y egistered medical p antimicrobial pocket guide for

Pocket Guide For

ANTIMICROBIAL DOSING

IN RENAL FAILURE

For

the

use

only

of

a R

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d M

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al P

ract

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Hos

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a La

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tory

.

Cefoperazone / Sulbactam IV / IM Injection 1.5g & 3g

Medicine is an ever-changing science.

This book is based on sources believed to be reliable in

providing information that is complete and generally in

accordance with standards accepted at the time of

publication.

Every effort has been made to ensure that the drug doses

and other information are presented accurately in this

publication.

However, the ultimate responsibility rests solely with the

prescribing physician.

PREFACE

suffering from renal insufficiency.

T

INDEX

ANTIBACTERIALS 7

1. Beta-lactam Class

2. Aminoglycosides

3. Polymyxins

4. Fluoroquinolones

5. Glycopeptides

6. Macrolides

7. Tetracyclines / Glycylcycline

8. Nitroimidazole

9. Oxazolidinones

10. Lincosamide

ANTIFUNGALS 22

11. Polyenes

12. Azoles

13. Echinocandins

ANTIVIRALS 26

INTRODUCTION 4

261 2

INTRODUCTION

In renally challenged individuals, the drug tends to be in the system for a longer period as compared to those with normal renal function hence dose adjustments are essential to avoid drug toxicity to compensate for the decreased clearance of the drug.

A number of clinical laboratory tests like creatinine clearance test, urea clearance test, urine osmolality

*test, urine protein test and BUN test are used to determine the cause and extent of kidney dysfunction.

Amongst these tests creatinine clearance test and creatinine test are more widely accepted by the clinicians.

Creatinine is a waste product of muscle energy metabolism which is produced at a constant rate that is proportional to the individual's muscle mass. Because the body does not recycle it, all creatinine filtered by the kidneys in a given amount of time is excreted in the urine, making creatinine clearance a very specific measurement of kidney function.

Creatinine clearance test. This test evaluates how efficiently the kidneys clear creatinine from the blood. Low clearance values for creatinine indicate a diminished ability of the kidneys to filter waste

* BUN-Blood Urea Nitrogen test263 4

products from the blood and excrete them in the urine.

For a 24-hour urine collection, normal results are 90 mL/min–139 mL/min for adult males younger than 40 years and 80–125 mL/min for adult females younger than 40 years. For people over 40 years, values decrease by 6.5 mL/min for each decade of life.

Creatinine test. This test measures blood levels of creatinine. An elevated blood creatinine level is a more sensitive indicator of impaired kidney function than the BUN. Creatinine should be 0.8–1.2 mg/dL for males, and 0.6–0.9 mg/dL for females.

DRUG DOSE ADJUSTMENT IN RENAL PATIENTS

Serum creatinine is used to estimate Glomerular Filtration Rate (GFR) in order to supply appropriate doses to renally insufficient patients. GFR is related directly to the urine creatinine excretion and inversely related to serum creatinine.

When creatinine clearance is unavailable, it can be calculated by using Cockcroft – Gault formula as mentioned below:

Creatinine

clearance (mL/min)

=(140-age) x lean body weight (kg)

Plasma creatinine (mg/dL) x 72

(In case of female patients this value should be multiplied by 0.85 since a lower fraction of the body weight is composed of muscle)

However, the clinician's decision should also be supported by the patient's clinical condition, diet, age, gender, weight and other parameters while dosing renally compromised patients.

