4. HISTORY:
Gram-positive
Spore forming
Aerobic
Saprotrophic form in
soil & water
Form branched
mycelium
Schering Corporation in Bloomfield,
N.J.
Soil Samples by Rico
Woyciesjes.
Gentamicin was discovered in
1963 by Weinstein, Wagman &
others.
Fermentation Of
Micromonospora
purpurea, a specie of
Actenomycese.
source
5. •It was patented in 1962.
•Approved for medical use in 1964.
•Gentamicin was approved by US Food &
Drug Administration (FDA) in 1966.
•Then it was purified and the structures of
its three components (C complex) were
determined by Cooper and others at the
Schering Corporation.
• It was initially used as a topical treatment
for burns at burn units in Atlanta and San
Antonio (USA).
6. introduced into IV usage in 1971
Gentamicin - a mainstay for use in sepsis.
“WHO” has now included it in the list of
essential medicines.
It is available as generic medication.
7. WHY IT HAS A SUFFIX
“MICIN”?
Various species are sources
of aminoglycoside antibiotics
with spellings that end with -
micin, such
as gentamicin, mutamicin, netil
micin, retymicin, sisomicin, v
erdamicin and turbinmicin.
Potent new antifungal
discovered in the
microbiome of marine
animals.
Stated for Generic Names;
“antibiotics not produced
by Streptomyces should not
use y in the ending of the name”.
streptomyces
8. INTRODUCTION:
Gentamicin is a broad spectrum
antibacterial drug.
It is widely used an aminoglycoside.
Which has Bactericidal activity.
Often, used in a combination with
other antibiotics.
Administered for serious infections
caused by gram-negative rods. Also
active against strains of gram-
positive bacteria.
Ineffective against anaerobes
because their transport into
bacterial cell requires oxygen.
Highly active at pH 8. It is 20 times
more active in alkaline solution.
It’s polar in nature, highly soluble in
water.
It is not absorbed orally.
9. COMPONENTS:
Gentamicin C complex composes approximately 80% of
Gentamicin and have been found to have the highest
antibacterial activity.
Gentamicin A,B,X and a few others make up the remaining
20% of gentamicin and have lower antibiotic activity.
C
complex
R1 R2
C1
Methyl g
roup
Methyl g
roup
C1a
Hydroge
n
Hydroge
n
C2
Hydroge
n
Methyl g
roup
C2a
Hydroge
n
Methyl g
roup
C2b
Methyl g
roup
Hydroge
n
10. Against-KILLS Combination-FRIENDS
Gram-negative bacilli E.Coli,
Klebsiella pneumoniae,
Enterobacter, H. influenza,
Proteus, Serratia, Pseudomonas
aeruginosa, Brucella,
Campylobacter, Citrobacter,
Fransisella, Yersinia.
Gram-positive bacteria Staph.
aureus, Strep. faecalis, listeria.
•Penicillin, Azithromycin, Beta lactams
come in combination with Gentamicin to
produce synergistic effect.
•Usually gentamicin + Cell wall inhibitor
(e.g. benzylpenicillin, flucloxacillin,
vancomycin).
Like:
Amoxicillin in Listeria meningitis,
Vanc & Met (in Peritonitis),
Fluclox/ Benpen (in Inefective
endocarditis),
Depto/Taz, Vanc (in Septicaemia).
11. SYNERGISTIC EFFECT-COMBINATION
Antibiotics work together to produce an effect more potent
than if each antibiotic were applied singly.
If bacteria become resistant to one drug, the second drug will
kill them to prevent the emergence of resistant stains.
12. MODE OF ACTION:
Inhibition of Protein
Synthesis
Bacteria have 70S ribosome with 50S & 30S subunits.
Aminoglycoside act on 30S subunit.
Blocks functioning of initiation complex & causes misreading of
mRNA.
Misreading of mRNA codon, leads to errors in amino-acid sequencing.
Disruption of polysomes, reducing efficiency of protein synthesis.
