical benefit for the patient? the patient?
- 7. Choice of an antibiotic Choice of an antibiotic To choose the appropriate antibiotic to use, one needs to consider: To choose the appropriate antibiotic to use, one needs to consider: 1. 1. Infectious agent. Infectious agent. 2. 2. Antimicrobial agent to use. Antimicrobial agent to use. 3. 3. Host factors. Host factors.
- 8. Factors affecting choice of an antibiotic Factors affecting choice of an antibiotic Host factors Host factors Concomitant disease states (e.g immune status) Concomitant disease states (e.g immune status) Prior adverse drug effects Prior adverse drug effects Impaired elimination of the drugs Impaired elimination of the drugs Age of the patient Age of the patient Pregnancy status Pregnancy status
- 9. Factors affecting choice of an antibiotics Factors affecting choice of an antibiotics Pharmacologic factors Pharmacologic factors Pharmacodynamics of the drug (concentration dependent vs. time dependent Pharmacodynamics of the drug (concentration dependent vs. time dependent killing) killing) Site of infection (BBB, vegetations in IE) Site of infection (BBB, vegetations in IE) Toxicity of the agent Toxicity of the agent Interactions with other drugs Interactions with other drugs Bactericidal or bacteriostatic Bactericidal or bacteriostatic Resistance patterns Resistance patterns
- 10. Antibiotic therapy Antibiotic therapy Empirical therapy. Empirical therapy. -Based on best guess guided by knowledge of likely pathogen in that site or clinical -Based on best guess guided by knowledge of likely pathogen in that site or clinical setting. setting. -appropriate in life threatening infections, justified for by the hope that early -appropriate in life threatening infections, justified for by the hope that early intervention will improve the outcome intervention will improve the outcome Rx comm. Acquired infections e.g. CAP, UTI Rx comm. Acquired infections e.g. CAP, UTI -Once MCS results out change to specific agent -Once MCS results out change to specific agent -Adv: immediate. Rx, short hosp. stay -Adv: immediate. Rx, short hosp. stay -Disadv: use of many drugs, unnecessary S/E, good clinical acumen needed. -Disadv: use of many drugs, unnecessary S/E, good clinical acumen needed.
- 11. Empirical therapy: Approach Empirical therapy: Approach Formulate a clinical diagnosis of microbial infection Formulate a clinical diagnosis of microbial infection Obtain specimen for laboratory examination Obtain specimen for laboratory examination Formulate a microbiologic diagnosis Formulate a microbiologic diagnosis Determine the necessity for empirical therapy Determine the necessity for empirical therapy Institute treatment Institute treatment
- 12. Examples of empiric antibiotic therapy based on Examples of empiric antibiotic therapy based on microbiological aetiology microbiological aetiology Suspected org. Suspected org. 1 1st st choice choice Alternative drug Alternative drug N. Gonorrhea N. Gonorrhea Ceftriaxone Ceftriaxone Spectinomycin Spectinomycin N.Meningitidis N.Meningitidis Pen G Pen G Ceftriaxone Ceftriaxone E.coli, klebsiella E.coli, klebsiella Septirin, Ceph, Septirin, Ceph, Quinolone, AG Quinolone, AG Pseudomonas Pseudomonas Antips+AG Antips+AG Antips+QN,CPH Antips+QN,CPH S. Pneu S. Pneu Pen Pen Cphl,macrldes,qnlns Cphl,macrldes,qnlns V.Strep V.Strep Pen Pen Cphl, vanco Cphl, vanco Enterococcus Enterococcus Pen+AG Pen+AG Vanc+AG Vanc+AG Clostrdm Clostrdm Metrndzle Metrndzle Vanc, bacitracin Vanc, bacitracin
- 13. Definitive therapy Definitive therapy -depend on susceptibility & sensitivity tests. -depend on susceptibility & sensitivity tests. -requires isolation of the pathogen. -requires isolation of the pathogen. -requires knowledge of the MIC and MBC. -requires knowledge of the MIC and MBC. -Advantage: accuracy, cheaper -Advantage: accuracy, cheaper -Disadvantage: delay treatment, specimen may be difficult to get, varying -Disadvantage: delay treatment, specimen may be difficult to get, varying sensitivity patterns in different hospitals. sensitivity patterns in different hospitals.
- 14. Methods of susceptibility tests Methods of susceptibility tests Broth microdilution Broth microdilution Microdilution Microdilution Agar dilution method Agar dilution method Disk diffusion test (Bauer Kurby procedure) Disk diffusion test (Bauer Kurby procedure) Susceptible Susceptible Intermediate Intermediate Resistant Resistant
- 15. Duration of therapy Duration of therapy Depends on: Depends on: the pathogen; the pathogen; site of infection and site of infection and host factors. host factors.
