Antibiotic dosing requirements in patients with chronic kidney disease and dialysis

OVERVIEW ― We're getting questions about how to dose oral antibiotics with dialysis since medication labels and references may conflict or be murky.

KEY POINTS

• Recommend usual doses of antibiotics that aren't renally cleared including azithromycin, clindamycin, and doxycycline. But advise adjusting other antibiotics by reducing the dose, extending the interval or both. For instance, cephalexin may be dosed 250 mg BID instead of 500 mg BID or cefuroxime 500 mg every OTHER day instead of BID.
• Be aware of medications that can be given at usual doses, but just ONCE daily including amoxicillin, ciprofloxacin, or clarithromycin. For example, consider amoxicillin 250 to 500 mg DAILY instead of TID. Keep in mind, it takes longer to reach therapeutic blood levels if dosing intervals are extended. That's why a loading dose is used for some medications that need a high peak concentration to kill bacteria. Think of levofloxacin as an example. Suggest a 500 mg loading dose, then 250 mg every OTHER day instead of the usual 500 mg daily.
• Educate on proper dosing, especially with unusual regimens. Don't typically advise adding "replacement doses" even for highly dialyzed drugs, such as amoxicillin. Instead, tell hemodialysis patients to take antibiotic doses AFTER dialysis especially once-daily medications to limit drug removal. But explain that the timing of doses isn't a consideration with peritoneal dialysis since it doesn't remove medications very well.
• If patients are on a phosphate binder (calcium carbonate, etc), generally remind them to take their antibiotic 1 hour before or 3 hours after the binder. Many antimicrobial agents (see Table 1) are eliminated renally and require dosing adjustments in patients with chronic kidney disease; however, several commonly used agents do not require adjustments.

