General Principles

Many medicines are excreted by the kidneys and require dose adjustment in renal impairment.
Antimicrobial dosage depends on the type and severity of the infection, sensitivity of the causative organism and the general condition of the patient.
For severe infections the higher end of the dose range should be used for loading dose/initial treatment.
For most drugs, although the size of the maintenance dose is reduced, it is important to still give a loading dose when recommended.
Caution if concomitant hepatic and renal impairment – a further reduction in dosing may be indicated.
Always check for drug interactions when prescribing antimicrobials. See Appendix 5 for information on resources available in LUH to check interactions.
There is inconsistency among published sources of information on drug dosing in renal impairment. Recommendations in these guidelines are largely derived from The Renal Drug Database, and in some cases from the BNF and Summary of Product Characteristics (SPC) for the drug. The BNF and manufacturers recommendations (SPC) tend to be more conservative than The Renal Drug Database.
Doses of Antimicrobials in renal impairment are outlined in the Table . Antimicrobials marked with an asterix have significant differences in dosing between reference sources. In some cases a dose range is give - the higher end of the range should be used for severe infections. See HPRA.ie for licensed dose recommendations.
“Usual” dose refers to the dose and interval recommended for adults with normal renal and hepatic function e.g. in LUH Antimicrobial Guidelines, BNF or SPC.

Assessing Renal Function

1. Published information on the effects of renal impairment on drug elimination has historically been stated in terms of Creatinine Clearance (CrCl), calculated using Cockcroft & Gault equation, as a surrogate for GFR.

2. The iCM system reports renal function as eGFR (estimated glomerular filtration rate) normalised to a body surface area of 1.73m ² , calculated using the CKD-EPI equation.

3. Although the two measures of renal function are NOT interchangeable, for most drugs and for most adult patients of average build and height, eGFR (rather than CrCl) can be used to determine dosage adjustments.

4. The BNF now uses eGFR for dose reduction for most (but not all) drugs. Exceptions to the use of eGFR, where calculation of creatinine clearance (Cockcroft & Gault equation) is recommended, include:

Elderly patients aged 75 years and over.
Patients at extremes of muscle mass (BMI less than 18kg/m ² or greater than 40 kg/m ² ).
Nephrotoxic drugs and drugs with a narrow therapeutic index that are mainly renally excreted. The BNF doesn’t specify which drugs but examples might include (these are also specified in the dosing table ):
- Aminoglycosides (e.g. Amikacin, Gentamicin, Tobramycin)
- Vancomycin
- Foscarnet
- Ganciclovir
- Valganciclovir

5. Using serum creatinine to derive eGFR has a number of limitations; serum creatinine levels are dependent on muscle mass and diet, therefore estimates should be interpreted with caution in certain individuals (e.g. elderly patients, body builders, amputees, in muscle-wasting disorders and vegans) - estimates will be higher or lower than the true value.

6. Creatinine-derived measurements are also not useful in periods of rapidly changing renal function (e.g. critical care) or in patients with Acute Kidney Injury (AKI).

7. In principle, in the acutely critically ill patient with AKI, antimicrobials with wide therapeutic indices and minimal safety concerns e.g. beta lactams should/may be given at full dose for the first 24-48h. Regular monitoring of renal function is advised in acutely ill patients to ensure drug use and dosing is appropriate.

8. Dosing should be assessed on an individual patient basis, balancing risk versus benefit, and taking urine output and clinical picture into account.

Cockcroft and Gault Equation ( click here to access an online calculator)

Creatinine Clearance (CrCl) (ml/min)

Calculate Ideal Body Weight (IBW) in kg (see below)
If actual body weight < IBW, use actual body weight in this equation

(140 – age) x (IBW in kg) x N

Serum creatinine (micromol/L)

N = 1.23 males & 1.04 females

Ideal Body Weight (IBW) (kg) =

Male:

50kg + (2.3kg x inches over 5 feet) OR 50kg + (0.9kg x cm over 152cm)

Female:

45.5kg + (2.3kg x inches over 5 feet) OR 45.5kg + (0.9kg x cm over 152cm)

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Cockcroft and Gault Equation

Cockcroft and Gault Equation ( click here to access an online calculator)

Creatinine Clearance (CrCl) (ml/min)

Calculate Ideal Body Weight (IBW) in kg (see below)
If actual body weight < IBW, use actual body weight in this equation

(140 – age) x (IBW in kg) x N

Serum creatinine (micromol/L)

N = 1.23 males & 1.04 females

Ideal Body Weight (IBW) (kg) =

Male:

50kg + (2.3kg x inches over 5 feet) OR 50kg + (0.9kg x cm over 152cm)

Female:

45.5kg + (2.3kg x inches over 5 feet) OR 45.5kg + (0.9kg x cm over 152cm)

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Doses of Antimicrobials in Renal Impairment (Adults)

Antimicrobials in Renal Impairment

1. The dosage adjustment table is intended for use in the treatment of infection of hospitalised patients only.

2. It recommends dose adjustment using the patient's eGFR value (or Creatinine Clearance using Cockcroft and Gault (CrCl) if specified ).

3. Please refer to General principles and Assessing renal function for more information. Clinical judgement should be used alongside any estimates derived from equations or suggested dose adjustments.

4. For some medicines, the renal dose information is presented as a dose range - use the higher end of the dose range for severe infections. Antimicrobials marked with an *asterix have significant differences in dosing between reference sources.

5. In situations where a range of dosing is recommended, patient, indication and severity of infection need to be considered. Specific factors include age, immune function, degree of renal impairment, risk of adverse effects etc.

6. More detailed information on antimicrobial dosing in renal impairment is available via the Renal Drug Database (details on how to access are available via Linkopolis -> Pharmacy Medicines Information -> Prescribing -> Renal Drug Database) and summary of product characteristics via the HPRA website .

7. The table below refers to patients with renal impairment only, for patients on dialysis please consult the Renal Drug Database for dosing and dialysability.

8. "Usual" dose refers to the dose and interval recommended for adults with normal renal and hepatic function in LUH Antimicrobial Guidelines.

