The Global Burden of Sepsis: Barriers and Potential Solutions

Kristina E. Rudd; Niranjan Kissoon; Direk Limmathurotsakul; Sotharith Bory; Birungi Mutahunga; Christopher W. Seymour; Derek C. Angus; T. Eoin West


Crit Care. 2018;22(232) 

In This Article

Sepsis Highlights Health System Challenges

In low-resource settings, poverty, political corruption, health inequity, and under-resourced and low-resilience public health and acute health care delivery systems are fundamental contributors to the burden of sepsis (Figure 1). For example, poverty-associated conditions such as poor preventive health care, limited vaccine coverage, malnutrition, substandard living conditions such as indoor air pollution, bed sharing, and inadequate ventilation and sanitation, and exposure to environmental and animal vectors increase risk for acute infection.[19–22] These factors are further exacerbated by disparate funding of health systems (Figure 2), delays in identifying and reaching appropriate care, and inadequate systems to prevent health care-associated infections.[23,24] Addressing these issues, which are broadly relevant to health, is likely the greatest but perhaps the most challenging approach to reduce the global burden of sepsis. Moreover, given the significant variability within and across LMICs, it is critical to recognize that health system challenges must be evaluated at the community level, and the issues outlined in the following cannot be uniformly generalized to all areas of all LMICs.

Figure 1.

Burden of sepsis highlights public health and acute health care delivery system challenges. ICU intensive care unit, PICU pediatric intensive care unit

Figure 2.

Annual health expenditure per capita in high-income countries (HICs) versus low or middle-income countries (LMICs). The 2014 health expenditure per capita from World Bank's DataBank Health, Nutrition, and Population Statistics database 23

Human Resources

Health care facilities frequently lack the personnel to care for patients with sepsis. Indeed, 83 countries—all of which are in Latin America, Africa, and Asia—do not meet the WHO standards for minimum health care worker-to-population ratios.[25] Inadequate staffing of health care centers and gaps in providers' knowledge can impede rapid identification and treatment of patients with sepsis.[26] These knowledge gaps may be greater for pediatric sepsis care, as many areas lack pediatricians, and providers who do not routinely care for children may be uncomfortable with the nuances of pediatric resuscitation.


Many countries do not have sufficient health care facilities to care for the population they serve, with overcrowded medical wards or long distances between patients' homes and the nearest health center. The available facilities are sometimes in poor condition, with inadequate sanitation, ventilation, electrical supply, or lighting to allow for safe patient care.[27] This can impede appropriate care and contribute to the spread of health care-acquired infections.

Surgical Capacity

Capacity for timely surgical intervention to eradicate infection may be limited due to a combination of inadequate facilities, essential medications, supplies, and human resources (including surgeons and anesthesiologists).[28] At least 4.8 billion people (67% of the world's population) do not have access to surgery—including more than 95% of the population in South Asia and central, eastern, and western sub-Saharan Africa.[28] Based on current surgical rates and rates of growth in surgical capacity, 73% of the world's population will still be living in countries below the minimal recommended surgical rate in 2035.[29] Pediatric surgical capacity is particularly problematic.[30]

Critical Care Capacity

Critical care capacity is suboptimal worldwide, with inadequate high acuity and intensive care unit (ICU) facilities, providers, and supplies.[31] ICUs are often so chronically overcrowded that they are unable to accommodate critically ill patients with sepsis or septic shock, resulting in patients requiring vasopressors or mechanical ventilation being managed outside of the ICU—where the degree of monitoring is highly variable, if not absent. In some countries, ICU care is only accessible to the wealthy. Even where high-quality critical care facilities are available, allocation of scarce resources may not be applied in a transparent, consistent, equitable, or accountable manner.[32]

Supplies and Diagnostic Capacity

Many hospitals lack the requisite resources to implement current sepsis management guidelines.[33] Lack of intravenous (IV) fluids, supplemental oxygen, simple positive pressure airway systems, and basic monitoring equipment such as pulse oximeters is common in low-resource settings.[34] The placement of central venous catheters in a safe and sterile manner is often difficult, especially in children.

