Mechanism of action of different classes of antibiotics

Antibiotic Grouping By Mechanism Cell Wall Synthesis Penicillins Cephalosporins Vancomycin Beta-lactamase Inhibitors Carbapenems Aztreonam Polymycin Bacitracin Inhibit 30s Subunit Aminoglycosides (gentamicin) Tetracyclines Inhibit 50s Subunit Macrolides Chloramphenicol Clindamycin Linezolid Streptogramins

Protein Synthesis Inhibitors

DNA Synthesis Inhibitors RNA synthesis Inhibitors Mycolic Acid synthesis inhibitors Folic Acid synthesis inhibitors

Fluoroquinolones Metronidazole Rifampin Isoniazid

Sulfonamides Trimethoprim

Antibiotic Grouping By Mechanism Cell wall synthesis inhibitor inhibits the synthesis of the peptidoglycan layer of bacterial cell walls. Peptidoglycan is important for cell wall structural integrity, especially in Gram-positive organisms, being the outermost and primary component of the wall. Penicillins Cephalosporins Vancomycin Beta-lactamase Inhibitors Carbapenems Aztreonam Polymycin Bacitracin

Penicillins (bactericidal: blocks cross linking via competitive inhibition of the transpeptidase enzyme that cross-links the peptidoglycan chains to form rigid cell walls)
Class/Mechanism Penicillin Drugs Indications Penicillin G Strep. pyogenes (Grp.A) Aqueous penicillin G Step. agalactiae (Grp.B) Procaine penicillin G C. perfringens(Bacilli) Benzathine penicillin G Penicillin V Ampicillin Amoxicillin Above + Gram-negative: E. faecalis E. Coli Above + PCNase-producing Staph. aureus Toxicity Hypersensitivity reaction Hemolytic anemia

Aminopenicillins

Above

Penicillinase-resistantpenicillins

Antipseudomonal penicillins

Methicillin Nafcillin Oxacillin Cloxacillin Dicloxacillin Carbenicillin Ticarcillin Piperacillin

Above + Interstitial nephritis

Above + Pseudomonas aeruginosa

Above

Cephalosporins (bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme) 1st generation Cefazolin Staph. aureus Allergic reaction Cephalexin Staph. epidermidis Coombs-positive Some Gramanemia (3%) negatives: E. Coli Klebsiella 2nd generation Cefoxitin Cefaclor Cefuroxime Ceftriaxone Cefotaxime Ceftazidime Cefepime (4th generation) Above + Gram-negative Allergic Reaction ETOH Disulfiram reaction Allergic Reaction ETOH Disulfiram reaction

3rd generation

Above + Gram-negative Pseudomonas

Other Cell Wall Inhibitors Vancomycin (bactericidal: disrupts peptioglycan cross-linkage) Beta-lactamase Inhibitors (bactericidal: blocking cross linking) Carbapenems Vancomycin MRSA S. aureus S. epidermidis Red man syndrome Nephrotoxicity Ototoxicity Hypersensitivity Reaction Hemolytic anemia

Clavulanic Acid Sulbactam Tazobactam

S aureus S epidermis E.Coli Klebsiella

Imipenem (+ cilastatin) Meropenem Doripenem Ertapenem

Broadest activity of any antibiotic (except MRSA, Mycoplasma)

Aztreonam

Other Cell Wall Inhibitors Aztreonam Gram-negative rods Aerobes Hospital-acquired infections

Polymyxins
Bacitracin

Polymyxin B Polymyxin E
Bacitracin

Topical Gramnegative infections

Topical Grampositive infections

Antibiotic Grouping By Mechanism Protein Synthesis Inhibitors 30s subunit inhibitor Binding to the bacterial 30S ribosomal subunit inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth Inhibit 30s Subunit Aminoglycosides (gentamicin) Tetracyclines

Antibiotic Grouping By Mechanism Protein Synthesis Inhibitors 50s subunit inhibitor inhibition of bacterial protein biosynthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl tRNA. Inhibit 50s Subunit Macrolides Chloramphenicol Clindamycin Linezolid Streptogramins

