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Antibiotics (anti-microbials)
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Introduction Antibiotics = a natural substance produced by a micro-organism to kill another Antiinfectives/Anti-microbrial = any agent (natural or synthetic) that kills pathogens (microbes)
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Overview Antibiotics are a large and diverse group of drugs which combat infections by suppressing the growth and reproduction of bacteria. However, many bacteria are now resistant to antibiotics and some are resistant to all known agents. New drugs are continually being introduced to combat evolving patterns of resistance.
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Antibiotics exploit the differences between bacterial and cells.
They prevent the renewal of the bacterial cell wall and inhibit protein formation. Note: bacteria are 'gram negative' or 'gram positive'. Gram negative bacteria have a tough wall
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Classification Bacteriostatic (inhibit growth without death) or Bactericidial (Kill) Dosage related? Mechanism of action: Spectrum of Activity: Broad or Narrow Chemical Structure
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Bacteriostatic and Bactericidal
Bacteriostatic allows for natural immunity to deal with the microbe Antibodies, Phagocytosis etc Bactericidial may lead to release of toxins and microbial contents leading to subsequent illness and inflammatory responses.
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Spectrum of Activity Relates to the number of microbes that are susceptible to the action of the drug Narrow (limited number) / Broad (wide) Penicillin G is a narrow spectrum drug as it is only effective against gram-positive microbe Tetracyclines are effective against gram-positive and gram-negative microbes (Broad) Note: Never confusion these terms with potency levels of the drugs or efficacy (ie. Narrow are weak, Broad are strong)
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Inhibition of Cell Wall Synthesis
Most bacteria possess a cell wall to protect from osmotic pressures Microbe divides – needs to create a new cell wall Interrupt this leads to new microbes being susceptible to external influences Cell ruptures Microbe death Eg. Penicillinsm cephalosporins, vancomycin and bacitracin
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Inhibition of Protein Synthesis
Proteins vital for growth and repair Act either at: Site of protein synthesis (ribosome) Within the nucleus by inhibiting synthesis of nucleic acids DNA replication / RNA synthesis = TRANSCRIPTION Eg. Tetracyclines, aminoglycosides and macrolides (erythromycin) Exploit structural differences between microbial and human cells High dose can lead to toxicity
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Table 1 Summary of some common antibiotics
Beta-lactams (penicillins, cephalosporins) Broad-spectrum antibiotics*. Flucloxacillin and co-amoxiclav are effective against some penicillin-resistant organisms. Aminoglycosides (streptomycin, gentamicin, tobramycin) Effective against gram negative bacteria e.g. Pseudomonas. Reserved for serious infections e.g. septicaemia, meningitis, hospital-acquired pneumonia. Glycopeptides (vancomycin, teicoplanin) Effective against Staphylococci resistant to other drugs, including many strains of MRSA**. Tetracyclines (doxycycline, minocycline) Broad-spectrum antibiotics
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Macrolides (erythromycin)
Broad-spectrum antibiotics, prescribed if patient is allergic to penicillins. Metronidazole Prescribed for surgical prophylaxis, bacterial vaginosis, pressure sores, leg ulcers. Quinolones (ciprofloxacin) Effective against gram negative bacteria, gonorrhoea, gastro-intestinal infections. Antitubercular drugs (rifampicin, isoniazid, rifabutin, streptomycin) Reserved for treatment/ containment of tuberculosis(TB). sulphonamides (co-trimoxazole, trimethoprin) Co-trimoxazole is reserved for serious infections associated with HIV/AIDS. Trimethoprin is prescribed for urinary tract infections. * Broad spectrum antibiotics are used when the infectious agent is unknown. Narrow spectrum antibiotics are prescribed when the micro-organisms have been identified from tissue samples. ** Many bacteria produce an enzyme which destroys beta lactam antibiotics. In addition to this, MRSA (methicilin-resistant Staphylococcus aureus) produces an inactivating protein which confers resistance to most other antibiotics.
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Susceptibility Testing Methods
Incubate plate 18-24 hr, 35 C Measure and record zone of inhibition around each disk Innoculate MH plate Place disks on agar plate
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Disk Diffusion Susceptibility Testing
Mueller Hinton agar & good disk placement Improper agar & disk placement Use Mueller Hinton agar
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Antibiotic sensitivity tests
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Antimicrobial susceptibility testing using micro-broth dilutions
ug/ml • 96 well microtiter plate
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Antimicrobial Gradient Testing E-test®
Read plates after recommended Incubation Read MIC where elipse intersects scale
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