Antibiotic Dosing in Kidney Disease

Antibiotic dosing in kidney disease keeps adequate exposure while avoiding accumulation. The first dose of any antibiotic is always the full dose, because the volume of distribution does not change with kidney function, and adjustment applies to later doses.

Patterns. Beta-lactams are time dependent, so adjust by lowering the dose or lengthening the interval, without reducing early doses in sepsis. Aminoglycosides are concentration dependent and need extended intervals with levels. Fluoroquinolones, co-trimoxazole and nitrofurantoin need dose reduction or avoidance.

Not needing adjustment. Ceftriaxone, doxycycline, clindamycin, linezolid, metronidazole, azithromycin, rifampicin and isoniazid.

Choice of estimate. Use Cockcroft-Gault clearance for these doses.

Preferences. When equally effective, choose agents with no renal dependence, such as ceftriaxone, doxycycline, clindamycin and azithromycin.

Avoid or restrict. Nitrofurantoin when clearance is under 30 mL/min, tetracyclines other than doxycycline, streptomycin and other aminoglycosides unless essential, and polymyxins unless no alternative exists.

Special groups.

• Children: dose by mg/kg and extend the interval for the same clearance bands.

• Pregnancy: avoid tetracyclines and aminoglycosides unless essential.

• Older adults: use Cockcroft-Gault clearance and recheck often.

• East Africa, malaria: artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then daily, needs no kidney adjustment. Reduce quinine to about one third to one half of the dose after 48 hours in acute kidney injury.

Clearance is Cockcroft-Gault in mL/min.

• Amoxicillin oral (500 mg every 8 hours normally): 10 to 30, at most 500 mg every 12 hours. Under 10, at most 500 mg every 24 hours.

• Amoxicillin with clavulanic acid intravenous (1.2 g every 8 hours normally): 10 to 30, 1.2 g then 600 mg every 12 hours. Under 10, 1.2 g then 600 mg every 24 hours.

• Cefazolin (1 to 2 g every 8 hours normally): 35 to 54, full dose at least 8 hours apart. 11 to 34, half dose every 12 hours. Under 11, half dose every 18 to 24 hours.

• Meropenem (1 g every 8 hours normally): 26 to 50, 1 g every 12 hours. 10 to 25, 500 mg every 12 hours. Under 10, 500 mg every 24 hours.

• Ciprofloxacin oral (500 mg every 12 hours normally): 30 to 50, 250 to 500 mg every 12 hours. 5 to 29, 250 to 500 mg every 18 hours.

• Levofloxacin (500 mg every 24 hours normally): 20 to 49, 500 mg then 250 mg every 24 hours. 10 to 19, 500 mg then 250 mg every 48 hours.

• Co-trimoxazole: full dose over 30, half dose at 15 to 30, avoid under 15 unless levels are available.

• Vancomycin: loading 25 mg/kg (maximum 3 g), then by level aiming for a pre-dose level of 15 to 20 mg/L.

• Gentamicin: 3 to 5 mg/kg as a single dose, repeated only when the pre-dose level is under 1 mg/L.

• Tuberculosis: isoniazid 300 mg and rifampicin 600 mg daily unchanged. Pyrazinamide 25 to 35 mg/kg and ethambutol 15 to 25 mg/kg three times weekly when clearance is under 30 mL/min, given after dialysis. Avoid streptomycin, and give pyridoxine with isoniazid.

• Tenofovir disoproxil: 300 mg every 48 hours at clearance 30 to 49 mL/min and avoid under 30. Fixed-dose combinations containing it cannot be adjusted, so use separate components.

Monitoring. Check creatinine every 48 to 72 hours and send drug levels for aminoglycosides and vancomycin. Review dose when function changes.

Stop rules. Stop or switch an antibiotic when levels are persistently high, creatinine rises with exposure, or neurotoxicity appears (confusion, myoclonus, seizures from cefepime, carbapenems or fluoroquinolones).

Referral and escalation. Involve a microbiologist, pharmacist or nephrologist for polymyxins, aminoglycosides in clearance under 30, drug-resistant tuberculosis, and dialysis patients.

Common errors. Reducing the first dose, using eGFR for a drug labelled by clearance, continuing nitrofurantoin, and not raising doses on recovery.