farmakologi-pengantar anti mikroba (dr. ika fikriah, m. kes.)
TRANSCRIPT
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PENGANTAR PENGANTAR ANTIMIKROBAANTIMIKROBA
Ika FikriahIka Fikriah
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AntibioticsAntibiotics
Substances produced by Substances produced by various species of various species of microorganisms : bacteria, microorganisms : bacteria, fungi, actinomycetes fungi, actinomycetes
that suppress the growth of that suppress the growth of other microorganisms and to other microorganisms and to destroy them.destroy them.
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Classification and mechanism of action
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ANTIMICROBA ACTIVITYANTIMICROBA ACTIVITY
Minimal inhibitory concentration Minimal inhibitory concentration (MIC)(MIC)
Minimal lethal concentration (MLC)Minimal lethal concentration (MLC)
Dilution Susceptibility Dilution Susceptibility TestsTests
determination of MIC and MLCdetermination of MIC and MLC Mueller-Hinton brothMueller-Hinton broth read at 16-20 hoursread at 16-20 hours
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Susceptibility Testing Antibiotic Susceptibility Testing Antibiotic
Determination of MICDetermination of MIC
8 4 02 1 Tetracycline (μg/ml)
MIC = 2 μg/ml
Determination of MIC
Chl Amp
Ery
Str
Tet
Disk Diffusion Test
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Selective toxicitySelective toxicity
therapeutic dose: drug level required therapeutic dose: drug level required for clinical treatmentfor clinical treatment
toxic dose: agent too toxic for hosttoxic dose: agent too toxic for host therapeutic index: ratio of therapeutic therapeutic index: ratio of therapeutic
dose to toxic dosedose to toxic dose
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Selection of the ATBSelection of the ATB Requires clinical judgment, detailed knowledge Requires clinical judgment, detailed knowledge
of pharmacological and microbiological factors.of pharmacological and microbiological factors.
Empirical therapy – initial – infecting organism Empirical therapy – initial – infecting organism not identified – single broad spectrum agent/ not identified – single broad spectrum agent/ combination combination
Definitive therapy- microorganism identified – Definitive therapy- microorganism identified –
a narrow –spectrum low toxicity regiment to a narrow –spectrum low toxicity regiment to complete the course of treatment complete the course of treatment
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Susceptibility vs. ResistanceSusceptibility vs. Resistance Dose of drug has to be sufficient to produce Dose of drug has to be sufficient to produce
effect inhibit or kill the microorganism:effect inhibit or kill the microorganism: However concentration of the drug must However concentration of the drug must
remain below those that are toxic to human remain below those that are toxic to human cells cells
If can be achieved – microorganism If can be achieved – microorganism susceptible to the ATBsusceptible to the ATB
If effective concentration is higher than If effective concentration is higher than toxic- microorganism is resistanttoxic- microorganism is resistant
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ResistanceResistance
Failure to reach the target ( absence/ Failure to reach the target ( absence/ mutation of porin, anaerobic condition)mutation of porin, anaerobic condition)
The drug is inactivated (aminoglycoside-The drug is inactivated (aminoglycoside-modyfing enzyme, beta lactamase)modyfing enzyme, beta lactamase)
The target is altered (reduced binding/ The target is altered (reduced binding/ substitution of a new target)substitution of a new target)
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Factors Influencing The Factors Influencing The
EffectivenessEffectiveness
Pharmacokinetic factorsPharmacokinetic factors Location of infectionLocation of infection Penetration of drugPenetration of drug The dose and dosis frequencyThe dose and dosis frequency Knowledge of the status of the patientKnowledge of the status of the patient Route of administration Route of administration
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Host factorHost factor Host defence mechanismHost defence mechanism Local factorLocal factor Age (biotransformation,distribution, Age (biotransformation,distribution,
elimination)elimination) Genetic factors (genetic & Genetic factors (genetic &
metabolic abnormalities) metabolic abnormalities) PregnancyPregnancy Drug allergyDrug allergy
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Host Defence MechanismHost Defence Mechanism
Immunocompetent host Immunocompetent host bacteriostaticbacteriostatic
Impaired host Impaired host bacteriocidic bacteriocidic
bacterial endocarditis~phagocitic cell bacterial endocarditis~phagocitic cell absent absent
