Intravenous Antibiotic Dosing in Renal Impairment in Adults

The chart below provides information to help clinicians craft intravenous antibiotic dosing regimens for patients with renal impairment, including those receiving intermittent hemodialysis or continuous renal replacement therapies. Use of clinical judgment is paramount; much dosing information in these populations is based on pharmacokinetics and expert experience and opinion. Most published doses assume that CRRT patients have minimal residual renal function and are getting an ultrafiltration and dialysis flow rate of 1 to 2 L/h. They also assume intermittent hemodialysis session are three times per week.11 Use the information in this chart as a guide to get the antibiotic started and consider infectious disease consult.

Some general considerations regarding renal replacement that might help in making dosing decisions include:

  • Consider aggressive dosing in CRRT; data suggest that some recommended dosing in the literature may lead to underdosing.11 Weigh risks of drug toxicity vs risk of therapeutic failure.
  • When dosing is unavailable (e.g., new drug), some clinicians dose empirically as for a CrCl of about 30 to 50 mL/min.15
  • Use therapeutic drug monitoring to guide therapy for drugs for which there is good data for an association between serum levels and efficacy/toxicity.11
  • CRRT modality (CVVH, CVVHD, CVVHDF) may affect dosing, but total effluent volume is the most important factor in drug removal.14
  • If CRRT is held, the dose may need to be held or reduced.11 In these cases, dose as per any residual renal function.3
  • SLED: Less is known about its effects on antibiotic pharmacokinetics vs other renal replacement therapies. Consider dosing as for
    CrCl 60 mL/min while on SLED, and as for CrCl <10 mL/min off SLED.10 For patients on SLED for six to 12 hours/day, dose as for CrCl 10 to 50 mL/min.12 Ensure nurses are aware of any post-SLED doses ordered.12 Try to schedule 12 hour dosing so that a dose is given immediately post-SLED.12 For antibiotics dosed every 24 hours, try to schedule the dose immediately post-SLED, or if that is not possible, consider giving a supplemental dose immediately post-SLED.12


Abbreviations: CRRT = continuous renal replacement therapy; CVVH = continuous venovenous hemofiltration; CVVHD = continuous venovenous hemodialysis CVVHDF = continuous venovenous hemodiafiltration; eGFR = estimated glomerular filtration rate; MDRD = Modification of Diet in Renal Disease; MIC = minimum inhibitory concentration; SLED: sustained low-efficiency dialysis (also called SLEDD = slow extended daily dialysis); UTI = urinary tract infection

Drug

Adult Dosing Information for Intravenous Formulation (treatment doses)

Aminoglycosides

(Plazomicin covered below)

A complete discussion of aminoglycoside dosing is beyond the scope of this document, but some general practice tips include:

Loading dose (for treatment) tobramycin or gentamicin 2 to 3 mg/kg (amikacin 10 mg/kg), then:3,11,16

    Renal impairment, non-dialysis (maintenance dosing):

    • CrCl 20 to 29 mL/min: gentamicin or tobramycin 1.7 mg/kg (1 mg/kg for synergy) or amikacin 5 to 7.5 mg/kg every 24 hours, then adjust dose/frequency based on aminoglycoside levels.4
    • CrCl <20 mL/min: use pharmacokinetic parameters to determine maintenance dose and frequency.4

    Hemodialysis (maintenance dosing):

    • Gentamicin or tobramycin 1.5 mg/kg (or 1 mg/kg for synergy) post-dialysis when post-dialysis level <1 mg/L, or pre-dialysis level <1 mg/L (mild UTI or synergy), <2 to 3 mg/L (moderate or severe UTI), or <3 to 5 mg/L (severe gram negative infection).4 Amikacin: 5 to 7.5 mg/kg post-dialysis.4 Before giving dose, wait one to two hours post-dialysis to check aminoglycoside trough, to allow for redistribution.11

    CRRT: For treatment of gram negative infections, typical dosing for gentamicin or tobramycin might be 2 mg/kg every 24 to 48 hours, or for amikacin, 7.5 mg/kg every 24 to 48 hours.2 Re-dose when level is tobramycin/gentamicin ≤3 mg/L for systemic gram negative infections, or <1 to 2 mg/L for cystitis, or <1 mg/L for synergy.11 To check an aminoglycoside peak, wait two hours after administration to allow for delayed distribution.11 Alternatively, provide loading dose, then dose based on levels.3

    SLED: gentamicin or tobramycin: consider starting critical care patients with 6 mg/kg lean body weight (adjusted weight if obese) every 48 hours starting one hour before SLED. Consider starting non-critical care patients with 2 to 2.5 mg/kg every 24 hours. Amikacin: start with 15 to 20 mg/kg every 48 hours. Re-dose as warranted by post SLED levels.12


