Pharmacy

Guideline

Antibiotic drug monitoring:

aminoglycosides and glycopeptides

1 Scope
Trust-wide.

2 Purpose
 To improve the prescribing and monitoring of antibiotics with narrow
therapeutic indices.

3 Definitions
IV intravenous
mg milligrams
mg/kg milligrams per kilogram
OD once a day
PO orally
BD twice a day
TDS three times a day
QDS four times a day
stat immediately

4 Guideline
Please refer to the antibiotic drug monitoring: Aminoglycosides and
glycopeptides guideline at the end of this document.

5 Responsibilities
All staff involved in the prescribing and monitoring of antimicrobials are
expected to adhere to the guidelines and seek expert advice if necessary.

6 Monitoring compliance with and the effectiveness of

this document
Prescribing of antibiotics is reviewed routinely for adherence to policy which
offers the measurable standard in terms of recommended prescribing
practices.

Cambridge University Hospitals NHS Foundation Trust Page 1 of 8

Antibiotic drug monitoring: aminoglycosides and glycopeptides

Version 4; Approved May 2016
Pharmacy

This review is achieved on daily ward rounds and more formally through an
annual audit programme.

The Trust antibacterial stewardship group (ASG), which reports to the joint
drug and therapeutics committee (JDTC), is responsible for review of the
policy and receiving audit returns. Audits are reported to directorates for
necessary interventions.

7 References
Drugdex: Vancomycin monograph
Gould F.K. et al. Guidelines for the antibiotic treatment of endocarditis in
adults: a report of the Working Party of the British Society for Antimicrobial
Chemotherapy. Journal of Antimicrobial Chemotherapy 2012. 67:269-289
Leeds Teaching Hospitals NHS Trust: Vancomycin Prescribing Guidelines
November 2009
SPC Vancomycin available at www.medicines.org.uk
Thompson A.H et al. Development and evaluation of vancomycin dosage
guidelines designed to achieve new target concentrations. Journal of
Antimicrobial Chemotherapy. 2009:63,1050-1057
Rybak M. et al. Therapeutic monitoring of vancomycin in adult patients: a
consensus review of the American Society of Health-System Pharmacists,
the Infectious Diseases Society of America, and the Society of Infectious
Diseases Pharmacists. Am J Health-Syst Pharm. 2009; 66:82-98
Renal Drug Handbook, 3rd Edition.
Gilbert D. and Leggett J.E in Mandell, Douglas and Bennett’s Principles and
Practice of Infectious Diseases. 7th Edition. Chapter 26 – Aminoglycosides.
The Sandford Guide to Antimicrobial Therapy 2009. 39th Edition

Equality and diversity statement

This document complies with the Cambridge University Hospitals NHS
Foundation Trust service equality and diversity statement. January 2013

Disclaimer
It is your responsibility to check against the electronic library that this
printed out copy is the most recent issue of this document.

Document management
Approval: Antimicrobial stewardship group (ASG), 09 May 2016
Owning department: Pharmacy
Author(s): Reem Santos, Antibiotic Pharmacist;
Denise Rosembert, Lead Pharmacist- Biologics (and Application Analyst)
File name: Antibiotic drug monitoring Aminoglycosides and glycopeptides Version4 May
2016 (1of2).doc
Supersedes: Version 3, January 2014
Version number: 4 Review date: May 2019
Local reference: Media ID: 20827

Cambridge University Hospitals NHS Foundation Trust Page 2 of 8

Antibiotic drug monitoring: aminoglycosides and glycopeptides

Version 4; Approved May 2016
Dosing and drug monitoring of selected antibiotics in
adults

Vancomycin and Teicoplanin

General information
 Dosing should take into account the type of infection, the patient’s weight and renal function.
 Teicoplanin is restricted for use in patients requiring glycopeptide therapy but are allergic to
vancomycin or candidates for Outpatient Parenteral Antimicrobial Therapy (OPAT).
 Caution is advised when using glycopeptides with other nephrotoxic drugs. This includes
gentamicin, NSAIDS, liposomal amphotericin or loop diuretics. Close monitoring for nephrotoxicity
is recommended.
 Paediatric patients are excluded from this guideline (consult a pharmacist for dose
recommendations).

Note that patients receiving oral vancomycin for treatment of C. difficile associated diarrhoea do not
normally require levels checked.