Doses of Antimicrobials in Renal Impairment (Adults)
Aciclovir IV If obese, consider using ideal or adjusted body weight to calculate dose – See Medinfo GUH IV guideline for more details.	eGFR 25 to 50 Usual dose every 12h	eGFR 10 to 25 Usual dose every 24h	eGFR <10 50% of usual dose every 24h	Maintain adequate hydration with prior volume repletion.
Aciclovir PO	eGFR 25 to 50 Usual	eGFR 10 to 25 Simplex: 200mg q6h Zoster: 800mg q8h	eGFR <10 Simplex: 200mg q12h Zoster: 800mg q12h	Maintain adequate hydration.
Amikacin Red light - on Micro approval only	CrCl <80: Reduce dose. See Amikacin Dosing Table	Monitor levels. Must use CrCl (not eGFR). If obese use adjusted dosing weight.
*Amoxicillin IV/PO	eGFR 10 to 50 Usual	eGFR <10 250mg to 1g q8h High dose regimens e.g. endocarditis & listeria meningitis: max 2g q8h
Amphotericin Liposomal AmBisome ^® Red light - on Micro approval only	Usual	Highly nephrotoxic – monitor renal function.
Anidulafungin Red light - on Micro approval only	Usual
Artesunate	Usual Consult ID GUH	Ref: SPC
Atovaquone	eGFR 10 to 50 Usual dose	eGFR <10 Usual dose with caution	Monitor more closely in renal impairment.
Azithromycin	eGFR 10 to 50 Usual dose	eGFR <10 Usual dose with caution	33% increase in systemic exposure to azithromycin in patients when GFR<10.
Aztreonam Red light - on Micro approval only	eGFR 30 to 50 Usual	eGFR 10 to 30 Usual first dose (loading dose), then 50% of usual as maintenance dose	eGFR <10 Usual first dose (loading dose), then 25% of usual as maintenance dose	Nebulised: Dose as in normal renal function.
Benzylpenicillin	eGFR 20 to 50 Usual	eGFR 10 to 20 600mg to 2.4g q6h	eGFR <10 600mg to 1.2g q6h	Increased risk of neurotoxicity (seizures) in renal impairment.
Use higher doses for severe infection e.g. endocarditis. Discuss with Microbiology.
Caspofungin	Usual
*CefALEXin	eGFR 40 to 50 Usual	eGFR 10 to 40 500mg q8h	eGFR <10 500mg q12h
*CefAZOLin	eGFR 35-54 Usual dose q8h	eGFR 11-34 50% usual dose q12h	eGFR <10 1-2g daily	Ref: Sanford, RDD High doses in severe infection please discuss with Micro only. Caution increased risk of convulsions in renal impairment.
*CeFIXime	eGFR 10 to 50 Usual	eGFR <10 Max 200mg q24h	Ref: RDD
CefoTAXime	eGFR 5 to 50 Usual	eGFR <5 Initial dose 1g then reduce dose by 50% and keep frequency the same. For severe/life-threatening infection contact Micro.	Reduce dose further if concurrent hepatic and renal failure. Ref: RDD
CefTAZidime	eGFR 31 to 50 1g to 2g q12h	eGFR 16 to 30 1g to 2g q24h	eGFR 6 to 15 500mg to 1g q24h eGFR <5 500mg to 1g q48h
CefTAZidime/ Avibactam (Zavicefta ^® ) Red light - on Micro approval only	eGFR 31 to 50 1g/0.25g q8h	eGFR 16 to 30 0.75g/0.1875g q12h	eGFR 6 to 15 0.75g/0.1875g q24h eGFR <5 0.75g/0.1875g q48h
Ceftolozane/ Tazobactam (Zerbaxa ^® ) Red light - on Micro approval only	eGFR <50 Reduce dose. Renal dose depends on indication. Contact micro/pharmacy.	Ref: RDD
*CefTRIAXone	eGFR 10 to 50 Usual	eGFR <10 Usual to max 2g q24h Meningitis only: 2g q12h – must be discussed with micro.	In patients with both hepatic dysfunction and significant renal disease, limit dosage to 2g q24. Ref: Sanford
CefUROXime IV	eGFR 20 to 50 Usual	eGFR 10 to 20 750mg to 1.5g q12h	eGFR <10 750mg to 1.5g q24h
*CefUROXime PO	Usual
Chloramphenicol	eGFR 10 to 50 Usual	eGFR <10 Usual - but use only if no alternative (Ref: BNF)	Monitor levels in renal impairment (but not routinely available). Please consult micro.
* Ciprofloxacin IV/PO	eGFR 30 to 50 Usual	eGFR 10 to 30 50 to 100% of usual dose	eGFR <10 50% of usual dose but if severe infection discuss with Micro (may consider higher dose for short period).	Higher end of dose range for severe infection should be discussed with Micro . Caution- higher risk of tendon injury in renal impairment – see quinolone warning .
* Clarithromycin IV/PO	eGFR 30 to 50 Usual	eGFR<30 250 to 500mg q12h. Use higher end of dose range for severe infection.	Use with caution in renal or hepatic failure. May cause vomiting if eGFR <10. Ref: RDD
Clindamycin IV/PO	Usual (but see comment if eGFR<10)	Dosage may require reduction in patients with severe renal impairment due to prolonged half-life. Ref: RDD & SPC
Co-amoxiclav IV	eGFR 30 to 50 Usual	eGFR<30 1.2g q12h
*Co-amoxiclav PO	Usual
Colistin IV Red light - on Micro approval only	Please consult Micro/Pharmacy – dosing depends on indication.
Co-trimoxazole IV/PO Treatment doses only*	eGFR 30 to 50 Usual	eGFR 15 to 30 PJP indication : 60mg/kg q12h for 3 days, then 30mg/kg q12h Other indications: 50% of dose	eGFR <15 PJP indication : 30mg/kg q12h Other indications: Avoid if possible, as levels cannot be monitored. (Or use 50% of dose if Micro approved). Use only if haemodialysis facilities available.
Daptomycin Red light - on Micro approval only	eGFR 30 to 50 Usual	eGFR <30 Usual dose q48h	Caution in renal impairment- monitor renal function & CK closely if eGFR <80
Doxycycline	Usual
Erythromycin IV/PO	Usual	Increased risk of ototoxicity in renal impairment especially at high doses.
Ertapenem Red light - on Micro approval only*	eGFR 30 to 50 Usual	eGFR 10 to 30 500mg to 1g q24h	eGFR <10 500mg q24h OR 1g three times weekly	Ref: RDD
*Ethambutol	eGFR 20 to 50 Usual	eGFR 10 to 20 7.5mg/kg to 15mg/kg q24h	eGFR <10 5mg/kg to 7.5mg/kg q24h	In eGFR <30 levels should be monitored but not routinely available, please discuss with Micro. Ref: RDD
Fidaxomicin	Usual	Use with caution in severe impairment.
*Flucloxacillin IV/PO	eGFR 10 to 50 Usual	eGFR <10 1g q6h For infective endocarditis please discuss with Microbiology	Use with caution if concomitant liver impairment/ consider lower doses. Ref: RDD
Fluconazole IV/PO	eGFR 10 to 50 Usual initial dose, then 50-100% of dose	eGFR <10 Give usual initial dose as a loading dose, then 50% of dose	Ref: SPC
Foscarnet Red light - on Micro approval only	Contact Microbiology for advice.	Must use CrCl (not eGFR). Maintain adequate hydration.
*Fosfomycin PO	eGFR 10 to 50 Uncomplicated UTI: 3g as a single dose	eGFR <10 Avoid if possible due to prolonged half-life. Discuss with microbiology.
Fosfomycin IV Red light - on Micro approval only	eGFR<40 Reduce dose according to indication. Contact Microbiology or Pharmacy for advice.
Fusidic Acid	Usual
Ganciclovir Discuss with Microbiology	CrCl <70 Dose reduction required see Renal Drug Database or Medinfo GUH for more information.	Must use CrCl (not eGFR). Maintain adequate hydration.
Gentamicin	CrCl 30 to 80 : Reduce dose. See Gentamicin Dosing Table and calculator . Please note more frequent monitoring of levels is required in patients with AKI or changing renal function.	Monitor levels. Must use CrCl (not eGFR). If obese use adjusted dosing weight.
Isoniazid	eGFR 10 to 50 Usual	eGFR <10 200 to 300mg q24h
Itraconazole PO	Usual
Itraconazole IV	eGFR 30 to 80 Use with caution	eGFR<30 Avoid	IV vehicle may accumulate in renal impairment.
Levofloxacin IV/PO	eGFR 20 to 50 500mg stat, then 250mg q12h	eGFR 10 to 19 500mg stat, then 125mg q12h	eGFR <10 500mg stat, then 125mg q24h	Ref: RDD Dosing advice is based on usual dose of 500mg q12h
Linezolid IV/PO Red light - on Micro approval only	Usual Monitor FBC closely if eGFR <10	Metabolites with MAOI activity may accumulate if eGFR<30.
Meropenem Red light - on Micro approval only	eGFR 26 to 50 500mg to 2g q12h	eGFR 10 to 25 500mg to 1g q12h	eGFR <10 500mg to 1g q24h	Higher end of dose range for CNS/ MDRO infection should be discussed with Micro.
Metronidazole IV/PO	Usual
Minocycline	Usual
Moxifloxacin IV/PO Red light - on Micro approval only	Usual
Nitrofurantoin	eGFR <45 Contraindicated. However, a short 3 to 7 day course may be used with caution in certain patients with an eGFR of 30 to 44ml/min - to treat lower UTI with suspected/proven multidrug resistant pathogens when the benefits of nitrofurantoin are considered to outweigh the risk of side effects.	Note it may be ineffective in CrCl <60ml/min due to inadequate urinary concentration. Ref: RDD
* Ofloxacin	eGFR 10 to 50 200 to 400mg q24h	eGFR <10 100 to 200mg q24h	Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning
Oseltamivir Treatment dose*	CrCl 31 to 60 75mg q12h	CrCl 11 to 30 75mg q24h or 30mg q12h	CrCl ≤10 75mg STAT as a single dose	Ref: RDD – note due to clinical experience and good tolerability RDD recommend higher doses when compared to the HSPC.
Oseltamivir Prophylaxis dose*	CrCl 31 to 60 75mg q24h	CrCl 11 to 30 75mg q48h or 30mg q24h	CrCl ≤10 30mg STAT dose, repeat after 7 days	Ref: RDD
Pentamidine IV	eGFR 10 to 50 Usual	eGFR <10 Please discuss with micro – depends on severity of infection.
Phenoxymethyl-penicillin	Usual
Piperacillin/ tazobactam (Tazocin ^® )	eGFR 20 to 40 4.5g q8h	eGFR <20 4.5g q12h
Posaconazole IV/PO Red light - on Micro approval only	Oral: Usual IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.	IV vehicle may accumulate in renal impairment.
*Pyrazinamide	eGFR 30 to 50 Usual	eGFR <30 Contact micro or pharmacy for advice in eGFR <30.	Ref: BNF & WHO
*Quinine IV/PO	eGFR < 50 Contact Microbiology or ID (GUH)	Ref: BNF & WHO
Rifampicin	eGFR 10 to 50 Usual	eGFR <10 50 to 100% of usual dose TB : Give usual dose	Use with caution in renal impairment if dose above 600mg daily – contact pharmacy for advice.
Teicoplanin	eGFR 30 to 80 Give usual dose on days 1 to 4, then give usual dose q48h	eGFR <30 Give usual dose on days 1 to 4, then give usual dose q72h	Levels not routinely available – can be sent outside of Ireland but take approx. 1 week to return.
Tigecycline Red light - on Micro approval only	Usual
Tobramycin	CrCl <80 : Reduce dose. See Tobramycin Dosing Table	Monitor levels. Must use CrCl (not eGFR). If obese use adjusted dosing weight.
*Trimethoprim	eGFR 15-30 Use normal dose for treatment	eGFR <15 50-100% of usual dose (Ref RDD)
Note may cause temporary rise in creatinine due to competition for renal secretion rather than a fall in CrCl, therefore avoid in AKI . 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.
VaLACIclovir	Dose reduction varies depending on indication. See Renal Drug Database for more information. HSV: eGFR <30: Reduce dose Herpes zoster: eGFR <50: Reduce dose CMV prophylaxis: eGFR <75: Reduce dose	Maintain adequate hydration
VaLGANCIclovir	CrCl <60 Reduce dose. See Renal Drug Database for more information.	Must use CrCl (not eGFR). Maintain adequate hydration and monitor FBC closely in renal impairment.
Vancomycin PO	Usual
Vancomycin IV	CrCl <50 : Reduce dose. See Vancomycin Dosing Table and calculator . Please note more frequent monitoring of levels is required in patients with AKI or changing renal function.	Monitor levels. Must use CrCl (not eGFR).
Voriconazole IV/PO Red light - on Micro approval only	Oral: Usual IV: eGFR< 50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk. Contact Micro/Pharmacy for advice.	IV vehicle may accumulate in renal impairment
Antimicrobials marked with an asterix have significant difference in dosing between reference sources.

Doses of Antimicrobials in Renal Impairment (Adults)

Antimicrobial

eGFR (ml/min/1.73m ² )

Comment

20 to 50

10 to 20

<10

Aciclovir IV

If obese, consider using ideal or adjusted body weight to calculate dose – See Medinfo GUH IV guideline for more details.

eGFR 25 to 50

Usual dose every 12h

eGFR 10 to 25

Usual dose every 24h

eGFR <10

50% of usual dose every 24h

Maintain adequate hydration with prior volume repletion.

Aciclovir PO

eGFR 25 to 50

Usual

eGFR 10 to 25

Simplex: 200mg q6h

Zoster: 800mg q8h

eGFR <10

Simplex: 200mg q12h

Zoster: 800mg q12h

Maintain adequate hydration.

Amikacin

Red light - on Micro approval only

CrCl <80: Reduce dose. See Amikacin Dosing Table

Monitor levels.

Must use CrCl (not eGFR). If obese use adjusted dosing weight.

*Amoxicillin IV/PO

eGFR 10 to 50

Usual

eGFR <10

250mg to 1g q8h

High dose regimens e.g. endocarditis & listeria meningitis: max 2g q8h

Amphotericin Liposomal

AmBisome ^®

Red light - on Micro approval only

Usual

Highly nephrotoxic – monitor renal function.

Anidulafungin

Red light - on Micro approval only

Usual

Artesunate

Usual

Consult ID GUH

Ref: SPC

Atovaquone

eGFR 10 to 50

Usual dose

eGFR <10

Usual dose with caution

Monitor more closely in renal impairment.

Azithromycin

eGFR 10 to 50

Usual dose

eGFR <10

Usual dose with caution

33% increase in systemic exposure to azithromycin in patients when GFR<10.

Aztreonam

Red light - on Micro approval only

eGFR 30 to 50

Usual

eGFR 10 to 30

Usual first dose (loading dose), then 50% of usual as maintenance dose

eGFR <10

Usual first dose (loading dose), then 25% of usual as maintenance dose

Nebulised: Dose as in normal renal function.

Benzylpenicillin

eGFR 20 to 50

Usual

eGFR 10 to 20

600mg to 2.4g q6h

eGFR <10

600mg to 1.2g q6h

Increased risk of neurotoxicity (seizures) in renal impairment.

Use higher doses for severe infection e.g. endocarditis. Discuss with Microbiology.

Caspofungin

Usual

*CefALEXin

eGFR 40 to 50

Usual

eGFR 10 to 40

500mg q8h

eGFR <10

500mg q12h

*CefAZOLin

eGFR 35-54

Usual dose q8h

eGFR 11-34

50% usual dose q12h

eGFR <10

1-2g daily

Ref: Sanford, RDD

High doses in severe infection please discuss with Micro only. Caution increased risk of convulsions in renal impairment.

*CeFIXime

eGFR 10 to 50

Usual

eGFR <10

Max 200mg q24h

Ref: RDD

CefoTAXime

eGFR 5 to 50

Usual

eGFR <5

Initial dose 1g then reduce dose by 50% and keep frequency the same.

For severe/life-threatening infection contact Micro.

Reduce dose further if concurrent hepatic and renal failure.

Ref: RDD

CefTAZidime

eGFR 31 to 50

1g to 2g q12h

eGFR 16 to 30

1g to 2g q24h

eGFR 6 to 15
500mg to 1g q24h

eGFR <5
500mg to 1g q48h

CefTAZidime/
Avibactam
(Zavicefta ^® )

Red light - on Micro approval only

eGFR 31 to 50

1g/0.25g q8h

eGFR 16 to 30

0.75g/0.1875g q12h

eGFR 6 to 15
0.75g/0.1875g q24h

eGFR <5
0.75g/0.1875g q48h

Ceftolozane/
Tazobactam
(Zerbaxa ^® )

Red light - on Micro approval only

eGFR <50

Reduce dose. Renal dose depends on indication. Contact micro/pharmacy.

Ref: RDD

*CefTRIAXone

eGFR 10 to 50

Usual

eGFR <10

Usual to max 2g q24h

Meningitis only: 2g q12h – must be discussed with micro.

In patients with both hepatic dysfunction and significant renal disease, limit dosage to 2g q24.

Ref: Sanford

CefUROXime IV

eGFR 20 to 50

Usual

eGFR 10 to 20

750mg to 1.5g
q12h

eGFR <10

750mg to 1.5g
q24h

*CefUROXime PO

Usual

Chloramphenicol

eGFR 10 to 50

Usual

eGFR <10

Usual - but use only if no alternative (Ref: BNF)

Monitor levels in renal impairment (but not routinely available). Please consult micro.

* Ciprofloxacin IV/PO

eGFR 30 to 50

Usual

eGFR 10 to 30

50 to 100% of usual dose

eGFR <10

50% of usual dose but if severe infection discuss with Micro (may consider higher dose for short period).

Higher end of dose range for severe infection should be discussed with Micro .

Caution- higher risk of tendon injury in renal impairment – see quinolone warning .

* Clarithromycin
IV/PO

eGFR 30 to 50

Usual

eGFR<30

250 to 500mg q12h. Use higher end of dose range for severe infection.

Use with caution in renal or hepatic failure. May cause vomiting if eGFR <10.
Ref: RDD

Clindamycin IV/PO

Usual

(but see comment if eGFR<10)

Dosage may require reduction in patients with severe renal impairment due to prolonged half-life.
Ref: RDD & SPC

Co-amoxiclav IV

eGFR 30 to 50

Usual

eGFR<30

1.2g q12h

*Co-amoxiclav PO

Usual

Colistin IV

Red light - on Micro approval only

Please consult Micro/Pharmacy – dosing depends on indication.

*Co-trimoxazole IV/PO

Treatment doses only

eGFR 30 to 50

Usual

eGFR 15 to 30

PJP indication : 60mg/kg q12h for 3 days, then 30mg/kg q12h

Other indications: 50% of dose

eGFR <15

PJP indication :
30mg/kg q12h

Other indications:
Avoid if possible, as levels cannot be monitored. (Or use 50% of dose if Micro approved).

Use only if haemodialysis facilities available.

Daptomycin

Red light - on Micro approval only

eGFR 30 to 50

Usual

eGFR <30

Usual dose q48h

Caution in renal impairment- monitor renal function & CK closely if eGFR <80

Doxycycline

Usual

Erythromycin IV/PO

Usual

Increased risk of ototoxicity in renal impairment especially at high doses.

*Ertapenem

Red light - on Micro approval only

eGFR 30 to 50

Usual

eGFR 10 to 30

500mg to 1g q24h

eGFR <10

500mg q24h OR 1g three times weekly

Ref: RDD

*Ethambutol

eGFR 20 to 50

Usual

eGFR 10 to 20

7.5mg/kg to 15mg/kg q24h

eGFR <10

5mg/kg to 7.5mg/kg q24h

In eGFR <30 levels should be monitored but not routinely available, please discuss with Micro.

Ref: RDD

Fidaxomicin

Usual

Use with caution in severe impairment.

*Flucloxacillin IV/PO

eGFR 10 to 50

Usual

eGFR <10

1g q6h

For infective endocarditis please discuss with Microbiology

Use with caution if concomitant liver impairment/ consider lower doses.

Ref: RDD

Fluconazole IV/PO

eGFR 10 to 50

Usual initial dose, then 50-100% of dose

eGFR <10

Give usual initial dose as a loading dose, then 50% of dose

Ref: SPC

Foscarnet

Red light - on Micro approval only

Contact Microbiology for advice.

Must use CrCl (not eGFR). Maintain adequate hydration.

*Fosfomycin PO

eGFR 10 to 50

Uncomplicated UTI: 3g as a single dose

eGFR <10

Avoid if possible due to prolonged half-life. Discuss with microbiology.

Fosfomycin IV

Red light - on Micro approval only

eGFR<40

Reduce dose according to indication. Contact Microbiology or Pharmacy for advice.

Fusidic Acid

Usual

Ganciclovir

Discuss with Microbiology

CrCl <70

Dose reduction required see Renal Drug Database or Medinfo GUH for more information.

Must use CrCl (not eGFR).

Maintain adequate hydration.

Gentamicin

CrCl 30 to 80 : Reduce dose. See Gentamicin Dosing Table and calculator .

Please note more frequent monitoring of levels is required in patients with AKI or changing renal function.

Monitor levels. Must use CrCl (not eGFR). If obese use adjusted dosing weight.

Isoniazid

eGFR 10 to 50

Usual

eGFR <10

200 to 300mg q24h

Itraconazole PO

Usual

Itraconazole IV

eGFR 30 to 80

Use with caution

eGFR<30

Avoid

IV vehicle may accumulate in renal impairment.

Levofloxacin IV/PO

eGFR 20 to 50

500mg stat, then 250mg q12h

eGFR 10 to 19

500mg stat, then 125mg q12h

eGFR <10

500mg stat, then 125mg q24h

Ref: RDD

Dosing advice is based on usual dose of 500mg q12h

Linezolid IV/PO

Red light - on Micro approval only

Usual

Monitor FBC closely if eGFR <10

Metabolites with MAOI activity may accumulate if eGFR<30.

Meropenem

Red light - on Micro approval only

eGFR 26 to 50

500mg to 2g q12h

eGFR 10 to 25

500mg to 1g q12h

eGFR <10

500mg to 1g q24h

Higher end of dose range for CNS/ MDRO infection should be discussed with Micro.

Metronidazole IV/PO

Usual

Minocycline

Usual

Moxifloxacin IV/PO

Red light - on Micro approval only

Usual

Nitrofurantoin

eGFR <45

Contraindicated.

However, a short 3 to 7 day course may be used with caution in certain patients with an eGFR of 30 to 44ml/min - to treat lower UTI with suspected/proven multidrug resistant pathogens when the benefits of nitrofurantoin are considered to outweigh the risk of side effects.

Note it may be ineffective in CrCl <60ml/min due to inadequate urinary concentration.

Ref: RDD

* Ofloxacin

eGFR 10 to 50

200 to 400mg q24h

eGFR <10

100 to 200mg q24h

Caution-Higher risk of tendon injury in renal impairment - see Quinolone warning

*Oseltamivir

Treatment dose

CrCl 31 to 60

75mg q12h

CrCl 11 to 30

75mg q24h or 30mg q12h

CrCl ≤10

75mg STAT as a single dose

Ref: RDD – note due to clinical experience and good tolerability RDD recommend higher doses when compared to the HSPC.

*Oseltamivir

Prophylaxis dose

CrCl 31 to 60

75mg q24h

CrCl 11 to 30

75mg q48h or 30mg q24h

CrCl ≤10

30mg STAT dose, repeat after 7 days

Ref: RDD

Pentamidine IV

eGFR 10 to 50

Usual

eGFR <10

Please discuss with micro – depends on severity of infection.

