Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response.
BACKGROUND
Melioidosis is a problem in the developing tropical regions of Southeast Asia and Northern Australia where the the Gram negative saprophytic bacillus Burkholderia pseudomallei is endemic with the risk of fulminant septicaemia. While diabetes mellitus is a well-established risk factor for melioidiosis, little is known if specific hypoglycemic agents may differentially influence the susceptibility and clinical course of infection with B. pseudomallei (Bp).


RESULTS
In this cohort study, patients with pre-existing diabetes and melioidosis were retrospectively studied.


METHODS
mortality, length of stay and development of complications (namely hypotension, intubation, renal failure and septicaemia) were studied in relation to prior diabetic treatment regimen. Peripheral blood mononuclear cells (PBMC) from diabetic patients and healthy PBMC primed with metformin, glyburide and insulin were stimulated with purified Bp antigens in vitro. Immune response and specific immune pathway mediators were studied to relate to the clinical findings mechanistically. Of 74 subjects, 44 (57.9%) had sulphonylurea-containing diabetic regimens. Patient receiving sulphonylureas had more severe septic complications (47.7% versus 16.7% p = 0.006), in particular, hypotension requiring intropes (p = 0.005). There was also a trend towards increased mortality in sulphonylurea-users (15.9% versus 3.3% p = 0.08). In-vitro, glyburide suppressed inflammatory cytokine production in a dose-dependent manner. An effect of the drug was the induction of IL-1R-associated kinase-M at the level of mRNA transcription.


CONCLUSIONS
Sulphonylurea treatment results in suppression of host inflammatory response and may put patients at higher risk for adverse outcomes in melioidosis.
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Xiang
X
Liu
Department of Pharmacy, National University Hospital, Singapore.
Geraldine
G
Foo
Department of Pharmacy, Tan Tock Seng Hospital, Singapore.
Wan Peng
WP
Lim
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Sharada
S
Ravikumar
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
Siew Hoon
SH
Sim
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Mar Soe
MS
Win
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Jessamine Geraldine
JG
Goh
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Joan Hui Juan
JH
Lim
Department of Pharmacy, National University Hospital, Singapore.
Ying Hui
YH
Ng
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore; Faculty of Medicine, National University of Singapore, Singapore.
Dale
D
Fisher
Faculty of Medicine, National University of Singapore, Singapore; Division of Endocrinology, University Medicine Cluster, National University Health System, Singapore.
Chin Meng
CM
Khoo
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
Gladys
G
Tan
Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
Louis Yi Ann
LY
Chai
D001210:Asia, Southeastern; D001315:Australia; D015331:Cohort Studies; D048909:Diabetes Complications / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D008554:Melioidosis / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D012189:Retrospective Studies; D018805:Sepsis / Q000401:mortality / Q000473:pathology; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds