Review antibiotic resistance mechanisms
Bacteria develop ability to hydrolyze these drugs using β lactamase
confers resistance to penicillin
e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae
add β lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin)
Genetic mutation of mecA
carried by Staphylococcal cassette chromosome (SCCmec) mobile genetic unit
a bacterial gene encoding a penicillin-binding protein (PBP2a).
PBP2a has reduced affinity for antibiotics
confers resistance to methicillin, oxacillin, nafcillin
SCCmec type IV has less genetic elements and is specific to CA-MRSA, making CA-MRSA less multi-drug resistant
Altered cell wall permeability
confers resistance to tetracyclines, quinolones, trimethoprim and β lactam antibiotics
Creation of biofilm barrier provides an environment where offending bacteria can multiply safe from the hoste immune system
Active efflux pumps
confers resistance to erythromycin and tetracycline
e.g. msrA gene in Staph
Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide)
confers resistance to vancomycin
e.g. vancomycin resistant enterococcus (VRE)
erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin) agents via methylation of 23s rRNA
demonstrate using D zone test
for inducible clindamycin resistance in Staph and beta hemolytic Strep
interferes with bacterial cell wall synthesis
Subclassification and tested examplesnatural
ampicillin (Omnipen, Polycillin)
blocks DNA replication via inhibition of DNA gyrase
inhibit early fracture healing through toxic effects on chondrocytes
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
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
an inhibitor of cell wall synthesis
increasing emergence of vancomycin-resistant enterococci has resulted in the development of guidelines for use by the (CDC)
indications for vancomycin
serious allergies to penicillins or beta-lactam antimicrobials
serious infections caused by susceptible organisms resistant to penicillins (MRSA, MRSE)
surgical prophylaxis for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE
Linezolid Mechanism of action
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 patients or patients with functional hyposplenism require the following vaccines and/or antibiotics
Haemophilus influenza type B vaccine
Meningococcal group C conjugate vaccine
Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)
antibiotic resistance examples
After the introduction of penicillins, bacteria developed the ability to hydrolyze these antibiotics using B-lactamase. In response, penicillinase-stable antibiotics were developed, the first of which was methicillin, since replaced with oxacillin and nafcillin. Drug resistance to this class of antibiotics is achieved via a genetic mutation of mecA encoding an altered penicillin binding protein. The gene product of this mutation, PBPa has a low affinity for these antibiotics and cannot be inhibited by them. Altering cell wall permeability is found in resistance to tetracyclines, quinolones, and trimethoprim, as well as B-lactam antibiotics. Biofilm barriers are produced by bacteria such as salmonella. Active efflux pumps provide resistance to erythromycin and tetracycline, and altering the peptidoglycan subunit is found in resistance to vancomycin.
antiobiotic mechanism of action overview
Antibiotics exert their effects via five basic mechanisms: (1) Inhibition of cell wall synthesis (cephalosporins, penicillins, vancomycin, imipenem). (2) Increasing cell membrane permeability (Bacitracin). (3) Ribosomal inhibition (gentamycin, erythromycins, linezolid, tetracyclines). (4) interference with DNA metabolism (quinolones), and (5) antimetabolite action (Trimethoprim).