STEP 1: LOADING DOSE

Give a loading dose based on the patient’s actual body weight (table 1 below for details).
 Loading are not recommended for patients with CrCl < 20 ml/min

LOADING DOSE
Weight (Actual body weight) <60 kg 60-85 kg > 85kg

Vancomycin (single dose IV) 1g 1.5g 2g

400mg 600mg
Teicoplanin loading dose regimen
(600mg for serious infections)
(3 doses at 12-hourly intervals)
Teicoplanin loading doses are traditionally 3 doses at 12-hourly intervals.
Alternative loading dose regimens may be employed by the OPAT team.

Antibiotic drug monitoring

STEP 2: CONTINUATION PHASE
Dose patient according to body weight and renal function
DOSE RECOMMENDATIONS
Vancomycin Teicoplanin†

Standard dosing based on weight

15mg/kg* (max 2g per doseª) <85kg: 400mg**
(round up to nearest 250mg) ≥85kg: 6mg/kg*
Dose (round up to nearest 100mg)
ª In severe renal impairment (CrCl < 10 ml/min)
max 1g per dose For doses above 1g, please consult Microbiology,
Infectious Diseases or a Pharmacist before
prescribing
Based on renal function for adult patients <65
yrs:
 CrCl >50 ml/min: twice daily
 CrCl 10-50 ml/min or patients >65 yrs if Give standard loading dose then adjust dosing
CrCl >50 ml/min: once daily interval depending on renal function:†
 CrCl <10 ml/min and in patients undergoing  CrCl >20 ml/min: continue once daily
Interval renal replacement therapies: single dose and  CrCl 10-20 ml/min: reduce dose to 400mg
then check level 24h later, give next dose every 24-48 hours
once trough level <20mg/L  CrCl <10 ml/min and in patients undergoing
renal replacement therapies: reduce dose to
Note that all patients >65 yrs with ‘normal 400mg every 48-72 hours
renal function’ should have once daily
vancomycin as per CrCl 10-50 ml/min

Check pre-dose (trough) levels routinely∆ Check pre-dose (trough) levels only if treatment
Timing of  CrCl >50ml/min: before 4th dose is likely to exceed 10 days‡
levels  CrCl 10-50ml/min: before 3rd dose
 CrCl <10 ml/min: before the 2nd dose Pre-dose (trough) levels should be taken after 7
days of therapy
Reference 10-20 mg/L
20-60 mg/L
range (15-20mg/L for Staph aureus infections)
* Use actual body weight however for obese patients with a BMI >40, use ‘adjusted body weight’ . See separate section
below for calculation formulae.
** Higher doses may be recommended in bone or joint infections. Refer to OPAT antibiotic guideline for further details
† For patients with renal impairment, dose adjustment is not required until the fourth day of treatment.
‡ Levels should only be collected Monday to Thursday as the assay is sent to the Antimicrobial Reference Unit in Bristol.
∆
Do not await results of levels before administering the next dose of vancomycin unless severe renal impairment with
CrCl <10ml/min

Antibiotic drug monitoring guideline; Version 4; Approved May 2016

.
Vancomycin and Teicoplanin

STEP 3: AMEND DOSE (IF INDICATED) ACCORDING TO ASSAY RESULT

VANCOMYCIN: INTERPRETATION OF TROUGH LEVELS

Pre-dose
Maintenance dose adjustment
(trough) level
<10 mg/L Subtherapeutic level.
Reassess dose according to renal function. Alternatively, consider increasing
the dose by 500mg increments (as a once daily dose or divided doses).
In some cases where borderline results are reported, administering the same
daily dose at more frequent intervals can lead to therapeutic levels e.g. 1.5g
BD amended to 1g TDS.
Re-assay after third dose.
10-20 mg/L Optimum dose: continue on current dose
Re-assay once or twice weekly if renal function remains stable
For severe infections involving MRSA pneumonia, osteomyelitis, endocarditis
and bacteraemias, adjust dose to achieve an optimal target concentration of
15-20 mg/L
20-25 mg/L Above recommended target level.
Amend regimen by extending the dosage interval (e.g. from BD to OD). Re-
assay after third dose or more frequently if renal function has deteriorated.
>25 mg/L Above recommended target level.
Omit next dose and re-evaluate dosing regimen. Re-assay after 24 hours. Do
not give further doses until level reported to be <20mg/L.