bacterial meningitis~phagocitic bacterial meningitis~phagocitic ineffective, neutropenic patients~totol ineffective, neutropenic patients~totol mass phagocitic cell reducedmass phagocitic cell reduced
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Local factorLocal factor pus, hemoglobin in infected pus, hemoglobin in infected
hematoma, pH, anaerobic, hematoma, pH, anaerobic, vascular supplyvascular supply
the presence of foreign bodythe presence of foreign body
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Disanvantages of Disanvantages of combinations of combinations of
antimicrobial agentsantimicrobial agents
Risk of toxicityRisk of toxicity The selection of multiple-The selection of multiple-drug resistantdrug resistant
Increased costIncreased cost Antagonism effectAntagonism effect
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The prophylaxis of The prophylaxis of infection with infection with
antimicrobial agentsantimicrobial agents Protection of healthy patients who are Protection of healthy patients who are
in close contact with a casein close contact with a case Patients with structural lesions of the Patients with structural lesions of the
heart predisposising to endocarditisheart predisposising to endocarditis Patients undergoing organ Patients undergoing organ
transplantation or cancer chemotherapytransplantation or cancer chemotherapy Prevention of wound infections Prevention of wound infections In dirty and contaminated surgical In dirty and contaminated surgical
proceduresprocedures
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SuperinfectionsSuperinfections The appearance of bacteriological The appearance of bacteriological
and clinical evidence of a new and clinical evidence of a new infection during the chemotherapy infection during the chemotherapy of a primary oneof a primary one
Very dangerous Very dangerous Very difficult to eradicateVery difficult to eradicate Broad spectrum, prolonged Broad spectrum, prolonged
administration administration
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Beta-Lactam AntibioticsBeta-Lactam Antibiotics PenicillinPenicillin
bactericide, broad spectrumbactericide, broad spectrumpenicillin G, nafcillin, procain penicillin, ampicillin, penicillin G, nafcillin, procain penicillin, ampicillin, amoxicillinamoxicillinresistance by beta-laktamaseresistance by beta-laktamase
CephalosporinCephalosporinbactericide, broad spectrum, stable beta-laktamasebactericide, broad spectrum, stable beta-laktamaseFirst gen (cefadroxil, cefazolin, cefalexin)First gen (cefadroxil, cefazolin, cefalexin)Second gen (cefaclor, cefuroxime, cefoxitin)Second gen (cefaclor, cefuroxime, cefoxitin)TTthth gen (cefotaxime, cefixime, ceftriaxone) gen (cefotaxime, cefixime, ceftriaxone)FFthth gen (cefepime gen (cefepimeOral, parenteralOral, parenteral
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Protein Synthesis InhibitorsProtein Synthesis Inhibitors Aminoglycosides Aminoglycosides
Streptomycin, GentamycinStreptomycin, Gentamycin Resistance by modification or target mutationResistance by modification or target mutation
TetracyclinesTetracyclines resistance by exportresistance by export
MacrolidesMacrolides erythromycin, clindamycin, azithromycinerythromycin, clindamycin, azithromycin used for patients allergic to penicillinused for patients allergic to penicillin resistance by target mutationresistance by target mutation
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streptomycin, kanamycin, neomycin, streptomycin, kanamycin, neomycin, tobramycintobramycin
inhibit protein synthesisinhibit protein synthesis cause misreading of mRNAcause misreading of mRNA
bactericidal: Gram -bactericidal: Gram - streptomycin: tuberculosis, plaguestreptomycin: tuberculosis, plague side effects include damage to 8th cranial side effects include damage to 8th cranial
nervenerve
Aminoglycosides: Aminoglycosides: StreptomycesStreptomyces
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Aminoglycosides: Aminoglycosides: StreptomycesStreptomyces Mode of actionMode of action - The tetracyclines reversibly bind to - The tetracyclines reversibly bind to
the 30S ribosome and inhibit binding of aminoacyl-t-the 30S ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site on the 70S ribosome.RNA to the acceptor site on the 70S ribosome.
Spectrum of activitySpectrum of activity - Broad spectrum; Useful - Broad spectrum; Useful against intracellular bacteriaagainst intracellular bacteria
ResistanceResistance - Common - Common Adverse effectsAdverse effects - Destruction of normal intestinal - Destruction of normal intestinal
flora resulting in increased secondary infections; flora resulting in increased secondary infections; staining and impairment of the structure of bone and staining and impairment of the structure of bone and teeth.teeth.
