I am professionally pharmacist. These slides for clinical subject. Especially for pharmacy department students. I hope these students get more benefits about it.

1. Gentamicin
• Clinical use
• The spectrum of activity of gentamicin is
similar to other aminoglycosides but its
most significant activity is against
Psuedomonas aeruginosa.
• It is still regarded by many as first choice for
this type of infection.

2. • Therapeutic range
• Gentamicin has a low therapeutic index, producing dose related side
effects of nephro- and ototoxicity.
• The use of TDM to aid dose adjustment if these toxic effects which appear
to be related to peak and trough plasma levels are to be avoided.
• It is generally accepted that the peak level (drawn 1 h post-dose after an
intravenous bolus or intramuscular injection) should not exceed 12 mg/L
and the trough level (drawn immediately pre-dose) should not exceed 2
mg/L.
• The above recommendations relate to multiple daily dosing of
gentamicin. If once daily dosing is used, then different monitoring and
interpretation parameters may apply.

4. • Distribution
• Gentamicin is relatively polar and distributes primarily into
extracellular fluid.
• Thus, the apparent volume of distribution is only 0.3 L/kg.
• Gentamicin follows a two-compartment model with
distribution being complete within 1 h.
• Elimination
• Elimination is by renal excretion of the unchanged drug.
• Gentamicin clearance is approximately equal to creatinine
clearance.

5. • Practical implications
• Therapeutic range is based on peak (1 h
post-dose to allow for distribution) and
trough (pre-dose) concentrations,

6. • Initial dosage. This may be based on the
patient's physiological parameters.
Gentamicin clearance may be determined
directly from creatinine clearance.
• The volume of distribution may be
determined from ideal body weight.

7. Single dose (STAT) and Once
daily (OD) gentamicin regimen
• 5mg/kg once daily
• Dose: 5mg/kg OD (Maximum daily dose: 480mg)
• Administration: in100ml normal saline or glucose 5%
infused over 60mins
• Advantages
• high peaks are more effective in achieving bacterial kill
• Long post antibiotic effect therefore not necessary to have
levels above the mean inhibitory concentration (MIC) all
day
• Reduced risk of nephrotoxicity due to washout period
allowed by infrequent dosing
• No greater risk of ototoxicity.
• Monitoring of levels is simpler
• Less nursing time required to administer the antibiotic

8. • Indications for OD Regimen
• Severe sepsis of unknown cause and/or oliguria
• Intra-abdominal sepsis
• Urological sepsis
• Hospital acquired pneumonia
• Exclusion of OD Regimen
• Significant renal impairment
• Pregnant patients
• Endocarditis
• Patients with cystic fibrosis
• Patients with severe burns

9. • However
• A second dose MAY be given after a 24 hour Interval if there
is no clinical improvement, and providing the renal function
has not become impaired.
• Should once daily gentamicin be required for more than two
doses, this should be guided by serum trough levels.
• Unless for specific conditions i.e infective endocarditis and
neutropenic sepsis, gentamicin should not be given > 5
days as this increase the risk of toxicity.

11. • Once daily dosing. There are theoretical arguments for once
daily dosing of gentamicin, since aminoglycosides display
concentration-dependent bacterial killing, and a high enough
concentration to minimum inhibitory concentration (MIC) ratio
may not be achieved with multiple dosing.
• Furthermore, aminoglycosides have a long post-antibiotic effect.
• Aminoglycosides also accumulate in the kidneys, and once daily
dosing could reduce renal tissue accumulation.

12. • There have been a number of clinical trials
comparing once daily administration of
aminoglycosides with conventional
administration.
• A small number of these trials have shown less
nephrotoxicity, no difference in ototoxicity, and
similar efficacy with once daily administration.

13. Initial dosage for a once daily regimen is 5–7 mg/kg/day for
patients with a creatinine clearance of >60 mL/min.
• This is subsequently adjusted on the basis of blood levels.
However, monitoring of once daily dosing of gentamicin is
different to multiple dosing.
• One approach is to take a blood sample 6–14 h after the first
dose and plot the time and result on a standard
concentration-time plot (the Hartford nomogram, Nicolau et
al., 1995).