Anti-30S ribosomal subunit Aminoglycosides (bactericidal: irreversible binding to 30S) Tetracyclines (bacteriostatic: blocks tRNA) Gentamicin Neomycin Amikacin Tobramycin Streptomycin Tetracycline Doxycycline Minocycline Demeclocycline Aerobic Gramnegatives Enterobacteriaceae Pseudomonas Rickettsia Mycoplasma Spirochetes (Lyme's disease) Nephrotoxicity Ototoxicity

Hepatotoxicity Tooth discoloration Impaired growth Avoid in children < 12 years of age

Macrolides (bacteriostatic: reversibly binds 50S)

Anti-50S ribosomal subunit Erythromycin Streptococcus Azithromycin H. influenzae Clarithromycin Mycoplamsa pneumonia Chloramphenicol H influenzae Bacterial Meningitis Brain absces Bacteroides fragilis S aureus Coagulase-negative Staph & Strep Excellent Bone Penetration Resistant Grampositives VRE GAS and S. aureus skin infections

Coumadin Interaction (cytochrome P450)

Chloramphenicol (bacteriostatic) Lincosamide (bacteriostatic: inhibits peptidyl transferase by interfering with amino acyl-tRNA complex) Linezolid (variable) Streptogramins

Aplastic Anemia Gray Baby Syndrome Pseudomembranous colitis Hypersensitivity Reaction

Clindamycin

Linezolid Quinupristin Dalfopristin

Antibiotic Grouping By Mechanism DNA synthesis inhibitor inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme leads to DNA fragmentation via the nucleasic activity of the intact enzyme domains inhibiting DNA replication and transcription. Fluoroquinolones Metronidazole

Fluoroquinolones (bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis)

1st generation

Nalidixic acid

Steptococcus Mycoplasma Aerobic Gram +

Phototoxicity Achilles tendon rupture Impaired fracture healing

as above

2nd generation

3rd generation

Ciprofloxacin Norfloxacin Enoxacin Ofloxacin Levofloxacin Gatifloxacin

As Above +Pseudomonas

As above + Grampositives
As above + Grampositives + anaerobes

as above

4th generation

Moxifloxacin Gemifloxacin

as above

Other DNA Inhibitors Metronidazole (bacteridical: metabolic biproducts disrupt DNA) Metronidazole (Flagyl) Anaerobics Seizures Crebelar dysfunction ETOH disulfram reaction

Antibiotic Grouping By Mechanism RNA synthesis inhibitor Binds to the subunit of RNA polymerase to inhibit transcription blocks RNA synthesis by physically preventing extension of RNA products beyond a length of 2-3 nucleotides ("steric-occlusion" mechanism) Rifampin

RNA Synthesis Inhibitors Rifampin (bactericidal: inhibits RNA transcription by inhibiting RNA polymerase) Rifampin Staphylococcus Mycobacterium (T B) Body fluid discoloration Hepatoxicity (with INH)

Antibiotic Grouping By Mechanism Mycolic acid synthesis inhibitor prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Isoniazid

Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall.
Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis

Mycolic Acids Synthesis Inhibitors

Isoniazid Isoniazid TB Latent TB

Mechanism Of Action (Folic acid synthesis inhibitor)

Competitive antagonists of PABA ( para-aminobenzoic acid). Hence they interfere and prevent the normal utilization of PABA for the synthesis of Folic Acid (Pteroylglutamic Acid). More Specific: Pteridine + PABA

Dihydropteroate Synthetase

Sulfonamides

Dihydropteroic Acid

Folic acid Synthesis Inhibitors Trimethoprim/Sulf onamides (bacteriostatic: inhibition with PABA) Trimethoprim/Sulfa methoxazole (SMX) Sulfisoxazole Sulfadiazine UTI organisms Proteus Enterobacter Thrombocytopenia Avoid in third trimester of pregnancy

Pyrimethamine

Pyrimethamine

Malaria T. gondii