Anti-microbial
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| Antimicrobial agents: | used for the treatment of infectious diseases caused by infective organisms
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| Antibiotics : | Are substances produced by MO or obtained from chemicals
→ which kill/destroy OR suppress the growth of other
microorganisms
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| Minimum inhibitory concentration (MIC): | The lowest concentration of AMAs to inhibit/prevents the multiplication of MO
-no visible growth of MO after 24-48 hrs of incubation
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| Concentration-dependent antibiotics : | thier optimum activity associated with peak concentrations → kill bacteria at a greater rate & to a greater extent with ↑ antibiotic concentrations
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| Time-dependent antibiotics: | with optimum activity associated with time of drug concentration above the MIC → kill bacteria at the same rate & to the same extent once an appropriate threshold concentration has been achieved
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| Post-antibiotic effect: | the period of time that bacterial growth remain inhibited after exposure to AB & removal of AB
-even after their plasma concentration falls below MIC
→ Aminoglycosides & Quinolones
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| Selective toxicity | Deleterious actions possessed by a drug effects directed against the target pathogenic cells without comparable effects on the host healthy tissues
→ most antiviral & anti-neoplastic drug & anti-metabolite drugs
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| AMA inhibit protein synthesis by | - misreading of m-RNA code
- insertion of incorrect amino-acid,
- inhibit tRNA attachment to the ‘A’ site,
- interferes with peptide-bond formation
- inhibit translocation of the elongated peptide-chain from ‘A’ site to ‘P’ site
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| the range of their antimicrobial activity | Narrow-spectrum →as Penicillin G
Extended-spectrum→as Ampicillin
Broad-spectrum →Carbapenem
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| Superinfections: (secondary infection) | appearance of new infection during therapy of the primary infection
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| -Superinfection can be minimized by : | -Using specific/narrow-spectrum AMA
-Avoiding unnecessary use of AMA
-Oral supplement use of probiotics e.g Lactobacillus
---- to restore ecological order in the gut
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| Drug resistance: | -the unresponsiveness of MO to AMA
-This resistance may be natural or acquired
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| Natural / intrinsic/inherent resistance: | --genetically the organisms have never responded to the antimicrobial therapy.
-always been resistant
due to- absence of the particular enzyme
-absence of the target site affected by the drug
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| Acquired resistance: | -organisms that are initially sensitive or respond to AMA at the beginning
later → become resistant
-may be developed by mutation or gene transfer
-is a major clinical problem
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| Mutation | -A random chromosomal genetic mutation that occurs spontaneously in a place that controls susceptibility to AMA
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| Transfer | -Extra-chromosomal genetic material→ transfer of genetic material containing antibiotic-resistance→ by plasmid-mediated conjugation
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| -Plasmid | -piece of extra-chromosomal DNA that carry genes coding for resistance “R-factor”
-plasmid-mediated resistance is the most important mechanism clinically as it can spreads / transferred easily among bacteria
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| Transfer takes place & occurs by :: | Transduction
Conjugation
Transformation
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| Transduction | -Is the transfer of plasmid DNA from one bacteria to another through bacteriophage “virus that infects bacteria”
-e.g: transfer of drug-resistance among the strains of Staph. aureus
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| Conjugation: | -Is the direct cell-to-cell transfer of extrachromosomal genetic material (plasmids / R-factor) between bacteria during mating by direct contact bridge
e.g: Enterococcal species
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| Transformation | Is the transfer of genetic material (R-factor) that released from resistant-bacteria into the medium through naked DNA which taken up by other sensitive bacteria
e.g: Penicillin-resistance in pneumococci
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| Cross-resistance: | When MO develops resistance to one drug → it’s also show resistance to other drugs.
-Share a MOA or a similar mode of binding site of action
-Share the same group or family (closely-chemically related drugs)
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| To minimize the emergence of resistance | - Only use AB when they are clearly indicated
- Use narrow-spectrum AB
- Use effective dose & adequate duration of AB
- Use older chemotherapeutic drugs whenever possible
- Use Multiple-Drugs combination Therapy (MDT)
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