TEICOPLANIN: INTERPRETATION OF TROUGH LEVELS

Antibiotic drug monitoring

Pre-dose
Maintenance dose adjustment
(trough) level
<20 mg/L Subtherapeutic level, especially if treating severe infections
Increase dose by 50%, round up to nearest 100mg†
Re-assay after 5 doses.
20-60 mg/L Optimum dose: continue on current dose
Re-assay not required within 4 weeks unless change in renal function
>60mg/L Above recommended target level.
Reassess dose according to renal function. Consider reducing the daily dose or
extending the dosage interval (eg from daily to every 48 hours). Re-assay
after 5 days.
†Teicoplanin dose can be increased up to 800mg daily. For further advice, consult a pharmacist,
Microbiology or the Infectious Diseases Team.

Instructions to Biochemistry

Instructions for sending trough (pre-dose) samples to biochemistry

Send serum sample (brown top bottle)
The following information is necessary to allow results to be interpreted: -
 The time that the last dose was administered
 The time that the sample was taken
 The dosage regimen that the patient is receiving

Antibiotic drug monitoring guideline; Version 4; Approved May 2016

Once Daily Aminoglycosides

Background
Once daily dosing for aminoglycosides has gained popularity in recent years due to several
factors. The simplified dosing regimen is not as labour-intensive as the multiple daily
dosing. The aim of once daily dosing is to minimise toxicity, reduce treatment failure,
morbidity and mortality.

The rationale for using once daily dosing has many advantages including concentration
dependent bactericidal activity, where the efficacy correlates with achieving drug plasma
levels 5-10 fold greater than the minimum inhibitory concentration (MIC) of the pathogen.
The post-antibiotic effect of aminoglycosides against Gram-negative bacilli is another
feature that translates to continued suppression of bacterial growth even in the presence
of declining aminoglycoside concentration.

The toxicity profile of once daily dosing appears to incur benefit. The renal cortical uptake
of gentamicin, amikacin (but not tobramycin) is saturable and the renal accumulation
appears to be less when given in one large dose compared to divided doses or continuous
infusions. This has resulted in less nephrotoxicity. Similar effects have been noted with
regard to ototoxicity.

Caution for once daily aminoglycosides

 Patients with established renal failure. Refer to table below for dosing guidance.
The recommended doses are to be used as a guide only for initial prescribing, with
doses reviewed in light of reported trough levels and alterations in renal function.

Antibiotic drug monitoring

Exclusions
This guideline dose not offers any dose recommendations for Cystic Fibrosis patients,
paediatrics or for surgical prophylaxis.

Contraindications to single daily dose regimen of

aminoglycosides
An alternative antibiotic should be used if possible in the following patients:
 Pregnancy
 Patients with extensive burns (>20% of body surface area)
 Blind patients
 Patients with a history or signs of hearing loss or vestibular dysfunction

Discuss therapy with a medical microbiologist if it is thought that the use of

aminoglycoside is still indicated in this group of patients, as traditional (conventional)
aminoglycoside dosing regimens will apply.

Patients with endocarditis also have different aminoglycoside dosing regimens and target
levels; see Cardiovascular infections guideline.

Avoid giving prolonged courses of aminoglycosides (>7-10 days) as this is

associated with increased risk of oto- and nephrotoxicity; discuss alternative
options with Microbiology.

Antibiotic drug monitoring guideline; Version 4; Approved May 2016

Once Daily Aminoglycosides

The doses below are a guide only. Doses should be based on ideal body weight or actual body
weight if patients are considered underweight (see formula below or use UKMI web based
calculator http://www.ukmicentral.nhs.uk/resource/culo.htm) and adjusted according to trough
levels. Seek the advice of a Pharmacist or a Microbiologist.

Normal Renal Moderate Renal

Mild Renal Severe Renal
function Impairment
Impairment Impairment
(CrCl (CrCl 10-
(CrCl 20-40ml/min) (CrCl <10ml/min)
>40ml/min) 20ml/min)

5mg/kg every 24
Gentamicin hours (max
500mg) 2mg/kg single dose
3mg/kg every 48
every 72 hours with
5mg/kg every 24 3mg/kg every 24 hours hours
daily trough levels
Tobramycin hours (max
500mg)
15mg/kg IV every
10mg/kg every 24 3-4mg/kg every 24 2mg/kg every 24 to 48
Amikacin* 24 hours (max
hours hours hours
1.5g)

* Maximum cumulative dose of amikacin is 15g

Regardless of body weight, no single dose of gentamicin or tobramycin should exceed 500mg

Additional dosing information

For adult patients round dose to nearest 40mg for gentamicin and tobramycin, and nearest 50mg for amikacin.
For obese patients (BMI>40), using ‘adjusted body weight’ may be more appropriate. Contact Microbiology for advice.

