2. Aminoglycosides Flashcards
Examples of aminoglycosides and their spectrum of activity
Amikacin, gentamicin, neomycin sulfate, streptomycin and tobramcyin. Active against some gram-positive organisms and many gram-negative organisms.
It is not anaerobic.
Aminolgycoside mechanism of action
Binds irreversibly to bacterial ribsomes so is bactericidal
Aminoglycoside indications
Septicaemia, endocarditis, hospital acquired pneumonia. Also treats infections caused by pseudomonas aeurginosa.
As they are inactive against anaerobes, it is usually given with a penicillin or metronidazole in blind therapy
Route of aminoglyosides
Aminoglycosides are not absorbed from the gut and therefore given by injection for systemic infection
Streptomycin typical indication
Tuberculosis
Tobramycin typical indication
Cystic fibrosis
Gentamicin therapeutic range
5-10mg/L after a dose
<2mg/L before a dose
The therapeutic range is very narrow.
This is lower in endocarditis
(Post dose 3-5mg/L and <1mg/L before a dose).
Gentamicin spectrum of activity
Inactive against anaerobes and has poor activity against haemolytic streptococci and pneumococci
How is tobramycin administered
Nebuliser or inhalation of a powder on a cyclical Basies, e.g 28 days of therapy then 28 days without therapy
Neomycin’s administration
Too toxic for parenteral administration therefore only used for infections of the skin or mucous membranes or prior bowel surgery or in hepatic failure
How are aminoglycoside levels monitored?
Serum concentrations to prevent excessive and subtherapaeutic concentrations
MHRA guidance surrounding aminoglycosides
Increased risk of deafness in patients with mitochondrial mutations (though mutations are rare). Genetic testing conducted on patients on long-term treatment. Continuous monitoring of renal and auditory function is needed.
MHRA have warned that some batches of aminoglycosides contain some amounts of histamine, which can cause an allergic reaction.
What are you monitoring for in aminoglycosides?
The ear is in the shape of….
Nephrotoxcitiy, auditory and vestibular function (otoxicity).
Patients must report signs of hearing loss, tinnitus, or dizziness
Warning signs in aminoglycosides
Hearing impairment, hearing disturbance
Increased risk of nephrotoxicity when aminoglycosides are given with
ciclosporin, tacromilus, vancomycin
Increased risk of otoxicity when aminoglycosides are given with…
loop diuretics, vancomycin
Common side effects of aminoglycosides
reduced apetite, chest discomfort, cough, fever, dizziness
Appropriateness of aminoglyosides in pregnancy
Aminoglyosides are unsuitable for use in pregnancy
Types of dosing with Gentamicin
Doses based on weight or IDBW in obese patients
Once-daily - where a high dose is given once a day (avoided in severe renal impairment <20mlmin or endocarditis).
Multiple daily - when gentamicin is given in 2-3 divided dose in 24 hrs (monitored after 3-4 doses). Patients with renal impairment require more frequent and earlier monitoring.
Actions to take with Gentamicin monitoring
If levels are high, 1 hour after a dose, reduce the next dose
If levels are high just before the next dose is due, lengthen the interval between doses
In patients with renal impairment, increase the dose interval.
Reduce the dose in patients with severe renal impairment
Appropriateness of aminoglycosides in pregnancy
AVOID, if essential gentamicin can be given
Aminoglycoside interactions
Increased risk of otoxicity if taken at the same time as other ototoxic drugs, e.g loop diuretics. Space the doses with by a long period as possible.
Increased risk of nephrotoxicity if taken at the same time as other nephrotoxic drugs, e.g methotrexate, NSAIDS, cyclosporin and tacromilus, vancomycin, plain chemotherapy
