STEPTRACKERMICROBIOLOGY + PHARMACOLOGY | PROTEIN SYNTHESIS INHIBITORS | HIGH-YIELD REVIEW

Protein Synthesis Inhibitors

Drugs that jam the bacterial 70S ribosome — 30S binders (aminoglycosides, tetracyclines) and 50S binders (macrolides, clindamycin, linezolid, chloramphenicol). Most are bacteriostatic; aminoglycosides kill.

FOCUS ON

30S: aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin) — bactericidal, block initiation complex and cause misreading; need O₂ for uptake (no anaerobes); synergy with β-lactams; nephrotoxicity, ototoxicity, neuromuscular blockade, teratogen. Tetracyclines (doxycycline, minocycline, tigecycline) — block aminoacyl-tRNA; rickettsiae, Chlamydia, Mycoplasma, Lyme, MRSA skin; avoid in children < 8 and pregnancy (teeth discoloration, bone), photosensitivity, esophagitis; chelated by Ca²⁺/Mg²⁺/Fe. 50S: macrolides (azithromycin, clarithromycin, erythromycin) — atypicals, chlamydia, pertussis; QT prolongation, GI motility (motilin agonist), CYP3A4 inhibition (not azithro); clindamycin — anaerobes above the diaphragm, GAS toxin suppression, C difficile; linezolid — MRSA, VRE; thrombocytopenia, serotonin syndrome, optic neuropathy; chloramphenicol — aplastic anemia, gray baby syndrome.

DRUG · CLASS

MECHANISM

USES

TOXICITY · NOTES

Aminoglycosides

30S: block initiation, misreading of mRNA; O₂-dependent uptake; concentration-dependent killing, post-antibiotic effect

Severe gram ⁻ (incl. Pseudomonas), synergy for enterococcal/strep endocarditis; streptomycin for plague, tularemia; neomycin for bowel prep

Nephrotoxicity (ATN), ototoxicity (↑ with loop diuretics), NM blockade, teratogen (CN VIII)

Aminoglycoside resistance

Modifying enzymes (acetylation, phosphorylation, adenylation)

Plasmid-borne

Amikacin resists most enzymes

Doxycycline · minocycline

30S: block aminoacyl-tRNA attachment to A site

Rickettsia, Chlamydia, Mycoplasma, Lyme, anthrax, Vibrio vulnificus, acne, MRSA skin infections

Teeth staining, bone growth ↓ (< 8 y, pregnancy) · photosensitivity · pill esophagitis · avoid with antacids, milk, iron

Tigecycline

Glycylcycline, evades efflux

MRSA, VRE, MDR gram ⁻ (not Pseudomonas)

Nausea; ↑ mortality warning

Tetracycline resistance

Efflux pumps, ribosomal protection proteins

—

Macrolides

50S (23S rRNA): block translocation

Atypical pneumonia, chlamydia, pertussis, Campylobacter, H pylori (clarithro), MAC (prophylaxis/treatment)

QT prolongation, GI upset (motilin), cholestatic hepatitis, ↑ levels of warfarin/theophylline/statins (CYP3A4 — clarithro, erythro) · infant pyloric stenosis

Macrolide resistance

Methylation of 23S rRNA (erm), efflux (mef)

Pneumococcus, GAS, M genitalium

erm also confers clindamycin resistance (D-test)

Clindamycin

50S: blocks peptide transfer (translocation)

Anaerobes above the diaphragm (aspiration, lung abscess, dental), GAS necrotizing fasciitis/TSS (stops toxin), MRSA skin

C difficile colitis (classic) · B fragilis resistance common

Linezolid

50S: blocks formation of initiation complex (23S)

MRSA pneumonia, VRE

Thrombocytopenia/myelosuppression (> 2 weeks), serotonin syndrome (weak MAOI), lactic acidosis, optic/peripheral neuropathy

Chloramphenicol

50S: blocks peptidyltransferase

Rarely: meningitis, rickettsiae in resource-limited settings

Dose-related anemia; idiosyncratic aplastic anemia; gray baby syndrome (no UDP-glucuronyltransferase)

Streptogramins

Quinupristin-dalfopristin, 50S

VRE faecium

Arthralgia, myalgia

Static vs cidal

Most protein inhibitors static; aminoglycosides cidal

Cidal preferred for endocarditis, meningitis, neutropenia

Linezolid cidal vs strep, static vs staph

Mechanism — the two subunits

30S subunit

→

AminoglycosidesInitiation, misreading

TetracyclinesBlock tRNA entry

50S subunit

→

ChloramphenicolPeptidyltransferase

Macrolides, clindamycinTranslocation

LinezolidInitiation complex

Signature toxicities

DRUG

TOXICITY

AVOID IN

Aminoglycosides

Kidney, ear, NMJ

Myasthenia, pregnancy

Tetracyclines

Teeth, bone, sun

< 8 years, pregnancy

Macrolides

QT, GI motility

Long QT

Clindamycin

C difficile

—

Linezolid

Platelets, serotonin

SSRIs

Chloramphenicol

Aplastic anemia, gray baby

Neonates

How it's tested

COMMON CONFUSIONClindamycin is added in GAS necrotizing fasciitis and toxic shock to shut down toxin synthesis — not for extra killing.

THE TRAPDoxycycline is still preferred for suspected RMSF even in young children — benefit outweighs the tooth-staining risk.

YOUR APPROACHRibosome subunit → static or cidal → spectrum niche (atypicals, anaerobes, MRSA/VRE, gram ⁻) → class toxicity and interactions.

If you see… think…

Hearing loss and rising creatinine on gentamicin + furosemide → aminoglycoside toxicity

Why aminoglycosides don't kill anaerobes → O₂-dependent uptake

Respiratory paralysis after aminoglycoside in myasthenia → NM blockade

Brown-gray teeth in a child → tetracycline exposure

Doxycycline failure taken with milk → divalent cation chelation

Syncope with long QT on azithromycin → macrolide QT prolongation

Diarrhea after clindamycin → C difficile

Low platelets after 3 weeks of an anti-MRSA drug → linezolid

Agitation, clonus on linezolid + sertraline → serotonin syndrome

Neonate with cyanosis, hypotension and gray skin → chloramphenicol (gray baby)