This unequal global distribution of medical resources may also limit resuscitation and organ support provided to septic patients in low-resource settings. For example, clinicians may avoid interventions deemed at higher risk, such as IV fluid resuscitation in a patient with respiratory insufficiency in a setting without available oxygen support or mechanical ventilation, for fear of doing harm by worsening pulmonary edema and respiratory failure.[35] Many guidelines and research studies have focused on bundled care,[36,37] which can be challenging for clinicians who are unable to administer all features of a bundle. It is often difficult or impossible to discern which features of a bundled management approach are most effective—and cost-effective—in reducing sepsis morbidity and mortality.[38,39]

There is a paucity of adequate microbiological diagnostic capacity in many settings, limiting clinicians' ability to tailor antimicrobial therapy to local pathogen and resistance profiles or individual patients' pathogen sensitivity and resistance patterns, as is recommended in many sepsis management guidelines.[40] Diagnostic capacity extends beyond just physical components of microbiology laboratories such as reliable access to consumable supplies, and includes staffing with adequate numbers of appropriately trained professionals such as phlebotomists and laboratory technicians, as well as necessary oversight and enforcement of good clinical laboratory practice.[41]

Inadequate, Inferior, and Misused Antimicrobials

In many low-resource settings, critical antimicrobials may not be available due to drug shortages, cost, or local import and regulation systems. Improving timely access to appropriate, effective, and affordable antimicrobials is of utmost importance. Counterfeit or substandard medications are a major problem, particularly where regulatory agencies are absent or ineffective, impacting millions of people annually.[42,43] Consequently, use of these medications can result in inadequate treatment of infection, increasing morbidity and mortality. Other potential consequences include exacerbation of antimicrobial resistance (AMR) or adverse effects due to exposure to contaminants or unknown ingredients.

Overuse and abuse of antimicrobials is a major challenge in both low and high-resource settings. In many countries, antimicrobials are available without prescription in community pharmacies, potentially delaying care and fueling antibiotic resistance. However, these risks must be balanced against the potential benefits of increased access to medications in settings with few trained health care workers or limited access to appropriate medical care. Improper physician prescribing practices, fueled by unregulated pharmaceutical company marketing to prescribers, can also contribute to antimicrobial misuse.[44,45] Poor antibiotic stewardship due to lack of access to adequate microbiology and diagnostic tests, and inadequate infectious disease and microbiology subspecialty expertise, can contribute to the increasing burden of AMR infections in LMICs.[46–48]

AMR may be a major driver of the global burden of both community and hospital-acquired sepsis. More than 700,000 deaths per year may be attributable to AMR infections globally, and this number could reach 10 million by 2050 if the current trend is not addressed.[49] Additionally, while patients in HICs with drug-resistant infections usually have access to alternative (and often more expensive) antibiotics, many in LMICs do not. Unfortunately, AMR data are not available for many LMICs (e.g., one recent review failed to identify any AMR data from 43% of African countries), and the quality of microbiological data is highly variable.[50] In areas of the world for which data are available, the level of resistance is frequently alarming.[50–52] The prevalence of AMR organisms has important implications for management of sepsis, particularly in areas without access to robust clinical microbiology facilities.

Addressing Acute Complications of Sepsis

Many health systems are unable to adequately address acute complications of sepsis. For example, venous thromboembolism prophylaxis is not appropriately employed in much of the world, and may be unavailable in low-resource settings.[53] Many hospitals in LMICs are unable to provide acute renal replacement therapies for the upwards of 30% of sepsis patients who develop acute kidney injury.[54,55] This lack of resources to manage life-threatening acute complications of sepsis almost certainly substantially increases sepsis-associated mortality in low-resource settings, even when the underlying infection may be treatable. The risk of developing a secondary health care-associated infection may be up to 20 times higher in LMICs than in HICs,[56] placing patients at risk for developing a second sepsis episode due to an antimicrobial resistant organism and increasing the burden on the health system.

Postdischarge Morbidity and Mortality

Long-term morbidity and mortality must be considered when evaluating the burden of sepsis globally. For example, one in every five pediatric sepsis survivors has a new functional disability.[57] Many health systems are unable to address short and long-term physical and psychological debility related to sepsis. Physical therapy, occupational therapy, rehabilitation medicine, and nursing care facilities are absent in many low-resource settings, impacting the functional outcomes of sepsis survivors and forming a significant barrier to reducing the burden of disability due to sepsis worldwide.

Among children, postdischarge mortality in LMICs is similar to, if not even higher than, in-hospital mortality.[58] This postdischarge mortality burden is borne by patients with identifiable risk factors, and these deaths occur early during the postdischarge period. While these observations suggest there may be early opportunities to decrease the burden and mortality,[59] these issues remain challenging even in highly resourced settings, and are vastly understudied or addressed in low-resource settings.