This document provides information on various aminoglycoside antibiotics, including gentamicin, amikacin, kanamycin, neomycin, and streptomycin. It discusses their indications, mechanisms of action, pharmacokinetics, adverse effects, and ways to maximize therapeutic effects and minimize adverse effects when using these antibiotics. The most important aspects covered are the serious risks of nephrotoxicity and ototoxicity, and the need to closely monitor peak and trough drug levels when patients are receiving aminoglycoside therapy.
5. Introduction
The Aminoglycosides have been in use since 1944.
They are extremely effective antibiotics for treating
severe infections.
Their general use, however, is limited because of the
potential for serious adverse effects, especially
ototoxicity and nephrotoxicity.
Aminoglycosides include gentamicin, amikacin,
kanamycin, netilmicin, tobramycin, paromomycin and
streptomycin.
6. Introduction
The most frequently used aminoglycosides are
gentamycin, tobramycin and amikacin.
Gentamicin is the most widely used, possibly because
of its availability as a generic formulation, and its
prototype drug for the aminoglycoside family.
7. Pregnancy Category C
inhibits protein synthesis in susceptible strains of gram-
negative bacteria.
Gentamicin must be transported across the cell memb.
in order to enter the cell and disrupt protein synthesis.
This process requires oxygen; therefore, gentamicin and
other aminoglycosides are ineffective against
anaerobes.
Gentamicin
8. Gentamicin
Action
Gentamicin, like all antibiotics, has no direct effect on
the cells of the body.
It exerts its effect by entering the bacterial cell and
binding to the 30S ribosomal subunit.
This event leads to a misreading of the information
used within the cell to form proteins.
The cell then produces amino acids that do not link
correctly.
9. Gentamicin
The result is a change in metabolic function that in turn
prevents bacterial reproduction and weakens the cell
wall, leading to cell wall rupture and death.
Many strains of bacteria are resistant to the
aminoglycosides and do not allow them to enter the
cell.
Because of this, aminoglycosides are often given with
synergistic antibiotics to increase their effectiveness or
to alter the cell wall so that the aminoglycoside can
enter.
10. Indications
Gentamicin is effective in managing infections caused
by gram-negative bacilli.
Susceptible organisms include: Pseudomonas
aeruginosa, Proteus mirabilis, Escherichia coli,
Klebsiella, Enterobacter, Serratia, and Citrobacter
species; and staphylococci (gram+).
Gentamicin
11. Gentamicin is NOT considered useful in treating
meningitis unless it is administered intrathecally.
Gentamicin is also indicated for topical treatment of
eye or skin infections caused by susceptible
organisms.
Gentamicin
12. Clinically, gentamicin is useful for urinary tracts
infections (UTIs), such as pyelonephritis, gynecological
infections, peritonitis, endocarditis, pneumonia,
bacteremia and sepsis, respiratory infections, including
those associated with cystic fibrosis, osteomyelitis, and
foot and other soft tissue infections associated with
diabetes.
Gentamicin
13. Pharmakinetics:
Parenteral genta is widely distributed through the body
in ECF; however, it does NOT penetrate appreciably
into the CNS.
It crosses the placenta and is secreted in breast milk.
Genta concentrates in the kidney, reaching levels 50
times higher than those in serum.
Gentamicin
14. It is also concentrates in the endolymph and perilymph
of the inner ear.
High concentration of genta in these fluids are
associated with its major adverse effects “
nephrotoxicity and ototoxicity.
Parenteral genta is excreted unchanged in urine,
whereas oral genta is excreted unchanged in feces.
Gentamicin
15. Because it is poorly absorbed when taken orally, genta
is usually reserved for parenteral or topical use.
It may, however, be given orally to exert a local
decrease in GIT bacteria before surgical or other
invasive procedures.
Gentamicin
16. o Most Common Adverse Effects:
o Nephrotoxicity occurs most frequently in infants or
elderly patients, or with prolonged or high-dose therapy.
o Ototoxicity occurs most frequently when serum trough
levels are elevated, in infants or elderly patients, or with
prolonged or high-dose therapy.
o Neuromuscular blockade may result in profound
respiratory depression. It occurs most frequently in patients
with myasthenia gravis and in patients receiving general
anesthetics or nondepolarizing skeletal muscle relaxants.
Gentamicin
17. CNS: confusion, depression, disorientation, numbness,
tingling and weakness.
Hemato: leukemoid rxns and depressed bone marrow
function.
GI: nausea, vomiting, diarrhea, w.t loss, stomatitis, and
hepatic toxicity.
CV: palpitations, hypotension, hypertension.
Hypersensitivity rxns.
