Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?

Pediatr Nephrol. 2002 Aug;17(8):633-7. doi: 10.1007/s00467-002-0867-5. Epub 2002 May 17.


Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

MeSH terms

  • Acyclovir / adverse effects*
  • Adolescent
  • Antiviral Agents / adverse effects*
  • Ceftriaxone / adverse effects*
  • Cephalosporins / adverse effects*
  • Child
  • Child, Preschool
  • Creatinine / blood
  • Drug Combinations
  • Female
  • Humans
  • Infant
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Function Tests
  • Male
  • Retrospective Studies


  • Antiviral Agents
  • Cephalosporins
  • Drug Combinations
  • Ceftriaxone
  • Creatinine
  • Acyclovir