Antimicrobials · Macrolides
The facts most likely to be tested
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Erythromycin acts as a motilin receptor agonist in the gastrointestinal tract, making it effective for treating gastroparesis.
The most significant adverse effect of erythromycin in neonates is an increased risk of pyloric stenosis.
Erythromycin is a potent CYP450 inhibitor, which frequently leads to drug-drug interactions with medications like theophylline or warfarin.
Systemic erythromycin use is associated with QT interval prolongation, increasing the risk of torsades de pointes.
Erythromycin is the preferred treatment for chlamydial conjunctivitis in newborns, though it carries a risk of hypertrophic pyloric stenosis.
The primary mechanism of action for erythromycin is the inhibition of bacterial protein synthesis by binding to the 50S ribosomal subunit.
Erythromycin is a common cause of cholestatic hepatitis, which typically presents with jaundice and elevated alkaline phosphatase.
Vignette unlocked
A 3-week-old male infant is brought to the clinic by his mother due to persistent non-bilious, projectile vomiting after feedings. The infant was treated with oral erythromycin two weeks ago for suspected chlamydial conjunctivitis. On physical examination, the infant appears hungry but dehydrated, and a palpable olive-shaped mass is noted in the epigastrium. Laboratory studies reveal a hypochloremic, hypokalemic metabolic alkalosis.
What is the most likely diagnosis and the underlying cause related to the infant's medication history?
Infantile hypertrophic pyloric stenosis secondary to erythromycin exposure.
This vignette tests the high-yield association between systemic macrolide use in neonates and the development of pyloric stenosis, a classic board examination topic.
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High yield triage
Classification
Macrolide antibiotic; bacteriostatic protein synthesis inhibitor.
Indications
Chlamydia (pregnancy), Pertussis, Gastroparesis (prokinetic).
Mechanism of Action
Binds 50S ribosomal subunit to inhibit protein synthesis.
Side Effects
GI upset (motilin agonist), QT prolongation, ototoxicity.
Contraindications / Monitoring
CYP3A4 inhibitors; monitor QTc interval and LFTs.
Full handout
Mechanism of Action
Erythromycin binds reversibly to the 50S ribosomal subunit, blocking the translocation of peptidyl-tRNA. This action inhibits bacterial protein synthesis, effectively halting bacterial growth. It also acts as a potent agonist of motilin receptors in the GI tract, stimulating smooth muscle contraction.
Unique Properties
Unlike other macrolides, erythromycin is a potent prokinetic agent used to treat diabetic gastroparesis. It is significantly more prone to causing GI distress due to its direct stimulation of motilin receptors.
Indications
First-line for Chlamydia trachomatis in pregnant patients and Bordetella pertussis (post-exposure prophylaxis). It is also utilized for erythrasma and as an alternative for streptococcal pharyngitis in penicillin-allergic patients.
Pharmacokinetics
Metabolized extensively by the hepatic CYP3A4 enzyme system, leading to numerous drug-drug interactions. It is primarily excreted in the bile, requiring caution in patients with hepatic impairment.
Side Effects & Adverse Events
Common effects include abdominal cramping, nausea, and diarrhea. QT prolongation is a major concern, potentially leading to Torsades de Pointes. Ototoxicity may occur, particularly at high doses or in patients with renal failure.
Contraindications
Absolute contraindication with concurrent use of CYP3A4 inhibitors or drugs that prolong the QT interval (e.g., cisapride, pimozide). Avoid in patients with a history of cholestatic jaundice associated with prior macrolide use.
Monitoring
Perform baseline and periodic ECG to monitor the QTc interval in high-risk patients. Monitor liver function tests if therapy is prolonged, as it can cause cholestatic hepatitis.
Clinical Pearls
Always remember the motilin agonist effect for board questions regarding drug-induced diarrhea or gastroparesis. If a question describes a pregnant patient with Chlamydia, erythromycin is the classic board answer over doxycycline.