Table (1). Antibiotic Dosing Requirements in Patients with Chronic Kidney Disease
DRUG	USUAL DOSAGE	DOSAGE ADJUSTMENT (PERCENTAGE OF USUAL DOSAGE) BASED ON GFR (ML PER MINUTE PER 1.73 m2)
		> 50	10 TO 50	< 10
Carbapenems
Ertapenem (Invanz)	1 g every 24 hours	100%	100%	50%
Imipenem	0.25 to 1 g every 6 hours	100%	50%	25%
Meropenem (Meronem)	1 to 2 g every 8 hours	100%	50% every 12 hours	50% every 24 hours (GFR < 20)
Cephalosporins
Cefaclor (Ceclor)	250 to 500 mg every 8 hours	100%	50 to 100%	50%
Cefadroxil (Duricef)	0.5 to 1 g every 12 hours	100%	Every 12 to 24 hours	Every 36 hours
Cefamandole (Mandol)	0.5 to 1 g every 4 to 8 hours	Every 6 hours	Every 6 to 8 hours	Every 8 to 12 hours
Cefazolin (Ancef)	0.25 to 2 g every 6 hours	Every 8 hours	Every 12 hours	50% every 24 to 48 hours
Cefepime (Maxipime)	0.25 to 2 g every 8 to 12 hours	100%	50 to 100% every 24 hours	25 to 50% every 24 hours
Cefixime (Suprax)	200 mg every 12 hours	100%	75%	50%
Cefoperazone (Cefobid)	No adjustment needed	—	—	—
Cefotaxime (Claforan)	1 to 2 g every 6 to 12 hours	Every 6 hours	Every 6 to 12 hours	Every 24 hours or 50%
Cefotetan (Cefotan)	1 to 2 g every 12 hours	100%	Every 24 hours	Every 48 hours
Cefoxitin (Mefoxin)	1 to 2 g every 6 to 8 hours	Every 6 to 8 hours	Every 8 to 12 hours	Every 24 to 48 hours
Cefpodoxime (Vantin)	100 to 400 mg every 12 hours	Every 12 hours	Every 24 hours	Every 24 hours
Cefprozil (Cefzil)	250 to 500 mg every 12 hours	100%	50% every 12 hours	50% every 12 hours
Ceftazidime (Fortaz)	1 to 2 g every 8 hours	Every 8 to 12 hours	Every 12 to 24 hours	Every 24 to 48 hours
Ceftibuten (Cedax)	400 mg every 24 hours	100%	25 to 50%	25 to 50%
Ceftizoxime (Cefizox)	1 to 2 g every 8 to 12 hours	Every 8 to 12 hours	Every 12 to 24 hours	Every 24 hours
Ceftriaxone (Rocephin)	No adjustment needed	—	—	—
Cefuroxime axetil (Ceftin)	No adjustment needed	—	—	—
Cefuroxime sodium (Zinacef)	0.75 to 1.5 g every 8 hours	Every 8 hours	Every 8 to 12 hours	Every 12 hours
Cephalexin (Keflex)	250 to 500 mg every 6 to 8 hours	Every 8 hours	Every 8 to 12 hours	Every 12 to 24 hours
Cephradine (Velosef)	0.25 to 1 g every 6 to 12 hours	100%	50%	25%
Macrolides
Azithromycin (Zithromax)	No adjustment needed	—	—	—
Clarithromycin (Biaxin)	250 to 500 mg every 12 hours (Biaxin); 1 g daily (Biaxin XL)	100%	50 to 100%	50%
Dirithromycin	No adjustment needed	—	—	—
Erythromycin	No adjustment needed	—	—	—
Penicillins
Amoxicillin	250 to 500 mg every 8 hours	Every 8 hours	Every 8 to 12 hours	Every 24 hours
Ampicillin	0.25 to 2 g every 6 hours	Every 6 hours	Every 6 to 12 hours	Every 12 to 24 hours
Ampicillin/sulbactam (Unasyn)	1 to 2 g ampicillin and 0.5 to 1 g sulbactam every 6 to 8 hours	100% (GFR ≥ 30)	Every 12 hours (GFR 15 to 29)	Every 24 hours (GFR 5 to 14)
Carbenicillin (Geocillin), 382-mg tablet	1 or 2 tablets every 6 hours	Every 6 to 12 hours	Every 12 to 24 hours	Every 24 to 48 hours
Carbenicillin IV (not available in the United States)	200 to 500 mg per kg per day, continuous infusion or in divided doses	Every 8 to 12 hours	Every 12 to 24 hours	Every 24 to 48 hours
Dicloxacillin (Dynapen)	No adjustment needed	—	—	—
Nafcillin	No adjustment needed	—	—	—
Penicillin G	0.5 to 4 million U every 4 to 6 hours	100%	75%	20 to 50%
Penicillin VK	No adjustment needed	—	—	—
Piperacillin	3 to 4 g every 6 hours	Every 6 hours	Every 6 to 12 hours	Every 12 hours
Piperacillin/ tazobactam (Zosyn)	3.375 to 4.5 g every 6 to 8 hours	100%	2.25 g every 6 hours; every 8 hours (GFR < 20)	2.25 g every 8 hours
Ticarcillin	3 g every 4 hours	1 to 2 g every 4 hours	1 to 2 g every 8 hours	1 to 2 g every 12 hours
Ticarcillin/clavulanate (Timentin)	3.1 g every 4 hours	100%	Every 8 to 12 hours	2 g every 12 hours
Quinolones
Ciprofloxacin (Cipro)	400 mg IV or 500 to 750 mg orally every 12 hours	100%	50 to 75%	50%
Gatifloxacin	400 mg every 24 hours	100%	400 mg initially, then 200 mg daily	400 mg initially, then 200 mg daily
Gemifloxacin	320 mg every 24 hours	100%	50 to 100%	50%
Levofloxacin	250 to 750 mg every 24 hours	100%	500 to 750 mg initial dose, then 250 to 750 mg every 24 to 48 hours	500 mg initial dose, then 250 to 500 mg every 48 hours
Moxifloxacin (Avelox)	No adjustment needed	—	—	—
Norfloxacin	400 mg every 12 hours	Every 12 hours	Every 12 to 24 hours	Avoid
Ofloxacin	200 to 400 mg every 12 hours	100%	200 to 400 mg every 24 hours	200 mg every 24 hours
Trovafloxacin	No adjustment needed	—	—	—
Sulfas
Sulfamethoxazole	1 g every 8 to 12 hours	Every 12 hours	Every 18 hours	Every 24 hours
Sulfisoxazole	1 to 2 g every 6 hours	Every 6 hours	Every 8 to 12 hours	Every 12 to 24 hours
Trimethoprim	100 mg every 12 hours	Every 12 hours	Every 12 hours (GFR > 30); every 18 hours (GFR 10 to 30)	Every 24 hours
Tetracyclines
Doxycycline (Vibramycin)	No adjustment needed	—	—	—
Tetracycline	250 to 500 mg two to four times daily	Every 8 to 12 hours	Every 12 to 24 hours	Every 24 hours
Other
Chloramphenicol	No adjustment needed	—	—	—
Clindamycin	No adjustment needed	—	—	—
Dalfopristin/ quinupristin	No adjustment needed	—	—	—
Linezolid (Zyvox)	No adjustment needed	—	—	—
Nitrofurantoin	500 to 1,000 mg every 6 hours	100%	Avoid	Avoid
Telithromycin (Ketek)	No adjustment needed	—	—	—

REFERENCES

• Vilay, A.M. (2019). Antibiotic Dosing in Chronic Kidney Disease and End-Stage Renal Disease: A Focus on Contemporary Challenges. Advances in Chronic Kidney Disease, 26(1), pp.61–71. Available at: https://pubmed.ncbi.nlm.nih.gov/30876619

  Smyth, B., Jones, C. and Saunders, J. (2016). Prescribing for patients on dialysis. Australian Prescriber, 39(1), pp.21–24. Available at: https://pubmed.ncbi.nlm.nih.gov/27041803

  Matzke, G.R., Aronoff, and others (2011). Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International, 80(11), pp.1122–1137. Available at: https://pubmed.ncbi.nlm.nih.gov/21918498

  Munar, M.Y., Munar, M.Y. and Harleen Signh (2013). Drug Dosing Adjustments in Patients with Chronic Kidney Disease. American Family Physician, [online] 75(10), pp.1487–1496. Available at: https://www.aafp.org/afp/2007/0515/p1487.html