Ampicillin

Renal impairment, non-dialysis:

  • CrCl 10 to 50 mL/minute: Give recommended dose every 6 to 12 hours.1
  • CrCl <10 mL/minute: Give recommended dose every 12 to 24 hours.1

Hemodialysis: Give recommended dose every 12 to 24 hours. Schedule such that a dose is given immediately after dialysis.1

CVVH: 1 to 2 g every 8 to 12 hours (flow rate 1 to 2 L/h).11

CVVHD: 2 g every 6 hours (dialysate flow rate <2 L/h); or 2 g every 4 hours (dialysate flow rate 2 to <6 L/h).9

CVVHDF: 1 to 2 g every 6 to 8 hours (dialysate flow rate 1 to 2 L/h).11


Ampicillin/
Sulbactam

Renal impairment, non-dialysis:

  • CrCl 15 to 30 mL/min: Give recommended dose every 12 hours.1
  • CrCl 5 to 15 mL/min: Give recommended dose every 24 hours.1

Hemodialysis: Give recommended dose every 12 to 24 hours. Schedule such that a dose is given immediately after dialysis.1

CVVH: 1.5 to 3 g every 8 to 12 hours.3

CVVHD: 1.5 to 3 g every 8 hours (dialysate flow rate 1 L/h); 1.5 to 3 g every 6 to 8 hours (dialysate flow rate 2 L/h); or 1.5 to 3 g every 6 h (dialysate flow rate 3 to 4 L/h).3

CVVHDF: 1.5 to 3 g every 6 to 8 hours (dialysate flow rate 1 to 2 L/h).11

Note: 3 g contains 2 g ampicillin plus 1 g sulbactam; 1.5 g ampicillin/sulbactam contains 1 g ampicillin plus 500 mg sulbactam.


Azithromycin

No dose reduction advised for renal impairment or renal replacement.5


Aztreonam

Renal impairment, non-dialysis:

  • CrCl 10 to 30 mL/min/1.73 m2: After a normal first dose, administer 50% of the standard dose but give at standard dosing intervals.1
  • CrCl <10 mL/min/1.73 m2 After a normal dose, administer 25% of the standard dose but give at standard dosing intervals.1

Hemodialysis: Dose as for CrCl <10 mL/min. For serious infections, give one-eighth of the dose after each dialysis session in addition to maintenance dosing.1

CVVH: 2 g x 1, then 1 g every 8 hours (flow rate 1 L/h); 2 g every 12 hours (flow rate 2 L/h); 2 g every 8 hours (flow rate 3 L/h); or 2 g every 6 hours (flow rate 4 L/h).3

CVVHD: 2 g x 1, then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h); or 2 g every 8 hours (dialysate flow rate 3 to <6 L/h).3,9

CVVHDF: 2 g x 1, then 1 g every eight hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h).11


Cefazolin

Renal impairment, non-dialysis:

  • CrCl 34 to 54 mL/min: Reduce frequency to at least every 8 hours.1
  • CrCl 11 to 34 mL/min: Give a normal first dose, then reduce maintenance dose by 50% and give every 12 hours.1
  • CrCl <10 mL/min: Give a normal first dose, then reduce the recommended dose by 50% and administer every 18 to 24 hours.1

Hemodialysis: 2 g x 1, then 2 g post-dialysis.17

CVVH: 2 g x 1, then 1 g every 12 hours (flow rate 1 to 2 L/h); or 1 g every 8 hours (flow rate 3 to 4 L/h).3

CVVHD: 2 g x 1, then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/hour); or 2 g every 8 hours (dialysate flow rate 3 to <6 L/h).3,9

CVVHDF: 2 g x 1, then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h).11


Cefepime

Renal impairment, non-dialysis:

  • CrCl 30 to 60 mL/minute: First dose same as for normal renal function. Reduce maintenance dose by one dose daily (e.g., reduce 500 mg every 12 hours to 500 mg every 24 hours; reduce 2 g every 8 hours to 2 g every 12 hours).1
  • CrCl 11 to 29 mL/minute: First dose same as for normal renal function. Reduce maintenance dose from 500 mg every 12 hours to 500 mg every 24 hours; reduce 1 g every 12 hours to 500 mg every 24 hours; reduce 2 g every 12 hours to 1 g every 24 hours; or reduce 2 g every 8 hours to 2 g every 24 hours.1
  • CrCl <11 mL/minute: First dose same as for normal renal function. Reduce maintenance dose from 500 mg every 12 hours to 250 mg every 24 hours; reduce 1 g every 12 hours to 250 mg every 24 hours; reduce 2 g every 12 hours to 500 mg every 24 hours; or reduce 2 g every 8 hours to 1 g every 24 hours.1