- 16. Duration of Therapy for Bacterial Infections Duration of Therapy for Bacterial Infections Duration of Duration of therapy therapy Infections Infections Single dose Single dose GU, Strep pharyngitis, prim and secondary syphilis GU, Strep pharyngitis, prim and secondary syphilis 3 days 3 days Cystitis in young women, community/travel acquired dirrhea Cystitis in young women, community/travel acquired dirrhea 3-10 days 3-10 days CAP(3-5days);CAM(pnemo or meningo);Antbtc assctd CAP(3-5days);CAM(pnemo or meningo);Antbtc assctd diarrhea(10 days);cellulitis ;epididymitis diarrhea(10 days);cellulitis ;epididymitis 2 weeks 2 weeks H.Pylori assctd PUD; neurosyphilis; disseminated gon infctns; H.Pylori assctd PUD; neurosyphilis; disseminated gon infctns; acute pyelonephritis; Pen-suscptble VSE acute pyelonephritis; Pen-suscptble VSE 3 weeks 3 weeks Lyme disease; septic arthritis (NG) Lyme disease; septic arthritis (NG) 4 weeks 4 weeks Acut and chronic prostitis; IE (Pen resistant) Acut and chronic prostitis; IE (Pen resistant) >4 weeks >4 weeks A and C ostemyltis; S.aureaus endocarditis; FB infections A and C ostemyltis; S.aureaus endocarditis; FB infections
- 17. Combination of antibiotics Combination of antibiotics USED USED Provide broad-spectrum empiric therapy in seriously ill patients. Provide broad-spectrum empiric therapy in seriously ill patients. Treat polymicrobial infection such as intraabdominal abscess. Treat polymicrobial infection such as intraabdominal abscess. To decrease emergence of resistance strains. To decrease emergence of resistance strains. To enhance antibacterial activity (synergy) To enhance antibacterial activity (synergy) To use lower doses of a toxic drug To use lower doses of a toxic drug
- 18. Antibiotic prophylaxis Antibiotic prophylaxis Risk of infection must be greater than S/E of drugs Risk of infection must be greater than S/E of drugs Shortest time possible Shortest time possible Primary or secondary prophylaxis Primary or secondary prophylaxis Surgical or nonsurgical prophylaxis Surgical or nonsurgical prophylaxis
- 19. Antibiotic prophylaxis Antibiotic prophylaxis Surgical Surgical Contaminated and clean contaminated procedures Contaminated and clean contaminated procedures Operations in which postop infections may be catastrophic eg open heart Operations in which postop infections may be catastrophic eg open heart surgery surgery Placement of prosthetic materials Placement of prosthetic materials Procedures in imunocompromised pts. Procedures in imunocompromised pts. Nonsurgical Nonsurgical Individuals at high risk for temporary exposure to selected virulant org. Individuals at high risk for temporary exposure to selected virulant org. Patients at increased risk for developing infection because of underlying Patients at increased risk for developing infection because of underlying disease e.g immunocompromised pts disease e.g immunocompromised pts
- 20. MISUSE OF ANTIBIOTICS MISUSE OF ANTIBIOTICS Treating FUO Treating FUO Improper dosing Improper dosing Inappropriate reliance on chemotherapy alone Inappropriate reliance on chemotherapy alone Lack of adequate bacteriological information Lack of adequate bacteriological information
- 21. Resistance to antibiotics Resistance to antibiotics
- 22. RESISTANCE TO ANTIBIOTICS RESISTANCE TO ANTIBIOTICS Genetic determinants of resistance Genetic determinants of resistance Biochemical mechanisms of resistance Biochemical mechanisms of resistance Current status of antibiotic resistance Current status of antibiotic resistance Limiting resistance to antibiotics Limiting resistance to antibiotics
- 23. Genetic determinant of Resistance Genetic determinant of Resistance Chromosomal determinant Chromosomal determinant Spontaneous mutation rate in bacteria popn. For any particular gene very low Spontaneous mutation rate in bacteria popn. For any particular gene very low (1: 1000000) (1: 1000000) In most org., resistance from chromosomal mutation not of great significance In most org., resistance from chromosomal mutation not of great significance coz mutants have decreased pathogenecity coz mutants have decreased pathogenecity Impo. in MRSA and mycobacterium infections - TB Impo. in MRSA and mycobacterium infections - TB
