Antimicrobials Flashcards
Non-ß-Lactam Cell Wall Synthesis Inhibitors
Vancomycin
Fosfomycin
Bacitracin
Cycloserine
Monobactam
Aztreonam—only one available.
Primarily active against gram negative, including Enterobacteriaceae and P. Aeruginosa. (Similar to 3rd gen. Cephalosporins)
Lack activity against gram positive and anaerobes.
No cross sensitivity.
Carbapenems
One of the most broad-spectrum antibiotics.
Imipenem, Meropenem, Ertapenem, Doripenem, Tebipenem and Faropenem.
General seizure risk in high doses. Need adjustment in renal impairment.
Imipenem/Cilastatin
Cilastatin prevents imipenem’s degradation by Dehydropeptidase renal enzyme. (Nephrotoxic metabolite)
Ertapenem
A carbapenem—inactive against P. Aeruginosa, Acintobacter and Enterococci.
Vancomycin
A glycopeptide—active against gram positive only. Weak oral bioavailability. (<10%)
First-line in MRSA and MRSE, Pseudomembranous Colitis (orally, act locally)
Mechanism: cell wall synthesis inhibition by binding firmly to D-alanyl-D-alanine in Peptidoglycan, preventing further elongation.
SLOW IV INFUSION. At least 60 minutes.
Monitoring: trough-based (10-20mg/L) or AUC-based monitoring—target AUC: 400-600 mg*h/L.
Steady State: After third dose administration.
RED MAN SYNDROME. Infusion reaction; decrease infusion rate.
Nephrotoxicity / Ototoxicity / Hypokalemia
Daptomycin
Lipopeptide—cell membrane disruption.
Active against infections caused by gram positive. Active against VRE and VRSA.
Myopathy and rhabdomyolysis have been reported when co-administered with statins.
Tetracyclines
High lipid solubility (long-acting)—Doxycycline and Minocycline.
Low lipid solubility (short-acting)—Tetracycline and Oxytetracycline.
The classic tetracyclines are now rarely used. They cause tooth bleaching, chelate with metals and cause Fanconi syndrome; nephrotoxic metabolites.
Mechanism: 30S ribosomal subunit binding reversibly.
Doxycycline doesn’t need dose adjustment in renal or hepatic impairment.
Glycylcyclines
Tigecycline—broad-spectrum antibiotic.
Not active against Proteus, Providencia and Pseudomonas spp. (PPP)
No dose adjustment in renal impairment. Dose adjustment is needed in severe hepatic dysfunction.
Tigecycline may decrease clearance of warfarin and increase prothrombin time.
Aminoglycosides
Streptomycin, Neomycin, Amikacin, Gentamicin, Tobramycin.
Once daily dosing is effective, more convenient and safer.
Monitoring: Peak, trough, ototoxicity and nephrotoxicity.
Amikacin: Peak 15-40 mg/L, Trough 5-10 mg/L
Gentamicin: Peak 4-12 mg/L and Trough 1-2 mg/L.
Steady state is achieved after the third dose administered.
Mechanism: irreversibly bind to the 30S subunit, causing misreading of mRNA—bactericidal.
Spiramycin
Macrolide—crosses the placenta and reaches concentrations in the placenta up to 5 times higher than serum; used to treat toxoplasmosis during pregnancy.
Azithromycin
Macrolide—doesn’t inactivate CYP450. It has a 15-member not 14-member lactone ring like Erythromycin and Clarithromycin.
Macrolides
Mechanism: Bind irreversibly to 50S ribosomal subunit, inhibiting translocation. (Bacteriostatic)
Chloramphenicol
Binds reversibly to 50S ribosomal subunit. It inhibits peptide bond formation (Peptidyl Transferase). It is a bacteriostatic.
CYP450 inhibitor.
Side effects: bone marrow suppression, hemolytic anemia (G6PD deficiency) and gray baby syndrome.
Linezolid
No dose adjustment in hepatic or renal impairments.
Side effects: thrombocytopenia, serotonin syndrome, lactic acidosis and optic/peripheral neuropathy (>28 days).
Clindamycin
Lincosamide—used mainly for anaerobic bacteria.
May cause pseudomembranous colitis.
Mupirocin
Impetigo—topical skin infection.
Causative agent: Streptococcus Pyogenes (GAS) or Staphylococcus Aureus.
