Classification of Antibiotics by Target site of activity:

1. Inhibitors of cell wall synthesis

Beta - lactam:

• Penicillins

• Cephalosporins

1st generation ( cephalexin ) has good G positive cover.
2nd generation ( Cefoxitin ) has good G negative and anaerobic cover.
3rd generation ( Ceftriaxone, Cefotaxime and Ceftazidime ) has good G negative cover.
4th generation ( Cefepime ) has good cover for both G positive and negative cover.

• Carbapenem - imipenem, meropenem and ertapenem

Imipenem and meropenem are essentially the same as giving combination of ampicillin, flucloxacillin, gentamycin and metronidazole. However, they don't cover Stenotrophomonas and E. faecium.
Ertapenem does not cover Pseudomonas and Acinectobacteria
Can be used in renal failure.

• Monobactam - Aztreonam

Aztreonam has the same antibiotics spectrum as gentamycin but it does not have renal toxicity.

Glycopeptides:

• Vancomycin

• Teicoplanin

Others:

• Cycloserine

• Bacitracin

2. Inhibition of protein synthesis

30s ribosomal subunit:

• Aminoglycosides

• Tetracycline

50s ribosomal subunit:

• Chloramphenicol

• Clindamycin

• Macrolides

• Fusidic Acid

3. Inhibition of nucleic acid synthesis

Block folic acid synthesis:

• Trimethoprim

• Sulphonamides

DNA Gyrase inhibition:

• Fluoroquinolones - Norfloxacin, Ciprofloxacin, Moxifloxacin, Gatifloxacin.

Covers G negative aerobic including Legionella
Only ORAL antibiotics which cover Pseudomonas
Cipro has poor G positive cover
Moxi and Gati have good G positive cover but slightly less G negative cover than Cipro
Cipro has poor anaerobic cover but Moxi and Gati has better anaerobic cover.

RNA polymerase inhibiton:

• Rifamycin e.g., Rifampicin

4. Inhibition of cell membrane function e.g., Colistin.

5. Newer antibiotics:

• Quinupristin - dalfopristin
• Linezolid - only ORAL antibiotics that cover Vancomycin resistant MRSA ( VRSA )
• Daptomycin
• Tigecycline - affect G positive ( including VISA, VRSA, MRSA, PRSP ), G negative and anaerobes but it does not cover Proteus mirabilis, Pseudomonas aeruginosa and Burholderia cepacia.

Mechanism of Antibiotics Resistance:

Four broad categories of resistance mechanism

1. Antibiotics Inactivation
2. Alteration in antibiotics target sites
3. Decreased antibiotics permeability of the cell wall preventing drug access to its target
4. Active antibiotics efflux from the bacteria

Antibiotics Inactivation

A. Beta lactamases: can be inhibited by clavulanic acid, tazobactam and sulbactam.

B. Inducible chromosomally mediated beta - lactamase production:

• Inactivate third generation cephalosporins.
• In particular, organisms which demonstrate this important form of Beta lactamase productions are ' ESCAAPPM ' -do not treat with penicillins or cephalosporins
  

• E - Enterobacter species
• S - Serratia species
• C - Citrobacter
• A - Acinectobacter
• A - Aeromonas
• P - Proteus
• P - Providentia
• M - Morganella morganii

C. Aminoglycoside modifying enzymes

D. Others - ESBL ( extended spectrum beta lactamase )

• now being common in large hospital.
• inactivate all cephalsporins.
• Klebsiella pneumoniae and E. coli are the usual organism to harbour ESBLs.
• Treatment is with meropenum or cotrimoxazole.

E. MBL - Metallobetalamase