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 with increased affinity due to decylaminoethyl group (big chain), allowing rapid bactericidal activity (depolarization/leakage of cell membrane)

Telavancin toxicity

GI events, caution in pregnancy

Oritavancin MOA

binds D-Ala D-Ala peptide precursors, increased affinity due to chlorobiphenylmethyl group (allows inhibition of transpeptidase rxn, stops peptides that terminate D-Ala D-Lac)

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 at PTC, blocking binding of aminoacyl tRNA

Linezolid resistance

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

Linezolid toxicity

thrombocytopenia, serotonin syndrome, black hairy tongue

Tedizolid phosphate MOA

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

prodrug, phosphate included to improve solubility/bioavailability

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)

glucosylated Rho is unable to activate due to C. diff toxins, epithelial cell function lost

Metronidazole MOA

prodrug converted in organism, reactive form destroys nucleic acids and proteins and targets anaerobic bacteria (bacteroides/clostridium)

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 3 days post admin.), metallic taste, CNS AEs with long term use, may exacerbate furry tongue

Nitrofurantoin MOA

bacterial enzymes reduce the drug, producing reactive metabolites that damage DNA and ribosomal proteins, inhibits translation

used only for UTIs

Nitrofurantoin resistance

fairly uncommon

Nitrofurantoin toxicity

pulmonary toxicity 

Mupirocin MOA

binds/inhibits isoleucyl tRNA synthetase 

Mupirocin resistance

emerging, mutation at tRNA synthetase and plasmid-mediated transfer

Daptomycin-lipopeptide MOA

inserts into bacterial cell membranes forms a pore, causing disruption of ion transport, loss of membrane potential, and decreased ATP/DNA/RNA

Daptomycin-lipopeptide resistance

charge repulsion or upregulation of dlt gene in staph

Daptomycin-lipopeptide toxicity 

few ADRs, myopathy rare

Quinupristin/Dalfopristin MOA

binds to 50s subunit (D bridges A/P sites), given together for bactericidal activity, multiple hydrophobic interactions and hydrogen binding responsible (streptogramin-rRNA interactions)

D inhibits EARLY stages of elongation, causing conformational changes and increasing affinity for Q

Q inhibits LATE stages of elongation

Quinupristin/Dalfopristin resistance

Q has MLSb resistance, methylation in 50S typically due to ermB (does not confer to D)

Expression of efflux pumps, inactivating enzymes

Bacitracin MOA

binds/inhibits dephosphorylation of bactoprenol, complex with zinc

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, also muscle weakness and neuromuscular blockade

Bacitracin toxicity

topical, allergic contact dermatitis

Mupirocin toxicity

rare, local effects (stinging, skin irritation)

Retapamulin, Lefamulin MOA

inhibits protein translation by binding to PTC of 50s subunit, disrupts tRNA at A/P site

Lefamulin binds with hydrogen bonds

Retapamulin, Lefamulin resistance

few reports of resistance, may have cross-resistance with other translation inhibitors (Cfr-mediated)

Retapamulin, Lefamulin toxicity

Retapamulin has topical effects (redness, itching, irritation)

Lefamulin has systemic or parenteral effects (N/V/D; redness/soreness at injection site)