Antibacterial Therapy I Flashcards
ADME
Absorption
Distribution
Metabolism
Excretion
Absorption
Drugs that have >80% bioavailability, basically the same as IV
eg. fluoroquinolones, clindamycin, fluconazole, metronidazole
Distribution
Volume of distribution:
- ratio of amount of drug in body to serum concentration of drug
- not an anatomical space in body
- can be altered by clinical factors (eg. protein binding, organ failure)
- half life of drug determined by volume of distribution and organ clearance of drug
Metabolism
- many antimicrobials undergo hepatic metabolism
- many inhibit or induce cytochrome 450 enzymes
Excretion
- may need to alter dosage in their is renal impairment (reduced excretion results in longer half life)
- ceftriaxone, metronidazole, moxifloxacin not renal eliminated
Antibacterial susceptibility testing
- eg. broth dilution tests, disk diffusion tests, E tests
- in vitro testing not representative of in vivo activity (does not account for immune system, site of inoculation, artificial growth conditions)
Bactericidal vs. bacteriostatic
- bactericidal usually DNA synthesis or cell wall inhibitors
- bacteriostatic usually protein inhibitors, requires functioning immune system to clear ix
- cidal better for deal seated ix’s, but induces immune response
- static better for slow growing bacteria
- organism dependent whether it’s cidal or static
Concentration dependent agents
- higher concentration results in higher killing of bacteria
- better to give fewer higher doses
- eg. fluoroquinolones, aminoglycosides
Time dependent agents
- higher concentrations do result in higher killing, but maxes out at 4-5x MIC
- better to give more frequent smaller doses
eg. beta lactams
Post antibiotic effect
- antibiotic continues to inhibit bacterial growth even after antimicrobial discontinued
- allows for less frequent dosing
- most have 1-2 hr PAE vs G+
- aminoglycosides and fluoroquinolones have extended PAE vs G-
Peak/MIC
- important parameter for concentration dependent agents
- Peak/MIC > 8 associated with best cure rates
Time/MIC
- important parameter for time dependent agents
- Time over MIC > 40% associated with best cure rates
AUC/MIC
-important parameter for vancomycin, fluoroquinolones, aminoglycosides
Factors involved in choosing an antimicrobial (5)
- Efficacy
- Toxicity
- Patient specific factors
- Ease of administration
- Cost
Efficacy
- spectrum of activity, pharmacodynamic properties of agent
- site of ix (likely causative organism, whether agent will reach sites, other treatments required to aid ix clearance)
- local susceptibility patterns (antibiograms, don’t use agent that has greater than 10% resistance in community)
- published evidence
Toxicity
- all have risk of adverse rx, vary in type and severity
eg. C diff risky abx (cephalosporins, fluoroquinolones, clindamycin)
Patient specific factors
- Hepatic, renal functioning
- Age, weight, social factors
- allergies
- pregnancy
- history of abx use
- immune status
Ease of administration
-less frequent oral dosing is best
Cost
- all else equal, consider cost
- oral forms usually cheaper
Beta lactam MOA
-inhibits cell wall synthesis by binding penicillin binding proteins, preventing cross linking
Betalactamases
- produced by various bacteria against various types of beta lactams
- can be plasmid or chromosomal
- some are inducible
Betalactamase inhibitor
- eg. clavulanate, tazobactam
- no antibacterial activity on their own
- bind betalactamases and inhibit them
Penicillin
-penicillins
S: Streptococci
CI: Bacterial pharyngitis, endocarditis
Amoxicillin
Penicillins
S: Streptococci and Enterococcus faecalis
CI: otitis media, CAP, enterococcal ix’s
Cloxacillin
Penicillins
S: MSSA
CI: Bacteremia, endocarditis, bone joint ix’s, SSTI
Amoxicillin/clavulanate
Penicillins
S: G+, G-, anaerobes
CI: polymicrobial ix’s (eg. diabetic foot ulcer)
Piperacillin/tazobactam or ticarcillin/clavulanate
Penicillins
S: G+, G-, Pseudo, anaerobes
CI: polymicrobial ix’s, febrile neutropenia, sepsis unknown source
Cephalexin
Cephalosporin
S: MSSA, beta hemolytic Strep.
CI: SSTI
Cefazolin
Cephalosporin
S: MSSA, E coli, Klebsiella, Proteus, Streptococci
CI: SSTI, Bone and joint ix’s, surgical prophylaxis
Cefuroxime
Cephalosporin
S: Penicillin S S. pneumo, H. influenzae, M. catarrhalis
CI: respiratory ix’s, not first line
Cefotaxime/Ceftriaxone
Cephalosporin
S: Penicillin I/R S. pneumo, G-, Streptococci
CI: SSTI, endocarditis, urosepsis
Cefixime
Cephalosporin
S: Penicillin S Streptococci, G-
CI: UTI, gonorrhea
Ceftazidime
Cephalosporin
S: Pseudo
CI: combo w/ aminoglycosides for severe Pseudo ix’s
Cefepime
Cephalosporin
S: MSSA, Penicillin I/R S. pneumo, G+, G-. Pseudo
CI: combo w/ aminoglycosides for Pseudo, febrile neutropenia, polymicrobial ix’s
Cephalosporins - No Activity vs. (2)
- Enterococci
- MSSA
Ertapenem
Carbapenem
S: G+, G-, anaerobes, ampC/ESBL producers
CI: polymicrobial ix’s w/ MDR
Meropenem
Carbapenem
S: G+, G-, anaerobes, ampC/ESBL producers, Pseudo
CI: post-trauma or neurosurgical meningitis, polymicrobial ix’s w/ MDR
Imipenem
Carbapenem
S: G+, G-, anaerobes, ampC/ESBL producers, Pseudo, E. faecalis
CI: intraabdominal, polymicrobial ix’s w/ MDR
Carbapenem Spectrum and Usage
- reserved for MDR ix’s
- not first line
- no activity vs. MRSA
Penicillin allergy
- less than 10% who report allergy have true anaphylactic reaction
- not genetic
- 50% will lose sensitivity in 5 years, 80% in 10 years
- need to clarify allergy history
Penicillin allergy cross-reactivity
- related to R side chains of beta lactam
- low cross reactivity between groups (eg. penicillins and cephalosporins)
- if life-threatening non-IgE mediated allergy, do not use any beta lactams