265 6

ANTIBACTERIALS

BETA-LACTAM CLASSBETA-LACTAM CLASS

*HD-Hemodialysis

ANTIMICROBIALS

USUAL DOSE (Normal Renal

Function)

CrCl(ml/min)

DOSAGE ADJUSTMENT (In Renal Insufficiency)

PENICILLINS

>40 No dose adjustment necessary

20-40 Serious systemic infections: 4g q8h

<20

*cUTI: 3g q8h

Serious systemic infections: 4g q8h

2g q8h, 1g additional dose after each dialysis

*HD

Uncomplicated & cUTI: 3g q12hPiperacillin3-4g q4h -6h

as 20-30 min

infusion

Ticarcillin

3g q4h

as 30 min

infusion

>60

30-60

10-30

<10

No dose adjustment necessary

2g q4h

2g q8h

2g q12h

<10 with hepatic

dysfunction2g q24h

Peritoneal dialysis

3g q12h

HD2g q12h supplemented

with 3g after each dialysis

267 8

1

*cUTI-Complicated Urinary Tract Infection


ANTIMICROBIALS


Function)

CrCl(ml/min)



ANTIMICROBIALS


Function)

CrCl(ml/min)


PENICILLINS

>50-90

10-50


250mg-2g q6-12h

<10

HD

250mg-2g q12-24h

Dose after dialysis

Ampicillin 250mg-2g q6h

CEPHALOSPORINS

Cefuroxime Sodium

Usual dose:750 mg -1.5 g q8h

Life threatening infections: 1.5g q6h

Meningitis:Maximum dose 3g q8h

>20

10-20

<10

HD

750mg -1.5 g q 8h

750mg q12h

750mg q24h

Further dose after dialysis

*CAPD 250mg q12h

*CAPD-Continuous Ambulatory Peritoneal Dialysis

Ceftriaxone Sodium

1-2g q24h in equally two divided dosesas 30 min infusion

Max dose : 4g

-

No dose adjustment necessary but serum monitoring is required in severe renal impairment and in patients with both renal and

hepatic dysfunction.

Ceftazidime

Usual dose:1g q8-12h

Serious infections:2g q8-12h

Loading dose : 1g

50-31

30-16

15-6

< 5

CAPD

1g q12h

1g q24h

500mg q24h

500mg q48h

500mg q24h

CEPHALOSPORINS

Cefotaxime 2g q12h

>50-90

10-50

<10

HD

CAPD

2 g q8-12h

2 g q12-24h

2g q24h

1g extra after dialysis

0.5-1g q24h

Cefoperazone

2-4g q12h(Maximum

dose)

12g q24h

Mild to

severe

No dose adjustment necessary when usual doses are administered,

serum monitoring required when high doses are administered

HD with hepatic

dysfunctionMax 1-2g/day

Cefepime

1-2g q12h(Maximum

dose)

Febrile Neutropenia

2g q8h

>50-90

10-50

<10

HD

CAPD

2g q8h

2g q12-24h

1g q24h

1g extra after dialysis

1-2g q48h

Cefpirome 1-2g q12h

Loading dose : 1-2g*

50-20

20-5

<5 (HD patients)

*Depending on the severity of infection

0.5-1g q12h

0.5-1g q24h

1.0g daily +0.5g immediately after dialysis

269 10


ANTIMICROBIALS


Function)

CrCl(ml/min)



ANTIMICROBIALS


Function)

CrCl(ml/min)


MONOBACTAMS

Aztreonam 1-2g q6-8h

10-30

<10

Normal dose followed by half of the initial dose

Normal dose followed by one quarter of the initial dose

Ertapenem

³13yrs

1g q24h as

30min infusion

(for cIAIs, cSSTIs,

CAP,cUTI)

>30

£ 30 - £ 10

HD500mg within 6h from HD

followed by 150mg after HD or500mg 6h prior to HD

CARBAPENEMS

Meropenem

(MEROCRIT)

0.5-1g q8h

Meningitis:2g q8h

as 15-30min infusion

26-50

10-25

<10

HD

1g q12h

0.5g q12h

0.5g q24h

At the completion of haemodialysis

Imipenem/

Cilastatin

(IMICRIT)

0.25-1g q6-8h

as 40 -60 min

infusion

31-70

21-30

6-20

0.5g q6-8h

0.5g 8-12h

0.25g q12h

£ 5Not recommended unless

HD is started within 48 hours.

