Macrolides, Ketolides, Streptogramins and Lincosamides Flashcards
Mechanism of Action: Clindamycin Macrolides: --Erythromycin --Clarithromycin --Azithromycin
- Inhibits protein synthesis by binding to 50S subunit
- Generally bacteriostatic, may be bacteriocidal at high concentrations
Mechanisms of Resistance: Clindamycin
Altered 50S target
Active efflux pump
Drug inactivation
Spectrum of Activity: Clindamycin
- Gram positive aerobes (not enterococcus), some CA-MRSA
- Anaerobes: not C. diff
Indications: Clindamycin
Anaerobic infections outside of the CNS
Skin and soft tissue infection (pen-allergies, CA-MRSA)
Adverse Effects: Clindamycin
Most common: Nausea, vomiting, diarrhea, dyspepsia Most severe: C. diff- one of the worst inducers Rare: cytopenia
Bioavailability: Clindamycin
Available IV and PO
Rapidly and completely absorbed (90%); food has minimal effect on absorption
Distribution: claritrhomycin
Good concentrations in most tissues
Does not penetrate the CNS
Is clindamycin metabolized by the kidneys or liver?
Clindamycin primarily metabolized by the liver (85%)
Is clindamycin removed from circulation during hemodialysis
No
Does erythromycin show time- or concentration- dependent killing?
Time-dependent killling
Does clarithromycin show time- or concentration- dependent killing?
Time-dependent killing
Does azithromycin show time- or concentration- dependent killing?
Concentration-dependent killing
Clindamycin: time or conc.- dependent
Time
Mechanism of Resistance: Macrolides
Active efflux– mef gene encodes for an efflux pump that pumps the macrolide out of the cell away from the ribosome; confers LOW level resistance to macrolides
Altered target sites – encoded by the erm gene which alters the macrolide binding site on the ribosome; confers HIGH level resistance to all macrolides, clindamycin, and Synercid®
Spectrum of Activity: Macrolides
G+ aerobes: MSSA, S.pneumo (not PRSP), all other strep, Bacillus spp., Corynebacterium spp.
G- aerobes: H. flu (not erythro), M. catarrhalis, Neisseria spp.
Does NOT have activity against any Enterobacteriaceae
Anaerobes – activity against upper airway anaerobes
Atypical Bacteria – all macrolides have excellent activity against atypical bacteria including:
Legionella – DOC*
Chlamydophila (psittacosis) and Chlamydia spp.
Mycoplasma spp.
Other Bacteria – Bordetella, Brucella, Pasteurella, H.pylori (combination tx), Mycobacterium avium complex (MAC – only azithromycin and clarithomycin), M. chelonae,
List the macrolides–> best to worst activity against G+ aerobes
Clarithro>Erythro>Azithro
List the macrolides–> best to worst activity against G- aerobes
Azithro>Clarithro>Erythro
Absorption of Erythromycin
Erythromycin – variable absorption (15 to 45%); food may decrease the absorption
Absorption of Clarithromycin
Clarithromycin – acid stable and well-absorbed (55%) regardless of presence of food
Absorption of Azithromycin
Azithromycin –acid stable; bioavailability = 37% regardless of presence of food
Distribution: Macrolides
Distributes to most tissues, clarithromycin and azithromycin have higher distributions
None cross the BBB
How are erythromycin and clarithromycin eliminated?
Erythromycin is excreted in bile and metabolized by CYP450
Clarithromycin is metabolized and also partially eliminated by the kidney (18% of parent and all metabolites)
Which macrolide does not inhibit CYP450 enzymes?
Azithromycin
Indications: Macrolides
Respiratory tract infections Uncomplicated skin infections STDs Mycobacterium avium complex (MAC) Alternative for PCN-allergic patients
Adverse Effects: Macrolides
Most common: Nausea, vomiting, diarrhea, dyspepsia Rare: Cholestatic hepatitis Thrombophlebitis - depends on dilution of dose Prolonged QTc Transient/reversible tinnitus
Quinupristin/Daltopristin (Synercid®): MOA
Inhibits protein synthesis by binding to 50S subunit -Generally bactericidal
Mech. of Resistance: Quin/Dalt
Alterations in ribosomal binding sites (erm)
Enzymatic inactivation
Active transport out of the cell
Spectrum: Quin/Dalt
G+:
MSSA, Coag. negative staph
Strep pneumo, incl. pen-R, Group strep, viridans strep
E. faecium, incl. VRE
Corynebacterium, bacillus, listeria, actinomyces
Clostridium spp, excl. diff, peptococcus, peptostreptococcus
Indication: Quin/Dalt
VRE bacteremia
Adverse Effects: Quin/Dalt
Most common: Venous irritation Nausea, vomiting, diarrhea Rare: Rash Myalgias Arthralgias
Bioavailability for Quin/Dalt?
None, only available parenterally
Quin/Dalt: Time- or concentration- dependent killing
Concentration
Post-antibiotic effect in gram-positive bacteria?
2 to 8 hours for S. aureus;
8.5 hours for VSE; 0.2 to 3.2 hours for VRE
Distribution: Quin/Dalt
Most tissues; does not penetrate CSF
Quin/Dalt Elimination
Hepatic and biliary
Which aspect of quin/dalt metabolism should be considered when it’s being co-administered with other drugs?
Quin/dalt inhibits cyp450 3A4
Adverse effects of quin/dalt
Most common: Venous irritation Nausea, vomiting, diarrhea Rare: Rash Myalgias Arthralgias
