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Antimicrobial Dosing and Renal Dosage Adjustment


Disclaimers

Recommendations on this page have been developed in collaboration with the Sinai Health Antimicrobial Stewardship Program.

This page is intended to provide recommendations that we expect to be appropriate for the majority of patients in a given clinical scenario, however may not encompass all scenarios. Clinical judgment is required when applying recommendations to an individual patient.

While we have attempted to incorporate available literature into recommendations wherever possible, some recommendations are based solely on expert opinion and local practice at University Health Network and/or Sinai Health System. Caution is advised when applying recommendations to patient populations at other institutions.

There are several equations used to estimate renal function, most commonly, the Cockroft-Gault equation to calculate CrCl and the CKD-Epi 2021 equation to calculate eGFR. For the purpose of this page, we have elected to report recommendations based on CrCl, acknowledging that CrCl may not be the best marker of renal function in all patients. This may be updated in the future, as more experience/literature becomes available to inform drug dosing recommendations based on eGFR.

Recommendations were designed primarily for use in inpatient settings, where frequent monitoring is possible. Clinical judgement is required when extrapolating to ambulatory care or outpatient settings.

Scope

  • Adult patients only
  • Intravenous and oral/enteral routes of therapy only
  • Dosage adjustments in the setting of renal impairment and renal replacement therapy

Recommendations DO NOT take into account the following factors

Additional dosage adjustments may be required in these scenarios:

  • Drug interactions
  • Hepatic impairment
  • Extremes of body weight (i.e. obesity)
  • Cystic fibrosis
  • Extracorporeal membrane oxygenation (ECMO)
  • Plasma exchange (PLEX)

Intermittent Hemodialysis (IHD)

  • Generally occurs over 3-6 hours, with sessions occurring every 2-3 days.
  • Dosing modifications may be required if dialysis is occurring more or less frequently than three times per week, or for nocturnal hemodialysis regimens.

Peritoneal Dialysis (PD)

  • Encompasses continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). APD includes NIPD, CCPD and ECCPD.
  • The majority of available literature describes dosing in CAPD. In situations where it is felt that different dosing should be utilized in APD modalities, this will be noted.

Sustained Low Efficiency Dialysis (SLED)

  • Generally occurs over 6-12 hours with sessions occurring daily or multiple times per week.
  • For sessions longer than 12 hours, recommendations for CVVHDF may be more applicable.
  • When SLED is not occurring daily, recommendations for ESRD dosing (e.g. CrCl < 10) may be more applicable on non-SLED days. This may require a separate order to be entered for non-SLED days.
  • Note: recommendations have not been provided for dosing of oral antimicrobials in SLED. Overall, there is minimal literature available to guide dosing in these scenarios, however this may be considered on a case-by-case basis.

Continuous Veno-Venous Hemodiafiltration (CVVHDF)

  • Generally occurs 24h/day
  • Note: mechanisms of solute removal and flow rate differ between various modalities of CRRT (continuous renal replacement therapy), and caution should be exercised when extrapolating recommendations for CVVHDF to other modalities of CRRT.

How were recommendations generated?

Recommendations from product monographs and tertiary references were explored first. When needed, a search of primary literature was undertaken. In the absence of literature, recommendations were made based on local practice, expert opinion, and the weighing of efficacy vs toxicity concerns.

All recommendations were circulated for stakeholder review prior to publication of this document.

What stakeholders were engaged in creating recommendations?

  • Antimicrobial stewardship and infectious diseases pharmacists and physicians
  • Clinicians practicing in Nephrology (including UHN's inpatient nephrology service, ambulatory hemodialysis unit, and peritoneal dialysis clinic), Critical care, and other select clinical areas at SHS and UHN

Why are only certain antimicrobials included?

The ultimate goal is to provide recommendations for most, if not all, antimicrobials used at our institutions. In order to make this information available in a more timely manner, we have opted to release recommendations incrementally, as they are developed and reviewed. Recommendations for additional antimicrobials will continue to be added to this page as they become available.

What should I do if the indication/syndrome for which I want to use the antimicrobial is not listed?

While we have tried to include the most common syndromes for use, this page is not all-encompassing. An approach would be to find the standard dosing for the indication for which you are using the antimicrobial, and see if similar dosing is recommended for an indication in this document. If so, you maybe able to extrapolate renal dosing recommendations, though clinical judgment should always be used to ensure that recommendations are appropriate for the patient at hand. Consultation with a unit and/or ID pharmacist is encouraged to help ensure that dosing is appropriate for the indication in question.

