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Background Sepsis is a major reason for intensive care unit (ICU) admission, also in resource-poor settings. ICUs in low- and middle-income countries (LMICs) face many challenges that could affect patient outcome. Aim To describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Findings Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Conclusions Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both at a macro- and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

Background Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. Methods We conducted a retrospective cohort study in Premier Perspective database (2009–2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Results Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/−15.3 vs. 69.1+/−15.9 years, p  < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p  < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/−2.0 vs. 1.9+/−2.1, p  = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p  < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p  < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p  < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p  < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p  < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p  < 0.001) in costs. Conclusions In this large US database, the prevalence of CRE among patients with Enterobacteriaceae UTI, pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

To evaluate the magnitude and impact of diabetic foot ulcers (DFUs) in emergency department (ED) settings from 2006-2010 in the United States (US). This cross-sectional study utilized Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) National Emergency Department Sample (NEDS) discharge records of ED cases among persons ≥18 years with any-listed diagnosis of DFUs. Multivariable analyses were conducted for clinical outcomes of patient disposition from the ED and economic outcomes of charges and lengths of stay based upon patient demographic and socioeconomic factors, hospital characteristics, and comorbid disease states. Overall, 1,019,861 cases of diabetic foot complications presented to EDs in the US from 2006-2010, comprising 1.9% of the 54.2 million total diabetes cases. The mean patient age was 62.5 years and 59.4% were men. The national bill was $1.9 billion per year in the ED and $8.78 billion per year (US$ 2014) including inpatient charges among the 81.2% of cases that were admitted. Clinical outcomes included mortality in 2.0%, sepsis in 9.6% of cases and amputation in 10.5% (major-minor amputation ratio of 0.46). Multivariable analyses found that those residing in non-urban locations were associated with +51.3%, +14.9%, and +41.4% higher odds of major amputation, minor amputation, and inpatient death, respectively (p<0.05). Medicaid beneficiaries incurred +21.1% and +25.1% higher odds for major or minor amputations, respectively, than Medicare patients (p<0.05). Persons within the lowest income quartile regions were associated with a +38.5% higher odds of major amputation (p<0.05) versus the highest income regions. Diabetic foot complications exact a substantial clinical and economic toll in acute care settings, particularly among the rural and working poor. Clear opportunities exist to reduce costs and improve outcomes for this systematically-neglected condition by establishing effective practice paradigms for screening, prevention, and coordinated care.

Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases “severe sepsis” and “septic shock” and the MeSH terms “epidemiology”, “statistics”, “mortality”, “economics”, and “quality of life”. Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use.

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. In 2000, about 14·5 million episodes of serious pneumococcal disease (uncertainty range 11·1–18·0 million) were estimated to occur. Pneumococcal disease caused about 826 000 deaths (582 000–926 000) in children aged 1–59 months, of which 91 000 (63 000–102 000) were in HIV-positive and 735 000 (519 000–825 000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449 000 [316 000–501 000]) occurred in ten African and Asian countries. S pneumoniae causes around 11% (8–12%) of all deaths in children aged 1–59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden. GAVI Alliance and the Vaccine Fund.

Limited data is available to describe clinical characteristics, long-term outcomes, healthcare resource use and the attributable costs of invasive meningococcal disease (IMD) in Germany. We aimed to examine demographic and clinical characteristics as well as healthcare resource use and related costs. We conducted a retrospective cohort study based on the InGef database in patients with IMD between 2009 and 2015. Cases were identified based on hospital main discharge diagnoses of IMD. Demographics, clinical characteristics, 30-day and 1-year mortality as well as IMD-related complications and sequelae in IMD cases were examined. In addition, short and long-term costs and healthcare resource use in IMD cases were analyzed and compared to an age- and sex-matched control group without IMD. The study population comprised 164 IMD cases between 2009 and 2015. The mean length of the IMD-related hospitalization was 13 days and 38% of all cases presented with meningitis only, 35% with sepsis only, 16% with both and 11% with other IMD. The 30-day and one-year mortality were 4.3% and 5.5%, respectively. Approximately 13% of IMD cases had documented IMD-related complications at hospital discharge and 24% suffered from sequelae during follow-up. The IMD-related hospitalization was associated with mean costs of € 9,620 (standard deviation: € 22,197). The difference of mean costs between IMD cases and matched non-IMD controls were € 267 in the first month and € 1,161 from one month to one year after discharged from IMD-related hospitalization. During the later follow-up period, the mean overall costs and costs associated with individual healthcare sectors were also higher for IMD cases without reaching statistical significance. IMD resulted in severe complications and sequelae and was associated with extensive costs and increased healthcare resource use in Germany, especially in the first year after IMD diagnosis and due the IMD-related hospitalization.

