Protein Synthesis Inhibitors Antibiotics

Question 1

Aminoglycosides

Answer 1

Gentamicin 5-7mg/kg IV synergy: 1mg/kg IV q8h
Tobramycin 5-7mg/kg IV
Amikacin 15mg/kg IV
Plazomicin (Zemdri)

MOA: Irreversibly inhibit 30S subunit of the ribosome leading to bactericidal killing. (concentration dependent- bactericidal)

ADR: Nephrotoxicity [BBW], Neurotoxicity [BBW], ototoxicity

Coverage:
Gram(+): Gentamicin only with β-lactam or vancomycin for Staphylococcus or enterococcus (endocarditis)

Gram (-): P. Aeruginosa (Amikacin > Tobramycin > Gentamicin), Citrobacter, Enterobacteriaceae

Pearls: exhibits post antibiotic effect (PAE), dosage based on ideal body weight (or ABW), once daily dosing (extended interval), Monitor trough levels

Question 2

Tetracyclines

Answer 2

Doxycycline (Vibramycin): 100mg PO/IV q 12h
Minocycline (Minocin) 100mg PO/IV q 12h
Tetracycline PO

NEW: Omadacycline (Nuzyra)
Eravacycline (Xerava)

MOA: Reversibly binds to the 30S subunit inhibiting protein synthesis.

Coverage:
G(+): CA-MSRA, MSSA, Streptococcus
G(-): H. flu, M. cat
Atypicals: Legionella, Mycoplasma, Chlamydia

Uses: Acne, CAP, some STDs, SSTI

ADR: photosensitivity, Avoid in pregnancy, Avoid in kids ≤ 8 y.o, Fanconi syndrome (expired tetracycline), N/V/D

Pearls: Do not take with multivalent cations, No renal adjustments (except tetracycline)

Question 3

Glycylcycline

Answer 3

Tigecycline IV

MOA: same as tetracyclines

Coverage:
G(+): MRSA, VRE, MSSA, Strep.
G(-): MDR enterobacteriaceae, +- A. baumannii
Atypicals: not typically used, but has coverage

ADR: N/V, Acute pancreatitis, Avoid in pregnancy, Avoid in kids ≤ 8 y.o

Pearls: Avoid in bacteremia (low plasma conc.), last line treatment for pathogens resistant to other antimicrobials.

Question 4

Macrolides

Answer 4

Erythromycin (PO)
Clarithromycin (Biaxin)
Azithromycin (Zithromax, Z-Pack): 500mg PO/IV q24h

Fidaxomicin (Dificid) - only used for C.diff (inhibits transcription RNA activity)

MOA: Reversibly binds to 50S subunit (prevents synthesis)

Coverage:
G(+): minimal Ery > Clarith > Azithromycin
G(-): Azithromycin > Clarithromycin > Erythromycin
Atypicals: great coverage

ADR: GI, QT prolongation
Erythromycin: QT, GI ++, 3A4 DDI

Pearls: Extensive CYP3A4 DDIs

Question 5

Lincosamide

Answer 5

Clindamycin (Cleoci) PO/IV

MOA: Binds to 50S subunit, inhibits toxin production

Coverage:
G(+): CA-MRSA, Strep.
Anaerobes: above the diaphragm anaerobes, +- Bacteroides

Uses: used for anaerobes or CA-MRSA SSTI

ADR: GI diarrhea (caution C.diff), increased LFTs, jaundice

Pearls: reduce dose in severe hepatic dysfunction

Question 6

Streptogramins

Answer 6

Quinopristin-Daflopristin

MOA: Acts on 50S subunit to inhibit early and late stage of protein synthesis. (bactericidal)

Uses: Not used often, used for G(+) persistent MRSA bacteremia

ADR: Pain and inflammation, Arthralgias and Myalgias, hyperbilirubinemia

Pearls: bactericidal when combined, no dose adjustments required.

Question 7

Oxazolidones

Answer 7

Linezolid (Zyvox) 600mg IV/PO q12h
Tedizolid (Sivextro) daily- only for SSTI

MOA: binds to 50S subunit, inhibits protein synthesis

Coverage: similar to Vancomycin + VRE.

Uses: SSTI, VRE, CAP/HAP

ADR: hematologic, serotonin syndrome (linezolid), Myleosuppression

Pearls: no dose adjustments needed

Question 8

Pleuromutilins

Answer 8

Lefamulin (Xenleta)

MOA: binds to 50S subunit , closes binding site around the drug. Bactericidal potential

Uses: CAP, MSSA, S. pneumoniae, respiratory G(-), Atypicals

ADR: infusion site reactions and GI

Pearls: prolongs QT interval, avoid in pregnancy, Dose adjust for liver dysfunction (no renal dosing)