Ribosomal and DNA Abx Flashcards
Tetracyclines
- Tetracycline
- Minocycline
- Doxycycline***
Tetracycline MOA/MOR
MOA: 30S bacterial ribosome inhibition
MOR: Ribosomal binding site alterations, efflux pumps
Tetracycline pharm/interactions
- May increase INR
- Can’t combine isotretinoin –> Causes pseudotumor cerebri
- Multivalent cations may decrease absorption
-Split excretion (60% hepatic/40% renal)
Tetracycline Pearls
- Doxy can come in many different “salts” that drastically vary in price
- Use generic doxycycline hyclate
- These drugs seem protective against C diff
Tetracycline ADRs
- Nausea
- Photosensitivity
- Contraindicated pregnant women
- Hyperpigmentation (minocycline)
- Black hairy tongue
Doxycycline microbial coverage
- CAP typicals
- CAP atypicals
- Rickettsia, Ehrlichia/Anaplasma, B burger
- Pasteurella
- Staph aureus
- Chlamydia trachomatis
Common indications for Doxycycline
- URTI*
- CAP
- NGU
- Tick-borne disease (cutaneous manifestations)
Extended-spectrum Tetracyclines
- Tigecycline
- Omadacycline
- Eravacycline
MOA: 30S ribosome inhibition
Extended-spectrum Tetracyclines pharmacology
- Drug interactions
- Split excretion
- Bacteriostatic
- Higher mortality, don’t use unless we have to!
Extended-spectrum tetracyclines
- Broad-spectrum of activity that includes G=, G-, atypical, & anaerobic pathogens
- Does NOT get pseudomonas
- Used mostly for nosocomial infections
Macrolides
- Erythromycin
- Azithromycin***
- Clarithromycin
MOA: 50S ribosome
MOR: Binding site alterations, efflux pumps
Macrolide interactions/pharm
- All agents known to increase INR
- Clarith/erythromycin: potent inhibitor of CYP3A4
- All agents should not be used with other QT prolongers
-Hepatic excretion, bacteriostatic
Macrolide class ADRs
-All associated with prolonged QTc
Erythromycin ADRs
- Activate motilin receptors causing uncoordinated peristalsis and N/V/D
- Used off-label as an agent in gastroparesis
Clarithromycin ADRs
-Metallic taste
Azithromycin ADRs
- Generally well tolerated
- high dose can cause N/V
Macrolide coverage
Azithromycin: S pyogenes, S pneumo, Hib, M catarrhalis, chlamydial, legionella, mycoplasma, Bordetella pertussis (resistance to S pneumo + Hib limits use)
Clarithromycin: mostly used for H. pylori
Macrolide indications
- URTIs ID hates em tho
- CAP*
- NGU*
- Enteritis
- H pylori (Clarithromycin)
Fidaxomicin pearls
MOA: Macrolide inhibits RNA polymerase
-BACTERICIDAL against C diff
Little to no activity against anything else other than clostridia
Lincosamides
-Clindamycin
MOA: 50S ribosomal inhibition
MOR: Efflux pump, ribosomal target modification
Lincosamides coverage
- Covers most anaerobes
- best above the diaphragm with oropharyngeal microbes
- Often used to cover SA, S pyogenes, viridans strep in those with serious PCN allergies
Lincosamide indications
- Substitute for B lactam allergy in SSTI, strep pharyngitis
- Anaerobic infections/abscesses
Oxazolidinones, drug and MOA and MOR
- Linezolid
- Tedizolid
- MOA: binds ribosomal 50s subunit
- MOR: multiple mutations, slow to develop
Drug interactions with oxazolidinones
- MAOI -> levodopa
- Concomitant serotonergic drugs -> serotonin syndrome
Oxazolidinones ADRs
- Reversible thrombocytopenia (monitor platelets x2 weeks)
- Watch dietary tyramine due to MAOI