Hemodialysis: 1 g every 24 hours.11 Give post-dialysis on dialysis days.1

CVVH or CVVHD: 2 g every 12 hours (febrile neutropenia and flow rate 1 to 2 L/h); 2 g every 8 hours (febrile neutropenia and flow rate 3 to 4 L/h OR other indication and flow rate 3 to 4 L/h); 2 g x 1, then 1 g every 8 hours (non-neutropenic and flow rate 1 L/h); or 2 g x 1, then 1 g every 6 hours (non-neutropenic and flow rate 2 L/h).3 Consider 2 g every 8 hours for gram negatives with MIC ≥4 mcg/mL.11

CVVHDF: 2 g x 1, then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h).11 2 g every 8 hours recommended for gram negatives with MIC 4 mcg/mL.11


Cefotaxime

Renal impairment, non-dialysis: CrCl ≤20 mL/min: reduce dose by 50%.1

Hemodialysis: 2 g every 24 hours, plus 1 gram post-dialysis.5

CVVH: 1 to 2 g every 8 to 12 hours (flow rate 1 to 2 L/hr).11

CVVHD: 2 g every 12 hours,2 or 1 to 2 g every 8 hours (dialysate flow rate 1 to 2 L/h).11

CVVHDF: 1 to 2 g every 8 hours (dialysate flow rate 1 to 2 L/h).11


Cefotetan

Renal impairment, non-dialysis:

  • CrCl 10 to 30 mL/minute: recommended dose every 24 hours or 50% of recommended dose every 12 hours.1
  • CrCl <10 mL/minute: recommended dose every 48 hours or 25% of recommended dose every 12 hours.1

Hemodialysis 1 to 2 g every 24 hours plus extra 1 g after dialysis.5

CRRT: 1 to 2 g every 24 hours.1


Cefoxitin

Renal impairment, non-dialysis:

  • CrCl 30 to 50 mL/min: 1 to 2 g every 8 to 12 hours.1
  • CrCl 10 to 29 mL/min: 1 to 2 g every 12 to 24 hours.1
  • CrCl 5 to 9 mL/min: 1 to 2 g x 1, then 0.5 to 1 g every 12 to 24 hours.1
  • CrCl <5 mL/min: 1 to 2 g x 1, then 0.5 to 1 g every 24 to 48 hours.1

Hemodialysis: Maintenance dose per residual renal function, plus 1 to 2 g post-dialysis.1

CRRT: 1 to 2 g every 8 to 12 hours.1


Ceftaroline

Renal impairment, non-dialysis:

  • CrCl 31 to 50 mL/minute: 400 mg every 12 hours.1
  • CrCl 15 to 30 mL/minute: 300 mg every 12 hours.1
  • CrCl less than 15 mL/minute: 200 mg every 12 hours.1

Hemodialysis: 200 mg every 12 hours. Schedule such that a dose is given immediately after dialysis.1

CRRT: no data.


Ceftazidime

Renal impairment, non-dialysis:1

  • CrCl 10 to 50 mL/min: 1 to 2 g every 12 to 24 hours.1
  • CrCl <10 mL/min: 1 to 2 g every 24 to 48 hours.1

Hemodialysis: 1 to 2 g every 24 to 48 hours, plus 1 g post-dialysis.1,5

CVVH: 2 g x 1 then 1 g every 12 hours (flow rate 1 L/h); 2 g every 12 hours (flow rate 2 L/h); or 2 g every 8 hours (flow rate 3 to 4 L/h).3

CVVHD: 2 g x 1 then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h); or 2 g every 8 hours (dialysate flow rate 3 to 4 L/h).3 Alternatively, 2 g every 12 hours (dialysate flow rate <2 L/h) or 2 g every 8 hours (dialysate flow rate 2 to <6 L/h).9

CVVHDF: 2 g x 1, then 1 g every 8 hours or 2 g every 12 hours (dialysate flow rate 1 to 2 L/h).11 Consider 2 g x 1, then 3 g as a continuous infusion over 24 hours will keep plasma concentration at least 4 times the MIC for all susceptible bacteria.11 2 g every 8 hours recommended for gram negatives with MIC ≥4 mcg/mL.11


Ceftazidime/
avibactam

Renal impairment, non-dialysis:

  • CrCl 31 to 50 mL/minute: 1.25 g every 8 hours.1
  • CrCl 16 to 30 mL/minute: 0.94 g every 12 hours.1
  • CrCl 6 to 15 mL/minute: 0.94 g every 24 hours.1
  • CrCl ≤5 mL/minute: 0.94 g every 48 hours.1

