sukhjinder sidhu interior health pharmacy resident kootenay lake hospital
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Sukhjinder Sidhu Interior Health Pharmacy Resident Kootenay Lake Hospital. 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. Terminology. - PowerPoint PPT PresentationTRANSCRIPT
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Sukhjinder SidhuInterior Health Pharmacy Resident
Kootenay Lake Hospital
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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
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Terminology
• Bacteriostatic– Stop growth of bacteria
• Bactericidal– Kill bacteria
www.amrls.cvm.msu.edu
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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
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Terminology
• Broad spectrum– Active on a larger
number of Gram-positive and Gram-negative bacteria
• Narrow spectrum– Active on smaller
number of bacterial species
www.amrls.cvm.msu.edu
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Broad vs. Narrow
CloxacillinAmoxcillinPenicillin GNitrofurantoinCephalexinMetronidazole
Amox/ClavFluoroquinolonesCeftriaxone
VancomycinLinezolidMacrolidesAminoglycosidesSulfonamides TetracyclinesCefazolinClindamycin
CarbapenemsPip/Tazo
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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
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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
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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
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Penicillins
• Generally non-toxic• Side effects:– GI upset nausea, vomiting, diarrhea, abdominal pain
– Pseudomembranous colitis broad spectrum agents
– Rash– Anaphylaxis
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Cephalosporins
• First Generation– Cefazolin– Cephalexin
• Second Generation– Cefuroxime
• Third Generation- Ceftazidime- Ceftriaxone- Cefixime
• Fourth Generation- Cefepime
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Aminoglycosides
• Side effects:– Nephrotoxicity irreversible
– Ototoxicity irreversible
– Skin rash– Fever– Paresthesia
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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
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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
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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
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Clindamycin
• Inhibits bacterial protein synthesis• Activity against Gram + and anaerobic bacteria• Side effects:– GI upset nausea, vomiting, diarrhea
– Pseudomembranous colitis**– Skin rashes
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Metronidazole
• Inhibits protein synthesis• Activity against anaerobic bacteria• Treatment of choice for C. difficile • Side effects:– GI upset nausea, vomiting
– Metallic taste
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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)