Antibiotic Therapy Terminology and Guidelines

1. Sukhjinder Sidhu Interior Health Pharmacy Resident Kootenay Lake Hospital

2. Terminology • Prophylactic therapy • Treatment with antibiotics to prevent an infection • Empiric therapy • Treatment of an infection before specific culture information has been reported or obtained

3. Terminology • Bactericidal • Kill bacteria • Bacteriostatic • Stop growth of bacteria www.amrls.cvm.msu.edu

4. Terminology • Time-dependent killing • Antimicrobial activity best when drug concentration remains constantly above MIC • Aiming for concentrations that are above MIC > 50% of the dosing interval • Ex: penicillins, cephalosporins, carbapenems, clindamycin, vancomycin • Concentration-dependent killing • Eradicate bacteria by achieving high concentrations at the binding site • Aiming for concentrations that are > 10 x above MIC • Ex: aminoglycosides, fluoroquinolones

5. Terminology • Narrow spectrum • Active on smaller number of bacterial species • Broad spectrum • Active on a larger number of Gram-positive and Gram-negative bacteria www.amrls.cvm.msu.edu

6. Broad vs. Narrow CloxacillinAmoxcillin Penicillin G Nitrofurantoin Cephalexin Metronidazole Amox/Clav Fluoroquinolones Ceftriaxone VancomycinLinezolid Macrolides Aminoglycosides Sulfonamides Tetracyclines Cefazolin Clindamycin Carbapenems Pip/Tazo

7. Antibiotic Step Down • Narrow the antibiotic spectrum once culture and susceptibility are available • Step down is an important component of antibiotic therapy because it can reduce cost and toxicity and prevent the emergence of antimicrobial resistance

8. Penicillins • Natural penicillins • Penicillin G • Penicillin V • Penicillinase-resistant • Cloxacillin • Penicillin plus β-lactamse inhibitors • Amoxicillin-clavulinic acid • Piperacillin-tazobactam • Aminopenicillins • Amoxcilin • Ampicillin • Ureidopenicillins • Piperacillin

9. Penicillins • Inhibit bacterial cell wall synthesis • Used for prevention and treatment of infections caused by • Streptococcus, Enterococcus, Staphylococcus spp. • DO NOT COVER MRSA • Absorption of oral penicillins much improved on empty stomach • Taken with food minimizes GI upset

10. Penicillins • Generally non-toxic • Side effects: • GI upset nausea, vomiting, diarrhea, abdominal pain • Pseudomembranous colitis broad spectrum agents • Rash • Anaphylaxis

11. Cephalosporins • First Generation • Cefazolin • Cephalexin • Second Generation • Cefuroxime • Third Generation • Ceftazidime • Ceftriaxone • Cefixime • Fourth Generation • Cefepime

12. Cephalosporins • Structurally and pharmacologically related to penicillins • Inhibits cell wall synthesis • 1st gen: mostly active against Gram + bacteria • Pneumococci, streptococci, staphylococci • 2nd gen: more active against Gram – bacteria • E. coli, K. pneumoniae, H. influenzae • 3rd gen: most active against Gram – bacteria • 4th gen: extended spectrum of activity against both Gram + and – bacteria • DO NOT COVER ENTEROCOCCUS or MRSA

13. Cephalosporins • Relatively safe • Side effects: • GI upset nausea, vomiting, diarrhea, abdominal pain • Pseudomembranous colitis broad spectrum agents • Rash • Super infections • Anaphylaxis • Hematological long term use

14. Carbapenems • Imipenem, meropenem, ertapenem • Inhibit cell wall synthesis • Most broad spectrum activity of all antimicrobials • Active against Gram + and – bacteria • Side effects: • GI upset nausea, vomiting, diarrhea • Rash • Seizures  those with compromised renal function • Hematological eosinophilia, neutropenia • Nephrotoxicity secondary to metabolite

15. Vancomycin • Inhibits cell wall synthesis at different site than β-lactams • Active against Gram + bacteria only • Use restricted for MRSA and Clostridium difficile • Always given IV, except for treatment of antibiotic associated enterocolitis • Must give over of at least 1 hour to minimize risk of “red man syndrome” • Red man syndrome = sudden drop in BP with flushing &/or rash on face, neck, chest and upper extremities

16. Vancomycin • Troughs are taken within 30 min prior to dose • Side effects: • Ototoxicity at supratherapeutic doses of > 80 mg/mL • Nephrotoxicity • Fever, chills, phlebitis at infusion site

17. Sulfamethoxazole/Trimethoprim • Prevent bacteria from synthesizing folic acid thereby disrupting DNA synthesis • Active against both Gram + and – bacteria • Mostly used in uncomplicated UTIs, and some respiratory infections • Side effects: • GI upset nausea, vomiting, diarrhea • Skin rashes, photosensitivity • Hematologic when used for long durations

18. Fluoroquinolones • Ciprofloxacin, levofloxacin, moxifloxacin • Inhibit bacterial DNA synthesis • Broad spectrum of activity against Gram + and – bacteria • Well absorbed orally • Concentrations achieved after PO dose are comparable to those with IV dose • Not recommended for use in children or pregnancy

19. Fluoroquinolones • Absorption limited when administered within 2 hours of cations aluminum, magnesium, calcium, iron, zinc • Side effects: • GI upset nausea, vomiting, diarrhea, abdominal pain • Pseudomembranous colitis with ciprofloxacin • Rash, photosensitivity, pruritus

20. Aminoglycosides • Gentamicin, tobramycin • Inhibit bacterial protein synthesis • As single agent active against Gram – bacteria • Used with other agents, some Gram + synergy • Only administered IV • Troughs are taken within 30 min prior to dose • Usually obtained when dosing q8h

21. Aminoglycosides • Side effects: • Nephrotoxicity irreversible • Ototoxicity irreversible • Skin rash • Fever • Paresthesia

22. Tetracyclines • Tetracycline, doxycycline, minocycline • Inhibit bacterial protein synthesis • Some Gram + and some Gram – bacteria coverage, but many strains resistant • Used primarily for infections caused by susceptible Rickettsia, Chlamydia, Mycoplasma and other uncommon bacteria • Avoid use in young children and pregnancy

23. Tetracyclines • Decreased absorption when administered with dairy products, antacids, and iron salts • Space by at least 2 hours • Side effects: • GI upset nausea, vomiting, diarrhea • Esophagitis and esophageal ulcers swallow with lots of water and avoid laying down for at least 30 min • Photosensitivity, rash

24. Macrolides • Azithromycin, erythromycin, clarithromycin • Inhibit bacterial protein synthesis • Active against Gram + bacteria and atypical pathogens Mycoplasma, Chlamydophila, Legionella • Numerous drug interactions with clarithromycin inhibits metabolism • Side effects: • GI upset nausea, vomiting, abdominal cramping • Especially with erythromycin

25. Clindamycin • Inhibits bacterial protein synthesis • Activity against Gram + and anaerobic bacteria • Side effects: • GI upset nausea, vomiting, diarrhea • Pseudomembranous colitis** • Skin rashes

26. Metronidazole • Inhibits protein synthesis • Activity against anaerobic bacteria • Treatment of choice for C. difficile • Side effects: • GI upset nausea, vomiting • Metallic taste

27. Nitrofurantoin • Mechanism not fully understood • Used primarily for lower UTIs caused by E. coli and Enterococcus, • Not to be used in pyelonephritis • Take with meals to improve absorption • Side effects: • Discolored urine (brown)