Hemodialysis: Dose per residual renal function. Schedule such that dose is given immediately after dialysis.1

CVVH: 1.25 g every 8 hours or 0.94 g every 12 hours.15


Ceftolozane/
tazobactam

Renal impairment, non-dialysis:

  • CrCl 30 to 50 mL/minute: 750 mg every 8 hours.1
  • CrCl 15 to 29 mL/minute: 375 mg every 8 hours.1

Hemodialysis: 750 mg x 1, then 150 mg every 8 hours. Schedule such that a dose is given immediately after dialysis.1

CVVH or CVVHD: 1.5 g x 1 then 375 mg every 8 hours (flow rate 1 L/h); 1.5 g x 1 then 750 mg every 8 hours (flow rate 2 L/h); or 1.5 g every 8 hours (flow rate 3 to 4 L/h). Data based on CVVH, flow rate 2 L/h.3

Note: each dose is 2/3 ceftolozane and 1/3 tazobactam (e.g., 750 mg = 500 mg ceftolozane and 250 mg tazobactam).


Ceftriaxone

Renal impairment, non-dialysis: No dose adjustment needed.1

Hemodialysis: No dose adjustment needed.1

CRRT: No dose adjustment needed.2


Cefuroxime

Renal impairment, non-dialysis:

  • CrCl 10 to 20 mL/min: 750 to 1,500 mg x 1, then 750 mg every 12 hours.1
  • CrCl <10 mL/min: 750 to 1,500 mg x 1, then 750 mg every 24 hours.1

Hemodialysis: 750 to 1,500 mg every 24 hours. Schedule such that dose is given immediately after dialysis.5

CRRT: 750 to 1,500 mg every 8 to 12 hours.5


Chloramphen-icol

Renal impairment, non-dialysis: Consider dose reduction based on drug levels.1

Hemodialysis: Consider dose reduction based on drug levels.1

CRRT: No dose reduction advised.5


Ciprofloxacin

Renal impairment, non-dialysis: 200 mg every 12 hours to 200 or 400 mg every 18 to 24 hours.1

Hemodialysis: Dose as for renal impairment, above, but schedule such that dose is given immediately after dialysis.1

CVVH: 200 to 400 mg every 12 to 24 hours.11

CVVHD: 400 mg every 12 to 24 hours (dialysate flow rate 1 to 2 L/h).11

CVVHDF: 400 mg every 12 hours (dialysate flow rate 1 to 2 L/h).11


Clindamycin

Renal impairment, non-dialysis: No dose adjustment needed for mild or moderate impairment, and most clinicians do not adjust the dose for severe renal impairment.1

Hemodialysis: Not removed by dialysis.1

CRRT: No dose reduction advised.5


Colistin

See our chart, Resistant Gram-Negative Bacterial Infection, for information.


Dalbavancin

Renal impairment, non-dialysis:

  • CrCl <30 mL/min: 1,125 mg IV x 1 (single-dose regimen); or 750 mg x 1, then 375 mg IV one week later (two-dose regimen).1

Hemodialysis:

    non-regular: 750 mg x 1, then 375 mg IV one week later.5

    regular: 1,000 mg x 1, then 500 mg one week later.5

CRRT: Full dose probably appropriate.1


Daptomycin

Renal impairment, non-dialysis:

  • CrCl <30 mL/min: 4 mg/kg every 48 hours (skin/skin structure infection) or 6 mg/kg every 48 hours (Staphylococcus aureus bacteremia)1

Hemodialysis: Dose as for renal impairment, above. Schedule such that dose is given immediately after dialysis.1

CVVH: Dose as for renal impairment, above.3

CVVHD: 4 to 6 mg/kg every 24 hours (dialysate flow rate 1 L/h); 6 mg/kg every 24 hours (dialysate flow rate 2 L/h); or
6 to 8 mg/kg every 24 hours (dialysate flow rate 3 to 4 L/h).3 Consider therapeutic drug monitoring and/or frequent creatine kinase monitoring.11

SLED: Dose every 24 hours on SLED, every 48 hours off SLED.10


Delafloxacin

Renal impairment, non-dialysis:

  • eGFR (calculated using MDRD equation) 15 to 29 mL/minute/1.73m2: 200 mg every 12 hours.1
  • eGFR (calculated using MDRD equation) <15 mL/minute/1.73m2: not recommended due to accumulation of vehicle.1

Hemodialysis: not recommended due to lack of information.1

CRRT: No data.5


Doripenem

Renal impairment, non-dialysis:

  • CrCl 30 to 50 mL/minute: 250 mg every 8 hours.1
  • CrCl 11 to 29 mL/minute: 250 mg every 12 hours.1
  • CrCl 10 mL/minute or less: no recommendation due to lack of data.1

Hemodialysis: 250 mg every 24 hours; or 500 mg every 12 hours x 1 day, then every 24 hours (Pseudomonas).18

CVVHDF: 500 mg every 8 hours.19


Doxycycline

Renal impairment, non-dialysis: No dosage adjustment needed.1

Hemodialysis: No dosage adjustment needed.1

CRRT: No dosage adjustment needed.5


Ertapenem

Renal impairment, non-dialysis:

  • CrCl ≤30 mL/min: 500 mg every 24 hours.1

Hemodialysis: 500 mg every 24 hours. If given within 6 hours before dialysis, give an additional 150 mg immediately post-dialysis.1

CVVHD: 500 mg to 1 g every 24 hours.3,5 Reduce dose only if anticipated clearance is <30 mL/min.1


Imipenem/
cilastatin

Renal impairment, non-dialysis:

  • CrCl 60 to 89 mL/minute: 400 mg every 6 hours if usual recommended dose is 500 mg every 6 hours; 500mg every 6 hours if usual recommended dose is 1 g every 8 hours; or 750 mg every 8 hours if usual recommended dose is 1 g every 6 hours.1
  • CrCl 30 to 59 mL/minute: 300 mg every 6 hours if usual recommended dose is 500 mg every 6 hours; 500 mg every 8 hours if usual recommended dose is 1 g every 8 hours; or 500 mg every 6 hours if usual recommended dose is 1 g every 6 hours.1
  • CrCl 15 to 29 mL/minute: 200 mg every 6 hours if usual recommended dose is 500 mg every 6 hours; 500 mg every 12 hours if usual recommended dose is 1 g every 6 to 8 hours.1
  • CrCl <15 mL/minute: Not recommended unless hemodialysis started within 48 hours.1

Hemodialysis: Dose as for CrCl 15 to 29 mL/min. Schedule such that dose is given immediately post-dialysis.1

CVVH, CVVHD, or CVVHDF: 1 g x 1, then 500 mg every 8 to 12 hours.6,11 For bacteria with higher MIC (4 to 8 mcg/mL), a dose of 1 g every 12 hours or 500 mg every 6 hours could be considered, but weigh risk of neurotoxicity vs benefit.6,11

SLED: 500 mg every 6 hours while on SLED if weight >70 kg.10


Levofloxacin

Renal impairment, non-dialysis:

  • CrCl 20 to 49 mL/minute: Give 750 mg doses every 48 hours. For 500 mg doses, give 500 mg x 1, then 250 mg every 24 hours. For 250 mg doses, no dose adjustment is needed.1
  • CrCl 10 to 19 mL/minute: For 750 mg doses, give 750 mg x 1, then 500 mg every 48 hours. For 500 mg doses, give 500 mg x 1, then 250 mg every 48 hours. For 250 mg doses, give 250 mg every 48 hours (except when treating uncomplicated UTI, for which no dosage adjustment necessary).1

Hemodialysis: Dose as for CrCl 10 to 19 mL/min.1

CVVH: 250 mg every 24 hours3 (If usual dose is 500 mg or 750 mg, give a 500 mg or 750 mg loading dose.11)

CVVHD: If usual dose is 750 mg every 24 hours, give 750 mg x 1, then 500 mg every 48 hours (dialysate flow rate <2 L/h) or every 24 hours (dialysate flow rate 2 to <6 L/h). If usual dose is 500 mg every 24 hours, give 500 mg x 1, then 250 mg every 24 hours (dialysate flow rate ≥1 L/h). If usual dose is 250 mg every 24 hours, give 250 mg every 24 hours (dialysate flow rate ≥1 L/h).9

CVVHDF: 250 to 750 every 24 hours.1


Linezolid

Renal impairment, non-dialysis: No dosage adjustment needed.1

Hemodialysis: Schedule such that dose is given immediately after dialysis.1

CVVHD: 600 mg every 12 hours for pathogen with MIC up to 2 mcg/mL.1 Standard dosing might not be sufficient for bacteria with higher MICs.1

SLED: Consider supplemental dose or dosing every 8 hours while on SLED.10


Meropenem

Renal impairment, non-dialysis:

  • CrCl 26 to 50 ml/min: Give the recommended dose every 12 hours.1
  • CrCl 10 to 25 ml/min: Give 50% of the recommended dose every 12 hours.1
  • CrCl <10 ml/min: Give 50% of the recommended dose every 24 hours.1

Hemodialysis: 500 mg every 24 hours. Schedule such that dose is given immediately post-dialysis.5

CVVH, standard dose: 1 to 2 g x 1 then 500 mg every 12 hours (flow rate 1 L/h); 1 to 2 g x 1, then 500 mg every

8 hours (flow rate 2 L/h); or 1 to 2 g x 1 then 500 mg every 6 hours (flow rate 3 to 4 L/h).3

CVVH, high dose (cystic fibrosis, meningitis, pathogen with MIC 4 mcg/mL): 2 g every 12 hours (flow rate 1 to 2 L/h); or 2 g every 8 hours (flow rate 3 to 4 L/h).3 Alternatively, 2 g every 8 hours for flow rates 2 to <6 L/h.9

CVVHD, standard dose: 1 to 2 g x 1, then 500 mg every 8 hours (dialysate flow rate 1 to 2 L/h); or 1 to 2 g x 1, then 500 mg every 6 hours (dialysate flow rate 3 to 4 L/h).3 Alternatively, 1 g every 12 hours (dialysate flow rate <2 L/h) or 1 g every 8 hours (dialysate flow rate 2 to <6 L/h).9

CVVHD, high dose (cystic fibrosis, meningitis, pathogen with MIC 4 mcg/mL): 2 g every 12 hours (dialysate flow rate 1 to 2 L/h); or 2 g every 8 hours (dialysate flow rate 3 to 4 L/h).3

CVVHDF: 500 mg every 6 to 8 hours, 750 mg every 8 hours, 500 mg to 1 g every 8 to 12 hours, or 1.5 g every 12 hours (dialysate flow rate 1 to 2 L/h).11

SLED: 500 mg to 1 g every 8 hours while on SLED.10


Meropenem/
vaborbactam

Renal impairment, non-dialysis:

  • eGFR (calculated using MDRD equation) 30 to 49 mL/minute/1.73 m2: 2 g every 8 hours1
  • eGFR (calculated using MDRD equation) 15 to 29 mL/minute/1.73 m2: 2 g every 12 hours.1
  • eGFR (calculated using MDRD equation) <15 mL/minute/1.73 m2: 1 g every 12 hours.1

Hemodialysis: 1 g (0.5 g meropenem/0.5 g vaborbactam) every 12 hours. Schedule such that dose is given immediately post-dialysis.5

CRRT: No data.

Note: each dose is 50% meropenem (2 g = 1 g meropenem and 1 g vaborbactam).


Metronidazole

Renal impairment, non-dialysis:

  • CrCl <10 mL/min: usual dose, or give usual dose every 12 hours.5

Hemodialysis: Dose as for renal impairment, above, but schedule such that dose is given immediately post-dialysis.1,5

CRRT: No dosage adjustment needed.1


Minocycline

Do not exceed a total daily dose of 200 mg in renal impairment.1


Moxifloxacin

Renal impairment, non-dialysis: No dosage adjustment needed.1

Hemodialysis: No dosage adjustment needed.1

CRRT: No dosage adjustment needed.5


Nafcillin

Renal impairment, non-dialysis: No dosage adjustment needed.1

Hemodialysis: No dosage adjustment needed.5

CRRT: No dosage adjustment needed.5


Oxacillin

Renal impairment, non-dialysis: No dosage adjustment needed.5

Hemodialysis: No dosage adjustment recommended.5

CRRT: No data.


Oritavancin

Renal impairment, non-dialysis: No dosage adjustment needed, but use caution in severe impairment due to lack of data.1

Hemodialysis: Not removed by dialysis.1

CRRT: No data.


Penicillin G

Renal impairment, non-dialysis:

  • CrCl 10 to 50 mL/min: Give recommended dose every 8 hours.5
  • CrCl <10 mL/min: Give recommended dose every 12 hours.5

Hemodialysis: Give recommended dose every 12 hours. Schedule such that a dose is given immediately post-dialysis.5

CVVH: 4 million units x 1, then 2 million units every 4 to 6 hours.a,1

CVVHD: 4 million units x 1, then 2 to 3 million units every 4 to 6 hours.a,1 Another maintenance option is 2 million units every 6 hours for dialysate flow rate <2L/h, or 2 million units every 4 hours for dialysate flow rate 2 to <6 L/h.9

CVVHDF: 4 million units x 1, then 2 to 4 million units every 4 to 6 hours.a,1

  1. Recommendations based on flow rate of 1 to 2 L/hr and minimal residual renal function.5 A general CRRT recommendation is 1 to 4 million units every 6 to 8 hours.5

Piperacillin/
tazobactam

Renal impairment, non-dialysis:

  • CrCl <20 mL/min: 4.5 g (over four hours) every 12 hours.20

Hemodialysis: 4.5 g (over four hours) every 12 hours.20

CRRT (including SLED): 4.5 g (over four hours) every 8 hours.20

Note: one-eighth of each piperacillin dose is tazobactam (e.g., 4.5 g = 4 g piperacillin plus 0.5 g tazobactam).7


Plazomicin

Renal impairment, non-dialysis:13

  • CrCl∗ 30 to <60 mL/min: 10 mg/kg** every 24 hours, then adjust based on plazomicin levels.
  • CrCl∗ 15 to <30 mL/min: 10 mg/kg** every 48 hours, then adjust based on plazomicin levels.
  • ∗Use total body weight in Cockcroft-Gault equation, but if total body weight is >25% over ideal body weight, use ideal body weight.

    ∗∗Weight is total body weight, or adjusted weight if >25% over ideal body weight. Adjusted weight =
    (total body weight - ideal body weight x 0.4) + ideal body weight.

Hemodialysis: No data.

CRRT: No data.


Polymyxin B

Renal impairment, non-dialysis: See our chart, Resistant Gram-Negative Bacterial Infection, for information.

Hemodialysis: No dosage adjustment needed.5

CRRT: No dosage adjustment needed.5


Quinupristin/
dalfopristin

Renal impairment, non-dialysis: No dose adjustment needed.1

Hemodialysis: No dose adjustment needed.1

CRRT: No dosage adjustment needed.5


Sulfa-methoxazole/
trimethoprim

Renal impairment, non-dialysis:

  • CrCl 10 to 29 mL/min: 2.5 to 5 mg/kg (trimethoprim) every 12 hours.5
  • CrCl <10 mL/min: Use not recommended, but if used, consider 5 to 10 mg/kg (trimethoprim) every 24 hours.5

Hemodialysis: Not recommended, but if used, consider 5 to 10 mg/kg (trimethoprim) every 24 hours, scheduled such that dose is given immediately post-dialysis.5

CRRT: Avoid if possible because clearance varies for each component. Specialist consultation suggested.9 Doses below are for treatment of serious infections, not prophylaxis.3

    CVVH: 2.5 to 7.5 mg/kg (trimethoprim) every 12 hours.3

    CVVHD: 5 mg/kg (trimethoprim) every 12 hours.3 Alternatively, for dialysate flow rate <2 L/h, 10 to 15 mg/kg/day (trimethoprim) divided every 8 hours x 48 hours, then reassess. For dialysate flow rate 2 to <6 L/h, 15 to 20 mg/kg/day (trimethoprim) divided every 6 to 8 hours x 48 hours, then reassess.9

    CVVHDF: 2.5 to 7.5 mg/kg (trimethoprim) every 12 hours.1 Patients with Pneumocystis jirovecii may need 10 mg/kg (trimethoprim) every 12 hours.11

Note: Use actual body weight for dosing.9


Tedizolid

Renal impairment, non-dialysis: No dose adjustment needed.1

Hemodialysis: No dose adjustment needed.1

CRRT: No dose adjustment needed.5


Telavancin

Renal impairment, non-dialysis:

  • CrCl 30 to 50 mL/min: 7.5 mg/kg IV every 24 hours.8
  • CrCl 10 to 29 mL/min: 10 mg/kg IV every 48 hours.8

Hemodialysis: No data.5

CRRT: No data.5


Tigecycline

Renal impairment, non-dialysis: no dose adjustment needed.1

Hemodialysis: no dose adjustment needed.1

CRRT: no dose adjustment needed.5


Vancomycin

Renal impairment, non-dialysis: See our commentary, Vancomycin Dosing and Monitoring for Adults. Expect dosing frequencies of every 24 to 96 hours.5

Hemodialysis: 15 to 25 mg/kg x 1, then 5 to 10 mg/kg post-dialysis.11 For the third post-dialysis dose, consider dosing per pre-dialysis levels as follows: <10 mg/L, give 1 g immediately post-dialysis; 10 to 25 mg/L, give 500 to 750 mg immediately post-dialysis; >25 mg/L, hold vancomycin.11 (Some clinicians will give a reduced dose for a level >25 mg/L). Alternatively, consider giving 500 mg to 1 g for a post-dialysis level 10 to 15 mg/L.11 Check post-dialysis vancomycin level 4 to 6 hours post-dialysis to allow for redistribution.11

Note that for CRRT, some clinicians use first-dose levels to guide dosing.

