Antimicrobial Families Flashcards
Physiochemical properties of beta-lactams
- water soluble, organic acids (extracellular)
- low to high protein binding
- acid labile
- metal ions can accelerate degradation process
- chemically incompatible with aminoglycosides in vitro
- initial fermentation product
Mechanism of action for beta lactams
Inhibit bacterial cell wall synthesis by binding to penicillin binding proteins
- cross linkage of peptidoglycan cell wall does not occur
Beta-lactams are typically ______ due to osmotic imbalance
Bacteriocidal
- bacteria cytoplasm is hypertonic compared to host isotonic environment
When does static action occur with beta lactams?
If bacteria treated with beta-lactams are in an environment isotonic to their cytoplasm
Which antibiotic class has decreased activity in the presence of purulent debris?
Beta lactams
MRSA implies resistance to _______
The entire beta lactam family
- resistance factors also carry resistance to a variety of other antibiotics
How does cefazolin differ from other first‐generation cephalosporins?
Is the only injectable 1st generation cephalosporin
- has better activity against E coli
- must be tested for gram neg susceptibility
Mechanisms of beta lactam resistance
- degradation by bacterial enzymes
- penicillin binding site alteration
- reduced penetration (impaired crypticity)
What allows passage of resistance between species of bacteria and between genera?
Plasmids and transposons
What is the pharmacodynamics of penicillins?
Time-dependent killing
- you are not looking at how high peak concentration is
What beta-lactam is measured in units?
Penicillin G
All beta lactams concentrate in _______
Urine
What is the drug of choice for most streps and anaerobes?
Penicillin
What are the 3 forms of penicillin G and their concentrations?
Crystalline (IV,IV,SQ) - rapid high conc - short duration Procaine (IM,SQ) - flip-flop kinetics - lower conc, prolonged duration Benzathene (IM) - flip flop kinetics - extremely low conc, prolonged duration (increased residue in food animals)
Penicillin G - adverse reactions
Nontoxic, primarily allergic rxns due to degradation product of penicilloic acid
- may have toxicity with salt (potassium pen G) or ester (procaine)
Why should pen G not be used in guinea pigs, hamsters, or rabbits?
Will disrupt hind gut flora
How is penicillinase-resistant penicillins similar to pen G?
Similar in structure, but is not inactivated by penicillinase
- use against staph that are resistant due to penicillinase
What 2 drugs are used to test bacteria against penicillinase-resistant penicillins?
Oxacillin or cefoxitin
Dicloxacillin
Acid stable (can be given orally) - approved for use in dogs, but 1st gen cephalosporins are used instead
Cloxacillin
Intramammary infusion for dairy cows
What are the 2 narrow spectrum penicillins?
Pen G and Penicillinase-resistant penicillin
What allows broad spec penicillins better penetration of gram negs?
Increased crypticity
What are the 3 broad spec penicillins
- ampicillin
- amoxicillin
- hetacillin
Hetacillin
Prodrug converted to ampicillin by metabolism
- used as intramammary infusion
Ampi and amoxicillin
Used interchangeably
- acid stable (oral)
- similar D, M, E as narrow specs
Which broad spec is absorbed twice as well orally in dogs and cats as ampicillin?
Amoxicillin
No _______ are absorbed orally in horses
Penicillins
Injectable broad spec penicillins
Sodium ampi and sodium amoxi are given by all parenteral routes
- rapid absorption and elimination (given every 8 hrs)
- repository trihydrate formulation used in vet med
How effective are the broad spec penicillins against enteric gram-neg?
Ampi/amoxicillin is unlikely to reach effective concentrations
- S breakpoint in dogs/cats: 0.25 mcg/ml
- S breakpoint in cattle: 0.03 mcg/ml
Adverse reactions to broad spectrum penicillins
- large doses of ampi can cause diarrhea in horses (entry into bile)
- disrupts flora if given orally to ruminants
- trihydrate form too irritating to use in horses
When is it okay to give oral amoxi (extra-labelly) to a ruminant?