Patients on renal replacement therapies

For patients on renal replacement therapies requiring repeated dosing (in excess of a single dose) contact Pharmacy for
advice.

Instructions for sending trough (pre-dose) samples to biochemistry

Send serum sample (brown top bottle)

Antibiotic drug monitoring

The following information is necessary to allow results to be interpreted: -
 The time that the last dose was administered
 The time that the sample was taken
 The dosage regimen that the patient is receiving

Trough (pre-dose) levels

When initiating therapy, take the first level 24 hours after the last dose and DO NOT GIVE A FURTHER DOSE –
AWAIT RESULT OF LEVEL. If within normal limits, subsequent dosing can be given while awaiting results provided
renal function is stable.

Peak levels (post dose)

DO NOT SEND POST DOSE LEVELS FOR PATIENTS ON ONCE DAILY AMINOGLYCOSIDE ADMINISTRATION unless treating
for bacterial endocarditis. See separate guidance on Connect.

Frequency of therapeutic drug monitoring

Twice to thrice weekly serum creatinine and aminoglycoside monitoring is recommended if renal function is stable.

In renal impairment or deteriorating renal function, daily trough levels will be necessary.

Deteriorating renal function while on aminoglycoside therapy

Discuss alternative regimens with Microbiology or the Trust Antibiotic Pharmacist.

AMIKACIN trough levels

<5mg/L 5-10mg/L >10mg/L

GENTAMICIN and TOBRAMYCIN trough level interpretations

<1mg/L 1-2mg/L >2mg/L

Continue on current dosage Borderline Unsatisfactory
regimen.
 Extend dose to 36 hourly.  Change to an alternative agent
 Recheck trough (pre) level in 3 if possible or discuss use of
days time and give next dose.  Recheck trough (pre) level lower dose regimen with a
before the next dose is due, Microbiologist or Pharmacist
 The level can be checked sooner and give the next dose.
if there are signs of renal
deterioration.

Monitoring Auditory Function

Baseline auditory function tests should be considered in patients with suspected hearing deficit prior to commencement of
therapy. There should be a low threshold for checking auditory function with suspected toxicity; early cessation of
aminoglycoside therapy is strongly recommended in such instances.

Antibiotic drug monitoring guideline; Version 4; Approved May 2016

Gentamicin multiple daily dosing for endocarditis

Where indicated, multiple daily dosing for gentamicin is recommended for treatment of
endocarditis, in combination with a beta-lactam or glycopeptides. Not all endocarditis cases
require an aminoglycoside (eg gentamicin) as part of a treatment regimen.

All patients with endocarditis should be referred to a cardiologist for evaluation. In

addition, Microbiology advice should be sought for all patients with endocarditis, especially
for patients with significant renal impairment where gentamicin is indicated.

The optimal antibiotic regimen will vary for each case and is dependent on whether the
patient has a native or prosthetic valve, as well as results of blood cultures and
susceptibility tests. The Trust’s guideline Antibiotic Therapy: Cardiovascular Infections
provides detailed advice on:
 assessment
 drug choice
 prescribing and monitoring of patients with endocarditis

but decisions regarding treatment must be discussed and agreed with a microbiologist.

The table below provides dosing advice where gentamicin is recommended by

Microbiology.

DOSE RECOMMENDATIONS
Gentamicin
1mg/kg* 12-hourly (max 500mg in 24 hours)
(round to nearest 40mg)
Dose
Note: Reduce dose to 1mg/kg OD in patients with mild to severe renal impairment (CrCl

Antibiotic drug monitoring

<40 ml/min)

 Pre and post dose serum levels are required.

Monitoring
 Levels should be monitored at least three times a week
of levels

.
 Post dose levels should be taken one hour after dose administration

Check pre-dose (trough) and post-dose (peak) levels routinely∆

 before and after the second dose (do not withhold dose if indication is endocarditis)
 thereafter: twice weekly (every third day) if levels are within range and renal function remains
Timing of stable
levels
For the majority of endocarditis patients treated with gentamicin the dose of drug should
continue to be administered whilst awaiting the results of the level, which should be
available within 24 hours.