  • aeCOPD = acute exacerbation of chronic obstructive pulmonary disease
  • CNS = central nervous system
  • ENT = ear, nose and throat
  • IAI = intra-abdominal infection
  • PID = pelvic inflammatory disease
  • PJP = Pneumocystis jirovecii pneumonia
  • SBP = spontaneous bacterial peritonitis
  • SSTI = skin and soft tissue infection
  • STI = sexually transmitted infection
  • UTI = urinary tract infection


Amoxicillin (PO/enteral)

Dosing recommendations for: Group A Streptococcus pharyngitis

Renal Function Recommended Dose
Any CrCl 500 mg q12h
IHD 500 mg q12h
PD 500 mg q12h

Dosing recommendations for: ENT infections, pneumonia

Renal Function Recommended Dose
CrCl ≥ 30 1 g q8-12h
CrCl 10-29 1 g q12h
CrCl < 10 500 mg – 1 g q12h
IHD 500 mg – 1 g q12h
PD 500 mg – 1 g q12h

Dosing recommendations for: Helicobacter pylori infections

Renal Function Recommended Dose
CrCl ≥ 10 1 g q12h
CrCl < 10 500 mg q12h
IHD 500 mg q12h
PD 500 mg q12h

Dosing recommendations for: UTI (upper), oral switch for bacteremia or deep-seated infections (where appropriate)

Renal Function Recommended Dose
CrCl ≥ 10 1 g q8h
CrCl < 10 1 g q12h
IHD 1 g q12h
PD 1 g q12h

Dosing recommendations for: UTI (lower), SSTI

Renal Function Recommended Dose
CrCl ≥ 10 500 mg q8h
CrCl < 10 500 mg q12h
IHD 500 mg q12h
PD 500 mg q12h

  1. Ashley C and Dunleavy A (2019). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners (5 th edition). CRC Press.
  2. Smit C, Sen S, von Dach E, et al. Steering away from current amoxicillin dose reductions in hospitalized patients with impaired kidney function to avoid subtherapeutic drug exposure. Antibiotics. 2022;11(9):1190. doi.org/10.3390/antibiotics11091190




Amoxicillin-clavulanic acid (PO/enteral)

Dosing recommendations for: ENT infections, pneumonia, IAI, UTI, SSTI

Renal Function Recommended Dose
CrCl ≥ 10 875/125 mg q12h
CrCl < 10 500/125 mg q12h
IHD 500/125 mg q12h
PD 500/125 mg q12h

Dosing recommendations for: oral switch for bacteremia or deep-seated infections (where appropriate)

Renal Function Recommended Dose
CrCl ≥ 10 875/125 mg q8-12h
CrCl < 10 875/125 mg q12h
IHD 875/125 mg q12h
PD 875/125 mg q12h

  1. Horber FF, Frey FJ, Descoeudres C, Murray AT, Reubi FC. Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin. Antimicrob Agents Chemother. 1986;29(4):614-619. doi:10.1128/AAC.29.4.614
  2. Hui K, Patel K, Kong DCM, Kirkpatrick CMJ. Impact of high flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy. Int J Antimicrob Agents. 2017;50(1):110-113. doi:10.1016/j.ijantimicag.2017.02.021




Amoxicillin-clavulanic acid (IV)

Dosing recommendations for: Bacteremia, ENT infections, pneumonia, IAI, UTI, SSTI, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 1000/200 mg q8h
CrCl 10-29 1000/200 mg x1, then 500/100 mg q12h
CrCl < 10 1000/200 mg x1, then 500/100 mg q12-24h
IHD 1000/200 mg x1, then 500/100 mg q12-24h*
PD 1000/200 mg x1, then 500/100 mg q12h
SLED 1000/200 mg q8h
CVVHDF 1000/200 mg q8h

*If using q24h dosing in IHD, an additional 500/100 mg dose should be given following each HD session. Note: doses as high as 500/100 mg q8h have been recommended in high flux hemodialysis2

  • For simplicity, we have elected to base all recommendations on use of the 5:1 (500 mg/100 mg or 1000 mg/200 mg) formulation of amoxicillin-clavulanic acid, however please note that the 10:1 (2000 mg/200 mg) formulation could be used as an alternative in select cases. See product monograph for dosing recommendations using the 10:1 formulation.
  • Per the product monograph, the dose may be increased up to a maximum of 2000/200 mg q8h for very severe infections.

  1. Horber FF, Frey FJ, Descoeudres C, Murray AT, Reubi FC. Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin. Antimicrob Agents Chemother. 1986;29(4):614-619. doi:10.1128/AAC.29.4.614
  2. De Schuyter K, Colin PJ, Vanommeslaeghe F, et al. Optimizing Amoxicillin/Clavulanic Acid Dosing Regimens in Patients on Maintenance High Flux Hemodialysis. Am J Kidney Dis. 2021;78(1):153-156. doi:10.1053/j.ajkd.2020.12.006
  3. Xu JH, Cheng V, Rawlins M, et al. Pharmacokinetics of Amoxicillin and Cefepime During Prolonged Intermittent Renal Replacement Therapy: A Case Report. EMJ Nephrol. 2020;8(1):78-83.
  4. Ashley C and Dunleavy A (2019). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners (5th edition). CRC Press.




Ampicillin (IV)

Dosing recommendations for: CNS infections, infective endocarditis, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 2 g q4h
CrCl 10-29 2 g q6h
CrCl < 10 2 g q12h
IHD 2 g q12h
PD 2 g q12h*
SLED 2 g q6-8h*
CVVHDF 2 g q4h*

*Limited data available for ampicillin dosing in patients receiving PD, SLED and CVVHDF. Recommendations are based primarily on local practice and expert opinion.

