Strategies to Reduce Mortality from Bacterial Sepsis in Adults in Developing Countries

Sepsis is a progressive injurious process resulting from a systemic inflammatory response to infection [1]. In developed countries, sepsis is an important cause of mortality: in the United States alone, up to 750,000 people annually suffer from severe sepsis—mostly bacterial in aetiology—of whom 29% may die [2,3]. Unfortunately, data on bacterial sepsis in developing countries are notably lacking, particularly in adults. Estimates of the burden of lower respiratory tract infections, meningitis, and “other infections”, of which a significant proportion are associated with severe sepsis, show that the majority of deaths and disability-adjusted life years lost occur in low-income countries (Figure 1) [4]. Additionally, severe sepsis is likely to complicate a varying proportion of cases of malaria, HIV/ AIDS, diabetes, maternal conditions, and cancer deaths globally. The standard of care varies significantly across lowerand middle-income developing countries, but published reports suggest that outcomes are poor even at major hospitals [5–10]. Melioidosis, a serious tropical infection caused by Burkholderia pseudomallei that often presents with sepsis, is endemic in a region containing both highand low-income countries [11]. Outcomes vary significantly: the case fatality rate for melioidosis is higher in Thailand (40%–50%) than in Australia (10%–20%) [11–13], and the case-fatality rate for melioidosis with severe sepsis is approximately 50% in Singapore compared with 90% in a Thai clinical trial [14,15]. The burden of disease and case fatality of patients with melioidosis in less developed countries such as Cambodia and Myanmar are unknown. Although melioidosis is not common outside of southeast Asia, extrapolating this experience suggests that the outcomes from all-cause bacterial sepsis in underdeveloped regions are likely to be poor. The recently updated “Surviving Sepsis Campaign” guidelines have been widely disseminated in the developed world as a model of optimal sepsis management [16]. Although there has been some controversy regarding the recommendations and the development of the guidelines [17–19], most interventions based on improving early management of septic patients are less controversial. Crucially, most of the studies on which these recommendations are based were undertaken in the developed world and may not be applicable to the majority of the world’s population who live in poorer regions. The purpose of this paper is to highlight the paucity of epidemiological or management data on bacterial sepsis in the developing world, discuss current management approaches to sepsis in adults, and examine how clinical sepsis management guidelines could be best adapted to provide improved care at low cost in under-resourced regions. We use the term “developing country” to refer to loweror middle-income countries as defined by the World Bank [20].