Protein Synthesis Inhibitors

Macrolides

Erythromycin

Clarithromysin

Axithromycin

Fidaxomicin (not absorbed)

Lincosamide

Clindamycin

Ketolides

nobody cared- no longer on US market

Tertracyclines

Tetracycline

Doxycycline

Minocycline

Sarecycline

Glycylcyclines (Tigecycline & Eravacycline)

Aminomethylcyclines (Omadacycline)

Oxazolidinones

Linezolid

Tedizolid

Aminoglycosides

Gentamicin

Tobramycin

Amikacin

Plazomicin

Pleuromutilin Protein Synthesis Inhibitor (50s)

Lefamulin (Xenleta)- IV/PO not so common

Indicated for CAP

Other Common Players

Chloramphenicol

Streptogramins

Nobody cares...anymore

Protein Synthesis Inhibitors MOA

works in 30S portion or 50S portion of ribosome

prevents translocation of ribosome down mRNA

30S subunit binders → mess up the "reading" of mRNA or the entry of new building blocks

50S subunit binders → mess up the "assembly" step (linking amino acids together, or moving the chain along)

50S and 30S ribosome creates

70S ribsome

Oxazolidinones MOA

Linezolid and Tedizolid

Works at 50S sub-unit (binding sit on 23S rRNA)- prevents formation of the ribosome complex that starts protein synthesis

Minimal cross-resistance with other classes (in theory)

Which protein synthesis inhibitors are known to decrease bacterial toxin production?

Clindamycin & Linezolid/Tidizolid

Possible benefits in SOME diseases (anthrax, invasive Group A strep etc)

Macrolides: Erythromycin

Route: PO, IV, Topical (ointment)

Coverage: Gram - , Gram + , Atypical

Indications: DOC for Legionella; oral for acne; Atypical (Walking pneumonia- Mycoplasma pneumoniae; CA-P), group B strep, gastroparesis

Contraindications: N/V/D & prolonged Q-T wave

Lots of drug interactions

Macrolides: Azithromycin

Route: PO & IV

Coverage: Gram - , Gram + , Atypical

Indications: H. flu, M. cat, Strep pneumo, atypicals, STI (if non-compliant), non-TB Mycobacterium (MAC)

Contraindications: N/V/D & prolonged Q-T wave

Long half-life

Alternative for strep throat

Macrolides: Clarithromycin

aka Biaxin

Route: PO BID

Coverage: Gram - , Gram + , Atypical

Indications: H. flu, M. cat, Strep pneumo, H. pylori induced GI ulcers, atypicals, non-TB Mycobacterium

Contraindications: N/V/D & prolonged Q-T wave

Macrolides: Fidaxomicin

Route: PO

Coverage: Gram - , Gram + , Atypical

Indications: C-diff only, first-line option

Less relapse than metronidazole and maybe less than PO vancomycin

Contraindications: N/V/D & prolonged Q-T wave

not absorbed, negligible systemic absorption

PO x10 days = $$

Macrolides Contraindications

N/V/D: Stimulate motilin receptor in GI tract which leads to cramping in GI tract & results in diarrhea

Add 1 tsp of Erythro suspension BID in ICU pt- using side effect to stimulate GI tract

Erythro + Clarithro have a lot of DDI (drug-drug-interactions)

Prolonged Q-T wave

Tetracyclines: Doxycycline

Route: PO or IV

great bioavailability; CHEAP

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: DOC for Chlamydia, RMSF, Lyme disease, atypicals, Strep pneumo, pre-travel/post-travel prophylaxis for malaria

Tetracyclines: Minocycline

Route: PO or IV

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: Acne & CA MRSA (staph)

Can cause CNS disturbances (dizziness, balance, gait vertigo)

Tetracyclines: Tigecycline

aka Tigicil

Route: IV only

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: Really sick pts- consult ID

Causes N/V

Black box warning for endovascular infections

Tetracyclines: Eravacycline

aka Xerava

IV only

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: Really sick pts- consult ID

Causes N/V

high protein binding

Tetracyclines: Omadacycline

aka Nuzyra

PO or IV

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: Really sick pts- consult ID

Causes N/V

Take on empty stomach

Tetracyclines: Serecycline

PO only

Coverage: Gram - , Gram + , Atypicals: "Weird" stuff

Indications: Acne

Tetracyclines Contraindications

Phototoxicity (sun sensitivity), discoloration of developing teeth in children < 8, contraindicated in pregnancy, di/tri valent cation interaction (vitamins, dairy products, TUMS, maalox)

Lincosamides: Clindamycin

aka Cleocin

Route: PO, IV, Topical, Vag Prep

Coverage: Gram + & Anaerobes

Indications: Staph, Strep pyogenes, CA-MRSA

Gold standard anaerobe coverage

Contraindications: doesn't get in head well; can cause diarrhea, leading to C. diff

Oxazolidinones: Linezolid

Route: PO & IV

Coverage: Gram +

Indications: MRSA & VRE

Contraindications: Decrease bone marrow function (suppression) resulting in low platelet count in CBC or pancytopenia if tx is >14 days

Peripheral neuropathy or lactic acidosis with chronic use

Serotonin syndrome with SSRI

Oxazolidinones: Tedizolid

Route: PO only

Coverage: Gram +

Indications: MRSA & VRE

Contraindications: Decrease bone marrow function (suppression) resulting in low platelet count in CBC or pancytopenia if tx is >14 days

One daily dosing for 6 days lessens risk of cytopenia

Aminoglycosides: Gentamicin

Route: IV

Coverage: Gram - (rod)

Indications: Pseudomonas aeruginosa, pyelonephritis; Synergistic against serious gram + infections like Staph, endocarditis, osteomyelitis, and sepsis with other antibiotics

Contraindications: Nephrotoxicity to renal, ototoxicity (hearing loss, gait/balance)

Monitor creatinine (increase SCR)

Aminoglycosides: Tobramycin

Route: IV

Coverage: Gram - (rod)

Indications: Pseudomonas aeruginosa

Contraindications: Nephrotoxicity to renal, ototoxicity (hearing loss, gait/balance)

Monitor creatinine (increase SCR)

Aminoglycosides: Amikacin

Route: IV

Coverage: gram - (rods)

Indications: Pseudomonas aeruginosa (most active)

Contraindications: Nephrotoxicity to renal, ototoxicity (hearing loss, gait/balance)

Monitor creatinine (increase SCR)

Aminoglycosides: Plazomicin

aka Zemdri

Route: IV

Coverage: Gram - (rod)

Indications: UTI

Contraindications: Nephrotoxicity to renal, ototoxicity (hearing loss, gait/balance)

Monitor creatinine (increase SCR)

Pleuromutilin Protein Synthesis Inhibitor (PPSI): Lefamulin

aka Xenleta

Route: PO & IV

Indications: CA-P

BID adjust dose in hepatic impairment