Dosing recommendations for: Bacteremia, IAI

Renal Function Recommended Dose
CrCl ≥ 50 2 g q4-6h
CrCl 30-49 2 g q6h
CrCl 10-29 2 g q8h
CrCl < 10 2 g q12h
IHD 2 g q12h
PD 2 g q12h*
SLED 2 g q8h*
CVVHDF 2 g q4-6h*

*Limited data available for ampicillin dosing in patients receiving PD, SLED and CVVHDF. Recommendations are based primarily on local practice and expert opinion.

Dosing recommendations for: UTI

Renal Function Recommended Dose
CrCl ≥ 50 1 g q6h
CrCl 30-49 1 g q8h
CrCl < 30 1 g q12h
IHD 1 g q12h
PD 1 g q12h*
SLED 1 g q8h*
CVVHDF 1 g q6h*

*Limited data available for ampicillin dosing in patients receiving PD, SLED and CVVHDF. Recommendations are based primarily on local practice and expert opinion.

  1. Ashley C and Dunleavy A (2019). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners (5th edition). CRC Press.
  2. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians;
  3. 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(5):562-577.




Atovaquone (PO/enteral)

Dosing recommendations for: PJP (treatment)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 750 mg q12h

Dosing recommendations for: PJP (prophylaxis)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 1500 mg q24h

  • Atovaquone is also used in the treatment and prophylaxis of toxoplasmosis infections, where dosing regimens vary based on patient population.




Azithromycin (IV, PO/enteral)

Dosing recommendations for: ENT, pneumonia*, aeCOPD*, infectious diarrhea

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg q24h

*At this dose, limit duration to three days for non-Legionella atypical pneumonia. Note that 500 mg x1, followed by 250 mg q24h x 4 days remains a reasonable alternative dosing strategy.

Dosing recommendations for: Non-tuberculosis mycobacterial infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 250-500 mg q24h OR 500 mg three times weekly

Dosing recommendations for: Prophylaxis in setting of emergent cesarean delivery

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg once

Dosing recommendations for: Chlamydia

Renal Function Recommended Dose
All (no adjustments for renal impairment) 1 g once





Cefazolin (IV)

Dosing recommendations for: bacteremia, pneumonia, infective endocarditis, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 2 g q8h
CrCl 10-29 2 g q12h
CrCl < 10 2 g q24h
IHD 2 g three times weekly after each HD session*
OR
1 g q24h (ensure dose is scheduled after HD on HD days)
PD 1-2 g q24hƗ
SLED 2 g q8hƗ
CVVHDF 2 g q8hƗ

*A 3 g dose can be considered in anticipation of a 72h intradialytic period for severe and/or deep seated infections 3-5

ƗLimited data available for cefazolin dosing in patients receiving PD, SLED and CVVHDF. Recommendations are based on local practice, expert opinion, and extrapolation from literature of other cephalosporins with similar kinetics.

Dosing recommendations for: IAI, UTI, SSTI

Renal Function Recommended Dose
CrCl ≥ 30 1-2 g q8h
CrCl 10-29 1-2 g q12h
CrCl < 10 1 g q24h
IHD 2 g three times weekly after each HD session
OR
1 g q24h (ensure dose is scheduled after HD on HD days)
PD 1 g q24hƗ
SLED 1 g q8hƗ
CVVHDF 1-2 g q8-12Ɨ

ƗLimited data available for cefazolin dosing in patients receiving PD, SLED and CVVHDF. Recommendations are based on local practice, expert opinion, and extrapolation of literature examining cephalosporins with similar kinetics.

  1. Kuypers D, Vanwalleghem J, Maes B, Messiaen T, Vanrenterghem Y, Peetermans WE. Cefazolin serum concentrations with fixed intravenous dosing in patients on chronic hemodialysis treatment. Nephrol Dial Transplant. 1999;14(8):2050-2051. doi:10.1093/ndt/14.8.2050
  2. Marx MA, Frye RF, Matzke GR, Golper TA. Cefazolin as empiric therapy in hemodialysis related infections: efficacy and blood concentrations. Am J Kidney Dis. 1998;32(3):410-414. doi:10.1053/ajkd.1998.v32.pm9740156
  3. Stryjewski ME, Szczech LA, Benjamin DK Jr, et al. Use of vancomycin or first generation cephalosporins for the treatment of hemodialysis dependent patients with methicillin susceptible Staphylococcus aureus bacteremia. Clin Infect Dis. 2007;44(2):190-196. doi:10.1086/510386
  4. Renaud CJ, Lin X, Subramanian S, Fisher DA. High dose cefazolin on consecutive hemodialysis in anuric patients with Staphylococcal bacteremia. Hemodial Int. 2011;15(1):63-68. doi:10.1111/j.1542 4758.2010.00507.x
  5. Cimino C, Burnett Y, Vyas N, Norris AH. Post Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High Flux Hemodialysis. Drugs. 2021;81(5):555-574. doi:10.1007/s40265-021-01469-2
  6. Manley HJ, Bailie GR, Frye R, Hess LD, McGoldrick MD. Pharmacokinetics of intermittent intravenous cefazolin and tobramycin in patients treated with automated peritoneal dialysis. J Am Soc Nephrol. 2000;11(7):1310-1316. doi:10.1681/ASN.V1171310