- Peripheral neuropathy
- Serotonin syndrome
Oxazolidinones uses
-MRSA and VRE infections (has broad gram + activity)
Aminoglycosides, main drugs and MOA and MOR
- Gentamicin
- Tobramicin
- Amikacin
- MOA: inhibits 30s ribosome
- MOR: ribosomal binding site alterations, efflux pumps, AGases
Aminoglycoside pharmacology
- Additive nephrotoxicity
- Renal excretion
- Bactericidal
- Measure trough conc 30 min before next dose
- Narrow spectrum abx, only covers aerobic gram negative**
Aminoglycosides ADRs
- Nephrotoxicity
- Ototoxicity (genta>tobra)
Aminoglycosides clinical indications
- Genta: aerobic GNBs (severe infections), endocarditis
- Tobra: most GNBs including pseudomonas
Aminoglycosides claim to fame on the small drugs including: amikacin, streptomycin, neomycin, kanamycin, paromomycin, and spectinomycin
- Amikacin: MDR GNBs
- Streptomycin: TB
- Neomycin: bowel cleansing
- Kanamycin: surgical irrigation
- Paromomycin: parasite and tapeworm infections
- Spectinomycin: gonorrhea tx for allergic pts
Pleuromutilins drug and MOA
- Lefamulin
- MOA: binds peptidyl transferase center of 50s subunit of bacterial ribosome, inhibits bacterial protein synthesis
Pleuromutilins pharmacology and ADRs
- Pharm: hepatic excretion and bacteriostatic
- ADRs: N/D, QT prolongation
Pleuromutilins microbial coverage:
- Respiratory microbes
- STI microbes
- Tx indications: CAP
FQs, drug MOA and MOR
- Non respiratory: cipro
- Respiratory: levo, moxi
- Anti-MRSA: delafloxacin
- MOA: inhibits DNA topoisomerases (unwinds), prevents replication
- MOR: alterations in DNA topo, efflux pumps
FQ interactions
- Multivalent cations decrease absorption
- Not with QT-prolonging agents
- Clinically may raise INR
FQ split excretion for levo, moxi, and cipro
- Levo: 100% renal
- Moxi: 90% hepatic
- Cipro: 50/50
FQ ADRs
- Tendinopathy
- Arthropathy (CI in kids <18, okay in CF kids)
- Anaphylaxis and AIN
- CNS toxicities (HA, anxiety; peripheral neuropathies)
FQ Robert’s Nail in the Coffin ADRs
- Photosensitivity (exaggerated sunburn)
- QT prolongation
- Dysglycemia*
- HTX/liver failure
You should not use FQ in these 3 diagnoses
- Sinusitis
- Bronchitis
- Uncomplicated UTIs (cystitis)
- HTN
- Connective tissue disorders
- Do not use under 18 yo
Non-respiratory FQ coverage and tx indications
- Coverage: aerobic GNBs
- Indications: diaphragm to pelvis (upper and lower UTI, tx of enteric infections/travelers diarrhea)
Respiratory FQ coverage and tx indications
- Coverage: increase activity for Strep pneumo and atypical respiratory/genital pathogens
- Indications: upper and lower UTI (not moxi), enteric infections, URI/LRTIs
Anti-MRSA FQ coverage and tx indications
- Coverage: Kills MRSA, drug-resistant gono
- Indications: SSTIs and CAP (last resort)
When should you use FQs?
When you are desperate
Nitroimidazoles
-Metronidazole
Nitroimidazole drug interactions (CYP)
-3A4 and 2C9 inhibitor (massive issues with Warfarin)
Nitroimidazole ADRs
- Metallic taste
- Disulfuram-like rxn (avoid ETOH)
- Fetotoxic in first trimester
- Neurotox with several 2 week pulses
Nitroimidazole coverage and tx indications
- Coverage: most anaerobes (best below diaphragm), + C. diff, various protozoa (trich, giardia, entamoeba)
- Indications: bacterial vaginosis, CDI, giardiasis and trichomoniasis, intrabd abscess