PurposeTo determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.MethodsWe conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.ResultsWe obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p = 0.86), self-care (24.7% vs. 26.0%, p = 0.44), usual activities (44.5% vs. 46.8%, p = 0.28), pain/discomfort (42.4% vs. 41.6%, p = 0.54) and anxiety/depression (36.9% vs. 37.7%, p = 0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p = 0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1 ± 11.9 vs. 8.0 ± 9.8 days (p < 0.0001) and 22.8 ± 21.2 vs. 19.1 ± 19.0 days, (p = 0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345 ± 46,263 (€35,109 ± 35,043) versus 34,844 ± 38,281 (€28,223 ± 31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517 ± 10,254), p < 0.001 as was the total cost of hospital treatment to 2 years: A$74,120 ± 60,750 (€60,037 ± 49,207) versus A$65,806 ± 59,856 (€53,302 ± 48,483), p = 0.005.ConclusionsCritically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

The objective of this study is to evaluate the number of diabetics that seek medical treatment in emergency departments or require hospitalization for infection management in the United States. This study also assesses the socioeconomic impact of inpatient infection management among diabetics. We accessed the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample database and the Nationwide Inpatient Sample database to perform a retrospective analysis on diabetics presenting to the emergency department or hospitalized for infection management from 2006 to 2011. Emergency Department: Since 2006, nearly 10 million diabetics were annually evaluated in the emergency department. Infection was the primary reason for presentation in 10% of these visits. Among those visits, urinary tract infection was the most common infection, accounting for over 30% of emergency department encounters for infections. Other common infections included sepsis, skin and soft tissue infections, and pneumonia. Diabetics were more than twice as likely to be hospitalized for infection management than patients without diabetes. Hospitalization: Since 2006, nearly 6 million diabetics were annually hospitalized. 8–12% of these patients were hospitalized for infection management. In 2011, the inpatient care provided to patients with DM, and infection was responsible for over $48 billion dollars in aggregate hospital charges. Diabetics commonly present to the emergency department and require hospitalization for infection management. The care provided to diabetics for infection management has a large economic impact on the United States healthcare system. More efforts are needed to develop cost-effective strategies for the prevention of infection in patients with diabetes.

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

PurposeBloodstream infections (BSIs) are associated with significant morbidity, mortality and costs, while prolonged blood culture (BC) diagnosis may delay the initiation of targeted therapy. This study evaluates the impact of an optimized microbiology laboratory process on turnaround times, antibiotic use, clinical outcomes and economics for hospitalized BSI patients.MethodsA pre-post study was conducted in a Chinese hospital in which BSI derived BC results before (Oct. 2020- Sep. 2021) and after (Oct. 2021- Sep. 2022) newly implemented microbiology diagnostics and workflow changes were analyzed. Turnaround times, antibiotic initiation, length of stay and in-hospital costs were compared.ResultsFrom 213 included patients, 134 were pre-optimization (pre-op) and 79 were post-optimization (post-op) cases. The median time from blood sample collection (BSC) to pathogen identification (ID) decreased from 70.12 to 47.43 h post-op (P < 0.001). The median time from BSC to the first ID report related initiation of pathogen-directed antibiotic use decreased from 88.48 to 47.85 h post-op (P < 0.001). The average hospital stay decreased from 19.54 to 16.79 days and 30-day readmissions declined from 18.7 to 13.9%, while the mean total antimicrobial drug usage costs decreased by 3,889 CNY per patient (P = 0.022) after optimization.ConclusionsImplementing new diagnostics technologies and optimizing laboratory workflows significantly reduced antimicrobial drug usage costs, shortened the time to ID results and improved the timeliness of appropriate antibiotic choices to treat BSIs. Investments in faster testing and process improvements were clearly beneficial for patient outcomes and healthcare economics.