Ceftazidime (IV)

Dosing recommendations for: CNS infections

Renal Function Recommended Dose
CrCl ≥ 30 2 g q8h
CrCl 10-29 2 g q12h
CrCl < 10 2 g q24h
IHD 2 g q24h (ensure dose is scheduled after HD)
PD 2 g q24h
SLED 2 g q8h
CVVHDF 2 g q8h

Dosing recommendations for: bacteremia, pneumonia, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 50 2 g q8h
CrCl 30-49 2 g q12h
CrCl 10-29 2 g q24h
CrCl < 10 1 g q24h
IHD 2 g three times weekly after each HD session*
OR
1 g q24h (ensure dose is scheduled after HD on HD days)
PD 1 g q24h
SLED 2 g q12h (one dose should be administered following cessation of SLED)
CVVHDF 2 g q8h

*A 3 g dose can be considered in anticipation of a 72h intradialytic period for severe and/or deep-seated infections

Dosing recommendations for: UTI, SSTI

Renal Function Recommended Dose
CrCl ≥ 50 1 g q8h
CrCl 30-49 1 g q12h
CrCl < 30 1 g q24h
IHD 2 g three times weekly after each HD session
OR
1 g q24h (ensure dose is scheduled after HD on HD days)
PD 1 g q24h
SLED 1 g q12h (one dose should be administered following cessation of SLED)
CVVHDF 1 g q8h

  1. Loo AS, Neely M, Anderson EJ, Ghossein C, McLaughlin MM, Scheetz MH. Pharmacodynamic Target attainment for various ceftazidime dosing schemes in high flux hemodialysis. Antimicrobial Agents and Chemotherapy. 2013;57(12):5854-5859. doi:10.1128/AAC.00474-13.
  2. Cimino C, Burnett Y, Vyas N, Norris AH. Post Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High Flux Hemodialysis. Drugs. 2021;81(5):555-574. doi:10.1007/s40265-021-01469-2.
  3. Maxwell Scott H, Thangarajah R, Arnold A, Wade P, Klein JL. Successful treatment of Pseudomonas aeruginosa infective endocarditis via haemodialysis outpatient parenteral antimicrobial therapy: case report. J Antimicrob Chemother. 2019;74(6):1757-1759. doi:10.1093/jac/dkz096
  4. Kim K, Hwang YH, Ro H, et al. Pharmacokinetic profiles of ceftazidime after intravenous administration in patients undergoing automated peritoneal dialysis. Antimicrob Agents Chemother. 2011;55(6):2523-2527. doi:10.1128/AAC.01543-10.
  5. König C, Braune S, Roberts JA, et al. Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low efficiency dialysis. J Antimicrob Chemother. 2017;72(5):1433-1440. doi:10.1093/jac/dkw592
  6. Jang SM, Gharibian KN, Lewis SJ, Fissell WH, Tolwani AJ, Mueller BA. A monte carlo simulation approach for beta lactam dosing in critically ill patients receiving prolonged intermittent renal replacement therapy. J Clin Pharmacol. 2018;58(10):1254-1265. doi:10.1002/jcph.1137.
  7. Grewal A, Thabet P, Dubinsky S, et al. Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review [published online ahead of print, 2023 Aug 19]. Pharmacotherapy. 2023;10.1002/phar.2861. doi:10.1002/phar.
  8. Traunmüller F, Schenk P, Mittermeyer C, Thalhammer Scherrer R, Ratheiser K, Thalhammer F. Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients. J Antimicrob Chemother. 2002;49(1):129-134. doi:10.1093/jac/4.1.129.
  9. Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy, Clinical Infectious Diseases. 2005;41(8):1159-1166. doi:10.1086/444500.




Ceftriaxone (IV)

Dosing recommendations for: CNS infections, infective endocarditis (Enterococcus spp)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 2 g q12h

Dosing recommendations for: Bacteremia, pneumonia, IAI, SPB prophylaxis in patients with cirrhosis and upper GI bleed, UTI, SSTI

Renal Function Recommended Dose
All (no adjustments for renal impairment) 1 g q24h

Dosing recommendations for: infective endocarditis (Streptococcus spp), SBP, bone and joint infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 2 g q24h

  • Ceftriaxone is not recommended for infections caused by Staphylococcus aureus. Alternative agents should be used when possible. If ceftriaxone use is deemed appropriate in select cases, higher doses are warranted.1

  1. European Committee on Antimicrobial Susceptibility Testing. Guidance Document on Cefotaxime and Ceftriaxone for Staphylococcus aureus infection. https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Guidance_documents/Cefotaxime_and_Ceftriaxone_for_Staphylococcus_aureus_Infections_Infections_-_January_2023.pdf. Accessed August 10, 2023




Ciprofloxacin (PO/enteral)

Dosing recommendations for: Febrile neutropenia prophylaxis, bacteremia (non-P. aeruginosa), pneumonia (non-P. aeruginosa), IAI (non-P. aeruginosa), UTI (lower), UTI (upper; non-P. aeruginosa), SSTI (non-P. aeruginosa)

