Mechanism of action of different classes of antibiotics

Antibiotic Grouping By Mechanism

Cell Wall Synthesis PenicillinsCephalosporins

VancomycinBeta-lactamase Inhibitors

CarbapenemsAztreonamPolymycinBacitracin

Protein Synthesis Inhibitors Inhibit 30s SubunitAminoglycosides (gentamicin)

TetracyclinesInhibit 50s Subunit

MacrolidesChloramphenicol

ClindamycinLinezolid

Streptogramins

DNA Synthesis Inhibitors Fluoroquinolones Metronidazole

RNA synthesis Inhibitors Rifampin

Mycolic Acid synthesis inhibitors

Isoniazid

Folic Acid synthesis inhibitors SulfonamidesTrimethoprim

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.

PenicillinsCephalosporinsVancomycinBeta-lactamase InhibitorsCarbapenemsAztreonamPolymycinBacitracin

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 Drugs Indications Toxicity

Penicillin Penicillin GAqueous penicillin GProcaine penicillin G

Benzathine penicillin GPenicillin V

Strep. pyogenes (Grp.A)Step. agalactiae (Grp.B)

C. perfringens(Bacilli)

Hypersensitivity reaction

Hemolytic anemia

Aminopenicillins AmpicillinAmoxicillin

Above + ↑ Gram-negative:

E. faecalisE. Coli

Above

Penicillinase-resistant-penicillins

MethicillinNafcillinOxacillin

CloxacillinDicloxacillin

Above +PCNase-producing

Staph. aureus

Above + Interstitial nephritis

Antipseudomonal penicillins

CarbenicillinTicarcillin

Piperacillin

Above +Pseudomonas

aeruginosa

Above

Cephalosporins(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the

transpeptidase enzyme)

1st generation CefazolinCephalexin

Staph. aureusStaph. epidermidis

Some Gram-negatives:

E. ColiKlebsiella

Allergic reactionCoombs-positive

anemia (3%)

2nd generation CefoxitinCefaclor

Cefuroxime

Above +↑ Gram-negative

Allergic ReactionETOH Disulfiram

reaction

3rd generation CeftriaxoneCefotaximeCeftazidime

Cefepime (4th generation)

Above +↑ Gram-negative

Pseudomonas

Allergic ReactionETOH Disulfiram

reaction

Other Cell Wall Inhibitors

Vancomycin (bactericidal:

disrupts peptioglycan cross-linkage)

Vancomycin MRSAS. aureus

S. epidermidis

Red man syndrome

NephrotoxicityOtotoxicity

Beta-lactamase Inhibitors

(bactericidal: blocking cross

linking)

Clavulanic AcidSulbactam

Tazobactam

S aureusS epidermis

E.ColiKlebsiella

Hypersensitivity Reaction

Hemolytic anemia

Carbapenems Imipenem (+ cilastatin)

MeropenemDoripenemErtapenem

Broadest activity of any antibiotic(except MRSA, Mycoplasma)

Other Cell Wall InhibitorsAztreonam Aztreonam Gram-negative rods

AerobesHospital-acquired

infections

Polymyxins Polymyxin BPolymyxin E

Topical Gram-negative infections

Bacitracin Bacitracin Topical Gram-positive 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 SubunitAminoglycosides (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 SubunitMacrolidesChloramphenicolClindamycinLinezolid Streptogramins

Anti-30S ribosomal subunit

Aminoglycosides(bactericidal:

irreversible binding to 30S)

GentamicinNeomycinAmikacin

TobramycinStreptomycin

Aerobic Gram-negatives

Enterobacteriaceae Pseudomonas

NephrotoxicityOtotoxicity

Tetracyclines(bacteriostatic:

blocks tRNA)

TetracyclineDoxycyclineMinocycline

Demeclocycline

RickettsiaMycoplasma

Spirochetes (Lyme's disease)

HepatotoxicityTooth discoloration

Impaired growthAvoid in children < 12

years of age

Anti-50S ribosomal subunitMacrolides

(bacteriostatic: reversibly binds 50S)

ErythromycinAzithromycin

Clarithromycin

StreptococcusH. influenzaeMycoplamsa pneumonia

Coumadin Interaction (cytochrome P450)

Chloramphenicol(bacteriostatic)

Chloramphenicol H influenzaeBacterial Meningitis

Brain absces

Aplastic AnemiaGray Baby Syndrome

Lincosamide(bacteriostatic:

inhibits peptidyl transferase by

interfering with amino acyl-tRNA

complex)

Clindamycin Bacteroides fragilisS aureus

Coagulase-negative Staph & StrepExcellent Bone

Penetration

Pseudomembranous colitis

Hypersensitivity Reaction

Linezolid(variable)

Linezolid Resistant Gram-positives

Streptogramins QuinupristinDalfopristin

VREGAS and S. aureus

skin infections

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 SteptococcusMycoplasma

Aerobic Gram +

PhototoxicityAchilles tendon

ruptureImpaired fracture

healing

2nd generation CiprofloxacinNorfloxacin

EnoxacinOfloxacin

Levofloxacin

As Above +Pseudomonas

as above

3rd generation Gatifloxacin As above + Gram-positives

as above

4th generation MoxifloxacinGemifloxacin

As above + Gram-positives + anaerobes

as above

Other DNA Inhibitors

Metronidazole(bacteridical:

metabolic biproducts disrupt

DNA)

Metronidazole (Flagyl)

Anaerobics SeizuresCrebelar

dysfunctionETOH disulfram

reaction

Antibiotic Grouping By Mechanism

RNA synthesis inhibitor

Binds to the β 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 StaphylococcusMycobacterium (T

B)

Body fluid discolorationHepatoxicity

(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.

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

Isoniazid

Mycolic Acids Synthesis Inhibitors

Isoniazid Isoniazid TBLatent 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

SulfonamidesDihydropteroate Synthetase

Dihydropteroic Acid

Folic acid Synthesis Inhibitors

Trimethoprim/Sulfonamides(bacteriostatic: inhibition with

PABA)

Trimethoprim/Sulfamethoxazole

(SMX)SulfisoxazoleSulfadiazine

UTI organismsProteus

Enterobacter

ThrombocytopeniaAvoid in third trimester of pregnancy

Pyrimethamine Pyrimethamine MalariaT. gondii