<5 and

undergoing

HD

0.25g, but only after HD and at 12h interval

Doripenem

(18yrs and

above)

0.5g q8h as 1h infusion

(for cIAIs, cUTIs including pyelonephritis)

>50

CARBAPENEMS

Dialysis patients with CNS disease should receive Imipenem/Cilastatin

only when the benefit outweighs the potential risk of convulsions


0.5g q24h


BETA-LACTAM/BETA-LACTAMASE INHIBITORS

Amoxicillin/

Clavulanic acid

(ADVENT)

1.2g q6-8h

>30 No dose adjustment necessary

<10

1.2g IV stat., followed by 600mg q24h

An additional 600mg IV dose may need to be given during

dialysis and at the end of dialysis.

Ampicillin/

Sulbactam

(2:1)

1.5 - 3g q6h

>30

Piperacillin/

Tazobactam

(TAZACT)

Nosocomial pneumonia:

4.5g q6h plus an

aminoglycoside

Other Infections:3.375g q6has 30 min infusion

>40

20-40

<20

HD

CAPD

3.375g q6h & for nosocomial pneumonia 4.5g q6h





30 – 50

10-30

HD

0.25g q8h

Insufficient data

0.25g q12h

10-30 1.2g IV stat., followed by 600mg q12h

1.5 - 3g q6-8h

1.5 - 3g q12h

1.5 - 3g q24h

15-29

5-14

2611 12

ANTIMICROBIALS


Function)

CrCl(ml/min)



ANTIMICROBIALS


Function)

CrCl(ml/min)


Cefoperazone/

Sulbactam

(2:1, VIATRAN)

BETA-LACTAM/BETA-LACTAMASE INHIBITORS

3.0-4.5g q12has 15-60 min infusion

(Maximum recommended dose

of cefoperazone is 8g & sulbactam is 4g)

15-30

<15

HD

3g q12h

1.5g q12h

Dose to be given after dialysis

Cefepime/Tazobactam

Recommended Maintenance Schedule

>60

30-60

11-29

<11

CAPD

HD

500mg q12h

1g q12h

2g q12h

2g q8h

500mg q24h

1g q24h

2g q24h

2g q12h

500mg q24h

500mg q24h

1g q24h

2g q24h

250mg q24h

250mg q24h

500mg q24h

1g q24h

500mg q48h

1g q48h

2g q48h

2g q48h

1g on day 1, then 500mg q24h after dialysis

1g q24h

On haemodialysis days, administer following haemodialysis.

Whenever possible administer at the same time each day

Uncomplicated / complicated UTI

(including pyelonephritis)

Mild to moderate: 500mg or 1000mg

IV/IM q12h.

Severe 2000mg IV q12h.

Moderate to severe Uncomplicated SSIs

2000mg IV q12h.

Complicated IAIs (used in combination with metronidazole): 2000mg IV q12h

Amikacin

7.5 mg/kg/day q12h(Equivalent to 500 mg

q12h in adults).

Pseudomonal Infections: 500mg (Should never

exceed 1.5 g/day, therapy not to exceed

10 days as 30 min infusion)

>50-90

10-50

<10

HD


7.5mg/kg/day q24h

7.5mg/kg/day q48h

Half of normal renal function

dose afterdialysis

Gentamicin(40 mg/mL)

Systemic and urinary

tract infections3 mg/kg/day up to

80mg q8h

Life threatening infections 5mg/kg/day

initially then 3mg/kg/day as soon as improvement

is indicated q6-8 has 20- 30 min infusion

The first dose should be as normal recommended

>70

35-70

24-34

16-23

10-15

5-9

80mg q8h

80mg q12h

80mg q18h

80mg q24h

80mg q36h

80mg q48h

Dosage in obese patients should be based on an estimate of lean body mass.

AMINOGLYCOSIDESAMINOGLYCOSIDES

2613 14Cefoperazone / Sulbactam

IV / IM Injection 1.5g & 3g

2

ANTIMICROBIALS


Function)

CrCl(ml/min)



Tobramycin(40 mg/mL)

Serious infections1mg/kg/day q8h

Life-threatening infections

5mg/kg/day may be administered

in three or four equal dosages.