Other: superinfections, fever, apnea, and joint pain may
also occur.
Gentamicin
18. Contraindications:
Pregnancy and lactation
Known allergy to any aminoglycoside
Cautions:
Renal and Hepatic disease
Dehydration
Pre-existing hearing loss
Myasthenia gravis
Parkinsonism
Infant botulism
Gentamicin
19. Maximizing Therapeutic Effects
Make sure that patients receive the full course as
prescribed.
Coordinate the administration of drugs to decrease
potential drug interactions.
Evaluate C/S reports to make sure that genta is the
appropriate drug.
Administer extended penicillins, such as carbenicillin
or ticarcillin at least 2 hrs apart to ensure the efficacy of
genta.
Gentamicin
20. Minimizing Adverse Effects:
To reduce the occurrence of adverse effects, it is
imperative to maintain blood levels of genta within a
therapeutic margin that is very narrow.
To do this, Peak and Trough drug levels are monitored
throughout therapy.
Blood for Peak levels is drawn 30 minutes after the
completion of IV administration and 1 hr after IM
administration.
Bloods for Trough levels is drawn just before the next
dose.
Gentamicin
21. Monitor for signs of ototoxicity. Before administering
each dose, assess the patient’s balance and gross
hearing.
Monitor for signs of nephrotoxicity. Assess the
hydration status of the patient and be alert for dilute
urine or proteinuria.
Monitor the patient for gentamicin-induced diarrhea
because diarrhea may also cause dehydration.
Gentamicin
22. If CNS effects occur, safety measures should be
instituted to protect the patient.
Small, frequent meals can be arranged for patient with
GI effects, and frequent mouth care and ice chips can
be offered to relieve stomatitis and sore mouth.
If a patient receiving genta requires surgery, the chart
should indicate prominently that genta has been given.
Remember that genta may interact with neuromuscular
blocking agents commonly used during surgery.
Gentamicin
23. Monitor lab. Tests such as renal and hepatic functions
( KFT & LFT ), Peak and Trough levels of genta, and
the fluid intake and output status of the patient.
Gentamicin
24. Memory Chip “ GentamicinGentamicin”
Used for serious gram-negative infections.
Major contraindications: hypersensitivity, pregnancy,
and breast-feeding.
Most common adverse effects: nausea, vomiting,
diarrhea, and w.t loss.
Most serious adverse effects: nephrotoxicity,
ototoxicity, neuromuscular blockade.
25. Maximizing therapeutic effects: administer al least 2 hrs
before or after extended infusions of penicillins.
Minimizing adverse effects: monitor Peak and Trough
levels throughout therapy.
Most important patient education: teach the patient the
S&S of both nephrotoxicity and ototoxicity and also the
importance of contacting the health care provider
immediately if any symptoms should occur.
Memory Chip “ GentamicinGentamicin”
26.
27. AmikacinAmikacin
Amikin ®
Is a parenteral aminoglycoside with a broader spectrum of
activity than gentamicin for gram-negative bacilli.
AmikacinAmikacin is also less likely to induce bacterial resistance.
Although some hospitals use AmikacinAmikacin as first-line
treatment of systemic infection because of an increased
resistance to gentamicin, may others reserve its use for
infections that do not respond to other aminoglycoside
antibiotics.
Its contraindications, adverse effects, drug interactions, and
patient management are similar to those of gentamicin.
28.
29. KanamycinKanamycin
Kantrex ®
Is used orally to reduce ammonia-forming bacteria in
hepatic coma and as an adjunctive therapy to decrease
GI flora.
It use for systemic infections is limited by the number
of bacteria that are resistant to it and the availability of
genta in its less expensive generic formulation.
Its contraindications, adverse effects, drug interactions,
and patient management are similar to those of
gentamicin.
30.
31. NeomycinNeomycin
Mycifradin ®
Has the highest risk for toxicity of all of the aminoglycosides.
Because it is so toxic, it is not administered parenterally.
It is available orally to decrease GI flora as a preparation for
bowel surgery and to treat hepatic encephalopathy.
Because it is not absorbed from the GI tract, it frequently
causes superinfection within the bowel.
Neomycin is also available in OTC drugs as a topical
antibiotic.
Its contraindications, adverse effects, drug interactions, and
patient management are similar to those of gentamicin.
32. StreptomycinStreptomycin
Is a parenteral aminoglycoside.
It is used as part of combination therapy for both active
TB and for treating streptococcal or enterococcal
endocarditis.
As a single agent, it is used for mycobacterial
infections, plague, tularemia, and brucellosis.
In addition to ototoxicity and nephrotoxicity,
streptomycin may include neurotoxicity.