Title of Guideline (must include the word “Guideline” (not
protocol, policy, procedure etc)
Contact Name and Job Title (author)
Directorate & Speciality
Date of submission
Date on which guideline must be reviewed (this should be one to
three years)
Explicit definition of patient group to which it applies (e.g.
inclusion and exclusion criteria, diagnosis)
Changes from previous guideline
Statement of the evidence base of the guideline – has the
guideline been peer reviewed by colleagues?
Evidence base: (1-5)
1a meta analysis of randomised controlled trials
1b at least one randomised controlled trial
2a at least one well-designed controlled study without
randomisation
2b at least one other type of well-designed quasi-
experimental study
3 well –designed non-experimental descriptive studies
(ie comparative / correlation and case studies)
4 expert committee reports or opinions and / or clinical
experiences of respected authorities
5 recommended best practise based on the clinical
experience of the guideline developer
Consultation Process
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.
Guideline for antimicrobial dosing for adults in
renal impairment
Annette Clarkson Specialist Clinical pharmacist
antimicrobials and Infection Control
Ian Hogg Specialist Clinical Pharmacist Renal
(adult)
Nicola Fawcett. Specialist Clinical Pharmacist
Antimicrobials (meropenem update Nov 2016)
Luke Dowdeswell, Antimicrobial Pharmacist
(Oseltamivir update, Dec 2016)
Riya Savjani. Anitmicrobial Pharmacist
(Teicoplanin + co-trimoxazole update, Dec 2016)
All adult directorates
June 2015 (Update May 2016)
Further update November 2016 – meropenem
Further updates December 2016 – Oseltamivir,
Teicoplanin, co-trimoxazole
June 2017
All adult patients with renal impairment who are
prescribed an antimicrobial.
Dose changes made for Levofloxacin,
meropenem, nitrofurantoin, tazocin, valaciclovir,
teicoplanin and oral fosfomycin. Update made to
fosfomycin IV in line with new preparation and
timentin added as new agent. May 2016-
Addition of anidulafungin and
ceftolozane/tazobactam. Oseltamivir dose
change.
Nov 2016 – meropenem dosing change
Dec 2016 – Oseltamivir, Teicoplanin, co-
trimoxazole updates
o BMA and RPSGB. British National
Formulary. Number 66. March 2014
o Summary of Product Characteristics from
electronic Medicines Compendium for
individual drugs. Available from
http://emc.medicines.org.uk Datapharm
Communications Ltd. Accessed 15/10/2014
o Ashley C and Dunleavy A. The Renal Drug
database. Available at http:
https://www.renaldrugdatabase.com.
Accessed 15/10/2014.
o Recommended best practice based on
clinical experience of guideline developers
o Nov 2016 – Supporting evidence for
meropenem therapeutic interchange and
dosing substitution policy. The Nebraska
Medical Center. Available from
www.nebraskamed.com. Accessed
02/11/2016
NUH Antibiotic Guidelines Committee
NUH Drugs and Therapeutics Committee
Renal consultants
Doctors, pharmacists
 ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT

Assessing Renal Function

Renal function in adults is now commonly reported via NOTIS on the basis of estimated glomerular
filtration rate (eGFR) normalised to a body surface area of 1.73m 2 and derived from the Modification
of Diet in Renal Disease (MDRD) formula. Published information on the effects of renal impairment
on drug elimination has historically been stated in terms of creatinine clearance (not normalised for
body surface area). The Cockgroft-Gault formula has been used to estimate this and in recent years
the advice has been to continue to use Cockcroft-Gault estimates for drug dosing in renal
impairment. The Cockcroft Gault equation is shown below and there is a calculator on the antibiotic
website.
where F
CrCl (ml/min) = F x (140-age) x weight (kg)
= 1.23 (male)
serum creatinine (micromol/L)
= 1.04 (female)

The latest edition of the British National Formulary gives dosage adjustments for many drugs
expressed in terms of eGFR rather than creatinine clearance. Although the two equations are not
interchangeable, there is relatively good correlation between the two for calculating renal function in
patients of average build and height, and either could be used for the majority of drugs. However,
eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI of
less than 18.5 kg/m2 or greater than 30 kg/m2), or for potentially toxic drugs of a narrow
therapeutic index. In these cases, the correlation between the two measures can be significant and
potential drug over/under doses could arise.
BMI = Weight (kg)
Height (m2)

 eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI
of less than 18.5 kg/m2 or greater than 30 kg/m2) therefore for those who are obese (>20% above
IBW) ideal body weight should be calculated and then used to create a creatinine clearance using
Cockcroft-Gault.
 IBW for males = 50 + (2.3 x (height in inches - 60))