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MacrolidesMacrolides ( (bacteriostaticbacteriostatic))
erythromycin, clarithromycin, azithromycin, erythromycin, clarithromycin, azithromycin, spiramycinspiramycin
Mode of actionMode of action - The macrolides inhibit - The macrolides inhibit translocationtranslocation by binding to 50 S ribosomal by binding to 50 S ribosomal subunitsubunit
Spectrum of activitySpectrum of activity - Gram-positive - Gram-positive bacteria, bacteria, Mycoplasma, LegionellaMycoplasma, Legionella (intracellular bacterias)(intracellular bacterias)
Resistance - CommonResistance - Common
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Erythromycin (macrolide): Erythromycin (macrolide): Streptomyces erythraeusStreptomyces erythraeus
bacteriostaticbacteriostatic binds to 23s rRNA of 50 S subunit: inhibits binds to 23s rRNA of 50 S subunit: inhibits
chain elongationchain elongation narrow to medium spectrum: gram + bacteria, narrow to medium spectrum: gram + bacteria,
penicillin allergic patients, diphtheria, penicillin allergic patients, diphtheria, mycoplasmas, mycoplasmas, LegionellaLegionella
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ChloramphenicolChloramphenicol, Lincomycin, , Lincomycin, Clindamycin (bacteriostatic)Clindamycin (bacteriostatic)
Mode of actionMode of action - These antimicrobials bind to the - These antimicrobials bind to the 50S ribosome and inhibit peptidyl transferase 50S ribosome and inhibit peptidyl transferase activity.activity.
Spectrum of activitySpectrum of activity - Chloramphenicol - Broad range- Chloramphenicol - Broad range- Lincomycin and clindamycin - Restricted range- Lincomycin and clindamycin - Restricted range
ResistanceResistance - Common - Common Adverse effectsAdverse effects - Chloramphenicol is toxic (bone - Chloramphenicol is toxic (bone
marrow suppression) but is used in the treatment of marrow suppression) but is used in the treatment of bacterial meningitis.bacterial meningitis.
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ChloramphenicolChloramphenicol
This inhibits bacterial protein synthesis. This inhibits bacterial protein synthesis. It is well absorbed and widely distributed , It is well absorbed and widely distributed ,
including to the CNS.including to the CNS. It is metabolized by glucoronidation in the It is metabolized by glucoronidation in the
liver.liver. Although an effective broad-spectrum Although an effective broad-spectrum
antibiotics, its uses are limitid by its serious antibiotics, its uses are limitid by its serious toxicity.toxicity.
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PENGGUNAAN ANTIBIOTIKA YANG TIDAK RASIONAL
MENGOBATI INFEKSI VIRUS DENGAN ANTIBIOTIKA
MENGOBATI SETIAP PANAS DENGAN ANTIBIOTIKA TANPA DATA KLINIS /MIKROBIOLOGIS
MENGGUNAKAN ANTIBIOTIKA TIDAK EFEKTIF INVIVO / TIDAK SAMPAI PADA TARGET
MENGGUNAKAN ANTIBIOTIKA EFEKTIF INVITRO TETAPI TIDAK INVIVO
MENGGUNAKAN ANTIBIOTIKA YANG TOKSIK
MENGGUNAKAN ANTIBIOTIKA BROAD SPEKTRUM DAN POTENT WALAUPUN ADA YANG SPESIFIK DAN TIDAK BROAD SPEKTRUM
MENGGUNAKAN ANTIBIOTIKKA YANG MAHAL WALAUPUN YANG MURAH MASIH EFEKTIF
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MONITORING HASIL PENGOBATAN DENGAN ANTI MIKROBA
MENEGAKKAN KEMBALI PENYEBAB INFEKSI APAKAH OLEH INFEKSI BARU (SUPERINFEKSI)
MENENTUKAN KEMBALI TEST KEPEKAAN INVITRO
MENGUKUR KADAR OBAT DALAM URINE, DARAH ATAU JARINGAN APAKAH KADAR OBAT MASIH CUKUP
MEMASTIKAN BAHWA KEGAGALAN TERAPI BUKAN OLEH TINDAKAN NON OBAT SEPERTI DRAINASE, INSISI ABSES, BENDA ASING DALAM TEMPAT INFEKSI
MENGHILANGKAN KEMUNGKINAN BAHWA INFEKSI DISEBABKAN OLEH FAKTOR LAIN SEPERTI PLEBITIS/HIPERSENSITIF