Protein Synthesis Inhibitors-Pharmacology - PART II ASYNC - (Aminoglycosides + End)

DDI/Food interactions:

•  When used with neuromuscular blockers (anti-paralytics) = neurologic side effects; avoid use

• Use with other nephrotoxins= ⬆ risk of nephrotoxicity

Adverse reactions:

• Nephrotoxicity

• Ototoxicity- If on this for > 2 week, needs baseline and follow-up audiology exams; NOT REVERSIBLE! 

• Avoid in pregnancy

Aminoglycosides DDI/FOod Interactions + Adverse reactions

• Enzymatic Modification

  • Methylation of 16S ribosomal subunit

• Active Efflux

  • EX: resistance to Pseudomonas

• Decreased Permeability

  • Resistance to Pseudomonas

Aminoglycosides Mechanisms of Resistance

Spectrum:

• Gram (-) organisms

  • Including Pseudomonas

• Gram (+) organisms

  • Synergy dosing for Enterococcal infective Endocarditis

• Amikacin

  • Mycobacterium

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Clinical Uses:

• Resistant gram (-) infections

• Synergy with Beta-Lactam in Enterococcal Endocarditis

Comments:

• AMIKACIN Dosing is different than Genta/Tobra

Aminoglycosides (Gentamicin, Tobramycin, Amikacin) Spectrum, clinical uses, and comments

Spectrum:

• Gram (-) organisms

  • Including Pseudomonas

• Gram (+) organisms

  • Synergy dosing for Enterococcal infective Endocarditis

• Amikacin

  • Mycobacterium

• PLUS

  • MDR Enterobacteriaceae including CRE

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Clinical Uses:

• Resistant gram (-) infections including UTI’s

• Plague

Comments:

• Dosing is different (15 mg/kg/day)

Aminoglycosides (Plazomicin) Spectrum, clinical uses, and comments

• Agents: Linezolid, Tedizolid

• Mechanism of Action:

  •  Binds to 50s subunit, blocking the creation of the 70s complex, prevents translation, which halts protein synthesis

  • Weak monoamine oxidase (MAO) inhibitor

• Spectrum of Activity

  •  Gram + (including MRSA and VRE) , some atypicals, Mycobacterium sp., Nocardia 

• Metabolism

  • Linezolid: Both hepatic and renal elimination

  • Tedizolid: Mainly all hepatic 

• Bacteriostatic

• Available IV/PO; High Bioavailability

Oxazolidinones MOA, Spectrum, etc (points)

DDI’s/Food Interactions:

•  Potential serotonin syndrome when used with SSRIs; not CI but need to minimize exposure to multiple serotonin active agents

• Avoid use with levodopa 

• Do not use with other MAO inhibitors

Adverse Reactions:

• When used > 2 weeks, thrombocytopenia and bone marrow suppression

• Linezolid= long term therapy can cause peripheral neuropathy, optic neuritis or lactic acidosis 

Oxazolidinones DDI’s/Adverse reactions

Spectrum:

• ALL Gram (+) organisms

  • MRSA, MSSA, VISA/VRSA

  • ENTEROCOCCI (including Vancomycin Resistant Entercocci (VRE))

  • Streptococcus

• Some Atypicals

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Clinical Uses:

• SSTI’s

• Infections suspected of MRSA or VRE

Comments:

• Available generic, but can be expensive

• Try to limit use to <2 weeks due to myelosuppressive effects

Oxazolidinones (Linezolid (Zyvoxx)) Spectrum, clinical uses, comments

Spectrum:

• ALL Gram (+) organisms

  • MRSA, MSSA, VISA/VRSA

  • ENTEROCOCCI (including Vancomycin Resistant Entercocci (VRE))

  • Streptococcus

• Some Atypicals

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Clinical Uses:

• SSTI’s

Comments:

• Daily Administration x 6 days vs. 10-14 days with Linezolid

• Also expensive

Oxazolidinones (Tedizolid (IV/PO)) Spectrum, clinical uses, comments

• Agent: Lefumulin 

• Mechanism of Action:

  •  Interferes with the 23 ribosomal RNA of the 50s subunit, which prevents correct positioning of RNA

• Spectrum of Activity

  •  Gram +, gram – and atypical organisms 

• Metabolism

  • Liver metabolism with some renal elimination

•  Available IV/PO; low BA (25%)

Pleuromutilins Points

DDI/Food:

• Moderate CYP3A4 Inhibitor, so multiple potential interactions as it may increase drug levels of multiple drugs

•  If used with colchicine, needs dose reduction of colchicine

• May enhance drugs that can cause QTc prolongation

Adverse Reactions:

• QTc prolongation

Pleuromutilins DDI/Food + Adverse reactions

Clinical Uses:

• Treatment of CAP

  • Gram (+)

  • Gram (-)

  • Atypicals

  • Limited Gram (-) coverage

Comments:

• Can cause increased LFTs

• Can cause QTc prolongation

• Avoid use in pregnancy

• Costly- $330/day for the PO

Pleuromutilins (Lefamulin) Clinical Uses and Comments

• Quinupristin/dalfopristine

• Mechanism of Action: Binds to 50S subunit to prevent bacterial protein synthesis

•  Adverse Effects: Phlebitis, myalgias, arthalgias

• DDIs: Many as it is an inhibitor of CYP450

Clinical Uses:

• Good gram + coverage including MSSA, MRSA, Strep and Enterococcus including VRE

Comments:

• Can cause phlebitis and should be administered via central line

• Can only be administered with D5W

Streptogramins Points + Clinical uses and comments

• Vancomycin

• Daptomycin

• Telavancin

• Dalbavancin

• Delafloxacin

• Ceftaroline

“Vampires Drink Thick Delicious Dark Coffee” - and KILL MRSA

Mnemonic for remembering the Bacteriocidal drugs that cover MRSA

• Linezolid

• Clindamycin

• Doxycycline

• Omadacycline

• Tetracycline

• Tigecycline

“Lazy Cats Don't Often Tackle Tigers” - But STOP MRSA

Mnemonic for remembering the BacterioSTATIC drugs that cover MRSA

• Daptomycin

“VRE is very Dapper (Daptomycin)! - KILLS VRE

Mnemonic for remembering the BacterioCIDAL drugs that cover VRE

• Quinupristin/dalfopristin

• Omadacycline

• Linezolid

• Tigecycline

“Quiet Owls Like Trees” - and STOP VRE

Mnemonic for remembering the BacterioSTATIC drugs that cover VRE

• Piperacillin/Tazobactam

• Ceftazidime

• Cefepime

• Ceftolozane/tazobactam

• Ceftazidime/avibactam

• Imipenem

• Meropenem

• Colistin

• Aminoglycosides

• Aztreonam

“Pharmacists Constantly Create Crazy Concoctions In Medical Clinics And Apothecaries”

Mnemonic for remembering the drugs that cover PSEUDOMONAS

• Metronidazole

• Piperacillin/Tazobactam

• Clindamycin

• Cefotetan

• Cefoxitin

• Amoxicillin/Clavulanate

• Ampicillin/Sulbactam

“My Pet Cat Can Catch All Anaerobes”

Mnemonic for remembering the drugs that cover ANAEROBES

• Macrolides

• Tetracyclines

“Atypicals are EMPTY (M-T)”

Mnemonic for remembering the drugs that cover ATYPICALS