1. Interior Health Pharmacy Resident Kootenay Lake Hospital
Sukhjinder Sidhu
Interior Health Pharmacy Resident
Kootenay Lake Hospital

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

3. Terminology Bacteriostatic Bactericidal Stop growth of bacteria
Kill bacteria

4. Terminology Concentration-dependent killing Time-dependent killing
Eradicate bacteria by achieving high concentrations at the binding site
Aiming for concentrations that are > 10 x above MIC
Ex: aminoglycosides, fluoroquinolones
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

5. Terminology Broad spectrum Narrow spectrum
Active on a larger number of Gram-positive and Gram-negative bacteria
Narrow spectrum
Active on smaller number of bacterial species
Collateral damage = antimicrobial resistance; adverse effects

6. Broad vs. Narrow Cloxacillin Amoxcillin Penicillin G Nitrofurantoin
Cephalexin
Metronidazole
Amox/Clav
Fluoroquinolones
Ceftriaxone
Vancomycin Linezolid
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
Antibiotic
Oral Absorption (%)
Amoxicillin
80%
Ciprofloxacin 80
Clindamycin 90
Metronidazole
100
Moxifloxacin

8. Penicillins Natural penicillins Penicillinase-resistant
Penicillin G
Penicillin V
Penicillinase-resistant
Cloxacillin
Penicillin plus β-lactamse inhibitors
Amoxicillin-clavulinic acid
Piperacillin-tazobactam
Aminopenicillins
Amoxcilin
Ampicillin
Ureidopenicillins
Piperacillin
** B-lactamase inhibitors have no antibacterial action

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
Mechanisms of resistance
Inactivation by b-lactamases
Modification of target PBPs
Impaired penetration of drug to target PBPs
Efflux pump mechanism to remove drug

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 Second Generation Third 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)