Renal Function Recommended Dose
CrCl ≥ 30 500 mg q12h
CrCl < 30 500 mg q24h
IHD 500 mg q24h (ensure dose is scheduled after HD on HD days)
PD 500 mg q24h*

*For PD peritonitis caused by non-P. aeruginosa organisms, higher doses of 750 mg q24h for CAPD and 750 mg q12h for CCPD may be considered3-5

Dosing recommendations for: Low-risk febrile neutropenia treatment, bacteremia (P. aeruginosa), pneumonia (P. aeruginosa), IAI (P. aeruginosa), UTI (upper; P. aeruginosa), SSTI (P. aeruginosa), bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 750 mg q12h
CrCl < 30 750 mg q24h
IHD 750 mg q24h (ensure dose is scheduled after HD on HD days)
PD 750 mg q24h*

*For PD peritonitis caused by P. aeruginosa, higher doses of 750 mg q12h may be considered for CCPD3-5

Dosing recommendations for: secondary SBP prophylaxis

Renal Function Recommended Dose
CrCl ≥ 30 500 mg q24h
CrCl < 30 250 mg q24h
IHD 250 mg q24h
PD 250 mg q24h

  1. Cipro Monograph: https://www.bayer.com/sites/default/files/2020 11/cipro-pm-en.pdf
  2. Shalit I, Greenwood RB, Marks MI, Pederson JA, Frederick DL. Pharmacokinetics of single dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 1986;30(1):152-156. doi:10.1128/AAC.30.1.152
  3. Lee C, Walker SAN, Palmay L, Walker SE, Tobe S, Simor A. Steady State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report. Perit Dial Int. 2018;38(1):73-76. doi:10.3747/pdi.2017.00052
  4. Yeung SM, Walker SE, Tailor SA, Awdishu L, Tobe S, Yassa T. Pharmacokinetics of oral ciprofloxacin in continuous cycling peritoneal dialysis. Perit Dial Int. 2004;24(5):447-453.
  5. Li PK, Chow KM, Cho Y, et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment [published correction appears in Perit Dial Int. 2023 May;43(3):279]. Perit Dial Int. 2022;42(2):110-153. doi:10.1177/08968608221080586




Ciprofloxacin (IV)

Dosing recommendations for: Febrile neutropenia prophylaxis, bacteremia (non-P. aeruginosa), pneumonia (non-P. aeruginosa), IAI (non-P. aeruginosa), UTI (lower), UTI (upper; non-P. aeruginosa), SSTI (non-P. aeruginosa)

Renal Function Recommended Dose
CrCl ≥ 30 400 mg q12h
CrCl < 30 400 mg q24h
IHD 400 mg q24h
PD 400 mg q24h*
SLED 400 mg q12hƗ (one dose should be administered following cessation of SLED)
CVVHDF 400 mg q12h

*For PD peritonitis caused by non-P. aeruginosa organisms, higher doses of 400 mg q12h may be considered for CCPD.2-4

Ɨ400 mg q24h may also be appropriate dosing in less severe infections, ensuring that one dose is scheduled post SLED.

Dosing recommendations for: Bacteremia (P. aeruginosa), pneumonia (P. aeruginosa), IAI (P. aeruginosa), UTI (upper; P. aeruginosa), SSTI (P. aeruginosa), bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 400 mg q8h
CrCl < 30 400 mg q12h
IHD 400 mg q12h
PD 400 mg q12h*
SLED 400 mg q12hƗ (one dose should be administered following cessation of SLED)
CVVHDF 400 mg q8h

*For PD peritonitis caused by P. aeruginosa, , higher doses of 400 mg q8h may be considered for CCPD.2-4

ƗAvailable data suggests an inability to achieve PK targets for P. aeruginosa isolates with higher MICs in plasma for patients on SLED, without exceeding usual maximum dosing recommendations.5,6 Alternative therapy should be considered where possible.

  1. Ciprofloxacin Intravenous Infusion Monograph: https://pdf.hres.ca/dpd_pm/00023583.PDF
  2. Lee C, Walker SAN, Palmay L, Walker SE, Tobe S, Simor A. Steady State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report. Perit Dial Int. 2018;38(1):73-76. doi:10.3747/pdi.2017.00052
  3. Yeung SM, Walker SE, Tailor SA, Awdishu L, Tobe S, Yassa T. Pharmacokinetics of oral ciprofloxacin in continuous cycling peritoneal dialysis. Perit Dial Int. 2004;24(5):447-453.
  4. Li PK, Chow KM, Cho Y, et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment [published correction appears in Perit Dial Int. 2023 May;43(3):279]. Perit Dial Int. 2022;42(2):110-153. doi:10.1177/08968608221080586
  5. Lewis SJ, Chaijamorn W, Shaw AR, Mueller BA In silico trials using Monte Carlo simulation to evaluate ciprofloxacin and levofloxacin dosing in critically ill patients receiving prolonged intermittent renal replacement therapy. Ren Replace Ther. 2016; 2(45). https://doi.org/10.1186/s41100-016-0055-x
  6. Olsen K, Plumb T, Reardon N, Bogard K, Branch Woods A, Peitz G. Pharmacodynamics and pharmacokinetics of ciprofloxacin during sustained low efficiency dialysis. Crit Care. 2014; (Suppl 1):P402. doi:10.1186/cc13592
  7. Onichimowski D, Wolska J, Ziółkowski H, Nosek K, Jaroszewski J, Czuczwar M. Pharmacokinetics of ciprofloxacin during continuous renal replacement therapy in intensive care patients-new assessment. Anaesthesiol Intensive Ther. 2020;52(4):267-273. doi:10.5114/ait.2020.99605