Only give to calves in their first 24 hrs while they are still considered to be a monogastric
Extended spectrum penicillins
Anti-pseudomonal penicillins
- increased crypticity, bind to altered PBP
- ticarcillin, piperacillin
- acid labile (6-8 hr dosing interval)
Potentiated penicillins
Penicillinase inhibitor is added to formulation to “release” penicillin (ticarcillin, piperacillin)
- clavulanic acid, sulbactam
- inhibitor looses stability once hydrated, so need to have tablets well wrapped
- only works in bacteria resistant by virtue of penicillinase
- ineffective against bacterial strains containing type 1 beta-lactamases
What potentiated penicillin is effective against chlamydia in cats?
Clavamox
With cephalosporins, activity against anaerobes is ______
Erratic
- clostridia are highly resistant
1st generation cephalosporins
Not affected by penicillinase, good activity against staph
- used in skin and bone infections
- not reliable against anaerobes
1st gen cephalosporin agents
- cephalothin - nepthrotoxic! still used for in vitro susceptibility test
- cephalexin and cefadroxil - used as orals in small animals
- cefazolin - better e coli activity than other 1st gens
- cephapirin - intramammary infusion for dairy cows
Which 1st gen ceph is injectable?
Cefazolin
2nd generation cephalosporins
- cefoxitin
- cefotetan
Cefoxitin and cefotetan
Have good anaerobic acitivty!
- 4 quadrant coverage!!
- are structurally considered to be cephamycins (other cephalosporins are cephems) making them less suceptible to cephalosporinase produced by anaerobes
- injectable only (IV, IM)
What is an injectable, 4 quadrant drug of choice in a non-critical patient
Cefoxitin
What 3rd gen cephalosporin is effective against pseudomonas?
Ceftazidime
What causes resistance to 3rd gen cephalosporins to pseudomonas?
Extended spectrum beta-lactamases
- increasing public health concern
Common 3rd gen injectables
- cefotaxime
- ceftriaxone (standard for meningitis)
- ceftazidime
What allows 3rd gens to cross the BBB?
Low MICs and low to moderate protein binding
- considered drug of choice for bacterial meningitis
What cephalosporins are not effective against carbapenem-resistant enterobacteriaceae?
4th gen, 5th gen, and potentiated cephalosporins
- not used in vet med
New-gen cephalosporins
Extensively protein bound causing long elimination half-lives and long dosing intervals
- goon non-enteric gram neg activity
Ceftiofur
Rapidly metabolized to desfuroylceftiofur
- most activity comes from metabolite
Cefpodoxime proxetil
Prodrug converted by intestinal wall esterases to active cefpodoxime
Cefovecin
Structurally is a 3rd gen, but high protein binding
Naxcel
Ceftiofur sodium
- requires reconstitution with a limited shelf life
- 4 day withdrawal for slaughter
- no withdrawal for milk*
Excenel
Ceftiofur HCL
- shelf stable formulation
- 2 day slaughter withdrawal no milk withdrawal
- exception: spectramast intramammary infusion that does have a milk withdrawal
Excede
Ceftiofur crystalline free acid
- approved for cattle for 1 or 2 doses
- -> 13 day slaughter withdrawal, no milk withdrawal
- approved in swine (14 day slaughter withdrawal) and horses
Cefpodoxime proxetil
Once daily oral dosing
- dogs used to treat skin and soft tissue infections
Cefovecin
Labelled for skin and soft tissue infections due to staph, strep, and pasturella and for UTI due to e coli
- long duration due to high protein binding and long half life
Monobactams
Spectrum limited to aerobic gram-neg bacilli
Carbapenems
Broadest spectrum of activity of any antibiotics
- penetrates BBB, inflammation enhances penetration
- imipenem and meropenam
Meropenem
Does not cause seizures or nephrotoxicity
- given SQ and IV
Carbapenem-resistant enterobacteriaceae
Enterobacteriaceae resistant to all beta-lactams including carbapenems
- reported in all 50 states
- resistant mechanisms: carbapenemases, decreased crypticity, active efflux pump
- horizontal transmission