The dosage should be reduced to

3mg/kg/day as soon as clinically

indicated. Dosage should not

exceed 5mg/kg/day, unless serum levels

are monitored in order to prevent

increased toxicity due to excessive blood levels as

20-60 min infusion

ANTIMICROBIALS


Function)

CrCl(ml/min)



Loading dose of 1mg/kg, for life-threatening infections,

dosages 50% above those normally recommended may be used.

The dosages should be reduced as soon as possible when

improvement is noted.

Weight

50-60 kg 60 – 80 kg

>70 80mg q8h60mg q8h

69 – 40 60mg q12h 80mg q12h

39 – 20

19 – 10

9 – 5

< 4

60mg q18h 80mg q18h

60mg q24h 80mg q24h

60mg q36h 80mg q36h

60mg q48h When dialysis

is not being performed.

80mg q48h When dialysis

is not being performed


Netilmicin

4–6mg/kg/day(150mg q12h

or100mg q8h

or300mg q24h)


Dosage at 8-hour intervals after the usual initial dose


80 % of usual dose

65 % of usual dose

55 % of usual dose

50 % of usual dose

40 % of usual dose

35 % of usual dose

30 % of usual dose

25 % of usual dose

20 % of usual dose

15 % of usual dose

10 % of usual dose

>100

70–100

55-70

45-55

40-45

35-40

30-35

25-30

20-25

15-20

10-15

<10

2615 16

ANTIMICROBIALS


Function)

CrCl(ml/min)


POLYMYXINSPOLYMYXINS

Colistimethate Sodium IV

(XYLISTIN)

Upto 60kg

50,000-75,000

units/kg/day

Above 60kg

1-2MIU q8h

as 30 min

infusion

20-50 1-2 MIU q8h

10-20 1MIU q12-18h

Polymixin B15,000 - 25,000

units/kg/day

1 MIU q18-24h<10

20-50

5-20

<5

75% to 100% of the

normal daily dose given in

divided doses q12 h

50% of normal daily dose

given in divided doses q12 h

15% of normal daily dose

given in divided doses q12h

ANTIMICROBIALS


Function)

CrCl(ml/min)


FLUOROQUINOLONESFLUOROQUINOLONES

Ciprofloxacin

400mg q8-12h

depending on the

severity of infection

as 1h infusion

>30

5-29

No dose adjustment required

200-400mg q18-24h

Levofloxacin

250-500mg q24h

as 1h infusion

or

750mg q24h

as 90min infusion

20-49750mg q48h OR 500mg initial

dose, followed by 250mg q24h

10-19

750mg initial dose, then 500mg

q48h or 500mg initial dose, then

250mg q48h or 250mg q48h

(uncomplicated UTI,

no dosage adjustment required)

HD/CAPD

750mg initial dose, then

500 mg q48h or 500mg

initial dose, then 250 mg q48h

Moxifloxacin

(IV/ Oral)

18yrs and above

400mg q24h-


including for those on HD/CAPD

Gemifloxacin

(Oral)320mg q24h

>40

£ 40


160mg q24h

Prulifloxacin

(Oral)600mg q24h

Sufficient

data lacking-

Pazufloxacin

500mg q12h over 30 min to 1hr infusion Dose can be reduced to 300mg q12h based on age and symptoms

44.7

13.6

Dialysis

300mg q12h

300mg q24h

300mg once every 3 days

2617 18

3

4

Colistimethate sodium 1 MIU & 2 MIU Injection, Infusion or Inhalation

ANTIMICROBIALS


Function)

CrCl(ml/min)


GLYCOPEPTIDESGLYCOPEPTIDES

*GIT-Gastrointestinal Tract

Vancomycin IV

(VANLID IV)

500mg q6h

or 1g q12h

as 1h infusion

>50-90

10-50

<10/HD/CAPD

1g q12h

1g q24-96h

1g q4-7days

Vancomycin Oral

(VANLID

Capsules)

0.5-2g in 3-4

divided doses.

