GENTAMICIN

AMINOGLYCOSIDE ANTIBIOTIC
Drug Development
Gentamicin was obtained from rare actinomycete genes of Micromonospora that
is Micromonospora purpurea.
The antibiotic is obtained from the culture by perforating the cell wall of the
bacterium.
It was discovered in 1960's by Marvin Weinstein
It was describe to show strong activity against a variety of microbes especially
in Pseudomonas aeruginosa (gram-negative bacteria) in particular.
 USES AND SIDE EFFECT
> It is use for the treatment of infectious and surgical prophylaxis
> Dose need to be correct and monitored regularly because it can cause serious dose-
related side effects including:
Nephrotoxicity
Irreversible hearing loss
 ROUTE OF
ADMINISTRATION
As it is not absorbed from the gut when
administered orally. Hence it is most
predominantly administered via:

1. Intramuscular injection
> Slowly over 2-3 minutes

2. Intraveneous infusion
> Over 30 -120 minutes

To diminish the theoretical risk of a rapid rise in

serum concentration
LOADING DOSE
/INITIAL DOSE
Standard dose: 5mg/kg
However,
1. Gentamicin predominantly clear via kidney
Dosage needs to be increase/decrease
depending on renal function
2. Gentamicin distributes poorly into adipose
tissue due to their high hydrophilicity
Obese patient relatively should receive lower
dose
RECOMMENDED INITIAL DOSE
BASED ON RENAL FUNCTION
ESTIMATED CrCl INITIAL DOSE

> 50 ml/min 5mg/kg

30-50 ml/min 3-5mg/kg

10-30 ml/min 3m/kg

< 10 ml/min 3mg/kg (re-dose as per levels)

CrCl means creatinine clearance

MULTIPLE DAILY DOSE
VS ONCE DAILY
Multiple Daily (MDD)
Divided into three doses
Pre dose check after 24
hours of treatment (Target:
<2mg/L)
Peak level measured one
hour post dose (Target: 5-
10mg/L)
Used for treatment of
endocarditis
Once daily (OD)/
Extended Interval
Initial dose of IV
Less nephrotoxic
Less complex administer and
monitor
Found to be as effective as
traditional MDD
 DOSAGE INTERVAL
The frequency and timing of next dose depends on the patient's renal function

01 24 Hours 02 36 Hours 03 48 Hours

CrCl CrCl CrCl >20-39
>60ml/min >40-59 ml/min ml/min

For patient with CrCl Pre-dose taken 1-4 hours

<20ml/min, gentamicin level before next dose is due
should be taken every 48 and must <1mg/L before
hours and must <1mg/L next dose can be given
before next dose
 PRE DOSE
Normal
Taken up to one hour
before second dose is
given
Checked twice weekly

Abnormal
Must be ≤1mg/litre or
2mg/L before any further
dose is given
Checked before each
dose
PRE-DOSE
> Selecting the optimum-dosing interval is achieved by monitoring pre-dose level

Pre-dose level ≤1mg/L

> Continue current theraphy

Pre-dose level >1mg/L (HIGH)

> Check if dose and timing correct
> Check where the blood sample taken from

> If dose, timing and sampling is correct, levels will need to be repeated 12-24 hours
depending on the original results. It may be necessary to increase dosing interval
> Monitor renal function: an increase pre-dose level may be asscociated with a
deteriorating renal function.
THERAPUTIC DRUG MONITORING (TDM)
Plan initial timing of TDM when more than one dose is intended

Recommended TDM Schedule

Estimated CrCl Dosing regimen Abnormal kidney

Normal kidney function function
(deteriorating)

> 50ml/min 5mg/kg Before 2nd dose

Before 2nd and 3rd dose
30-50ml/min 3-5mg/kg

Before 2nd dose but hold

10-30ml/min 3mg/kg Before 2nd dose
dose until level <1mg or
2mg/L
3mg/kg Before 2nd dose but hold dose
< 10ml/min
(re-dose per level) until level <1mg or 2mg/L
 MAINTAINANCE DOSE
Lower dose compared to initial
3mg/kg
Duration should be limited
Given in divided 2-4 times
Approximately 7 days
Not more than 10 days

Gentamicin’s bactericidal activity is concentration-dependent, and treatment

should aim for a peak concentration of eight to ten times the mean inhibitory
concentration (MIC).
THANK YOU
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