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[Severe complications following intermittent administration of rifampicin]
Abstract:
In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.
Insights
Intermittent Rifampicin treatment for tuberculosis can cause acute kidney injury and liver failure in some patients. Prompt medical intervention, including dialysis, may be necessary to manage these severe adverse effects.
Area of Science:
- Nephrology
- Hepatology
- Immunology
- Pharmacology
Background:
- Pulmonary tuberculosis requires effective treatment regimens.
- Intermittent dosing of antitubercular drugs is employed in clinical practice.
- Potential adverse effects of drug combinations need careful monitoring.
Purpose of the Study:
- To report cases of acute renal and liver failure associated with intermittent Rifampicin and Ethambutol therapy.
- To investigate the potential immunological basis for these adverse events.
- To highlight the clinical presentation and management of these complications.
Main Methods:
- Observational case series of five patients with pulmonary tuberculosis.
- Administration of intermittent Rifampicin (twice weekly, 600-900 mg/day) with Ethambutol.
- Clinical monitoring for renal, hepatic, and hematological function.
- Histopathological examination of renal biopsies.
- Immunological testing including Coombs test and immunelectrophoresis.
Main Results:
- All five patients developed acute renal failure 2-6 months after treatment initiation, occurring 24-72 hours post-Rifampicin dose.
- Two patients exhibited signs of liver failure, and one had a hematological syndrome (hemolytic anemia, thrombocytopenia).
- Renal biopsies showed glomerular lesions with PAS-positive deposits.
- Immunological tests suggested an immune-mediated origin for the observed toxicity.
- Four patients responded to supportive care including diuretics and hemodialysis; one patient died.
Conclusions:
- Intermittent Rifampicin therapy, in combination with Ethambutol, poses a risk of severe renal and hepatic toxicity.
- The observed adverse events may have an immunological basis.
- Close monitoring for organ-specific toxicity is crucial in patients receiving this treatment regimen.
- Management strategies involve supportive care and potentially renal replacement therapy.