Mechanisms of antimicrobial action
- Lyse cell membrane
- Inactivate microbe
- Inhibit cell wall synthesis
- Inhibit microbial ribosome
- Inhibit enzymes required form nucleoside/DNA synthesis
- Inhibit machinery of viral replication
Bacteriostatic
Stop or slow bacterial growth, need immune system to finish off the microbe.
Bactericidal
Results in bacterial death
Mechanisms of resistance
- Decrease penetration of antibiotic – eg biofilm
- Increase efflux with pumps
- Alter site of action
- Develop an enzyme to breakdown the antibiotic
Penicillins:
- Bacteriocidal
- Beta lactam antibiotic
- All have beta lactam ring that binds to D-ala- D ala of PBP and intefere with transpeptidation of bacterial cell wall
- Cell lyse as a result
- Only kills when the cells are growing and synthesising cell wall
- Natural Penicillins e.g. Benzylpenicillin
- GP org and GNC
- No GN bacilli cover
- Susceptible to beta lactamase
- Semi-synthetic Penicillins e.g. Flucloxacillin, Dicloxacillin
- Resistant to staph B lactamase
- Effective against staph and strep
- No effect on enterococci, anaerobic bacteria or GN Bacteria
- Extended-spectrum Penicillins e.g. Amoxycillin / Ampicillin. Ticarcillin. Piperacillin.
- Antipseudomonal
- GP and Gn coverage
- Susceptible to beta lactamase
- Side Effects – allergy
Cephalosporins:
Also beta lactam containing but less susceptible to beta lactamase
| First | Second | Third | Fourth |
|---|---|---|---|
| Cephazolin,
cephalexin |
Cefaclor,
cefotetan |
Ceftriaxone | Cefepime |
| GP cocci, no pseudomonas cover | Anaerobes, some GN, GP, no pseudomonas cover | GP and expanded GN cover, cross BBB, effective against some b lactamase strains not all. | Good pseudomonas cover, can be hydrolysed by extended spectrum B lactamase, penetrates well into csf |
- Renally cleared
- SE – allergy, cross allergenicity with penicillins 5-10%, local irritation after injection, disulfiram like effect with some. Renal toxicity/nephritis/ATN.
- Clavulanic acid is a beta lactamase inhibitor.
- Carbapenams – eg meropenam – structurally related to B lactam. Good activity against GN rods, GP and anaerobes. Resistant to most Beta lactamases.
Vancomycin.
- bacteriocidal
- For gram positive bacteria esp staph (methicillin resistant staph)
- Watersoluble, needs parenteral administration.
- Inhibits cell wall synthesis by binding to D-ala D-Ala terminus and prevents further elongation at the site and therefore prevents peptidoglycan cross linking.
- Oral vanc used for clostridium difficile
- SE – phlebitis at site of injection, red man syndrome (flushing due to histamine release)
Tetracyclines
- Bacteriostatic
- GP, GN, anaerobes, chlamydia, mycoplasma, rickettsia
- Enter partly by diffusion and partly by active transport. Bind reversibly to 30S subunit of ribosome preventing ongoing growth of the peptide.
- Resistance is mediated by efflux pump, impaired entry, proteins intefering with binding at ribosome, enzymatic inactivation.
- Doxycycline not renally excreted.
- SE – crosses placenta, chelates with calcium so deposits in teeth and growing bones. Nausea, vomiting, diarrhoea, photosensitivity, renal toxicity.
- Metabolised in liver and excreted in mainly bile and urine.
Macrolides.
- All contain macrocyclic ring.
- Bacteriostatic, bacteriocidal at high concetration
- Pneumonia, diptheria, chlamydial, ocular infections.
- Good substitute for penicillin.
- Bind to 50S ribosome and blocks aminoacyl translocation. Covers gram positive and negative organism.
- Erythromycin. Roxithromycin. Clarithromycin Azithromycin
- SE – annorexia, nausea, vomiting, diarrhoea, hepatic toxicity/hepatitis, inhibits cytP450 so results in drug interactions.
Chloramphenicol
- Bacteriostatic – aerobic and anaerobic GP and GN organisms.
- Binds reversibly to bacterial 50S ribosome and inteferes with protein synthesis
- Hepatic metabolism, renally excreted