This document summarizes guidelines for gentamicin use and monitoring. It describes gentamicin as a aminoglycoside antibiotic used for gram-negative infections. Once daily dosing is now preferred over multiple daily doses for better efficacy and reduced toxicity. Therapeutic drug monitoring is important given gentamicin's narrow therapeutic index, with target trough levels below 2 mg/L for once daily dosing. Dose adjustments may be needed based on gentamicin levels and renal function to ensure therapeutic levels are achieved safely.

1. Gentamicin – principles
of use and monitoring
September 2013
Dr Robert Jackson

2. ESSENTIAL INFORMATION - GENTAMICIN
 Gentamicin Policy (adults)
http://intranet/en/Trust-Staff/Antibiotic-Guidelines/Gentamicin-Protocol/
 Paediatric aminoglycoside policies can be navigated to
from:
http://intranet/en/Trust-Staff/Antibiotic-Guidelines/Paediatric-Guidelines/
 How to do Gentamicin levels
http://intranet/en/Your-Division/Diagnostic-Specialties-Division/Pathology1/Gentamicin-Assay/

3. GENTAMICIN
 Aminoglycoside antibiotic – same group as Streptomycin,
tobramycin, netilmicin, amikacin, neomycin, kanamycin
 Broad-spectrum vs Gram negative and Gram positive aerobic
bacteria
 Most important activity is against aerobic Gram negative bacilli ie
coliforms and pseudomonas
 Not active against strict anaerobes
 Synergistic activity vs Streptococci (endocarditis)
 Only active when used topically or given parenterally
 Main uses – UTI, intra-abdominal sepsis (combined with eg
amoxicillin and metronidazole) and “Gram-negative sepsis”
 Narrow therapeutic index – dose needs to be carefully calculated
and levels monitored to ensure therapeutic and non-toxic levels
achieved

4. GENTAMICIN AND RENAL FUNCTION
 Renal impairment – use gentamicin with caution
 See Gentamicin policy for advice on dose adjustment
according to creatinine clearance
 Creatinine clearance calculated using Cockcroft-Gault
equation rather than eGFR
 All patients on gentamicin need levels monitoring and
U+Es monitoring (U+Es every 48 hours)
 Sepsis can lead to transient renal impairment
 Acute renal impairment in sepsis – give “full”
gentamicin dose initially to avoid undertreatment of
more severe sepsis

5. CALCULATING THE INITIAL GENTAMICIN DOSE
IN RENAL IMPAIRMENT
Dose adjustment for impaired renal function
Cockroft-Gault equation for estimating creatinine clearance:
Creatinine Clearance (GFR) = (140 - Age) x Weight (Kg) x F
Serum Creatinine (µmol/litre)
Where F = 1.23 (For Men)
1.04 (For Women)
Dose adjustment recommendations:
Cr Cl (ml/min) Dose
30-70 3-5mg/kg once-daily
10-30 2-3mg/kg once-daily
5-10 2mg/kg every 48 to 72 hours according to
levels

6. GENTAMICIN ADMINISTRATION
 Twice and thrice daily dosing with gentamicin used
to be the norm – more likely to achieve low peak
levels near bacterial MICs and drug accumulation
with rising trough (pre-dose) levels – high risk of
toxicity
 Last two decades – once daily dosing has
become the most popular way to give gentamicin
(can also be used for tobramycin and amikacin)

7. ONCE DAILY GENTAMICIN
Systems available
 Prinz scheme – 5 mg/kg (3 mg/kg for the elderly or
lower if renal impairment) ~ initially used only at
GRH but now used across the Trust
 Hartford scheme – 7 mg/kg ~ used to be used at
CGH – adjustment was to dose interval rather than
the dose – doses given either every 24, 36 or 48
hours

8. ONCE DAILY GENTAMICIN
Advantages
 Less likely to cause toxicity
 Probably more effective (reliably high peak levels well
above bacterial MICs and bacteria also affected when
serum levels reach trough because of the post-
antibiotic effect [high intrabacterial levels when serum
levels have dropped])
 Easier to administer, cheaper
 Easier to do levels (no need for the paired pre and 1
hour post-dose levels needed for bd and tds regimes)

9. EXCLUSIONS FOR USE OF OD GENTAMICIN
Once daily dosing is inappropriate and should not be
used in:
 Endocarditis (lack of experience)
 Pregnancy (lack of experience)
 Major Burns
 Ascites – liver impairment a predisposition to renal
impairment – fluid compartment distribution issue
 Osteomyelitis
 Myeloma patients (renal amyloid)

10. HOW OFTEN TO MEASURE LEVELS ?
 Depends on renal function (particularly baseline
renal function)
 Depends on whether initial gentamicin level is
normal or not – if not => dose adjusted => repeat
level after first adjusted dose
 Depends on the regime – od, bd or tds

11. FREQUENCY OF MONITORING LEVELS
 OD regime and normal renal function and first level
satisfactory => twice weekly gentamicin levels
 BD or TDS regime – first levels after patient on
gentamicin for 48 hours
 if those levels are satisfactory then repeat every 5-7 days
 If those levels are unsatisfactory – repeat after dose change
when established on altered regime for 48 hours

12. “NORMAL RANGE”
Target levels
Once daily gentamicin
 12 hour post-dose level <2.0 mg/l
 18 hour post-dose level <1.0 mg/l
BD or TDS gentamicin
 Pre-dose <2.0 mg/l
 Post-dose 5-10 mg/l
Endocarditis gentamicin regime (bd or tds)
 Pre-dose <1.0 mg/l
 Post-dose 3-5 mg/l

13. INTERPRETATION OF LEVELS
POST-DOSE LEVEL OF 3.5, REGARDLESS OF TIMING IS
WORRYINGLY HIGH
0
0.5
1
1.5
2
2.5
3
3.5
12 13 14 15 16 17 18 19 20 21 22 23 24
Gentamicin
level in
mg/l
Hours post last dose of gentamicin next
dose
Potentially toxic
Intermediate
Safe

14. INTERPRETATION
 If Serum gentamicin concentration is:
<2mg/L (12 hrs post infusion) or <1mg/L (18 hrs post infusion) then the
present dose is correct for the patient’s existing renal function. This shows
no accumulation; therefore continue with the same daily dose.
 If Serum gentamicin concentration is:
>2mg/L (12 hrs post infusion) or >1mg/L (18 hrs post infusion) then the
present dose is too high for the patient’s existing renal function. Dose
reduction to a new dose will be required as per this equation:
New Dose = Previous daily dose x Target serum value
Actual serum level
Serum gentamicin levels should be rechecked 12 to 18 hours after the new
dose.
 If gentamicin levels are within the recommended range with normal
renal function then monitor levels and U&Es twice weekly.

15. INTERPRETATION AND REGIME MODIFICATION
 If the level has been taken at the correct time interval and
is found to be in the “potentially toxic area” omit the next
dose –consider doing a trough (random) level the
following morning to see if the level has dropped to a
amount where it would be safe to give a further (but
reduced) dose of gentamicin
 Random level should be less than 1 before the patient can
have a further dose
 Review whether gentamicin is still clinically necessary or
whether an alternative, less nephrotoxic, antibiotic should
be used instead
 Discuss with ward pharmacist, senior colleague or duty
consultant microbiologist if in doubt
0
0.5
1
1.5
2
2.5
3
3.5
12 13 14 15 16 17 18 19 20 21 22 23 24
Gentamicin
level in
mg/l
Hours post last dose of gentamicin next
dose
Potentially toxic
Intermediate
Safe