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Gentamicin
Title of Guideline (must include
the word “Guideline” (not
protocol, policy, procedure etc)
Contact Name and Job Title
(author)
Guideline for the treatment of children and
young people with intravenous gentamicin
Directorate & Speciality
Directorate: Family Health – Children
Speciality: Therapeutics
Date of submission
Date on which guideline must be
reviewed (one to five years)
Explicit definition of patient group
to which it applies (e.g. inclusion
and exclusion criteria, diagnosis)
Abstract
Key Words
June 2014
June 2019
Dr Mamatha Mallya SpR Paediatrics
Andrew Wignell, Senior Clinical Pharmacist, Paediatrics
Dr Meeta Mallik, Consultant Paediatric Nephrologist
Children and young people aged 0-18 yrs requiring
intravenous gentamicin treatment
Gentamicin, intravenous antibiotics monitoring,
nephrotoxic, ototoxic
Statement of the evidence base of the guideline – has the guideline been peer reviewed
by colleagues?
1a
2a
2b
3
4
5
meta analysis of randomised controlled
trials
at least one well-designed controlled study
without randomisation
at least one other type of well-designed
quasi-experimental study
well –designed non-experimental
descriptive studies (ie comparative /
correlation and case studies)
expert committee reports or opinions and /
or clinical experiences of respected
authorities
recommended best practise based on the
clinical experience of the guideline
developer
Consultation Process
linicians and healthcare professionals
caring for children and young people (018yrs) who require treatment with
intravenous gentamicin
Paediatric Clinical Guidelines Group
Target audience
This guideline has been registered with the trust. However, clinical guidelines are
guidelines only. The interpretation and application of clinical guidelines will
remain the responsibility of the individual clinician. If in doubt contact a senior
colleague or expert. Caution is advised when using guidelines after the review
date.
Andrew Wignall
July 2014
Document Control
Document Amendment Record
Version
V1
V2
Issue Date
Dec 2010
Jun 2014
Author
Andy Lunn
General Notes:
Summary of changes for new version:
1) Updated with local eGFR formula
Andrew Wignall
July 2014
Gentamicin
Introduction
Background
•
Gentamicin is a broad spectrum aminoglycoside antibiotic.
•
It is active against some gram positive and many gram negative organisms:
Staphylococcus aureus (including MRSA), Escherichia coli, Pseudomonas
aeruginosa and Klebsiella sp.
•
It is inactive against anaerobes and has poor activity against Haemolytic
Streptococci, Pneumococci, Enterococcus and H.influenza.
•
Once daily dosing (ODD) is an easier and possibly superior alternative to multiple
daily dosing (MDD) and is recommended for most paediatric patients
•
Benefits of ODD include, enhanced concentration- dependent bactericidal activity,
post antibiotic effect (PAE), decreased risk of adaptive resistance and less
accumulation in the renal tubules and inner ear.
•
Extended dosing profile is recommended for neonates
Post Antibiotic Effect (PAE)
This refers to suppression of bacterial growth even when no extracellular drug is present,
allowing continued efficacy even when serum concentrations fall below the expected
minimum inhibitory concentration (MIC). The PAE is longer with a higher aminoglycoside
peak serum concentration and in the presence of neutrophils.
Toxicity
•
Excretion of Gentamicin is principally via the kidney.
•
The two most important adverse effects are nephrotoxicity and ototoxicity. Both
relate to serum drug concentration and duration of therapy. The rate of uptake of
gentamicin into the renal tissue is related to the time of exposure to higher levels
rather than the absolute concentration. Therefore, giving high doses less frequently
may reduce toxicity
Monitoring of serum gentamicin levels, renal function (urea, electrolytes and
creatinine) and fluid balance is essential
Andrew Wignall
July 2014
Once Daily Gentamicin Regimen
Indications
•
•
•
•
Meningitis/Sepsis in neonates
Febrile Neutropenia (stat dose then review– see oncology guideline in addition)
Surgical conditions- perforated or gangrenous appendicitis (on microbiology advice)
Urosepsis- see Paediatric UTI Guideline
Exclusion Criteria
1)
Multiple daily gentamicin dosing regimens are still recommended for patients
in the following categories (please refer to the BNFc for dosing and monitoring
recommendations and liaise with pharmacist)
•
•
•
•
•
2)
Endocarditis
Extensive burns
Concurrent pregnancy
Ascites/excessive third-space volume
Where intramuscular gentamicin is necessary (i.e. where intravenous
access is not possible)
Increased risk of gentamicin toxicity. Patients in the categories below are at
increased risk of gentamicin toxicity. The use of gentamicin should be discussed with
the patient’s consultant and where appropriate an alternative antibiotic should be
considered. The gentamicin dosing and monitoring regimen will need to be adjusted
(see dosing in renal impairment section later).
