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Macrolides are NOT useful against... (3)
- Enterobacteriacea (acquired)
- Pseudomonas (intrinsic)
- Enterococcus (acquired)
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What drugs are in the macrolide class? (7)
- Erythromycin
- Tylosin
- Spiramycin
- Tilmicosin
- Tulathromycin
- Clarithromycin
- Azithromycin
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What drug is the class representative of macrolides?
Erythromycin
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Describe the pharmcokinetic properties of erythromycin. (5)
- orall bioavailable if enterically coated
- high Vd- does cross BBB
- gets intracellular
- good for respiratory
- almost exclusive biliary excretion
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Erythromycin is not a good ________ drug because...
UTI; it is not renally excreted
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What are some side effects of erythromycin? (2)
- Promotility- (sometimes desirable, used as pro-motility drug) motilin receptor agonist, stimulates MMCs--> diarrhea and disrupts flora
- Irritation- injection site redness
-
What are macrolide drug interactions?
- inhibits cytochrome P450, may need to decrease dose of other drugs
- (Azithro is only one that does not do this)
-
What are the new generation macrolides and what are advantages?
- Azithromycin, Clarithromycin
- fewer GI side effects
- higher gram - activity
- excellent intracellular and respiratory concs (others have this too)
-
What is the general spectrum of macrolides?
- Best for aerobic/ fac Gram +
- good Gram + coverage- aerobes and anaerobes
- some Gram - coverage for aerobes and anaerobes
- [varies by drug]
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What are clinical applications of Clarithromycin? (3)
- Rhodococcus equi with Rifampin
- Canine Nocardia and rapidly growing Mycobacteria
-
What are clinical applications of Azithromycin? (2)
- Dogs- Bartonella (questionable)
- Cats- URI
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What are resistance mechanisms to macrolides? (3)
- Acquired via plasmids and transposons (G+, G-)
- Target site modification (G+)- methylation of RNA, encoded by erm genesEfflux pump (G+) encoded by mef gene
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What is the MOA of macrolides?
inhibits protein synthesis by binding the 50S ribosome and preventing tRNA translocation
-
What are pharmacodynamic properties of macrolides?
-
What is the MOA of lincosamides?
inhibits protein synthesis by binding the 50S ribosome and preventing tRNA translocation
-
What are pharmoacodynamic properties of lincosamides?
-
What are pharmacokinetic properties of lincosamides? (3)
- high Vd- crosses BBB, bone, rep penetration
- good oral absorption (better on empty stomach)
- eliminated in bile and urine (still not a good UTI drug tho)
-
What is the spectrum of lincosamides?
- Gram + aerobes and anaerobes
- Gram - anaerobes
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What drugs are members of the lincosamide class? (2)
-
What microbes have intrinsic resistance to lincosamides?
- Enterococcus
- Enterobacter
- Pseudomonas
-
What organisms other than bacteria are lincosamides useful for?
anti-protozoal at higher doses
-
What are drug interactions with lincosamides? (3)
- synergistic with metronidazole when treating B. fragilis
- antagonizes macrolides and chloramphenical (50S binding site is very close)
-
What are toxicities of lincosamides? (2 species)
- Horses- fatal C. diff diarrhea and pseudomembranous colitis
- Dogs- mild hepatotoxicity, hypersensitivity, diarrhea
-
What are clinical applications of Clindamycin in dogs and cats? (4)
- Staph (maybe MR organisms)
- Strep
- Anaerobic infections (mouth, peritonitis, severe pneumonia)
- high dose for toxoplasmosis
-
What are resistance mechanisms to lincosamides? (1)
- encoded by erm genes- methylation of adenine in 50S rRNA
- consistutive and inducible expression of resistance genes (exposure to a macrolide activates gene expression)
-
How do you test for lincosamide resistance?
- D-test tests for inducible clinda resistance
- don't trust a lab report (S) if it doesn't include the D-test
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What is the spectrum of Rifampin?
- primarily Gram + aerobes/ facs
- SOME gram + anaerobes
- some Mycobacteria
-
What microbes have intrinsic resistance to Rifampin? (2)
- Enterobactericiaea
- Pseudomonas
-
What are pharmacodynamic properties of Rifampin?
- Bacteriostatic (or cidal?)
- AUC:MIC
-
What are pharmacokinetic properties of Rifampin? (4)
- orally bioavailable
- high Vd- crosses BBB, gets into milk, bone, abscesses
- hepatic metabolism- deacetylation and demethylation with P450, glucuronidation
- eliminated primarily in bile, some in urine
-
What is the MOA or Rifampin?
inhibits initiation of RNA synthesis (already bound RNA chains are not affected)
-
What are mechanisms of resistance to Rifampin? (1)
mutations to RNA polymerase preventing binding
-
What is important to remember when using Rifampin?
- must use with another agents or mutants will be selected for rapidly
- MONOTHERAPY WITH RIFAMPIN IS HIGHLY DISCOURAGED
-
What are clinical applications of Rifampin? (3)
- Rhodococcus equi with a macrolide
- Dogs- MR-Staph with Amikacin, rapidly growing Mycobacteria with Clarithromycin
-
What are drug interactions (1) and toxicity (1) with Rifampin?
- induces P450- increase dose of other drug
- GI side effects in dogs (sterile hepatitis)
-
What is the rule of thumb for nosocomial infections?
- infections occurring:
- after 48hr in hospital admission
- within 3 days of hospital discharge
- within 30 days after an operation
-
What is a superinfection?
a secondary infection resistant to therapy used to treat the primary infection.
-
What is Tylosin labelled for?
- Mycoplasma in chickens, turkey, and swine
- growth promotion in swine
-
What is Tylosin frequently used for in dogs?
sprinkled on food for dogs with chronic small bowel diarrhea and EPI
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