18 - Antibiotik
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ANTIMICROBIAL AGENTSGENERAL CONSIDERATION
NUR PERMATASARI
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Antibiotics
Substances produced by various species of microorganisms: bacteria, fungi, actinomycetes- that suppress the growth of other microorganisms and to destroy them.
Today the term ATB extends to include synthetic antibacterial agents: sulfonamides and quinolones.
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Sir Alexander Fleming
In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture.
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1941 : Clinical uses of PenicillinAfter War II: Identification of streptomycin, chloramphenicol, chlor tetracyline30% of hospitalized patients treated with antimicrobial agentsMisused : 50% patients diagnosed with viral resp.tract infection are prescribed ATBThe problem: ATB-resistant pathogens physicians must be wiser and more selective in the use of ATB
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Classification and mechanism of action
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Susceptibility vs. Resistance
Dose of drug has to be sufficient to produce effect inhibit or kill the microorganism:However concentration of the drug must remain below those that are toxic to human cells
If can be achieved – microorganism susceptible to the ATBIf effective concentration is higher than toxic- microorganism is resistant
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Resistance
Failure to reach the target ( absence/ mutation of porin, anaerobic condition, efflux pump mechanism)
The drug is inactivated (aminoglycoside-modyfing enzyme, beta lactamase)
The target is altered (reduced binding/ substitution of a new target)
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Selection of the ATB
Requires clinical judgment, detailed knowledge of pharmacological and microbiological factors.
Empirical therapy – initial – infecting organism not identified – single broad spectrum agent/ combination
Definitive therapy- microorganism identified – a narrow –spectrum low toxicity regiment to complete the course of treatment
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Empirical and Definite Therapy
Knowledge of the most likely infecting microorganism and its susceptibility
Simple and rapid laboratory- Gram stain
Help to narrow the list of potential pathogen and permit rational selection of initial ATB therapy
Definite therapy (more narrow spectrum and susceptibility test are known)
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Factors Influencing The Effectiveness (1)
Pharmacokinetic factorsLocation of infectionPenetration of drugThe dose and dosis frequencyKnowledge of the status of the patientRoute of administration
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Factors Influencing The Effectiveness (2)
Host factorHost defence mechanismLocal factorAge (biotransformation,distribution, elimination)
Genetic factors (genetic & metabolic abnormalities) PregnancyDrug allergy
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Factors Influencing The Effectiveness (2)
Host defence mechanismImmunocompetent host bacteriostaticImpaired host bacteriocidic(bacterial endocarditis~phagocitic cell
absentbacterial meningitis~phagocitic
ineffective, neutropenic patients~totol mass phagocitic cell reduced)
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Factors Influencing The Effectiveness (2)
Local factor-pus, hemoglobin in infected
hematoma, pH, anaerobic, vascular supply
- the presence of foreign body
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Indications for the use of combinations of antimicrobial agents
Empirical therapy of unknown cause of infectionTreatment of polymicrobial infectionsEnhancement of antimicrobial activityPrevention of the emergence of resistant microbial
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Disanvantages of combinations of antimicrobial agents
Risk of toxicityThe selection of multiple-drug resitantIncreased costAntagonism effect
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The prophylaxis of infection with antimicrobial agents
Protection of healthy patients who are in close contact with a casePatients with structural lesions of the heart predisposising to endocarditisPatients undergoing organ transplantation or cancer chemotherapyPrevention of wound infections In dirty and contaminated surgical procedures
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The appearance of bacteriological and clinical evidence of a new infection during the chemotherapy of a primary oneVery dangerous Very difficult to eradicateBroad spectrum, prolonged administration
Superinfections
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Misuses of antibiotics
Treatment of untreatable infectionTherapy of fever of unknown originImproper dosageInappropriate reliance on chemotherapy aloneLack of adequate bacteriological information