18 - antibiotik
DESCRIPTION
.TRANSCRIPT
ANTIMICROBIAL AGENTSGENERAL CONSIDERATION
NUR PERMATASARI
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.
Sir Alexander Fleming
In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture.
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
Classification and mechanism of action
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
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)
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
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)
Factors Influencing The Effectiveness (1)
Pharmacokinetic factorsLocation of infectionPenetration of drugThe dose and dosis frequencyKnowledge of the status of the patientRoute of administration
Factors Influencing The Effectiveness (2)
Host factorHost defence mechanismLocal factorAge (biotransformation,distribution, elimination)
Genetic factors (genetic & metabolic abnormalities) PregnancyDrug allergy
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)
Factors Influencing The Effectiveness (2)
Local factor-pus, hemoglobin in infected
hematoma, pH, anaerobic, vascular supply
- the presence of foreign body
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
Disanvantages of combinations of antimicrobial agents
Risk of toxicityThe selection of multiple-drug resitantIncreased costAntagonism effect
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
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
Misuses of antibiotics
Treatment of untreatable infectionTherapy of fever of unknown originImproper dosageInappropriate reliance on chemotherapy aloneLack of adequate bacteriological information