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Kidney Week

Abstract: FR-PO0705

Azithromycin for the Prevention of Hemolytic Uremic Syndrome in Shiga Toxin-Positive Diarrhea: Proof of Concept

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Ardissino, Gianluigi, Pediatric Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • Dato, Letizia, Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
  • Mancuso, Maria Cristina, Pediatric Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • Ria, Thomas, Pediatric Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • Rossetti, Daniele, Pediatric Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • Tomassini, Elena, Microbiology and Virology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  • Daprai, Laura, Microbiology and Virology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Group or Team Name

  • ItalKid-HUS Network.
Background

During the last decade, it has become increasingly common to diagnose Shiga Toxin-producing Escherichia coli (STEC) infection before hemolytic uremic syndrome (HUS) has developed, providing a potential window of treatment opportunity that, besides generous rehydration, goes underexploited. Antibiotic treatment is historically contraindicated in Shiga Toxin (Stx)-positive diarrhea on the assumption that it may trigger STEC-HUS. However, this concept is based on weak evidence mostly concerning bactericidal agents and it does not apply to bacteriostatic antibiotics. Several in vitro and in vivo studies both on animal models and on human beings indicate that azithromycin may be safe and effective in preventing STEC-HUS or mitigating disease severity.

Methods

Within the ItalKid-HUS network, devoted to the screening for Stx of bloody diarrhea in children, we have treated positive patients with azithromycin 10 mg/kg/die orally until the remission of diarrhea (maximum 5 days).
The present analysis is meant to be a proof of concept for a future study on the use of azithromycin treatment in STEC infected patients.

Results

Forty-seven patients (24 males, median age 6.4 years) with Stx-positive diarrhea were treated with azithromycin. The treatment was started after a median time of 4 days since the onset of symptoms (3 days since the onset of bloody diarrhea) and it was continued for a median time of 5 days. Of the enrolled patients, 8 were positive for Stx1, 18 for Stx2, 8 for both Stx1 and Stx2, and 13 for unspecified Stx. Only one patient out of 47 developed HUS after the first dose of azithromycin, while historical data indicate that the expected number of STEC-HUS was six (conversion in STEC-HUS of 2.1% vs. 15.0%; p < 0.02). No treatment-related side effects have been observed.

Conclusion

Azithromycin is safe and may represent a useful therapeutic option in patients with Stx-positive diarrhea to prevent HUS or to mitigate its severity. A controlled study is necessary but, in the meantime, Stx-positive patients should be treated based on the currently available evidence.

Digital Object Identifier (DOI)