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
