Olah Antibiotics

Vancomycin MOA

inhibits cell wall biosynth, terminates D-Ala D-Ala so enzymes can’t build their cell wall

Vancomycin resistance

VanA converts D-Ala D-Ala to D-Ala D-Lac so vanco can’t bind

VISA increases cell wall thickness and overexpresses fake D-Ala D-Ala

Vancomycin toxicity

infusion reaction (histamine release, occurs with fast infusion), ototoxicity/nephrotoxicity

Dalbavancin MOA

interferes with bacterial cell wall synth., high affinity for D-Ala D-Ala

Telavancin MOA

binds to D-Ala D-Ala, rapid bactericidal activity

Telavancin toxicity

GI events, caution in pregnancy

Ortavancin MOA

binds D-Ala D-Ala peptide precursors

Ortavancin resistance

may depend on amounts of D-ala D-ala vs D-ala D-lac

Ortavancin toxicity

N/V/D

Linezolid MOA

binds to 50s on A-site, blocking aminoacyl tRNA

Linezolid resistance

target modification at rRNA binding sites (mutation, cfr resistance)

Linezolid toxicity

thrombocytopenia, serotonin syndrome

Tedizolid phosphate MOA

binds 50S subunit to aminoacyl tRNA (A-site)

Tedizolid phosphate toxicity

caution in neutropenic pts, weak MAOi activity

Clindamycin MOA

binds to PTC of 50s subunit to inhibit protein translation

Clindamycin Resistance

MLSb modifies target w/ methylation, mutations, enzyme-mediated nucleotidylation

Clindamycin toxicity

diarrhea, pseudomembranous colitis (C. diff in colon)

Metronidazole MOA

reactive form destroys nucleic acids and proteins

Metronidazole resistance

alterations in enzymes responsible for activation, induction of enzymes that inactivate the active form of drug

Metronidazole toxicity

disulfiram-like rxn (avoid alcohol), metallic taste, CNS AEs with long term use, may exacerbate furry tongue

Nitrofurantoin MOA

bacterial enzymes reduce the drug, producing reactive metabolites

Nitrofurantoin resistance

fairly uncommon

Nitrofurantoin toxicity

pulmonary toxicity 

Mupirocin MOA

binds/inhibits isoleucyl tRNA synthetaseM

Mupirocin resistance

mutation at tRNA synthetase and plasmid-mediated transfer

Daptomycin-lipopeptide MOA

inserts into bacterial cell membranes, forms a pore

Daptomycin-lipopeptide resistance

charge repulsion or upregulation of dlf gene in staph

Daptomycin-lipopeptide toxicity 

few ADRs, myopathy rare

Quinupristin/Dalfopristin MOA

binds to 50s subunit

Q inhibits EARLY stages of elongation

D inhibits LATE stages of elongation

Quinupristin/Dalfopristin resistance

Q has MLSb resistance, methylation in 50S typically due to ermB

Expression of efflux pumps, inactivating enzymes

Bacitracin MOA

binds/inhibits dephosphorylation of bactoprenol

Bacitracin resistance

rare due do topical prep

Polymixin B and Colistins MOA

binds to lipopolysaccharides of outer cell membrane to form a pore and promote cell lysis

Polymixin B and Colistins resistance

target modification, decreased LPS expression

Polymixin B and Colistins toxicity

nephrotoxic/neurotoxic w/ parenteral use