Clindamycin (PO/enteral)

Dosing recommendations for: PID

Renal Function Recommended Dose
All (no adjustments for renal impairment) 450 mg q6h

Dosing recommendations for: Non-necrotizing SSTI

Renal Function Recommended Dose
All (no adjustments for renal impairment) 450 mg q8h OR 300 mg q6h




Clindamycin (IV)

Dosing recommendations for: PID, suppression of toxin production (necrotizing fasciitis, invasive group A streptococcal infections)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 900 mg q8h

Dosing recommendations for: Non-necrotizing SSTI

Renal Function Recommended Dose
All (no adjustments for renal impairment) 600 mg q8h





Cloxacillin (IV)

Dosing recommendations for: CNS infections, bacteremia, pneumonia, infective endocarditis, bone and joint infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 2 g q4h

Dosing recommendations for: SSTI

Renal Function Recommended Dose
All (no adjustments for renal impairment) 2 g q4-6h

  • Oral cloxacillin is not recommended due to relatively low oral bioavailability and poor GI tolerability.
  • Based on results of the SNAP trial (not yet published), cefazolin is preferred over cloxacillin for cases of MSSA bacteremia, as a result of a higher incidence of nephrotoxicity observed with cloxacillin use.




Doxycycline (IV, PO/enteral)

Dosing recommendations for: Pneumonia, SSTI, bone and joint infections, STI, Lyme disease (Borrelia spp. infection)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 100 mg q12h

  • Intravenous doxycycline requires approval for use through Canada's Special Access Program. An Infectious Diseases consult is strongly recommended.




Ertapenem (IV)

Dosing recommendations for: Bacteremia, pneumonia, IAI, UTI, SSTI, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 30 1 g q24h
CrCl < 30 500 mg q24h
IHD 500 mg q24h (ensure dose is scheduled after HD on HD days)*
PD 500 mg q24h
SLED 1 g q24h (dose should be administered following cessation of SLED)
CVVHDF 1 g q24h

* Can consider 1 g three times weekly after each HD session as an alternate regimen4

  1. Invanz Monograph: https://www.merck.ca/en/wp-content/uploads/sites/20/2021/04/INVANZ-PM_E.pdf
  2. Ashley C and Dunleavy A (2019). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners(5th edition). CRC Press.
  3. Mistry GC, Majumdar AK, Swan S, et al. Pharmacokinetics of ertapenem in patients with varying degrees of renal insufficiency and in patients on hemodialysis. J Clin Pharmacol. 2006;46(10):1128 1138. doi:10.1177/0091270006291839
  4. Geerlings CJ, de Man P, Rietveld AP, Touw DJ, Cohen Tervaert JW. A practical thrice weekly Ertapenem dosage regime for chronic hemodialysis patients?. Clin Nephrol. 2013;80(4):312. doi:10.5414/cn108071
  5. Cardone KE, Grabe DW, Kulawy RW, et al. Ertapenem pharmacokinetics and pharmacodynamics during continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 2012;56(2):725 730. doi:10.1128/AAC.05515 11
  6. Burkhardt O, Hafer C, Langhoff A, et al. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol Dial Transplant. 2009;24(1):267 271. doi:10.1093/ ndt /gfn472
  7. Grewal A, Thabet P, Dubinsky S, et al. Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review [published online ahead of print, 2023 Aug 19]. Pharmacotherapy. 2023;10.1002/phar.2861. doi:10.1002/phar.2861.




Linezolid (IV, PO/enteral)

Dosing recommendations for: CNS infections, bacteremia, pneumonia, IAI, UTI, SSTI, bone and joint infections, suppression of toxin production

Renal Function Recommended Dose
All (no adjustments for renal impairment) 600 mg q12h

Dosing recommendations for: Drug-resistant tuberculosis, non-tuberculosis mycobacterial infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 600 mg q24h

  1. Nahid P, Mase SR, Migliori GB, et al. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline [published correction appears in Am J Respir Crit Care Med. 2020 Feb 15;201(4):500-501. doi: 10.1164/rccm.v201erratum2.]. Am J Respir Crit Care Med. 2019;200(10):e93-e142. doi:10.1164/rccm.201909-1874ST
  2. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56(1):2000535. Published 2020 Jul 7. doi:10.1183/13993003.00535-2020




Meropenem (IV)

Dosing recommendations for: CNS infections

Renal Function Recommended Dose
CrCl ≥ 50 2 g q8h
CrCl 25-49 2 g q12h
CrCl 10-24 1 g q12h
CrCl < 10 1 g q24h
IHD 1 g q24h (ensure dose is scheduled after HD on HD days)*
PD 1 g q24h*
SLED 2 g q8h*
CVVHDF 2 g q8h*

* Limited data available for high-dose meropenem in patients receiving renal replacement therapy. Recommendations based on local practice and expert opinion.

Dosing recommendations for: Septic shock, febrile neutropenia, bacteremia, pneumonia, IAI, UTI, SSTI, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 50 1 g q8h
CrCl 25-49 1 g q12h
CrCl 10-24 500 mg q12h
CrCl < 10 500 mg q24h
IHD 500 mg q24h (ensure dose is scheduled after HD on HD days)
PD 500 mg q24h*
SLED 1 g q8h
CVVHDF 1 g q8h

* Limited data available for IV meropenem dosing in peritoneal dialysis. Recommendations based on local practice and expert opinion.

  1. Merrem Monograph: https://pdf.hres.ca/dpd_pm/00045774.PDF
  2. Kielstein JT, Czock D, Schöpke T, et al. Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis. Crit Care Med. 2006;34(1):51-56. doi:10.1097/01.ccm.0000190243.88133.3f
  3. Braune S, König C, Roberts JA, et al. Pharmacokinetics of meropenem in septic patients on sustained low efficiency dialysis: a population pharmacokinetic study. Crit Care. 2018;22(1):25. Published 2018 Jan 30. doi:10.1186/s13054-018-1940-1
  4. Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update. Ann Pharmacother. 2020;54(1):43-55. doi:10.1177/1060028019865873
  5. Thalhammer F, Hörl WH. Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy. Clin Pharmacokinet. 2000;39(4):271-279. doi:10.2165/00003088-200039040-00003
  6. Grewal A, Thabet P, Dubinsky S, et al. Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review [published online ahead of print, 2023 Aug 19]. Pharmacotherapy. 2023;10.1002/phar.2861. doi:10.1002/phar.
  7. Jamal JA, Mat Nor MB, Mohamad Nor FS, et al. Pharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration : a randomised controlled trial of continuous infusion versus intermittent bolus administration. Int J Antimicrob Agents. 2015;45(1):41-45. doi:10.1016/j.ijantimicag.2014.09.009.




Metronidazole (PO/enteral)

Dosing recommendations for: CNS infections, amoebic infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg q8h

Dosing recommendations for: Bacteremia, empyema, IAI, PID, SSTI, bone and joint infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg q12h

  • Metronidazole is also used in multidrug regimens for H. pylori infections. Please note that dosing differs based on the treatment regimen used.
  • Some references recommend three times daily dosing of metronidazole for all indications, which differs from the recommendation provided in this document. Twice daily dosing is supported by pharmacokinetic parameters and has shown equivalent clinical effectiveness to three-times daily dosing in observational studies. Furthermore, metronidazole use can be associated with significant adverse effects, and higher cumulative doses could pose an increased risk, although this association is not well-established.1,2

  1. Shah S, Adams K, Merwede J, McManus D, Topal J. Three is a crowd: Clinical outcomes of a twice daily versus a thrice daily metronidazole dosing strategy from a multicenter study. Anaerobe. 2021;71:102378. doi:10.1016/j.anaerobe.2021.102378.
  2. Daneman N, Cheng Y, Gomes T, et al. Metronidazole-associated Neurologic Events: A Nested Case-control Study. Clin Infect Dis. 2021;72(12):2095-2100. doi:10.1093/cid/ciaa395.





Metronidazole (IV)

Dosing recommendations for: CNS infections, amoebic infections, fulminant C. difficile infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg q8h

Dosing recommendations for: Bacteremia, empyema, IAI, PID, SSTI, bone and joint infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 500 mg q12h

  • Some references recommend three times daily dosing of metronidazole for all indications, which differs from the recommendation provided in this document. Twice daily dosing is supported by pharmacokinetic parameters and has shown equivalent clinical effectiveness to three-times daily dosing in observational studies. Furthermore, metronidazole use can be associated with significant adverse effects, and higher cumulative doses could pose an increased risk, although this association is not well-established. 1,2

  1. Shah S, Adams K, Merwede J, McManus D, Topal J. Three is a crowd: Clinical outcomes of a twice daily versus a thrice daily metronidazole dosing strategy from a multicenter study. Anaerobe. 2021;71:102378. doi:10.1016/j.anaerobe.2021.102378.
  2. Daneman N, Cheng Y, Gomes T, et al. Metronidazole-associated Neurologic Events: A Nested Case-control Study. Clin Infect Dis. 2021;72(12):2095-2100. doi:10.1093/cid/ciaa395.




Minocycline (IV, PO/enteral)

Dosing recommendations for: Infections caused by gram-negative organisms demonstrating high levels of resistance, such as S. maltophilia and A. baumanii (bacteremia, pneumonia, IAI, bone and joint infections)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 200 mg q12h

  • Intravenous minocycline requires approval for use through Canada's Special Access Program. An Infectious Diseases consult is strongly recommended.
  • Recommended minocycline dosing varies for other indications. As minocycline is a non-formulary agent at our institution, an alternative tetracycline (e.g. doxycycline) would typically be used where possible, unless there is a clear rationale for minocycline use.




