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