- 24. Genetic determinant of Resistance Genetic determinant of Resistance Extrachromosomal determinants Extrachromosomal determinants Plasmids: extra chromosomal genetic elements called plasmids that exist Plasmids: extra chromosomal genetic elements called plasmids that exist free in the cytoplasm. These genetic elements can replicate on their own. 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. They are closed loops of DNA that consist of single gene or many genes. Plasmids that carry genes for resistance for antibiotics ( Plasmids that carry genes for resistance for antibiotics (r r genes) are called genes) are called R plasmids. Much drug resistance in clinical medicine is plasmid R plasmids. Much drug resistance in clinical medicine is plasmid mediated. mediated. Transfer of r genes between bacteria take place in one of these form: Transfer of r genes between bacteria take place in one of these form: 1. 1. Transposons: stretches of DNA that can be transferred (transposed) from Transposons: stretches of DNA that can be transferred (transposed) from one plasmid to another or plasmid to chromosome. one plasmid to another or plasmid to chromosome. 2. 2. Conjugation: conjugate plasmids which cause bacteria to make a Conjugation: conjugate plasmids which cause bacteria to make a connecting tube btn bacteria through which the plasmid or other plasmids connecting tube btn bacteria through which the plasmid or other plasmids can pass. can pass. 3. 3. Transduction: transmission of r gene-carrying plasmid by bacteriophage Transduction: transmission of r gene-carrying plasmid by bacteriophage (bacteria virus) (bacteria virus)
- 26. BIOCHEMICAL MECHANISM OF RESISTANCE BIOCHEMICAL MECHANISM OF RESISTANCE TO ANTIBOITICS TO ANTIBOITICS 1. 1. Production of enzymes that inactivate the drug:B lactamase –penicillins, Production of enzymes that inactivate the drug:B lactamase –penicillins, cephalosporins, acetyltransferase –CAF cephalosporins, acetyltransferase –CAF 2. 2. Alteration of drug sensitive site or binding site Alteration of drug sensitive site or binding site -plasmid mediated alt 50s binding site-erythromycin -plasmid mediated alt 50s binding site-erythromycin - alt of 30s subunit- amino glycoside (xsomal mutation) - alt of 30s subunit- amino glycoside (xsomal mutation) 3. 3. Decreased drug accumulation in the bacteria Decreased drug accumulation in the bacteria -active efflux of the drug: resistance to B lactams, amino glycosides, quinolones. -active efflux of the drug: resistance to B lactams, amino glycosides, quinolones. -plasmid mediated resistance to TCs through efflux of the TCs -plasmid mediated resistance to TCs through efflux of the TCs 4. 4. Alteration of enzyme pathways Alteration of enzyme pathways -plasmid mediated synthesis of DHFR with low affinity for trimethoprim -plasmid mediated synthesis of DHFR with low affinity for trimethoprim. .
- 27. Examples of antibiotic resistance Examples of antibiotic resistance Enteroccocci: Enteroccocci: B-lactam: b-lactamse enzyme B-lactam: b-lactamse enzyme AG: enzymes that modify the drugs AG: enzymes that modify the drugs Clindamycin:gene that effluxes the drug Clindamycin:gene that effluxes the drug Vancomycin: modified targets of vanco (low level and high level resistance) Vancomycin: modified targets of vanco (low level and high level resistance)
- 28. Examples..ctd Examples..ctd MRSA MRSA Many strains of staph now resistant to all currently available antibiotics. Many strains of staph now resistant to all currently available antibiotics. Produce B-latamase –resist to B-lactams Produce B-latamase –resist to B-lactams -B-lactam binding protein –resist to methicillin -B-lactam binding protein –resist to methicillin -staph also show resistance to other antibiotics: -staph also show resistance to other antibiotics: streptomycic(alt of target site) streptomycic(alt of target site) -CAF & macrolides, (change enzymes -CAF & macrolides, (change enzymes -trim/sulfo,(DHFR, incr PABA) -trim/sulfo,(DHFR, incr PABA) -amino glycosides (alt target site) -amino glycosides (alt target site) -quinolones( decr uptake. -quinolones( decr uptake.
- 29. Summary Summary 1. 1. Make a diagnosis Make a diagnosis as precisely as possible as precisely as possible state org. responsible and site of infection state org. responsible and site of infection 2. 2. Decide if chemotherapy is necessary: if no symptomatic rx. If yes: Decide if chemotherapy is necessary: if no symptomatic rx. If yes: 3. 3. Select best drug Select best drug 4. 4. Administer drug: best route, optimum dose , freq & duration. Administer drug: best route, optimum dose , freq & duration. 5. 5. Continue therapy until cured/improvement. Continue therapy until cured/improvement. 6. 6. Test for cure/improvement. (clinical & lab.) Test for cure/improvement. (clinical & lab.) 7. 7. ? Prophylaxis & how long ? Prophylaxis & how long EXAMPLE: IE EXAMPLE: IE
- 30. Referances: Referances: Katzung pharmacology Katzung pharmacology Harrisons internal med 17 Harrisons internal med 17th th ed ed Uptodate.com Uptodate.com Hopkins-abxguide.com Hopkins-abxguide.com Idsociety.org Idsociety.org
- 31. YA MUNGU NI YA MUNGU NI MENGI!!!! MENGI!!!!