Phenoxymethyl-penicillin

Usual

Piperacillin/
tazobactam

(Tazocin ^® )

eGFR 20 to 40

4.5g q8h

eGFR <20

4.5g q12h

Posaconazole IV/PO

Red light - on Micro approval only

Oral: Usual

IV: eGFR<50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk.

IV vehicle may accumulate in renal impairment.

*Pyrazinamide

eGFR 30 to 50

Usual

eGFR <30

Contact micro or pharmacy for advice in eGFR <30.

Ref: BNF & WHO

*Quinine IV/PO

eGFR < 50

Contact Microbiology or ID (GUH)

Ref: BNF & WHO

Rifampicin

eGFR 10 to 50

Usual

eGFR <10

50 to 100% of usual dose

TB : Give usual dose

Use with caution in renal impairment if dose above 600mg daily – contact pharmacy for advice.

Teicoplanin

eGFR 30 to 80

Give usual dose on days 1 to 4, then give usual dose q48h

eGFR <30

Give usual dose on days 1 to 4, then give usual dose q72h

Levels not routinely available – can be sent outside of Ireland but take approx. 1 week to return.

Tigecycline

Red light - on Micro approval only

Usual

Tobramycin

CrCl <80 : Reduce dose. See Tobramycin Dosing Table

Monitor levels.

Must use CrCl (not eGFR).

If obese use adjusted dosing weight.

*Trimethoprim

eGFR 15-30

Use normal dose for treatment

eGFR <15

50-100% of usual dose (Ref RDD)

Note may cause temporary rise in creatinine due to competition for renal secretion rather than a fall in CrCl, therefore avoid in AKI .
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.

VaLACIclovir

Dose reduction varies depending on indication. See Renal Drug Database for more information.

HSV: eGFR <30: Reduce dose

Herpes zoster: eGFR <50: Reduce dose

CMV prophylaxis: eGFR <75: Reduce dose

Maintain adequate hydration

VaLGANCIclovir

CrCl <60

Reduce dose. See Renal Drug Database for more information.

Must use CrCl (not eGFR).
Maintain adequate hydration and monitor FBC closely in renal impairment.

Vancomycin PO

Usual

Vancomycin IV

CrCl <50 : Reduce dose. See Vancomycin Dosing Table and calculator .

Please note more frequent monitoring of levels is required in patients with AKI or changing renal function.

Monitor levels. Must use CrCl (not eGFR).

Voriconazole IV/PO

Red light - on Micro approval only

Oral: Usual

IV: eGFR< 50: Avoid IV if possible (use oral), unless benefit of IV outweighs risk. Contact Micro/Pharmacy for advice.

IV vehicle may accumulate in renal impairment

*Antimicrobials marked with an *asterix have significant difference in dosing between reference sources.

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Renal Replacement Therapy

Recommendations for dose adjustment in renal replacement therapy are largely derived from The Renal Drug Database, and in some cases from the Summary of Product Characteristics (SPC), and the Sanford Guide to Antimicrobial Therapy.

Intermittent Haemodialysis (IHD) : Assume GFR <10ml/min . Many drugs are removed by haemodialysis. In LUH most patients are dialysed using high flux filters. If a drug is dialysed, it is recommended to time administration to take place post dialysis and at the same time every day including dialysis days (to avoid the need to give a supplemental dose post dialysis). See LUH guidelines for Vancomycin, CefAZOLin & Gentamicin dosing in haemodialysis.

Peritoneal Dialysis (PD) : Some drugs are removed by peritoneal dialysis - please consult the Renal Drug Database for dosing. Alternatively contact the renal team. For peritonitis or catheter related infection please see the Peritoneal Dialysis section.

Continuous renal replacement (CRRT): In LUH, continuous venovenous haemodiafiltration (CVVHDF) is the type of continuous renal replacement used in intensive care. Recommendations for dosing of antimicrobials for patients on CRRT in critical care are outside of the scope of these guidelines. ICU/antimicrobial pharmacist is available for advice during working hours. Alternatively please contact renal for advice.

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Vancomycin, CefAZOLin & Gentamicin Dosing in Haemodialysis

Vancomycin, Gentamicin & CefAZOLin Dosing Information for Patients on Intermittent Haemodialysis in LUH.

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Peritoneal Dialysis

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Exit site infection

Initial Empiric therapy for suspected Exit-site Infection

Check previous microbiology history i.e. history of colonisation, infection and previous sensitivities.
Prescribe anti-fungal prophylaxis while on antibiotics (see section on Prophylaxis ).
Consider PD catheter removal in patients with exit site or tunnel infection that progresses to, or occurs simultaneously with, peritonitis due to the same organism.

Empiric Antibiotics for suspected Exit-site Infection
	1 ^st Line Antibiotics	Penicillin allergy: delayed onset non-severe reaction	Penicillin allergy: immediate or severe delayed reaction	Comment
		See penicillin hypersensitivity section for further information
No previous microbiology history of note	Flucloxacillin PO 500mg (mild) – 1g (moderate to severe) every 6 hours	CefALEXin PO 500mg every 12 hours	Clindamycin PO 300mg every 6 hours	Duration: 7 to 10 days for most * infections if resolution of infection is confirmed by clinical evaluation at around 1 week. This may be extended to 2 weeks if the infection is slow to resolve following clinical review. *Note: at least 3 weeks for pseudomonas infections. In addition, when there is unsatisfactory treatment response, a second antipseudomonal drug should be added. Please discuss with Microbiologist.
Previous history of infection or colonisation with MRSA	Doxycycline PO 100mg every 12 hours
Previous history of infection or colonisation with (ciprofloxacin sensitive) Pseudomonas	Add Ciprofloxacin PO 500mg every 12 hours (i.e. in addition to empiric cover above while awaiting sensitivities)
*Follow culture and sensitivity and modify antibiotic choice based on results* When an exit site infection does not resolve with effective antibiotics, consider simultaneous removal and reinsertion of PD catheters with a new exit site, under appropriate antibiotic coverage.