CVVH: 15 to 25 mg/kg x 1, then 10 to 15 mg/kg every 24 to 48 hours.11 Adjust per desired target level.11

CVVHD: 15 to 25 mg/kg x 1, then 10 to 15 mg/kg every 24 hours or 7.5 mg/kg every 12 hours.11 Adjust per desired target level.11

CVVHDF: 15 to 25 mg/kg x 1, then 7.5 to 10 mg/kg every 12 hours.11 Adjust per desired target level.11

SLED: 15 to 25 mg/kg every 24 to 72 hours. Re-dose as warranted by post-SLED level.12


Project Leader in preparation of this clinical resource (340819): Melanie Cupp, Pharm.D., BCPS

References

  1. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2018. http://www.clinicalkey.com. (Accessed June 21, 2018).
  2. Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis 2005;41:1159-66.
  3. Peitz G, Rolek K, Van Schooneveld T. Renal dose adjustment guidelines for antimicrobials, CRRT dosing recommendations. The Nebraska Medical Center. June 2016. https://www.nebraskamed.com/sites/default/files/documents/for-providers/asp/Renal-Dose-Adjustment-Guidelines-for-Antimicrobial.pdf. (Accessed June 21, 2018).
  4. Stanford Hospital & Clinics aminoglycoside dosing guidelines 2013. http://med.stanford.edu/content
    /dam/sm/bugsanddrugs/documents/dosing/2013AminoglycosideDosingGuide.pdf
    . (Accessed June 22, 2018).
  5. Gilbert DN, Chambers HF, Eliopoulos GM, et al, Eds. Sanford Guide Web Edition. Sperryville, VA: Antimicrobial Therapy, Inc., 2018. http://webedition.sanfordguide.com/. (Accessed June 2, 2018).
  6. Fish DN, Teitelbaum I, Abraham E. Pharmacokinetics and pharmacodynamics of imipenem during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 2005;49:2421-28.
  7. Product information for Zosyn. Wyeth Pharmaceuticals, Inc. Philadelphia, PA 19101. June 2017.
  8. Product information for Vibativ. Theravance Biopharma US. South San Francisco, CA 94080. May 2016.
  9. Continuous renal replacement therapy (CRRT): antimicrobial dosing recommendations. January 2015. http://www.uphs.upenn.edu/surgery/Education/trauma/SCCS/protocols/
    CRRT_Antimicrobial_Dosing_Table.pdf
    . (Accessed June 27, 2018).
  10. Bogard KN, Peterson NT, Plumb TJ, et al. Antibiotic dosing during sustained low-efficiency dialysis: special considerations in adult critically ill patients. Crit Care Med 2011;39:560-70.
  11. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy 2009;29:562-77.
  12. Mushatt DM, Mihm LB, Dreisbach AW, Simon EE. Antibiotic dosing in slow extended daily dialysis. Clin Infect Dis 2009;49:433-7.
  13. Product information for Zemdri. Achaogen. South San Francisco, CA 94080. June 2018.
  14. Thompson A, Li F, Gross AK. Considerations for medication management and anticoagulation during continuous renal replacement therapy. AACN Adv Crit Care 2017;28:51-63.
  15. Wenzler E, Bunnell KL, Bleasdale SC, et al. Pharmacokinetics and dialytic clearance of ceftazidime-avibactam in a critically ill patient on continuous venovenous hemofiltration. Antimicrob Agents Chemother 2017;61(7). doi: 10.1128/ACC.00464-17.
  16. Guglielmo J. Principles of infectious diseases. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Wolters Kluwer Health, 2018. p: 1319-42.
  17. University of California, San Francisco. Infectious diseases management program at UCSF. https://idmp.ucsf.edu/antimicrobial-dosing-intermittent-continuous-hemodialysis. (Accessed July 21, 2018).
  18. Tanoue K, Nishi K, Kadowaki D, Hirata S. Removal of doripenem during hemodialysis and the optimum dosing regimen for patients undergoing hemodialysis. Ther Apher Dial 2011;15:327-33.
  19. Roberts JA, Udy AA, Bulitta JB, et al. Doripenem population pharmacokinetics and dosing requirements for critically ill patients receiving continuous venovenous haemodialfiltration. J Antimicrob Chemother 2014;69:2508-16.
  20. Njoku JC, Hermsen ED, Van Schooneveld T. Supporting evidence for extended-infusion piperacillin/tazobactam dosing substitution. The Nebraska Medical Center. September 2011. https://www.nebraskamed.com/sites/default/files/documents/for-providers/asp/pip-tazoei_protocol_detail-final.pdf. (Accessed July 21, 2018).

Cite this document as follows: Clinical Resource, Intravenous Antibiotic Dosing in Renal Impairment in Adults. Hospital Pharmacist’s Letter/Prescriber’s Letter. August 2018.

Related Articles