Lecture 13 3/19/24 Flashcards
What are the general characteristics of aminoglycosides?
-irreversibly bind to 30S ribosomal unit
-bactericidal
-O2-dependent transport
-lose activity in acidic environments
-lose activity due to purulent debris
What is the spectrum of aminoglycosides?
-high susceptibility of gram neg. aerobes and FAs
-decent susceptibility of gram pos. FAs
-some susceptibility of gram pos. aerobes
-no susceptibility of anaerobes
Which aminoglycoside has the broadest spectrum of activity?
amikacin
Which aminoglycoside is the least nephrotoxic?
amikacin
What are the characteristics of aminoglycoside pharmacokinetics?
-poor oral absorption
-distribute in extracellular fluid only
-actively accumulated by renal tubular cells
-excreted unchanged in urine via glomerular filtration
-short plasma half-life
What best determines the efficacy of aminoglycosides?
how high the peak concentration of the antibiotic is compared to the MIC
Which ratio is best correlated with efficacy for aminoglycosides?
Cmax/MIC ratio
What is post-antibiotic effect?
residual antibacterial effect seen after concentrations of the antibiotic decrease below the MIC
Which type of drug regimen minimizes adaptive resistance to aminoglycosides?
high, infrequent doses
What is adaptive resistance?
temporary refractoriness to drug penetration that occurs in bacterial cells surviving the initial ionic binding
What are the characteristics of amingolycoside-related nephrotoxicity?
-reversible renal impairment with short term use
-acute tubular necrosis
-more serious renal damage with long term use
Which measurements can indicate nephrotoxicity?
-increased GGT:urine Cr ratio
-proteinuria
-elevated BUN and serum creatinine
What allows for aminoglycosides to cause nephrotoxicity?
uptake/accumulation of aminoglycosides into the renal tubular epithelium requires a carrier, and thus is saturable
What are the characteristics of aminoglycoside-related ototoxicity?
-can be vestibular or cochlear, depending on antibiotic
-usually irreversible
-increased risk when also using diuretics
What are the risk factors for aminoglycoside toxicity?
-long duration of therapy
-volume depletion
-pre-existing renal disease
-age
-concomitant nephrotoxic drugs
-elevated trough concentrations
What are the main clinical uses for aminoglycosides?
-severe infections with gram neg. aerobes
-local therapy of musculoskeletal infections
-combinations with other drugs
Why is extra-label use of aminoglycosides uncommon in food animals?
prolonged persistance in renal tissues
What is neomycin used for?
local treatment of intestinal/wound/ear/skin infections
Which strategies can be used when delivering aminoglycosides to a specific region in order to reduce drug exposure?
-intravenous regional limb perfusion
-antibiotic-impregnated beads
What is intrinsic resistance?
when a bacterial species is naturally resistant to a certain antibiotic/family of antibiotics, without need for mutation/gain of further genes
What is adaptive resistance?
temporary increase in the ability of a bacterium to survive an antibiotic
What is acquired resistance?
when a particular microorganism obtains the ability to resist the activity of a particular antimicrobial agent to which it was previously susceptible
What are the characteristics of PPG + gentamicin?
-commonly used in equine practice
-not recommended to mix in same syringe
What is the spectrum of PPG + gentamicin?
-high susceptibility of gram neg. bacteria and all gram pos. except FAs
-decent susceptibility of gram pos. FAs
What are the characteristics of the voluntary aminoglycoside ban in cattle?
-not approved for use in cattle
-no established tolerance for aminoglycoside residues in edible cattle tissue
-aminoglycoside use in cattle is legal, but many veterinarians are against it due to kidney residues
What are the general characteristics of tetracyclines?
-broad spectrum
-increasing acquired resistance
-approved for animal use
-bind to 30S ribosomal subunit
-bacteriostatic
What is the spectrum of tetracyclines?
decent susceptibility of all bacterial classes
Which important species exhibit inherent resistance to tetracyclines?
-Pseudomonas
-some Enterobacteriaecae
Which important species exhibit acquired resistance to tetracyclines?
-Enterococci
-Staphylococci
-Streptococci
-enteric bact.
-gram neg. anaerobes
What is important about tetracycline absorption?
oral bioavailability is greater for doxycycline and minocycline than older tetracyclines
What are the characteristics of tetracycline distribution?
-wide distribution, esp. with doxycycline and minocycline
-accumulate in bone and forming enamel
-poor distribution across BBB
What are the characteristics of tetracycline elimination?
-excreted in urine and bile
-enterohepatic recirculation with half-life of 6-10 hrs
What are the characteristics of tetracycline toxicity and adverse effects?
-irritants
-disturb intestinal flora
-rapid IV bolus can lead to collapse (fatal in horses)
-pigmentation/softening of teeth in fetus/neonate
-nephrotoxicity
What are the primary clinical uses for tetracyclines?
-resp. infections
-intracellular organisms
Why are tetracyclines not administered via IM in horses and companion animals?
-local tissue damage
-local pain
-erratic absorption
What are the clinical uses of oxytetracycline and doxycycline in small animals?
-UTIs
-brucellosis
-chlamydiosis
-leptospirosis
-Ehrlichia canis
-Rickettsia rickettsi
-Haemobartonella felis
What are the clinical uses of doxycycline or minocycline in small animals?
-deep tissue infections
-superficial pyoderma
-periodontal disease
