IngentaConnect Use of a low-dose steroid as an adjunct in the treatment, in mice...

Authors: Panomket, P.¹; Chetchotisakd, P.²; Sermswan, R.W.³; Pannengpetch, P.⁴; Wongratanacheewin, S.⁵

Source: Annals of Tropical Medicine and Parasitology, Volume 103, Number 7, October 2009 , pp. 635-646(12)

Abstract:

Human melioidosis caused by Burkholderia pseudomallei is a severe septic disease that is associated with high mortality, even under appropriate antibiotic treatment. The therapeutic effects of low-dose hydrocortisone plus ceftazidime, and of ceftazidime alone, have recently been investigated in the treatment of acute, severe sepsis caused by B. pseudomallei, both in normal BALB/c mice and in BALB/c mice with streptozotocin-induced diabetes. The mice were infected and then treated intravenously, from day 1 or day 2 post-infection, with saline (as a control, given twice daily for 10 days), low-dose hydrocortisone (given in twice-daily doses of 5 mg/kg, for 5 days) plus ceftazidime (given in twice-daily doses of 1200 mg/kg, for 10 days), or the same doses of ceftazidime alone. Although the infected, untreated mice all died within 14 days, almost all of the treated animals were still alive at the end of the follow-up, 30 days post-infection. The addition of the steroid appeared to have no benefit, with bacterial loads and plasma concentrations of tumour necrosis factor, aspartate aminotransferase, alanine aminotransferase and creatinine decreasing similarly in all the treated groups. The infected diabetic mice given hydrocortisone-ceftazidime from day 1 (but not those given just ceftazidime from day 1) showed an increase in their blood glucose concentrations. When infected mice were treated with the low-dose steroid and lower doses of the antibiotic (in twice-daily doses of 120-600 mg/kg), the steroid not only offered no apparent benefit but seemed to reduce survival.

It therefore appears that low-dose hydrocortisone, as an adjunct to antibiotic treatment, does not provide benefit in the treatment of murine melioidosis and may have negative effects on human cases of the disease who have diabetes mellitus.

Document Type: Research article

DOI: 10.1179/000349809X12502035776117

Affiliations: 1: Graduate School, Khon Kaen University, 123 Mitraphab Road, Khon Kaen, 40002, Thailand 2: Department of Medicine, Faculty of Medicine, Khon Kaen University, 123 Mitraphab Road, Khon Kaen, 40002, Thailand 3: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraphab Road, Khon Kaen, 40002, Thailand 4: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, 123 Mitraphab Road, Khon Kaen, 40002, Thailand 5: Department of Microbiology and Melioidosis Research Centre, Faculty of Medicine, Khon Kaen University, 123 Mitraphab Road, Khon Kaen, 40002, Thailand

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$51.00 plus tax Refund Policy

Use of a low-dose steroid as an adjunct in the treatment, in mice, of severe sepsis caused by Burkholderia pseudomallei