•
•
•
Patients with acute kidney injury or chronic renal impairment (eGFR
< 90 ml/min/1.73 m2 1).
Renal transplant patients
Dialysis patients
3)
Patients with myasthenia gravis - gentamicin may impair neuromuscular
transmission and must not be given in myasthenia gravis.
4)
Neonates with a postmenstrual age of less than 32 weeks - please refer to
Neonatal Service clinical guideline (no. 27), the interval between doses is increased
to 36 hours.
Cautions
•
•
Renal function and gentamicin levels should be monitored very carefully in patients
who are receiving additional nephrotoxic drugs such as:
• Cyclosporine
• Tacrolimus
• Aciclovir
• Amphotericin
• NSAIDs.
Gentamicin should preferably not be given with other ototoxic drugs (e.g.
Furosemide). If concomitant use cannot be avoided, administration should be
staggered.
1
eGFR (ml/min/1.73 m2) = (height in cm x k) / Creatinine (µmol/L) w h e r e k = 3 6 i n m a l e s 1 3
y e a r s o r o v e r a n d 3 0 i n a l l o t h e r c a s e s ( Local modification of Schwartz-Haycock
formula)
Andrew Wignall
July 2014
Dosing
Once daily dose regimen
Most side effects are dose related, therefore care must be taken with dosage and whenever
possible treatment should not exceed 7 days.
Table 1: Once daily gentamicin recommended dosages and administration
Age
Once Daily Dose
Administration
Neonates
(< 28 days)
4 mg/kg
intravenously
Slow bolus over 3 mins or
infusion over 30 mins
Children
(1 month- 18 years)
7 mg/kg
intravenously
(maximum 500mg)
Infusion over at least 30
mins
When prescribing gentamicin o Round doses down to the nearest 0.5 mg for neonates and to the nearest 1mg
for older children
o Use the 24 hour clock and avoid midday and midnight
o Indicate the timing of levels clearly on the drug chart
o Initially prescribe the first 3 doses only to ensure that levels are checked
Dosing in obese patients
Aminoglycosides distribute poorly into adipose tissue. Ideal body weight (IBW) should be
used if the child is obese (extrapolate estimated IBW from the height centiles on growth chart)
Administration
•
•
•
•
Parenteral gentamicin should be administered via the intravenous route where
possible.
Interruptions during the preparation and administration of gentamicin should be
minimised, staff should not be disturbed
A double checking prompt should be used during the preparation and administration
of gentamicin
The prescribed dose of gentamicin should be given within 1 hour of the prescribed
time. If the dose given is delayed, the prescription chart should be re-written with the
exact time of the dose given
Monitoring
All patients with normal baseline renal function receiving once daily gentamicin should
have:
•
Measurement of renal function (creatinine, urea and electrolytes) at baseline and at
least twice weekly thereafter.
•
Measurement of a pre-dose gentamicin level taken before the 2nd dose.
•
Measurement of fluid balance and daily weight where possible.
Gentamicin Assays
Weekdays
Samples must reach the microbiology laboratory by 3-30 pm for results to be available on the
same day.
Weekends and Bank Holidays
Samples must reach the microbiology laboratory by 10 am for results to be available the
Andrew Wignall
July 2014
same day.
Sampling
o Take a blood sample (minimum of 0.5 ml in gold top serum separator tubes
(preferred) or red top) 18 to 24 hours after the first dose
o If sampling from a central venous line, do not sample from the same lumen
through which gentamicin was administered, peripheral venous/ finger prick
sampling may therefore be required instead
o This sample should be labelled as a "Pre-dose"
o Post-dose samples are NOT required for those on once daily dosing
Request cards
These must include the following information to allow accurate interpretation of the
assay result:
Patient Details
• Name
• Hospital number
• Date of birth
• Last creatinine and date
Drug Details
•
Antibiotic
•
Dose
•
Frequency
•
Indication
Sample Details
• Date and time of sample
• Date and time of last
dose
• Type of sample (random,
pre-dose, post-dose)
Failure to provide this information may result in the sample being rejected by the lab, or
incorrect interpretation of the assay result.
