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Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?
Gemma Vomiero1, Blair Carpenter, Ian Robb
1Department of Pediatrics, Division of Nephrology, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada.
Abstract:
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.
Insights
Combination therapy of ceftriaxone and acyclovir for meningo-encephalitis in children may increase the risk of acute kidney injury. Close monitoring of serum creatinine is crucial when using this potentially nephrotoxic treatment.
Area of Science:
- Pediatric Nephrology
- Infectious Diseases
Background:
- Meningo-encephalitis management often requires combined antibiotic and antiviral therapy.
- Ceftriaxone and acyclovir are commonly used in treating pediatric meningo-encephalitis.
Purpose of the Study:
- To evaluate the incidence and severity of renal injury in pediatric patients treated with combination ceftriaxone and acyclovir therapy.
- To determine the correlation between drug dosage and renal impairment.
Main Methods:
- Retrospective analysis of 17 pediatric patients (age 1-14 years) treated with ceftriaxone and acyclovir.
- Analysis of serum creatinine levels, proteinuria patterns, and renal biopsy findings.
- Correlation analysis between drug doses and serum creatinine increase.
Main Results:
- 12 out of 17 patients (70%) experienced a significant increase in serum creatinine, a rate higher than with acyclovir monotherapy.
- Acute renal failure occurred in 3 patients, characterized by tubular proteinuria and tubulotoxicity on biopsy.
- Renal impairment correlated significantly with the acyclovir dose but not the ceftriaxone dose.
Conclusions:
- Combination therapy with ceftriaxone and acyclovir is associated with a higher risk of nephrotoxicity in children.
- The mechanism of renal injury appears to be tubulotoxicity, exacerbated by the combination of drugs.
- Caution and clear initiation criteria are advised for this treatment, alongside close renal function monitoring.