Macrolides
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| Macrolides | Erythromycin
Clarithromycin
Azithromycin
Fidaxomicin
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| Macrolide MoA | Mainly static: reversible binding to 50S ribosomal subunit; inhibit protein synthesis
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| Mech of Resistance to Macrolides | 1) induction of active efflux pumps
2) induction of methylase enzyme: decreased drug binding
3) production of an esterase enzyme or phosphorylase enzyme
4) chromosomal mutation of 50s ribosome
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| Macrolide PK | Low conc in urine (goes to bowel instead) -> not for UTI Tx. Ok for STDs though.
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| Macrolide available forms | IV & PO: Erythromycin, Azithromycin
Oral only: Clarithromycin
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| Erythromycin SoA | G+ cocci and bacilli: Staph., Strept., Corynebacterium diphtheriae, Clostridium perfringens
Also C. trachomatis, E. histolytica, L. monocytogenes, B. burgdorferi, M. pneumoniae, T. pallidum, U. urealyticum
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| Erythromycin clinical use | PCN allergic patients
Chlamydia
acne (as topical ointment, solution or gel)
ophthalmic
surgical prophylaxis with neomycin
promote GI motility for post-op atonic colon
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| Pediazole (erythromycin and sulfisoxazole) | Not given if under 2 years because of sulfonamide issues in pediatrics
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| Clarithromycin SoA (Synthetic modification of erythromycin) | Spectrum same as erythro, but more against G+, H. flu, M. catarrhalis, CAP atypicals, and MAC. Also Tx M. leprae, toxoplasmosis and cryptosporidium plasmodium
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| Clarithromycin use | CAP, COPD exacerbation, Bronchitis, Tonsilitis, OM (good ear conc), STD’s, MAC (only as combo with ethambutol +/- rifabutin), H. Pylori
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| Erythromcin ADRs | GI problems (NVD)
Jaundice & hepatotoxcitiy
rash
nephritis
dose-related ototoxicity
prolonged QT interval
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| Clarithromycin ADRs | Fewer GI issues than erythromycin & augmentin
rarely: rash, hepatic dysfxn, CNS problems, QT prolongation, nephritis
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| Azithromycin (Z-Pak, Tri-Pak, Zmax) PK | Synthetic modification of erythromycin: less acid degredation
Long half-life!
Good for Kids & Adults
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| Azithromycin ADRs | Less GI issues (NVD)
Rare: Hepatitis & LFT increases
Rare: otoxicity (hearing problems)
QT prolongation
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| Azithromycin usage | CAP, bronchitis, Sinusitis, STDs
Also for pneumonia & otitis media in kids
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| Fidaxomicin (Dificid) | Oral, nonsystemic macrolide.
Like Vanco, Fidaxomicin shouldn't be used for systemic infection!
Main target: C. diff
Must be 100% compliant or else resistance!
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