Effects of chelators (desferal, deferiprone & deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassemia patients

Abstract

Infection is among the leading causes of death for thalassemia major patients. The known predisposing factors of infection include prior splenectomy, iron overload and use of iron chelator such as desferal (desferrioxamine). While encapsulated organisms frequently found in splenectomized patients were readily controlled by prophylactic vaccination and vigilant antibiotic treatment, ferrophilic organisms such as Yersinia and Klebsiella remains common among Thalassemic patients. The inductive iron overloaded environment favours the growth of these organisms but their growth is also affected by the environment temperature. For example, Yersinia infection is more prevalent in temperate regions and Klebsiella infection is commonly found in subtropical areas. Furthermore, the use of iron chelator in the form of desferal further aggravates the risk of Yersinia infection. It is because the iron membrane transport protein siderophore found in desferal can be adopted by the bacteria for iron acquisition. However, oral chelators such as deferiprone do not enhance growth of Yersinia in vitro or in vivo. In order to find out whether such observation can be extended to Klebsiella and Aeromona infection, in vitro culture assay using Klebsiella pneumoniae and Aeromonas hydrophila obtained directly from our transfusion dependent thalassaemic patients were performed. The growth rates of the bacteria under iron rich, iron poor with or without different chelators were assessed. The growth rates were analyzed by both: (1) optic density of bacterial broth; and (2) colony count by bacterial agar plate. We found that the growth of Klebsiella was marginally enhanced by desferal in vitro when compared to Yersinia. Such unfavourable effect was not found in either deferiprone or deferasirox in vitro. On the other hand, the growth of Aeromonas was not affected by the presence of any of the 3 chelators. Therefore, we suggested that factors other than desferal may account for the increase prevalence of Klebsiella and Aeromonas infection among Asian thalassemic patients. It also suggests that oral chelators are safe for thalassemic patients during febrile illness. Unlike desferal, withholding iron chelator during infectious period may not be mandatory. But care has to be exercised especially for patients on deferiprone, since neutropenia has to be ruled out during febrile illness. This project was supported by the Children's Thalassaemia Foundations