BACTERIAL RESISTANCE TO ANTOMICROBIAL AGENTS:

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A brief introduction of certain factore

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BACTERIAL RESISTANCE TO ANTOMICROBIAL AGENTS:

Dr. Asad Ali Azeemi BACTERIAL RESISTANCE TO ANTOMICROBIAL AGENTS

…….RESISTANCE cont…..:

…….RESISTANCE cont….. Microbes such as bacteria, viruses, fungi and parasites are living organisms that evolve over time. Adapt to their environment and change in a way that ensures their survival. Increasing use of these antimicrobials has led to the development of strains which are unresponsive to the therapeutic effects of these antimicrobials.

Definition:

Definition RESISTANCE IS THE ABILITY OF A MICROBE TO GROW IN THE PRESENCE OF THE DRUG THAT WOULD NORMALLY KILL OR LIMIT THE GROWTH OF THAT MICROBE.

CAUSES::

CAUSES: 1. NATURAL (BIOLOGICAL )CAUSES: A) MUTATIONS. B)TRANSDUCTION. C) TRANSFORMATION. D) CONJUGATION.

……CAUSES::

……CAUSES: 2. SOCIAL CAUSES: A) INAPPROPRIATE USE. B) INADEQUATE DIAGNOSTICS. C) HOSPITAL USE.

…..RESISTANCE:

…..RESISTANCE For an antibiotic to be effective, it must reach its target, bind to it, and interfere with its functions.

…..RESISTANCE:

…..RESISTANCE Bacterial resistance to an antibiotic falls into three general categories:- A) THE DRUG DOES NOT REACH ITS TARGET. B) THE DRUG IS NOT ACTIVE. C) THE TARGET IS ALTERED.

……RESISTANCE:

……RESISTANCE Absence of, mutation in, or loss of appropriate porin channel can slow the rate of drug entry altogether. If the target is intracellular and the drug requires active transport across the cell membrane, a mutation or environmental condition that shuts down this transport mechanism can confer resistance. e.g. resistance in case of Gentamycin .

…..RESISTANCE:

…..RESISTANCE . Bacteria also have efflux pumps that may transport drugs out of the cell. e. g resistance to Tetracyclines and β - lactum antibiotics.

…..RESISTANCE:

…..RESISTANCE INACTIVATION is the second general mechanism of resistance. e. g resistance to Aminoglycosides and β - lactum antibiotics often is due to the production of aminoglycoside modifying enzymes and β lactamase respectively. A variation of this mechanism is failure of the bacterial wall to convert an inactive drug to its active metabolite. e. g resistance of Mycobacterium Tuberculosis to Isoniazid .

…..RESISTANCE:

…..RESISTANCE Alteration of the target may be due to :- Mutation of the natural target ( Floroquinolone resistance). Target Modification (ribosomal protection type of resistance to Macrolides and Tetracycline). Substitution with a resistant alternative to the native , susceptible target ( Methicilin resistance in staphylococci).

…..RESISTANCE:

…..RESISTANCE Resistance may be acquired by mutation and selection , with the passage of trait vertically to daughter cells. e.g resistance to streptomycin (ribosomal mutation), quinolones ( gyrase gene mutation), and rifampicin (RNA polymerase mutation).

…..RESISTANCE:

…..RESISTANCE More commonly, it is acquired by:- HORIZONTAL TRANSFER of resistance determinants from a donor cell, often of another bacterial species by TRANSDUCTION (particularly important in the transfer of resistance among strains of S.aureus , where some phages carry PLASMIDS-autonomously replicating pieces of extra chromosomal DNA-that code for penicillamase , while others TRANSFER GENES encoding resistance to Erythromycin, Tetracyclines and Chloramphenicol ), TRANSFORMATION (molecular basis of Penecillin resistance in Pneumococci and Neisseria ), or CONJUGATION (passage of genes from cell to cell by direct contact through a sex pilus or bridge. e. g Vancomycin resistance in case of enterococci ).

PREVENTION OF RESISTANCE:

PREVENTION OF RESISTANCE Doctors should have clear understanding of signs & symptoms of disease, so he may prescribe appropriate medicine. Doctor and patient should discuss appropriate medication of the illness and avoid overusing or misusing medicines.

……PREVENTION:

……PREVENTION Patient should strictly follow prescription medications & never share or take medications prescribed for someone else. Patients should not keep the medicine with them after they get cure (so that they may not start their medications by themselves).

CHIOCE OF ANTIMICROBIAL AGENT:-:

CHIOCE OF ANTIMICROBIAL AGENT:- It depends upon HOST FACTORS:- 1) Concomitant disease states e. g AIDS, severe chronic liver failure. 2) Prior adverse drug effects. 3) Impaired elimination or detoxification of the drug (this may be genetically predetermined but more frequently is associated with impaired hepatic or renal functions due to underlying disease). 4) Age of the patient. 5) Pregnancy status.

PHARMACOLOGIC FACTORS:-:

PHARMACOLOGIC FACTORS:- 1) The kinetics of absorption, distribution and elimination. 2) The ability of the drug to be delivered to the site of action. 3) The potential toxicity of an agent. 4) Pharmacokinetic or pharmacodynamic interactions with other drugs.

….Antimicrobial agents:

…. Antimicrobial agents Knowledge of susceptibility of an organism to a specific agent in a hospital or community settings is important in the selection of empirical therapy.

…..Antimicrobial agents:

…..Antimicrobial agents Pharmacokinetic differences among agents with similar antimicrobial spectrums may be exploited to reduce the frequency of dosing.

…..Antimicrobial agents:

…..Antimicrobial agents Lastly, increasing concentration is being given to the cost of antimicrobial therapy, especially when multiple agents with comparable efficacy and toxicity are available for a specific infection.

THANK YOU:

Cirin pharmaceuticals (PVT) ltd . THANK YOU

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