Target Gentamicin Levels (once daily dose regimen)
Age
Neonates <28 days
Children 1month- 18 years
Target Pre-Dose (trough) Level
< 2 mg/L
< 1 mg/L
Table 2: Target pre-dose levels
In children with normal renal function (eGFR >90 ml/min/1.73m 2 ) and good urine output,
measure gentamicin pre-dose level before the 2rd dose and the dose can be given without
waiting for the result.
If renal function deteriorates (10 point rise in creatinine in µmol/L from baseline), then further
doses of gentamicin should be withheld until the trough level is available for review (see
below).
If pre dose level is within target range –Continue current regimen. Further pre-dose levels
must be performed every 3-4 days so long as renal function is stable. Adjustments required
for higher levels are summarised in the table below.
Andrew Wignall
July 2014
Gentamicin Pre-Dose Level and Response
>3 mg/L
2-3 mg/L
< 2mg/L
Age
Neonate
<28 days
Child
1month – 18
years
< 1mg/L
1-2 mg/L
Action
Continue current
regimen.
Repeat level after
3-4 days provided
renal function
stable
If renal function
stable, increase
dosing interval to
36 hourly and
repeat levels with
the next dose
(giving the dose).
>2 mg/L
Review the need for
gentamicin therapy,
assess renal function.
Withhold further
doses until
discussed with
microbiology and
levels within target
trough range (repeat
after 24 hours).
Table 3: Management of pre-dose gentamicin level results
Renal Function Monitoring
•
•
•
All children should have creatinine and U+Es checked at least thrice weekly- ideally
at baseline, at the same time as the first level and once thereafter. The eGFR should also
be calculated to ensure normal renal function on each occasion.
Measure fluid balance and daily weight (where possible) in all children.
If any acute deterioration in renal function (10 µmol/L or greater rise in creatinine from
baseline) occurs a pre-dose level should be taken before the next dose is due and the
dose withheld.
o The result must be reviewed before any further gentamicin is given (unless on the
direct advice of the patient’s consultant, usually in discussion with microbiology).
o The requirement for gentamicin should be reassessed and further doses should
only be given once the serum level is <1mg/L.
Renal Impairment
In patients with renal impairment, give a one-off dose according to eGFR, as below.
eGFR (ml/min/1.73m2)
One-off Gentamicin Dose
70-90
30-70
10-30
5-10 / Dialysis patient
5-7 mg/kg
3-5 mg/kg
2-3 mg/kg
2 mg/kg
Table 4: Gentamicin dosing in patients with renal impairment
Check gentamicin levels 24 hours after the first dose and await the result.
• If the level is ≥1 mg/L, recheck levels after 12-24 hours.
• Do not give any further doses of gentamicin until the level is <1 mg/L.
Gentamicin is removed by dialysis. In haemodialysis patients the dose should be given after
dialysis.
Andrew Wignall
July 2014
Indications for Hearing Test
•
•
•
•
•
New onset Nephrotoxicity
Subsequent gentamicin dose administration despite high trough level
Longer duration of therapy (> than 7 days)
Family history of ototoxicity
Concomitant use of Furosemide or other ototoxic drugs
Audit Criteria
•
•
Aminoglycoside fluid balance audit (attached)
Gentamicin care bundle compliance chart (attached)
Standard:
All patients on an aminoglycoside will have their renal function checked at least three times a
week and their fluid intake and output accurately monitored to allow early detection of
nephrotoxicity.
Exceptions to strict fluid balance monitoring include:
•
•
•
•
Oncology patients who leave the ward between doses of antibiotics providing they
are well and have normal renal function (must be agreed with registrar or consultant).
Cystic fibrosis patients who are well and receiving planned treatment and have
normal renal function (must be agreed with registrar or consultant).
Breast fed babies whose intake cannot be measured in which case recording all wet
nappies is sufficient rather than weighing nappies.
Haemodialysis patients who are well enough to be at home between dialysis sessions
Patients in the above groups should have their weight measured daily or each time they come
to the hospital.
References
BNF for children 2010-2011
Safer use of intravenous gentamicin for neonates: National Patient Safety Agency
Once daily Gentamicin in adults –Trust Guidelines
Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.
Smyth AR, Bhatt J, Cochrane Database Syst. Rev. 2010 Jan 20;(1):CD002009
Extended –Interval Aminoglycoside administration for children :A meta-analysis. ContopoulosIoannidis et al. Pediatrics 2004 114(1) e111-8
Nottingham Neonatal Service Clinical Guideline No. 27 - Gentamicin Use
The Renal Drug Handbook, UK Renal Pharmacy Group, 3rd edition, 2009
Andrew Wignall
July 2014