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Tunnel infection

Initial Empiric therapy for suspected Tunnel Infection

Check microbiology history i.e. history of colonisation, infection and previous sensitivities
Prescribe anti-fungal prophylaxis while on antibiotics (see section on Prophylaxis )
Consider PD catheter removal in patients with exit site or tunnel infection that progresses to, or occurs simultaneously with, peritonitis due to the same organism.

Empiric Antibiotics for suspected tunnel infection
	1 ^st Line Antibiotics	Penicillin allergy: delayed onset non-severe reaction	Penicillin allergy: immediate or severe delayed reaction	Comment
		See penicillin hypersensitivity section for further information
No previous microbiology history of note	Flucloxacillin PO 1g every 6 hours	CefALEXin PO 500mg every 12 hours	Clindamycin PO 450mg every 6 hours	Duration: 3 weeks Note : at least 3 weeks for pseudomonas (i.e. may require longer treatment). In addition, when there is unsatisfactory treatment response, a second antipseudomonal drug should be added. Please discuss with consultant microbiologist.
Previous history of infection or colonisation with MRSA	Vancomycin IP (intraperitoneal)* Loading dose = 30mg/kg (Max 3g) IP (intraperitoneal) stat. Check level every 3 days and re-dose as appropriate; target trough level: 15-20mg/L Maintenance dose = 15mg/kg (or adjusted if required) (Max 2g) *If Vancomycin cannot be administered by the IP (intra-peritoneal) route, or if there will be a significant delay, then it should be administered by the IV route. Give a loading dose: 25mg/kg (rounded to the nearest 250mg, Max 2g) IV dose and adjust as per renal team advice; switch to the intra-peritoneal route as soon as possible. Allergy to Vancomycin : Discuss with Microbiologist.
Previous history of infection or colonisation with (ciprofloxacin sensitive) Pseudomonas	Add Ciprofloxacin PO 500mg every 12 hours (i.e. in addition to empiric cover above while awaiting sensitivities)
*Follow culture and sensitivity and modify antibiotic choice based on results* When a tunnel infection does not resolve with effective antibiotics, consider simultaneous removal and reinsertion of PD catheters with a new exit site, under appropriate antibiotic coverage.

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Peritonitis

Initial Empiric Therapy for suspected Peritonitis

Check microbiology history i.e. history of colonisation, infection and previous sensitivities
Prescribe anti-fungal prophylaxis while on antibiotics (see section on Prophylaxis )
Consider PD catheter removal in patients with exit site or tunnel infection that progresses to, or occurs simultaneously with, peritonitis due to the same organism.

Empiric Antibiotics for suspected Peritonitis

Empiric Antibiotics for suspected Peritonitis
	1 ^st Line Antibiotics	Comment
	Vancomycin IP (intraperitoneal)* Loading dose = 30mg/kg (Max 3g) IP* Check level every 3 days and re-dose as appropriate; target trough level: 15-20mg/L Maintenance dose = 15mg/kg (or adjusted if required) (Max 2g) AND Ciprofloxacin PO 500mg every 12 hours or IV 400mg every 12 hours If the patient is systemically unwell and showing signs of sepsis please ADD Gentamicin IP (intraperitoneal)* 0.6mg/kg once daily IP* Check trough level daily and re-dose when necessary; target < 2mg/L Consider discussion with microbiology if concerned.
If antibiotics cannot be administered by the IP (intra-peritoneal) route, or if there will be a significant delay, then they should be administered by the IV route; switch to the IP (intraperitoneal) route as soon as possible. Vancomycin: Give a loading dose: IV 25mg/kg (rounded to the nearest 250mg, Max 2g) and adjust as per renal team advice. Gentamicin: Give IV 2mg/kg. If the patient is obese (i.e. actual body weight exceeds Ideal Body Weight by ≥20%), please use the Adjusted Dosing Weight . Check trough level daily, re-dose when necessary; target < 2mg/L. Follow culture and sensitivity and modify antibiotic choice based on results*

Culture negative Peritonitis

If the dialysis effluent culture is negative and patient is improving clinically stop gram negative agent i.e. ciprofloxacin and continue the gram-positive treatment for a total of 14 days.

If the dialysis effluent culture is negative and patient is not improving, consider other causative organisms - contact microbiologist for advice.

Directed Treatment of Infection due to Gram-positive organisms

Directed Treatment of Infection due to Gram-positive organisms

Enterococcus

*Check sensitivity*

Sensitive to Amoxicillin:

Amoxicillin PO 500mg every 8 hours

Stop Vancomycin and Ciprofloxacin

Duration:

21 days

Resistant to Amoxicillin:

Continue Vancomycin IP based on levels

Stop Ciprofloxacin

Resistant to Vancomycin :

Discuss with microbiologist

Consider Daptomycin IP 300mg once daily or Linezolid PO 600mg every 12 hours

Stop Vancomycin and Ciprofloxacin

Staphylococcus Aureus

*Check sensitivity*

Methicillin sensitive (MSSA)*:

CefAZOLin IP 15mg/kg once daily

Stop Vancomycin and Ciprofloxacin

Duration:

21 days

Methicillin resistant ( MRSA )*:

Continue Vancomycin IP based on levels

Stop Ciprofloxacin

*For MSSA or MRSA consider adding Rifampicin PO (discuss with Microbiologist):

Weight < 50kg: Dose = 450mg once daily

Weight > 50kg: Dose = 600mg once daily

Coagulase negative Staphylococcus

(including MRSE)

Continue Vancomycin IP based on levels

Stop Ciprofloxacin

Duration:

14 days

Streptococcus

*Check sensitivity*

CefAZOLin IP 15mg/kg once daily

Stop Vancomycin and Ciprofloxacin

Duration:

14 days

Resistant to cefazolin or if a cephalosporin is not appropriate:

Continue Vancomycin IP based on levels

Stop Ciprofloxacin

Directed treatment of infection due to Gram-negative organisms

Directed Treatment of Infection due to Gram-negative organisms

1 ^st Line Antibiotics

Penicillin allergy

Comment

See penicillin hypersensitivity section for further information

Single organism

e.g. E Coli, Klebsiella

*Check sensitivity*

Please review with sensitivity results and change to an appropriate antibiotic.