Moxifloxacin (IV, PO/enteral)

Dosing recommendations for: Bacteremia, pneumonia, aeCOPD, IAI, SSTI, bone and joint infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 400 mg q24h




Piperacillin-tazobactam (IV)

Dosing recommendations for: Septic shock, febrile neutropenia, bacteremia, pneumonia, IAI, SSTI, UTI, bone and joint infections

Renal Function Recommended Dose
CrCl ≥ 40 4.5 g q6h
CrCl 20-39 4.5 g q8h
CrCl < 20 4.5 g q12h
IHD 4.5 g q12h
PD 4.5 g q12h
SLED 3.375 g q6h or 4.5 g q8h
CVVHDF 4.5 g q6h

  • Due to recent breakpoint changes from The Clinical and Laboratory Standards Institute (CLSI)1 , a dosing interval of q6h is recommended to be used for all indications when using intermittent dosing. This is in contrast to prior practice at SH & UHN, where q6h dosing was reserved primarily for infections caused by Pseudomonas aeruginosa.
  • All renal dosage adjustments are therefore based off of a starting dose of piperacillin tazobactam 4.5 g q6h.

  1. Clinical and Laboratory Standards Institute (2022). CLSI MR14: Piperacillin tazobactam breakpoints for Enterobacterales , 1st Edition. https://clsi.org/standards/products/microbiology/companion/mr14/
  2. Ashley C and Dunleavy A (2019). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners (5th edition). CRC Press.
  3. Patel N, Scheetz MH, Drusano GL, Lodise TP. Identification of optimal renal dosage adjustments for traditional and extended infusion piperacillin tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother . 2010;54(1):460-465. doi:10.1128/AAC.00296-09
  4. Thabit AK, Grupper M, Nicolau DP, Kuti JL. Simplifying Piperacillin/ Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function. J Pharm Pract. 2017;30(6):593-599. doi:10.1177/0897190016684453
  5. Manley HJ, Bailie GR, Frye R, McGoldrick MD. Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients. Perit Dial Int. 2000;20(6):686-693.
  6. Kanji S, Roberts JA, Xie J, et al. Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis. Ann Pharmacother. 2018;52(10):965-973. doi:10.1177/1060028018773771
  7. Jang SM, Gharibian KN, Lewis SJ, Fissell WH, Tolwani AJ, Mueller BA. A Monte Carlo Simulation Approach for Beta‐Lactam Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy. The Journal of Clinical Pharmacology. 2018;58(10):1254-1265. doi:10.1002/jcph.1137.
  8. Shotwell MS, Nesbitt R, Madonia PN, et al. Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. Clin J Am Soc Nephrol. 2016;11(8):1377-1383. doi:10.2215/CJN.10260915
  9. Rungkitwattanakul D, Charoensareerat T, Chaichoke E, et al. Piperacillin-tazobactam dosing in anuric acute kidney injury patients receiving continuous renal replacement therapy [published online ahead of print, 2023 Feb 20]. Semin Dial. 2023;10.1111/sdi.13148. doi:10.1111/sdi.13148




Rifampin (PO/enteral)

Dosing recommendations for: Active tuberculosis

Renal Function Recommended Dose
All (no adjustments for renal impairment) 10 mg/kg daily*

*Use of intermittent rather than daily dosing may be considered in some circumstances.1,2

Dosing recommendations for: Latent tuberculosis

Renal Function Recommended Dose
All (no adjustments for renal impairment) 10 mg/kg daily (max 600 mg daily)

Dosing recommendations for: Non-tuberculosis mycobacterial infections

Renal Function Recommended Dose
All (no adjustments for renal impairment) 10 mg/kg (450 or 600 mg) daily or 600 mg three times weekly

Dosing recommendations for: Staphylococcal infections involving prosthetic material (adjunctive therapy)

Renal Function Recommended Dose
All (no adjustments for renal impairment) 600-900 mg/day divided q12h-q8h*

*The evidence surrounding rifampin use for this indication is conflicting, and optimal dosing has not been defined.5

  1. Johnston JC, Cooper R, and Menzies D (2022). "Chapter 5: Treatment of tuberculosis disease." In Canadian Tuberculosis Standards – 8th edition. Can J Respir Crit Care Sleep Med. 2022;6(sup1): 66–76. doi.org/10.1080/24745332.2022.2036504
  2. Nahid P, Dorman SE, Alipanah N, et al. ATS/CDC/IDSA Guidelines for Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7): e147-e195. doi.org/10.1093/cid/ciw376
  3. Alvarez GG, Pease C, and Menzies D (2022). "Chapter 6: Tuberculosis preventive treatment in adults." In Canadian Tuberculosis Standards – 8th edition. Can J Respir Crit Care Sleep Med. 2022;6(sup1): 77–86. doi.org/10.1080/24745332.2022.203949
  4. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56(1):2000535. Published 2020 Jul 7. doi:10.1183/13993003.00535-2020
  5. Durham SH, Covington EW, Roberts MZ, Chahine EB. Rifampin in device-related infections: Assessing the modern evidence. Am J Health Syst Pharm. 2025;82(4):184-202. doi:10.1093/ajhp/zxae263


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