Sukhjinder SidhuInterior Health Pharmacy Resident

Kootenay Lake Hospital

Terminology

• Empiric therapy– Treatment of an infection

before specific culture information has been reported or obtained

• Prophylactic therapy– Treatment with

antibiotics to prevent an infection

Terminology

• Bacteriostatic– Stop growth of bacteria

• Bactericidal– Kill bacteria

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Terminology

• 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

• 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

Terminology

• Broad spectrum– Active on a larger

number of Gram-positive and Gram-negative bacteria

• Narrow spectrum– Active on smaller

number of bacterial species

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Broad vs. Narrow

CloxacillinAmoxcillinPenicillin GNitrofurantoinCephalexinMetronidazole

Amox/ClavFluoroquinolonesCeftriaxone

VancomycinLinezolidMacrolidesAminoglycosidesSulfonamides TetracyclinesCefazolinClindamycin

CarbapenemsPip/Tazo

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 90

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

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

Penicillins

• Generally non-toxic• Side effects:– GI upset nausea, vomiting, diarrhea, abdominal pain

– Pseudomembranous colitis broad spectrum agents

– Rash– Anaphylaxis

Cephalosporins

• First Generation– Cefazolin– Cephalexin

• Second Generation– Cefuroxime

• Third Generation- Ceftazidime- Ceftriaxone- Cefixime

• Fourth Generation- Cefepime

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

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

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

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

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

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

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

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

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

Aminoglycosides

• Side effects:– Nephrotoxicity irreversible

– Ototoxicity irreversible

– Skin rash– Fever– Paresthesia

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

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

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

Clindamycin

• Inhibits bacterial protein synthesis• Activity against Gram + and anaerobic bacteria• Side effects:– GI upset nausea, vomiting, diarrhea

– Pseudomembranous colitis**– Skin rashes

Metronidazole

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

– Metallic taste

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)