14. • Once daily dosing of gentamicin has not been
well studied in pregnant or breastfeeding
women, patients with major burns, renal failure,
endocarditis or cystic fibrosis.
• Therefore, it cannot b recommended in these
groups and multiple daily dosing should be
used

15. Once Daily Dose in Renal
Impairment
• Dose: 3 mg/kg OD
• Administration: In 100ml normal saline or
glucose 5% infused over 60mins
• In patients receiving ≥ 2 doses, a post
dose gentamicin level should be
collected 18 –24 hours after the last dose
(i.e., a pre-dose level)

16. Monitoring for Once Daily
Regimen
• Aim for a pre-dose (trough) level of < 1mg/L.
• Take a pre-dose level (18-24hours) before giving the next dose.
• Clearly mark on the request form how many hours after the dose
the sample has been taken.
• Unless patients are at risk of nephrotoxicity due to pre-existing
renal impairment or are receiving multiple nephrotoxic agents
(e.g some chemotherapy agents).
• Do not wait for the result to come back before giving the next
dose, adjust the regimen around the next and subsequent dose if
applicable

17. • Post dose (peak) levels are not required.
• When the first dose of gentamicin has been given in the evening or night,
the level should be taken by 1500hr the following day if this falls within
18-24 hour window and sent for analysis immediately.
• Renally Impaired
• Await assay result and give dose when level <1mg/L.
• Always monitor renal function carefully by checking urine output daily
and serum creatinine levels 2 –3 times per week, especially for courses
longer than 5 days duration.
• Risk of toxicity increases when duration of the treatment course exceeds
5 days.
• Prolonged courses of gentamicin must only be given only when there is a
clear clinical need e.g. endocarditis.

18. Multiple daily dose synergistic
regimen for infective endocarditis
• All cases of infective endocarditis must be
referred to a cardiologist
• Dose:1mg/kg every 12 hours (Max 240mg/day)
• Administration: IV injection in 10-20ml saline or
glucose 5% over at 3–5 mins IV infusion in 50ml
normal saline or glucose 5% infused slowly over
20mins –30mins

19. • Gentamicin is given in low doses primarily for its
synergistic effect with beta-lactam antibiotics.
• Regular monitoring of serum levels is important to ensure
that there is enough drug is present throughout a 24-hour
period to act with the beta-lactam.
• Because gentamicin may be given for several weeks in this
context, it is also important to ensure that the drug is being
adequately renally excreted.
• Baseline audiometry is recommended for patients who
require extended treatment (>2 weeks) with this agent

20. Monitoring
• Take pre-dose (trough level) sample before giving the 3rd or
4th dose after commencement.
• This should also be the case after any dose adjustment.
• Post-dose (peak level) should be taken ONE HOUR after the
end of the infusion.
• For streptococcal/enterococcal endocarditis infections aim
for:
• Pre-dose levels: <1mg/L
• Post-dose levels: 3-5mg/L

21. Serum levels Actions
Pre-dose level <1mg/L
Post-dose level around 3-5mg/L
Continue current regimen
Re-check levels after a further 3 or 4
doses
Pre-dose level >2mg/L
Post dose level 5mg/L or above
Omit further doses until level <1mg/L
Increase the dosing interval to 24-hourly
Re-check levels after a further 3 or 4
doses
Pre-dose level <1mg/L
Post dose level <3mg/L
Increase dose and remain on 12
-hourly dosing interval
Re-check levels after a further 3 or 4
doses

22. Conventional Multiple Dose
Regimen
• Multiple daily doses therapeutic regimen has largely been
superseded by once daily gentamicin regimen and is
generally not recommended
• Except for pregnant patients, patients with cystic fibrosis or
severe burns
• Dose: 3-5mg/kg in divided doses (8 -12 hourly)
• Administration: IV injection in 10-20ml saline or glucose 5%
over at 3–5 mins IV infusion in 50ml normal saline or
glucose 5% infused slowly over 20mins –30mins

23. Monitoring
• Both pre and post dose levels are required.
• Take pre-dose (trough level) sample before giving the 3rd or 4th
dose after commencement.
• This should also be the case after any dose adjustment.
• Pre-dose (trough level) should be taken 8 or 12 hours after the
previous dose for tds and bd regimens respectively
• Post-dose (peak level) should be taken ONE HOUR after the end
of the infusion.
• Aim for pre-dose (trough) level < 2mg/L
• For most infections, aim for post-dose level of 5 –10mg/L

24. Pre-dose
Level
Action
< 2mg/L Continue current regimen.
Ensure the patient is responding clinically.
Further pre-dose level to be monitored twice weekly so long
renal function is stable
2 – 3 mg/L Increase dosing interval i.e. from tds to bd provided renal
function is unchanged.
> 3 mg/L Further gentamicin doses should be withheld until level
<1mg/L.
If further doses are required, re-start with increased
interval/decreased dose.

25. Post-dose
Level
Action
Below Target Check previous dose(s) have been given as prescribed.
If the low post-dose level appears genuine, gentamicin is sub-
therapeutic. Consider increasing the dose
High Levels Ensure level is not taken via an intravenous catheter that is
used for the administration of the antibiotic as this will give
false high level.
Consider reducing the dose (and the dose frequency). Final
action dependent on trough level also.

26. Post-dose Level Action
Pre-dose level < 2mg/L
(normal)
Post dose level is above target
range
Reduce the Dose
Both pre-dose and post-dose
levels are above target range
Omit next dose
Review need for further gentamicin
Consider increasing the interval between
doses
Restart gentamicin when pre-dose level
<2mg/L