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Antibiotic Classification & Mechanism

Bacterial Overview

Antibiotic Resistance Mechanisms

Bacteria develop ability to hydrolyze these drugs using lactamase


o confers resistance to penicillin
o e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella
pneumoniae
o add lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate
(Augmentin)

Genetic mutation of mecA


o a bacterial gene encoding a penicillin-binding protein. New PBP has reduced
affinity for antibiotics
o confers resistance to methicillin, oxacillin, nafcillin
o e.g. MRSA

Altered cell wall permeability


o confers resistance to tetracyclines, quinolones, trimethoprim and lactam
antibiotics

Creation of biofilm barrier

o provides an environment where offending bacteria can multiply safe from the

hoste immune system

Salmonella

Staph epidermidis

Active efflux pumps


o confers resistance to erythromycin and tetracycline
o e.g. msrA gene in Staph

Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide)


o confers resistance to vancomycin
o e.g. vancomycin resistant enterococcus (VRE)

Ribosome alteration
o erm gene confer inducible resistance to MLS (macrolide lincosamide
streptogranin) agents via methylation of 23s rRNA
o demonstrate using D zone test

for inducible clindamycin resistance in Staph and beta hemolytic Strep

Penicillins

Mechanism
o interfer with bacterial cell wall synthesis

Subclassification and tested examples


o natural

penicillin G

o penicillinase-resistant

methicillin (Staphcillin)

o aminopenicillins

ampicillin (Omnipen, Polycillin)

Cephalosporins

Overview
o bactericidal

Mechanism
o disrupts the synthesis of the peptidoglycan layer of bacterial cell walls

does so through competitive inhibition on PCB (penicllin binding


proteins)

peptidoglycan layer is important for cell wall structural integrity.

o same mechanicsm of action as beta-lactam antibiotics (such as penicillins)

Subclassification and tested examples


o first generation

cefazolin (Ancef, Kefzol)

o second generation

cefaclor (Ceclor)

o third generation

cefriazone (Rocephin)

o fourth generation

cefepime (Maxipime)

Fluoroquinolones

Mechanism
o blocks DNA replication via inhibition of DNA gyrase

Side effects
o inhibit early fracture healing through toxic effects on chondrocytes
o increased rates of tendinitis, with special predilection for the Achilles tendon.

tenocytes in the Achilles tendon have exhibited degenerative changes


when viewed microscopically after fluoroquinolone administration.

recent clinical studies have shown an increased relative risk of Achilles


tendon rupture of 3.7.

Subclassification and tested examples


o ciprofloxacin (Cipro)
o levofloxacin (Levaquin)

Aminoglycosides

Mechanism
o bactericidal
o inhibition of bacterial protein synthesis

work by binding to the 30s ribosome subunit, leading to the misreading


of mRNA. This misreading results in the synthesis of abnormal
peptides that accumulate intracellularly and eventually lead to cell
death. These antibiotics arebactericidal.

Subclassification and tested examples

o gentamicin (Garamycin)
Vancomycin

Coverage
o gram-positive bacteria

Mechanism
o bactericidal
o an inhibitor of cell wall synthesis

Resistance
o increasing emergence of vancomycin-resistant enterococci has resulted in the
development of guidelines for use by the (CDC)

o indications for vancomycin

serious allergies to penicillins or beta-lactam antimicrobials

serious infections caused by


to penicillins (MRSA, MRSE)

surgical prophylaxis for major procedures involving implantation


of prostheses in institutions with a high rate of MRSA or MRSE

susceptible

organisms

resistant

Rifampin

Most effective against intracellular phagocytized Staphylococcus aureus in


macrophages
Linezolid

Linezolid binds to the 23S portion of the 50S subunit and acts by preventing the
formation of the initiation complex between the the 30S and 50S subunits of the
ribosome.
Splenectomy

Splenectomy patients or patients with functional hyposplenism require the following


vaccines and/or antibiotics
o Pneumococcal immunization
o Haemophilus influenza type B vaccine
o Meningococcal group C conjugate vaccine
o Influenza immunization
o Lifelong prophylactic
erythromycin)

antibiotics

(oral

phenoxymethylpenicillin

or