STEPTRACKERPHARMACOLOGY + MICROBIOLOGY | ANTIMICROBIALS | HIGH-YIELD REVIEW

Protein Synthesis Inhibitors

Bacterial ribosomes (70S) differ from ours (80S), so drugs can block the 30S or 50S subunit selectively — the subunit, spectrum and signature toxicity identify each class.

FOCUS ON
30S: aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin) — bind 30S → misreading, block initiation; bactericidal, concentration-dependent; need O₂ for uptake (no anaerobes); synergy with β-lactams; toxicity — nephrotoxicity (ATN), ototoxicity (↑ with loops), NM blockade, teratogen. Tetracyclines (doxycycline, minocycline, tigecycline) — block aminoacyl-tRNA binding; rickettsia, chlamydia, Lyme, mycoplasma, acne, MRSA skin; avoid with Ca²⁺/Mg²⁺/Fe²⁺, children < 8 (teeth), pregnancy; photosensitivity, pill esophagitis. 50S: macrolides (azithromycin, clarithromycin, erythromycin) — block translocation; atypicals, pertussis, chlamydia, MAC; QT, GI motility, cholestasis, CYP3A4 inhibition (not azithromycin), infantile pyloric stenosis. Clindamycin — anaerobes above diaphragm, GAS toxin suppression, MRSA; C. difficile. Linezolid — blocks initiation complex; MRSA, VRE; thrombocytopenia, optic/peripheral neuropathy, serotonin syndrome (MAO inhibition). Chloramphenicol — peptidyltransferase; aplastic anemia, gray baby. Streptogramins (quinupristin-dalfopristin).
DRUG · SUBUNIT
MECHANISM
KEY USES
SIGNATURE TOXICITY
Aminoglycosides · 30S
gentamicin, tobramycin, amikacin
Irreversible 30S binding → mRNA misreading; O₂-dependent uptake
Severe gram-negative (Pseudomonas), synergy for enterococcal/strep endocarditis
Nephrotoxicity, ototoxicity, NM block (myasthenia), teratogen; trough monitoring
Streptomycin · neomycin
30S
TB, plague, tularemia · bowel prep, hepatic encephalopathy (oral)
Vestibular toxicity
Doxycycline · minocycline · 30S
Block aminoacyl-tRNA to A site; bacteriostatic
Rickettsia, Lyme, chlamydia, mycoplasma, MRSA skin, acne, anthrax, malaria prophylaxis
Teeth discoloration, bone growth, photosensitivity, pill esophagitis, pseudotumor cerebri
Tigecycline
Glycylcycline (30S)
MDR organisms, complicated skin/abdominal
Nausea, ↑ mortality signal
Macrolides · 50S
azithromycin, clarithromycin, erythromycin
Block translocation (23S rRNA)
Atypical pneumonia, pertussis, chlamydia, MAC, H. pylori (clarithro), gastroparesis (erythro)
QT, GI upset (motilin), cholestatic hepatitis, CYP3A4 inhibition, pyloric stenosis in infants
Clindamycin · 50S
Blocks peptide transfer (translocation)
Anaerobes above diaphragm (aspiration, abscess), GAS/C. perfringens toxin, MRSA skin, BV
C. difficile colitis
Linezolid · tedizolid · 50S
Bind 23S rRNA → block initiation complex
MRSA, VRE, pneumonia
Thrombocytopenia, optic and peripheral neuropathy, serotonin syndrome, lactic acidosis
Chloramphenicol · 50S
Blocks peptidyltransferase
Meningitis, rickettsia (resource-limited)
Dose-related anemia, idiosyncratic aplastic anemia, gray baby syndrome
Quinupristin-dalfopristin · 50S
Streptogramins
VRE (E. faecium)
Infusion phlebitis, arthralgia
Mupirocin · fusidic acid
Isoleucyl-tRNA synthetase · EF-G
Topical/nasal MRSA decolonization, impetigo
—
Resistance mechanisms
Aminoglycosides: modifying enzymes · tetracyclines: efflux, ribosomal protection · macrolides: 23S methylation (erm), efflux (mef) · linezolid: 23S mutation
—
Clindamycin inducible resistance (D-test)

Mechanism — why aminoglycosides miss anaerobes

Aminoglycoside entry needs O₂-dependent transport
→
Anaerobes can't take it up
β-lactam weakens the wall
→
More aminoglycoside entersSynergy (enterococcal endocarditis)

30S vs 50S

SUBUNIT
DRUGS
CIDAL / STATIC
30S
Aminoglycosides
Bactericidal
30S
Tetracyclines
Static
50S
Macrolides, clindamycin, chloramphenicol
Static (mostly)
50S
Linezolid, streptogramins
Variable

How it's tested

COMMON CONFUSIONTetracyclines bind divalent cations — antacids, milk, iron and calcium cut absorption; doxycycline is the one safe in renal failure (fecal elimination).
THE TRAPLinezolid in a patient on an SSRI → serotonin syndrome; linezolid for > 2 weeks → thrombocytopenia and neuropathy.
YOUR APPROACHOrganism (intracellular, anaerobe, MRSA, VRE) → class → subunit → toxicity and interactions.

If you see… think…

Hearing loss and rising creatinine on IV antibiotic → aminoglycoside
Respiratory paralysis after aminoglycoside in myasthenic → NM blockade
Sunburn-like rash on tick-bite antibiotic → doxycycline photosensitivity
Projectile vomiting in a neonate given erythromycin → pyloric stenosis
Watery diarrhea after aspiration pneumonia treatment → clindamycin C. difficile
Platelets fall during long VRE therapy → linezolid
Cyanotic, hypotensive neonate on old antibiotic → gray baby syndrome (chloramphenicol)
Torsades on atypical pneumonia antibiotic → macrolide QT
Toxin-suppressing add-on in necrotizing fasciitis → clindamycin
Antibiotic class needing oxygen to enter bacteria → aminoglycosides