Antibacterial Therapeutics Part 2 2024 PDF

“Drugs & Bugs” Antibacterial Therapeutics Part 2 BRANDON SING, PHARM.D., M.S., BCIDP [email protected] Objectives 2  Identify the drug class for various antibiotics and describe their mechanism(s) of action  Defin...

“Drugs & Bugs” Antibacterial Therapeutics Part 2 BRANDON SING, PHARM.D., M.S., BCIDP [email protected] Objectives 2  Identify the drug class for various antibiotics and describe their mechanism(s) of action  Define antimicrobial PK-PD relationships  Differentiate the basic spectrum of activity of antimicrobials  List common clinical uses of different antimicrobials  Identify adverse effects and serious warnings associated with various antimicrobials  Recognize patients who may be at increased risk of adverse effects with different antimicrobials  List clinically relevant drug interactions involving various antimicrobial agents  Distinguish between antimicrobials that require/don’t require dose adjustment in renal impairment  List the antimicrobials that have activity against MDROs (Pseudomonas aeruginosa, MRSA, VRE, ESBL, CRE) Antibiotic MOA 3  4 Protein Synthesis Inhibitors Aminoglycosides 5  Drugs and Standard Doses: ® = renal dose adjustment  Amikacin – IV,IM ® required  15-20 mg/kg/day  Gentamicin – IV, IM, topical, ophthalmic ®  5-7 mg/kg/day  Tobramycin – IV, IM, inhalational, ophthalmic ®  4-7 mg/kg/day  Streptomycin – IM ®  15-30 mg/kg/day  Plazomicin (Zemdri) – IV ® (FDA approved June 2018)  15 mg/kg IV daily  Mechanism of Action:  Inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit  Bactericidal or Bacteriostatic & Concentration-dependent Aminoglycosides 6  Spectrum of Activity:  Gram-positive (NOT ALONE, only when used in synergy with a beta-lactam or vancomycin)  Synergy activity against Staphylococci (including MRSA), Streptococci, and Enterococci  Gram-negative: Very broad!  Enteric gram-negative rods (PEK, SPACE)  Pseudomonas aeruginosa (Amikacin appears to be the MOST active)  Not active against anaerobes or atypicals  Streptomycin has activity against Mycobacterium tuberculosis Aminoglycosides 7  Clinical Use:  Aminoglycosides are rarely used as monotherapy  Complicated UTI – when no alternative treatment options  Empiric therapy - Typically reserved for serious infections likely caused by gram-negative bacilli  Synergy for gram-positive organisms (gentamicin)  i.e. Infective endocarditis due to Enterococcus  Tobramycin (TOBI) is used in cystic fibrosis – via inhalational route  Streptomycin may have utility in drug-resistant tuberculosis  Plazomicin may have utility in UTI caused by CRE  We will learn Aminoglycosides more about this next 8 time!!!  We will learn Traditional Dosing more about this next 9 time!!!  Dosed 2 to 3 times daily  Less frequently in patients with significant renal impairment  Dosing is weight-based (TBW, IBW, ABW)  A loading dose may be utilized followed by maintenance dose  Check levels after the third or fourth dose (steady state)  Draw peak 30 min after end of IV infusion or 1 hour after IM injection to monitor efficacy  Draw trough immediately prior to dose to monitor toxicity  Peak and trough goals vary depending on the aminoglycoside used and the type of infection being treated  Traditional dosing is preferred for synergy when treating Enterococcal endocarditis  We will learn Aminoglycosides more about this next 1 time!!! 0  Peak and Trough Goals for Traditional Dosing Peak Trough Peak Trough (mcg/mL) (mcg/mL) (synergy) (synergy) Gentamicin 4-10 0.5-2 3-4