 IBW for female = 45 + (2.3 x (height in inches - 60))

 Equally for those patients who have a BMI<18.5kg/m2 creatinine clearance using
Cockcroft-Gault should be calculated.
 eGFR should not be used for calculating drug doses for potentially toxic drugs of a
narrow therapeutic index. For the purposes of this guideline creatinine clearance using
Cockcroft-Gault should always be used for vancomycin, gentamicin, foscarnet,
ganciclovir, valganciclovir.
 Neither equation is a perfect marker of renal function. When using the equation, creatinine
levels should be stable and the clinical picture should always be taken into account.
 Patients that are oligoanuric or dialysis dependent should be assumed to have a GFR <10 ml/min
and neither equation is valid.

Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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Renal dosing monographs

 The doses recommended are derived from the references stated and represent those commonly
used in Nottingham (these may vary from the SPC)

Dosing in renal replacement therapy

 Give post HD (haemodialysis): If patient is on daily or alternate day therapy this advice refers
only to administration on dialysis days: ie on non-dialysis days the drug is given at the normal
time.

For dosing advice in continuous veno-venous haemofiltration (CVVH): refer to Critical Care
Pharmacist

Contact pharmacy for advice on dosing in renal impairment for any antimicrobial agents that
are not included in the table below.

Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate

Creatinine clearance (CrCl) (ml/min)

Antimicrobial Comments
50-20 20-10 <10
CrCl 10-25 The higher dose should be used for those patients with
CrCl 25-50 2.5-5mg/kg every
*Aciclovir IV 5-10mg/kg encephalitis and those who are immunocompromised. PD
5-10mg/kg every 12h 24h
every 24h same as <10. HD give doses post HD
Cr-Cl 10-25
CrCl 25-50 Simplex: 200mg qds
Simplex: 200mg bd
Aciclovir po Doses should be given post HD
Normal Zoster: 800mg tds Zoster: 800mg bd
2mg/kg 24-48h
Therapeutic drug monitoring required, refer to antibiotic
Amikacin 5-6 mg/kg 12h 3-4 mg/kg 24h website. Subsequent doses should be adjusted according to
HD: 5mg/kg post
levels.
each HD session
Give post HD. For endocarditis and CrCl <10, maximum
Amoxicillin IV and dose of 6g per day this should be given as 1g four hourly. All
Normal Normal 250mg-1g 8h
PO cases of endocarditis should be discussed with microbiology.

Lipid associated Amphotericin is highly NEPHROTOXIC.

Amphotericin IV Daily monitoring of renal function is essential
Normal Normal Normal
(Abelcet© and For further advice on dosing and administration see antibiotic
Ambisome©) website, local guidelines and Trust IV guide
Anidulafungin Normal Normal Normal HD or CAPD: Not dialysed dose as in normal renal function.
Azithromycin Normal Normal Normal Give doses after HD
CrCl 10-30
CrCl 30-50 Give 1-2g loading
Give 1-2g loading
Aztreonam dose then 250- Usual dose in normal renal function is 1-2g 8h. Give post HD
dose then
Normal 500mg 8h
500mg-1g 8h
For endocarditis and CrCl <10, maximum dose of 4.8g per
day this should be given as 1.2g qds. All cases of
600mg-1.2g every 6 600mg-1.2g every
Benzylpenicillin Normal endocarditis should be discussed with microbiology. Give
hours 6 hours
post HD