If patient is clinically unwell, please discuss with microbiologist and considering:

Adding Gentamicin IP 0.6mg/kg once daily
(Check trough level daily, re-dose when necessary; target < 2mg/L)

Duration:

21 days

Pseudomonas

*Check sensitivity*

Piperacillin/Tazobactam IV
4.5g every 12 hours

and

Gentamicin IP 0.6mg/kg once daily

(Check trough level daily; target < 2mg/L)

Stop Vancomycin and Ciprofloxacin

Continue Ciprofloxacin

Add

Gentamicin IP 0.6mg/kg once daily

(Check trough level daily; target < 2mg/L)

Stop Vancomycin

Duration:

21 days

Consider catheter removal

Directed Treatment of Infection due to multiple organisms

Directed Treatment of Infection due to multiple organisms
	1 ^st Line Antibiotics	Penicillin allergy	Comment
		See penicillin hypersensitivity section for further information
Multiple bacteria isolated *Immediate surgical assessment is mandatory*	Piperacillin/Tazobactam IV 4.5g every 12 hours and Gentamicin IP 0.6mg/kg once daily (Check trough level daily, re-dose when necessary; target < 2mg/L) Stop Vancomycin and Ciprofloxacin	Discuss with microbiology to determine cover required.	Duration: 21 days

Directed treatment of infection due to Fungal organisms

Directed Treatment of Infection due to Fungal organisms

*Immediate catheter removal is recommended*

Consult with Microbiologist

Candida albicans

*Check sensitivity*

Fluconazole PO 200mg once daily

Stop Vancomycin and Ciprofloxacin

Duration:

14 days after catheter removal

Candida non-albicans

*Check sensitivity*

Caspofungin IV

Loading dose: 70mg on Day 1

Maintenance dose: from Day 2

Weight < 80kg: 50mg once daily

Weight > 80kg: 70mg once daily

Stop Vancomycin and Ciprofloxacin

Duration:

14 days after catheter removal

Other fungal organisms

Contact Microbiologist

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Anti-microbial prophylaxis for peritoneal dialysis patients

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Anti-fungal prophylaxis while on antibiotics

Anti-fungal prophylaxis while on antibiotics
All peritoneal dialysis patients should receive concomitant antifungal prophylaxis while on antibiotics for any indication .
	1 ^st Line	Alternative option if contraindication to Nystatin:	Comment
Anti-fungal prophylaxis	Nystatin PO 500,000units every 6 hours	Fluconazole PO 200mg on alternate days Note: Potential for significant drug interactions – please check (ciprofloxacin and fluconazole prolong QTc - if they are prescribed concurrently regular ECG monitoring is required).	Duration: To be taken for the duration of antibiotics

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Prophylaxis prior to Colonoscopy or invasive Gynaecological procedures

Prophylaxis prior to colonoscopy or invasive gynaecological procedures
Note: Drain PD fluid to keep the abdomen empty prior to procedure
	1 ^st Line	Penicillin allergy	Duration
		See penicillin hypersensitivity section for further information
Prophylaxis	CefTRIAXone IV 1g STAT dose	If patient has history of severe penicillin allergy: Ciprofloxacin IV 400mg STAT and Metronidazole IV 500mg STAT	1 dose only

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Contamination of PD system

Contamination of PD system
‘Wet’ contamination is contamination with an open system, when either dialysis fluid is infused after contamination or if the catheter administration set has been left open for an extended period.
	1 ^st Line	Penicillin allergy
		See penicillin hypersensitivity section for further information
Prophylaxis	CefAZOLin IP 1g STAT	If patient has history of severe penicillin allergy : Vancomycin IP 15mg/kg STAT

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References

1. The Renal Drug Database www.renaldrugdatabase.com (Accessed May 2024).

2. BNF accessed online via Medicines complete (Accessed December 2023).

3. Health Products Regularoty Authority. Summary of Product Characteristics (SPC): https://www.hpra.ie/

4. The Sanford Guide to Antimicrobial Therapy Digital Update Feb 2018

5. Vidal et al. Systematic comparison of four sources of drug information regarding adjustment of dose for renal function. BMJ 2006;331:263

6. Dowling. Evaluation of renal drug dosing: Prescribing information and clinical pharmacist

approaches. Pharmacotherapy 2010;30:776-786

7. Nottingham University Hospital Antimicrobial Doses for Adults in Renal Impairment September 2019

8. International Society Peritoneal Dialysis Catheter-related Infection Recommendations: 2023 Update

9. Galway University Hospital Peritoneal Dialysis Catheter-related Guidelines 2024

10. Altnagelvin Area Hospital Peritoneal Dialysis Catheter-related Guidelines 2018

11. Discussion with Dr O Dunne (Nephrologist), Dr A Moran (Nephrologist), Dr I Yousif (Nephrologist), Dr M Mulhern (Consultant Microbiologist), Ms C McCloskey (Renal Home Therapies CNM), Ms E McLoone (Renal Pharmacist), Ms R Mc Menamin (Antimicrobial Stewardship Pharmacist)

Renal Dosing (Adults)

General Principles

General Principles

Assessing Renal Function

Assessing Renal Function

Cockcroft and Gault Equation

Doses of Antimicrobials in Renal Impairment (Adults)

Antimicrobials in Renal Impairment

Renal Replacement Therapy

Renal Replacement Therapy

Vancomycin, CefAZOLin & Gentamicin Dosing in Haemodialysis

Peritoneal Dialysis

Exit site infection

Tunnel infection

Peritonitis

Empiric Antibiotics for suspected Peritonitis

Culture negative Peritonitis

Directed Treatment of Infection due to Gram-positive organisms

Directed treatment of infection due to Gram-negative organisms

Directed Treatment of Infection due to multiple organisms

Directed treatment of infection due to Fungal organisms

Anti-microbial prophylaxis for peritoneal dialysis patients

Anti-fungal prophylaxis while on antibiotics

Prophylaxis prior to Colonoscopy or invasive Gynaecological procedures

Contamination of PD system

References

References