Gentamicin – principles of use and monitoring September 2013

Gentamicin –
principles of use and
monitoring
September 2013
Dr Robert Jackson
ESSENTIAL INFORMATION - GENTAMICIN

Gentamicin Policy (adults)
http://intranet/en/Trust-Staff/Antibiotic-Guidelines/Gentamicin-Protocol/
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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/
GENTAMICIN
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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 nontoxic levels achieved
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 CockcroftGault 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
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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)
30-70
10-30
5-10
Dose
3-5mg/kg once-daily
2-3mg/kg once-daily
2mg/kg every 48 to 72 hours according to
levels
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)
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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
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 postantibiotic 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)
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)
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
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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
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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
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“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
INTERPRETATION OF LEVELS
POST-DOSE LEVEL OF 3.5, REGARDLESS OF TIMING IS
WORRYINGLY HIGH
Gentamicin
level in 3.5
mg/l
Potentially toxic
3
2.5
Intermediate
2
1.5
1
Safe
0.5
0
12
13
14
15
16
17
18
19
20
Hours post last dose of gentamicin
21
22
23
24
next
dose
INTERPRETATION
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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.
Gentamicin
level in 3.5
mg/l
Potentially toxic
3
INTERPRETATION AND REGIME
MODIFICATION
2.5
Intermediate
2
1.5
1
Safe
0.5
0
12
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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
13
14
15
16
17
18
19
20
Hours post last dose of gentamicin
21
22
23
24
next
dose