Caspofungin Normal Normal Normal Can reduce tacrolimus levels

250-500mg every 8- 250-500mg every
Cefalexin Normal Give post HD
12 hours 8-12hr
CrCl 6-15
CrCl 31-50 CrCl 16-30 500mg-1g 24h
Ceftazidime For Haemodialysis give 500mg-2g every 48h or post dialysis
1-2g 12h 1-2g 24h CrCl<5
500mg-1g 48h
Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate
Creatinine clearance (CrCl) (ml/min)
Antimicrobial Comments
50-20 20-10 <10
CrCl <15
HD: Single loading dose of 500mg ceftolozane/250mg
No dosing
CrCl 15-29 tazobactam followed after 8 hours by 100mg
information
CrCl 30-50 250mg ceftolozane/50mg tazobactam every 8 hours. On HD days,
Ceftolozane/tazoba available from
500mg ceftolozane/250mg ceftolozane/125mg give the dose immediately post HD.
ctam (Zerbaxa®) manufacturer.
tazobactam every 8 hours tazobactam every 8
Contact renal or
hours CAPD- No dosing information available from manufacturer
antimicrobial
contact renal/antimicrobial pharmacist for advice.
pharmacist
Normal
Ceftriaxone Normal Normal
Max 2g/day
Cefuroxime IV Normal 750mg – 1.5g 12h 750mg 12h Give post HD
Give post HD, levels can be checked, see antibiotic website
Chloramphenicol Normal Normal Normal
for further information.
If use is considered essential, contact antimicrobial or renal
Cidofovir Avoid, manufacturers and renal drug handbook advise to avoid in CrCl <55
pharmacist.
For CrCl <10mL/min 250mg bd should routinely be used,
PO 250mg-500mg
increase dose if severe sepsis or treating pseudomonas.
PO 250-500mg 12h 12h
Ciprofloxacin IV+po Normal Interacts with phosphate binders, see mineral bone disease
IV 200mg-400mg 12h IV 200mg-
guidelines on intranet.
400mg12h
If patient on ciclosporin contact pharmacist.
Clarithromycin CrCl 30-50 CrCl 10-30 Give post HD.
250-500mg 12h
IV + po Normal 250-500mg 12h May increase tacrolimus, ciclosporin and sirolimus levels.
Clindamycin
Normal Normal Normal
IV +po
Co-Amoxiclav IV CrCl 30-50 CrCl 10-30
1.2g 12h Give post HD
Normal 1.2g 12h
Co-Amoxiclav po Normal Normal Normal Give post HD
1 million units
1million units 12h or if Usual dose in normal renal function 1-2 million units tds. If
every 24hr or if
Colistin IV Normal <60kg 50% of normal <60kg 50,000-75,000 units/kg in three divided doses.
<60Kg 30% of
dose Post HD
normal dose
Colistin PO Normal Normal Normal Not absorbed orally
CrCl 15-30 Give post HD
*Co-trimoxazole IV CrCl 30–50 CrCl <15 Monitor sulfamethoxazole levels
PCP: Normal for 3/7
+ po PCP 30mg/kg 12h
then 30mg/kg 12h
(Treatment doses Other infections:
Normal Other infections: 50% of Co-trimoxazole 960mg and 480mg tablets can be halved.
only) 50% of normal dose
normal dose
Dapsone Normal Normal 50-100mg 24h In those with CrCl<10 monitor FBC
Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate
Creatinine Clearance (CrCl) (ml/min)
Antimicrobial Comments
50-20 20-10 <10
Patients on haemodialysis should be discussed with
pharmacy.
Dose varies dependent on indication, 6mg/kg is used in
CrCl 30-50 bacteraemia and up to 8mg/kg in endocarditis Monitor CK
Daptomycin CrCl<30 4-8mg/kg every 48 hours
4-8mg/kg 24h levels speak to pharmacy

All other tetracyclines contraindicated in renal impairment

Doxycycline Normal Normal Normal Interacts with phosphate binders, separate doses by 2 hours
before and after
CrCl 30-50 CrCl 10-30 50% of dose or 1g Give post HD. Patients on haemodialysis should be
Ertapenem
Normal 50-100% of dose three times a week discussed with pharmacy
Erythromycin po Normal Normal 250-500mg qds
Give post HD
*Ethambutol Normal 7.5-15mg/kg/day 5-7.5mg/kg/day
Monitor levels if CrCl<30ml/min (contact micro)
Flucloxacillin IV+po Normal Normal Normal Max 4g/day
50% of normal
Give post HD
dose
Fluconazole Normal Normal Dose is dependent on indication. No adjustments for single
Oral dose min
doses required
50mg
50mg/kg immediately
*Flucytosine CrCl 20-40 50mg/kg 12h 50mg/kg 24h then dose according Give post HD. Monitor pre-dialysis levels
to levels.
Dose reduction required seek further advice from pharmacy/renal drug
Foscarnet
handbook
CrCl >40
Normal
CrCl 30-40 4g loading dose then 2g loading dose HD- 2g loading dose and then 2g at the end of each dialysis
Fosfomycin IV
8g loading dose then 4g 8h 2g 8h then 1g 8h session.
CrCl 20-30
6g loading dose then 3g 8h
For CrCl <10ml/min or those patients on dialysis, fosfomycin
Fosfomycin oral Normal 3g single dose Not recommended has been used please discuss with renal or antibiotic
pharmacist.
Fusidic acid
Normal Normal Normal
(sodium fusidate)

Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate
Creatinine Clearance (CrCl) (ml/min)
Antimicrobial Comments
50-20 20-10 <10

Dose reduction required seek further advice from pharmacy/renal drug

Ganciclovir
handbook

CrCl 10–40 CrCl<10

BOTH METHODS:
1) Gentamicin 3mg/kg (max 300mg) 2 mg/kg (max
Give post HD
Check levels 18-24 hours 200mg) re-dose
Monitor blood levels & U&Es. See antibiotic website. In the
ONCE DAILY after first dose. according
obese use a dose determining weight- see antibiotic website.
Re-dose only when level < 1mg/L. to levels
2) ) Gentamicin 80mg 48h
80mg 12h 80mg 24h
Multiple daily (60mg if <60kg)
(60mg if <60kg) (60mg if <60kg)
dosing regimen
Isoniazid Normal Normal 200mg-300mg 24h Give post HD
Itraconazole Normal Normal Normal
If normal dose 500mg
If normal dose 500mg od od give 500mg
give 500mg immediately immediately
then 250mg od then 125mg od 500mg immediately
Levofloxacin
If normal dose 500mg bd If normal dose 500mg then 125mg od
give 500mg immediately bd give 500mg
then 250mg bd immediately then
125mg bd
Give post HD
Linezolid Normal Normal Normal CrCl<10 monitor platelets
Be alert to drug interactions
Meropenem
Adjust depending on CrCl 50-25 ml/min CrCl 25-10 ml/min CrCl <10ml/min
normal dose:
Meropenem
500mg TDS 500mg BD 500mg–1gram OD
500mg QDS
Meropenem
1gram BD 500mg BD 500mg–1gram OD Give post HD
1g TDS
Meropenem
2gram BD 1gram BD 500mg–1gram OD
2g TDS
Metronidazole Normal Normal Normal Give post HD
Interacts with phosphate binders, separate doses by 2 hours
Moxifloxacin Normal Normal Normal
before and after

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate

Creatinine Clearance (CrCl) (ml/min)

Antimicrobial Comments
50-20 20-10 <10
CrCl >45  Nitrofurantoin is contra-indicated in patients with
Normal dose for cystitis (lower CrCl<30 mL/min as the drug is ineffective due to
UTI) only inadequate urine concentrations.
CrCl<30 CrCl<30  Unsuitable for pyelonephritis or patients with sepsis of a
Nitrofurantoin
CrCl 30-45 Contraindicated Contraindicated likely urinary origin.
Only if no other agents suitable  Use for short courses of 3-7 days, if using for long term
and on the advice of prophylaxis do not use in CrCl <45mL/min.
microbiology for 3-7 days only  Nitrofurantoin gives false positive urinary glucose
Post HD
Ofloxacin 200-400mg od 200-400mg od 200mg od Interacts with phosphate binders, separate doses by 2 hours
before and after
HD: 30mg immediately then 30mg after each dialysis session
Oseltamivir CrCl 30-60 PD: 30mg single dose, if duration of treatment continues for
CrCl 10-30
(treatment 30mg 12h 30mg single dose more than 5 days give a further 30mg dose on day 7.
30mg 24h
dose) CVVH: Seek advice from critical care pharmacist if need for
treatment arises.
HD: 30mg immediately then 30mg after each dialysis session
30mg single dose
Oseltamivir PD: 30mg on day 1, and then further 30mg dose on day 7.
CrCl 30-60 CrCl 10-30 on day 1 then a
(prophylaxis (remains in body for 7 days)
30mg 24h 30mg 48h further 30mg on a
dose) CVVH: Seek advice from critical care pharmacist if need for
day 7
treatment arises.
Penicillin V Normal Normal Normal Give post HD
Piperacillin/
Tazobactam Normal 4.5g 12h 4.5g 12h Give post HD
(Tazocin)
Not Works by renal excretion into the bladder so unlikely to work in
Pivmecillinam Normal Normal
recommended those with little residual function
Posaconazole Normal Normal Normal
Use 50-100% of
Pyrazinamide Normal Normal Post HD
dose
CrCl 10-30 CrCl <10
CrCl 30-50
Rifabutin Maximum 300mg Maximum 300mg
Normal
daily daily
Rifampicin Normal Normal 50-100%
CrCl 30-80 CrCl <30 Use actual body weight and round dose to the nearest 200mg.
Teicoplanin Loading dose: normal For patients greater than 125kg contact your pharmacist for
Loading dose: normal Day 3 and 4 maintenance dose: normal dosing advice.
Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate
Day 3 and 4 maintenance dose: Day 5 onwards: One third of normal Dosing in normal renal function as follows:
normal maintenance dose (max 800mg) Cellulitis: Loading dose 6mg/kg every 12 hours for 3 doses then
Day 5 onwards: 50% of normal (round dose to nearest 200mg) maintenance dose 6mg/kg once daily.
maintenance dose (max 800mg) Give post HD Bone and joint infection/endocarditis: Loading dose 12mg/kg
(round dose to nearest 200mg) (no maximum dose) every 12 hours for 3 doses then
maintenance dose 12mg/kg once daily. (Maximum starting
maintenance dose 800mg daily).
Monitor levels- see antibiotic website
Creatinine Clearance (CrCl) (ml/min) Comments
Antimicrobial
50-20 20-10 <10
Tetracycline Use Doxycycline see above