Inhibition of translocation of tRNA between A & P ribosomal binding sites.
As a result membrane damage occurs & bacterium dies.
13. GENETIC BASIS OF RESISTANCE:
“Plasmid Mediated resistance”
Plasmids frequently mediate resistance
to multiple drugs.
They have high rate of transfer from one
cell to another by conjugation.
They are extra chromosomal,
circular, double-strand DNA
molecules that carry the genes
for a variety of enzymes that can
degrade antibiotics & modify
membrane membrane transport
system.
14. Gentamicin is
used to treat
many types of
serious bacterial
infections.
Meningitis
Urinary tract
infection
Bone
infection
Uses:
16. ADVERSE EFFECTS: They are dose-related,
plasma levels should be
monitored during treatment
& it shouldn’t exceed 14days
of daily 2 to 3 time dosage as
per requirements.
Toxic Effects:
Nephrotoxicity
Ototoxicity
Neurotoxicity
Allergic Reactions:
Nausea
Vomiting
Rashes
17. CAUTION & CONTRA-INDICATIONS:
Containdicated:
In Hypersensitivity like anaphylaxis.
In severe renal impairment.
In pregnancy, cause irreversible bilateral congenital
deafness in newborn.
In myasthenia gravis (effects nerve cells) & other
neuromuscular disorders as there is a risk of worsening
weakness. Because it can increase the activity of
neuromuscular blocking agents.
May cause respiratory paralysis with curare-type muscle
relaxants.
18. FLASH CARDS:
*Regarding the toxicity of
aminoglycoside which statement is
accurate?
a. Gentamicin & tobramycin are least
likely to cause renal damage.
b. Reduced blood creatinine is early
sign of aminoglycoside
nephrotoxicity.
c. Ototoxicity due to amikacin &
gentamicin includes vestibular
dysfunction, which is often
irreversible.
*The minimal inhibitory concentration
(MIC) of patients organism to penicillin is
1ug/mL and MIC to gentamicin is 8ug/mL.
However, the MIC to a combination of
penicillin & gentamicin is 0.01ug/mL.
Which one of the following term is the
most accurate to describe this effect?
a. Antagonism
b. Reassortment
c. Synergism
*Your patient is a 70year old man with
endocarditis caused by Enterococus
faecalis. Which one of the following is
the best combination of antibiotics to
treat the infection?
a. Doxacycline & Levofloxacin
b. Metronidazole & clindamycin
c. Penicillin G & gentamicin
*Patient has 3rd degree burns over most of
his body. He was doing well until 2 days
ago, when he spiked a fever & his
dressings revealed pus that had a blue-
green color. Gram stai of pus revealed a
gram-negative rod that formed colorless
colonies on EMB agar. Which one of the
following bacteria is the most likely cause
of this infection?
a. Camphylobacter jejuni
b. Escherichia coli
c. Pseudomonas aeruginosa
19. REFERENCES:
Hugo and Russell`s Pharmaceutical Microbiology
7th Edition edited by Steph P Denyer, Norman A
Hodges, Sean P Gorman in Blackwell Science (Part
2: Chapter#10 Types of antibiotics and synthetic
antimicrobial agents by A Denver Russell; Page#
153, 166.
Review of Medical Microbiology and Immunology
by Warren Levinson 13th edition a LANGE medical
book Page#172, 191, 203, 204, 212, 213, 260,
327, 347, 363, 364 & some self assessment
questions with keys.
Microbiology Principles and Explorations 7th
edition by Jacquelyn G.Black contributor Laura
J.Black Page#383, 387.
https://en.wikipedia.org/wiki/Gentamicin
https://en.wikipedia.org/wiki/Micromonospora
https://www.slideshare.net/kevfrost/gentamicin-
and-the-yorkshirehartford-regimen
https://www.sciencedirect.com/topics/biochemistr
y-genetics-and-molecular-biology/gentamicin
KEY:
All
“c”
options
are
correct
in
Flash
Cards.