Reference  Pre-dose (trough): < 1 mg/L

range  Post-dose (peak): 3-5mg/L

Please ensure that when ordering levels the correct option is selected on HISS or Web OCS. Ordering
levels for gentamicin pre-dose for endocarditis does not differ from once daily gentamicin, however
for post dose ‘peak’ levels the reference ranges differ markedly.
Ordering
levels Instructions for sending trough (pre-dose) samples to biochemistry
 For pre-dose gentamicin, select: ‘gentamicin – pre dose’ or code ‘GentPRE’ as for once daily
gentamicin.
 For post-dose gentamicin, select: ‘gentamicin endocarditis – post dose’ or code
‘GentPOSTEN’

Comments:

* Doses should be based on ideal body weight or actual body weight if patients are
considered underweight (see formula below or use UKMI web based calculator
http://www.ukmicentral.nhs.uk/resource/culo.htm) and adjusted according to trough levels. Seek
the advice of a Pharmacist or a Microbiologist.

For patients continuing to experience high trough or peak levels on either TDS or BD dosing, consult a
Pharmacist or Microbiologist for advice on appropriate dosage adjustments.

Antibiotic drug monitoring guideline; Version 4; Approved May 2016

Index: Useful Calculation Guides and links

Creatinine clearance

Creatinine clearance should always be used for calculating the doses of potentially toxic
drugs with a narrow therapeutic index (eg aminoglycosides). Do NOT use eGFR for this
purpose, as it is likely to underestimate or overestimate renal function in obese or
underweight patients respectively.

Calculate creatinine clearance (ml/min) using Cockcroft-Gault equation below (or use eBNF calculator
http://cgeneral/bnf/lform1/current/index.htm - type ‘creatinine clearance calculator’ in the search
engine, then click on this when it appears in the left hand side).

MALE: 1.23 x (140 – Age) x ideal body weight* (kg)

Serum Creatinine (micromoles/L)

FEMALE 1.04 x (140 – Age) x ideal body weight* (kg)

Serum Creatinine (micromoles/L)

* Use actual body weight if ideal body weight cannot be calculated (e.g. height not
available) or patient is underweight. ‘Adjusted body weight’ should be used for obese
patients (BMI >40). Use the eBNF to search for ‘Body Mass Index’ calculator.
Alternatively, see separate section below for calculation formulae.

How to calculate Ideal and Adjusted Body Weight

IDEAL BODY WEIGHT (IBW)
Male IBW (kg): 50 + [(2.3 x height in cm above 152.4)/2.54]

Antibiotic drug monitoring

Female IBW (kg): 45.5 + [(2.3 x height in cm above 152.4)/2.54]
Example: A male of 172cm weighing 70kg
IBW = 50 + [(2.3 x (172-152.4)/2.54] = 67.7kg
Alternatively, for electronic calculator click on UKMI link
http://www.ukmicentral.nhs.uk/resource/culo.htm
ADJUSTED BODY WEIGHT (ABW) - for BMIs >40
Adjusted body weight = Ideal body weight + 0.4 (Actual body weight – Ideal
body weight)
Example: A female of 168cm weighing 180kg
IBW (kg) = 45.5 + [(2.3 x 168-152.4)/2.54] = 59.6kg
Adjusted body weight (kg) = 59.6 + 0.4(180-59.6) = 107.8kg
To convert inch and foot to cm:
1 inch = 2.54cm
1 foot = 30.48cm

References
1. Drugdex: Vancomycin monograph
2. Leeds Teaching Hospitals NHS Trust: Vancomycin Prescribing Guidelines November
2009
3. SPC Vancomycin
4. Thompson A.H et al. Development and evaluation of vancomycin dosage guidelines
designed to achieve new target concentrations. Journal of Antimicrobial
Chemotherapy. 2009:63,1050-1057
5. Rybak M. et al. Therapeutic monitoring of vancomycin in adult patients: a
consensus review of the American Society of Health-System Pharmacists, the
Infectious Diseases Society of America, and the Society of Infectious Diseases
Pharmacists. Am J Health-Syst Pharm. 2009; 66:82-98
6. Renal Drug Handbook, 3rd Edition.
7. Gilbert D. and Leggett J.E in Mandell, Douglas and Bennett’s Principles and Practice
of Infectious Diseases. 7th Edition. Chapter 26 – Aminoglycosides.
8. The Sandford Guide to Antimicrobial Therapy 2009. 39th Edition.

Antibiotic drug monitoring guideline; Version 4; Approved May 2016