Tigecycline Normal Normal Normal

CrCl 30-60 CrCl 10-30 CrCl<10
Timentin Post HD
3.2g 8h 3.2g 12h 3.2g 24 h
CrCl 10–40 CrCl<10
3mg/kg (max 300mg) 2 mg/kg (max
Tobramycin See separate dosing guidance if using in cystic fibrosis
Check levels 18-24 hours 200mg) re-dose
ONCE DAILY
after first dose. according
Re-dose only when level < 1mg/L. to levels
Give post HD

NB May cause temporary rise in creatinine due to reduced

creatinine secretion rather than a fall in CrCl, therefore avoid in
CrCl 15-20 those where acute rises in creatinine would complicate the
CrCl <15
Trimethoprim Normal Normal (see clinical picture.
Avoid
comments)
Can cause hyperkalaemia, do not use in patients with
CrCl<30ml/min where hyperkalaemia is a problem or if they are
on other medications which can cause hyperkalaemia (e.g. ACE
inhibitor, spironolactone)
CrCl 30-50 Dose reduction required for CrCl<30 seek
Valaciclovir Zoster: 1g bd further advice from pharmacy/renal drug Post HD
Simplex: Normal handbook
Dose reduction required seek further advice from pharmacy/renal drug
Valganciclovir Post HD
handbook
Refer to vancomycin dosing guideline or the antibiotic website or the Monitor blood levels & adjust dose as required see antibiotic
Vancomycin vancomycin dosing calculator on the antibiotic website. Patients should website.
receive a loading dose followed by a maintenance dose based on Creatinine
Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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 Drugs marked * = Contact microbiologist for advice on assays where appropriate
Clearance.
Consider oral preparation as first choice in patients with renal
impairment. Accumulation of the vehicle, sulfobutyl ether-B-
cyclodextrin, occurs but this does not appear to lead to any toxic
Voriconazole Normal Normal Normal
effects.
If IV preparation indicated use with caution and monitor serum
creatinine levels closely

Nottingham Antimicrobial Guidelines Committee June 2015 Review June 2017

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Equality Impact Assessment Report

1. Name of Policy or Service

Response to external best practice policy

2. Responsible Manager
Annette Clarkson Specialist Clinical pharmacist antimicrobials and Infection
control

3. Name of person Completing EIA

Annette Clarkson

4. Date EIA Completed

19/06/2015

5. Description and Aims of Policy/Service

This guideline details the dosing of antimicrobials in varying degrees of renal

impairment.

6. Brief Summary of Research and Relevant Data

There is no research or relevant data at the present time.

7. Methods and Outcome of Consultation

Consultations have been carried out with the following:

NUH Antibiotic guidelines committee

NUH Drugs and Therapeutics committee

Comments from the above consultations have been received and

incorporated where appropriate.

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8. Results of Initial Screening or Full Equality Impact Assessment:

Equality Group Assessment of Impact

Age No Impact Identified

Gender No Impact Identified

Race No Impact Identified

Sexual Orientation No Impact Identified

Religion or belief No Impact Identified

Disability No Impact Identified

Dignity and Human Rights No Impact Identified

Working Patterns No Impact Identified

Social Deprivation No Impact Identified

9. Decisions and/or Recommendations (including supporting rationale)

From the information contained in the procedure, and following the initial
screening, it is my decision that a full assessment is not required at the
present time.

10. Equality Action Plan (if required) N/A

11. Monitoring and Review Arrangements Review June 2017

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