Sukhjinder Sidhu Interior Health Pharmacy Resident Kootenay Lake Hospital
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Transcript of Sukhjinder Sidhu Interior Health Pharmacy Resident Kootenay Lake Hospital
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)