Poor

absorption *through GIT

No dose

adjustment required

Teicoplanin (TICOCIN)

Moderate Infections:

(SSTIs, UTIs, LRTIs)

Loading dose:

400mg q24h

Maintenance dose:

200mg q24h

Severe Infections:

(B&J, sepsis,

endocarditis)

Loading dose:

Three 400mg

injections &

administered

12h apart.

Maintenance dose:

400mg q24h

No dose adjustment till 4th day, after 4th day

40-60 Half of normal dose q24h

<40 One third of normal dose q24h

HD

One third of normal dose q24h. Teicoplanin is not removed

by dialysis.

CAPD

After a single loading IV dose of 400mg if the patient is febrile, the recommended

dosage is 20mg/L per bag in the first week, 20mg/L in

alternate bags in the second week and 20mg/L in the overnight dwell bag only

during the third week.

ANTIMICROBIALS


Function)

CrCl(ml/min)


MACROLIDESMACROLIDES

Clarithromycin I.V500mg q12h

as 60 min infusion<30 Half of normal dose

Azithromycin

500mg q24h for

first two days

followed by

500mg oral dose

-No dose adjustment required,

however caution must be exercised

in severe renal insufficiencies

<10 Administer with caution

ANTIMICROBIALS


Function)

CrCl(ml/min)


TETRACYCLINES / GLYCYLCYCLINETETRACYCLINES / GLYCYLCYCLINE

Tigecycline

Initial dose of

100mg followed by

q12h as 30-60 min

infusion.

Mild,

moderate,

severe & HD


NITROIMIDAZOLENITROIMIDAZOLE

ANTIMICROBIALS


Function)

CrCl(ml/min)


Metronidazole

Prophylaxis: 500mg

before surgery;

repeated 8 hourly

Treatment:

500mg q8-12h

Mild, moderate,

severe

HD


Dose after dialysis

2619 20

5

6

7

8

ANTIFUNGALS

ANTIMICROBIALS


Function)

CrCl(ml/min)


OXAZOLIDINONESOXAZOLIDINONES

Linezolid

(IV/Oral)

12yrs & older

600mg q12h-

No dose adjustment

required.

However, in severe renal

insufficiency should be

used with special caution

and only when the

anticipated benefit is

considered to outweigh

the theoretical risk.

LINCOSAMIDELINCOSAMIDE

ANTIMICROBIALS


Function)

CrCl(ml/min)


Clindamycin IV

(DALCINEX)

600mg- 2.7 g

in 2-4 divided

doses as

30min infusion

-

No dose

adjustment

required

2621 22

9

10

ANTIMICROBIALS


Function)

CrCl(ml/min)


POLYENESPOLYENES

Conventional

Amphotericin B0.3-1.5mg /kg

as 1-4h infusion

<10 q24-36h

HD

CAPD

no supplement

q24-36h

Liposomal

Amphotericin B

(PHOSOME)

3–5mg/kg

once daily.

For cryptococcal

meningitis in

HIV positive

individuals

6mg/kg OD

as 120 min

infusion

-

Disposition of

amphotericin B after

administration of

liposomal amphotericin

B has not been studied.

However, liposomal

amphotericin B has

been successfully

administered to patients

with pre-existing renal

impairment.

ANTIMICROBIALS


Function)

CrCl(ml/min)


Fluconazole

(FORCAN)

Loading dose:

100-800mg q12h

Maintenance dose:

50-800mg q24h

{Depending on

severity

of infection}

>50

11-50

Dialysis


50% normal dose q24h

Normal dose after dialysis

Voriconazole

(VORITEK)

Loading dose:

6mg/kg q12h stfor 1 24hrs

Maintenance dose:

4mg/kg q12h

as 1-2h infusion

>50

<50

No dose adjustment required.

Accumulation of

vehicle occurs so switch to

oral formulation

AZOLESAZOLES

2623 24

11

12

ANTIVIRALS

ANTIMICROBIALSUSUAL DOSE

(Normal Renal Function)CrCl

(ml/min)DOSAGE ADJUSTMENT (In Renal Insufficiency)

ECHINOCANDINSECHINOCANDINS

* HSCT- Hematopoietic Stem Cell Transplant

Caspofungin

Loading dose: 70mg q24h

Maintenance dose:

50mg q24h as 1h infusion

-

No dose

adjustment

required

Anidulafungin -

No dose

adjustment

required

Micafungin

Candidemia & other

candidial infections:

Loading Dose: 200mg on day 1

Maintenance dose:

100mg daily dose

Esophageal candidiasis:

Loading Dose: 100mg on day 1

Maintenance dose:

50mg daily dose

A loading dose is not required. Infuse over 1 hour

Candidemia, Acute

Disseminated Candidiasis,

Candida Peritonitis and

Abscesses: 100mg q24h

Esophageal Candidiasis

150mg q24h

Prophylaxis of Candida * Infections in HSCT

Recipients 50mg q24h

-No dose

adjustment

required

2625 26

13

REFERENCES

Drugs Facts & Comparisons (2007 Edition) PiperacillinTicarcillinCaspofungin

The Sanford Guide to Antimicrobial Therapy 2009 (Thirty Ninth Edition) AmpicillinCefotaximeCefipimeVancomycinAmikacin

The electronic Medicines Compendium (eMC) http://emc.medicines.org.uk/ AztreonamImipenem CilastatinGentamicinTobramycinTigecyclineMetronidazoleFluconazoleVoriconazoleAcyclovirColistimethate sodiumClindamycinFluconazoleTeicoplanin

Indian J crit care Med Apr-Jun 2009,Vol 13,Issue 2.Polymixin B

Cefobid Pack Insert, June 2006,Pfizer:Cefeperazone

Unasyn Pack Insert, April 2007, PfizerAmpicillin/sulbactam

Eraxis Pack Insert, June 2009,Pfizer : Anidulafungin

Magnex Forte Pack Insert, 2009,Pfizer Cefoperazone Sulbactam

Factive Pack Insert, 2009, OscientGemifloxacin

Augmentin Pack Insert, 2009, Glaxo SmikthlineAmoxicillin clavulanic acid

Pasil Pack Insert, September 2005, Taisho Toyama Pharmaceutical Co., Ltd.Pazufloxacin

Drugs 2004; 64 (19): 2221-2234Prulifloxacin

Netromycin Pack Insert, 2009 Fulford IndiaNetilimicin

Physician's Desk Reference 2009 (PDR) Cefuroxime SodiumCeftriaxone SodiumCeftazidimeErtapenemMeropenemImipenem/CilastatinDoripenemLevofloxacinMoxifloxacinLinezolidLiposomal Amphotericin BPiperacillin /TazobactamMicafungin

Medsafe ( http://www.medsafe.govt.nz/ )CefpiromeClarithromycin

Drugs @ FDA (http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/ )Cefipime

AHFS 2009 AzithromycinConventional Amphotericin BGanciclovir

Aciclovir

(ACIVIR)

Herpes simplex or

Varicella zoster infection:

5mg/kg q8h

Immunocompromised

patients with Varicella

zoster infection or

Herpes encephalitis:

10mg/kg q8h

Obese patients:

As per actual body weight

25-50

10-25

0-10

HD

5-10mg/kg IV q12h

Half of the above dose

immediately after dialysis

and thereafter q24h

5-10mg/kg IV q24h

Half of the above

dose q24h.

CMV Infections Initial induction therapy:

5 mg/kg every q12h for 14–21 days as 1h infusion.

Maintenance regimen:6 mg/kg once daily

5 days weekly.

Prevention of CMV in HIV-Infected Individuals

5–6 mg/kg once daily 5–7 days each week

Prevention of CMV in Transplant Recipients

5 mg/kg q12 h for 7–14 days

Ganciclovir

ANTIMICROBIALSUSUAL DOSE

(Normal Renal Function)CrCl

(ml/min)DOSAGE ADJUSTMENT (In Renal Insufficiency)

50–69 2.5 q12h

25–49 2.5q12h

10–24 1.25q24h

2627 28

y egistered medical p antimicrobial pocket guide for

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