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Epidemiology and microbiology of sepsis in mainland China in the first decade of the 21st century

  • Xin-Chuan Chen
    Affiliations
    Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
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  • Author Footnotes
    1 Co-first authors: Dr. Yun-Fan Yang and Dr. Hong-Feng Gou, contributed equally as co-first authors.
    Yun-Fan Yang
    Footnotes
    1 Co-first authors: Dr. Yun-Fan Yang and Dr. Hong-Feng Gou, contributed equally as co-first authors.
    Affiliations
    Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
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  • Rui Wang
    Affiliations
    Nursing Section, Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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  • Author Footnotes
    1 Co-first authors: Dr. Yun-Fan Yang and Dr. Hong-Feng Gou, contributed equally as co-first authors.
    Hong-Feng Gou
    Footnotes
    1 Co-first authors: Dr. Yun-Fan Yang and Dr. Hong-Feng Gou, contributed equally as co-first authors.
    Affiliations
    Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
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  • Xin-Zu Chen
    Correspondence
    Corresponding author. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu 610041, Sichuan Province, China.
    Affiliations
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China

    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
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  • Author Footnotes
    1 Co-first authors: Dr. Yun-Fan Yang and Dr. Hong-Feng Gou, contributed equally as co-first authors.
Open AccessPublished:November 29, 2014DOI:https://doi.org/10.1016/j.ijid.2014.11.027

      Highlights

      • Differences in the mortality of sepsis become smaller among major cities, small sized cities, and rural area in mainland China.
      • Males, elders, or neonates are subpopulations at high risk of mortality from sepsis.
      • Proportion of Gram (+) bacteria inducing sepsis was predominant among neonates, but equal to that of Gram (–) bacteria among adults.
      • The “Surviving Sepsis Campaign” should be further practiced nationwide for improving outcomes of patients with sepsis in mainland China.

      Summary

      Objectives

      This study describes the epidemiological and microbiological profile of sepsis during the first decade of the 21st century in mainland China.

      Methods

      The sepsis-related mortality data from 2003 and 2007 were retrieved from the China Health Statistical Yearbook. The microbiology data were retrieved and selected from a literature search of the China Academic Journal Database between 2001 and 2009. A meta-analysis was performed to synthesize the available data on the proportion of positive blood cultures in septic patients and the microorganism distribution.

      Results

      The sepsis mortality in small and medium-sized cities and rural areas declined obviously over time. The mortality of the subpopulations aged 1–54 years tended to be lower than the national averages. In contrast, the sepsis mortality among neonates and the elderly (≥75 years) was obviously higher than national averages. While the mortality in the elderly declined between 2003 and 2007, the neonate sepsis mortality increased dramatically, especially among male neonates. The overall positivity of blood culture were 17.0%, 13.3% and 10.6% among neonatal, pediatric and adult patients with suspected sepsis, respectively; this proportion tended to decrease over time. Among identified microorganisms, the proportions of Gram (+) and (–) bacteria were similar (47.2% vs. 44.5%) among adult patients, while Gram (+) bacteria was predominant among neonatal (77.4%) and pediatric (73.2%) patients and increased in prevalence over time. The positivity of blood cultures and proportions of microorganisms varied by geographical region across mainland China. Sepsis with fungus was rare but was more prevalent in adult sepsis patients (6.4%) than in neonatal patients (0.8%).

      Conclusions

      The difference in sepsis mortality between urban and rural areas decreased over time. Males, the elderly, and neonates were found to be high-risk subpopulations. Gram (+) bacteria were predominant among neonates with sepsis, but the proportion of patients with Gram (+) or Gram (–) bacteria was similar among adults with sepsis.

      Keywords

      1. Introduction

      Sepsis is a significant cause of mortality worldwide, and its cost is a significant burden to the healthcare system.
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      The incidence of sepsis is increasing globally according to certain estimates.
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      In 2003, management guidelines for severe sepsis and septic shock were developed under the auspices of the Surviving Sepsis Campaign.
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      The campaign is an international effort to increase awareness and improve the outcomes for patients with sepsis; the guidelines were updated in 2008 and 2013.
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      • et al.
      Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.
      In a study from Finland, the incidence of severe sepsis in the intensive care units was as high as 0.38/1,000 adult patients.
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      • et al.
      Incidence, treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis study.
      Esteban et al. reported a hospital mortality of 12.8%, 20.7% and 45.7% for patients with sepsis, severe sepsis and septic shock, respectively.
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      The decision to use empirically prescribed antimicrobials for managing sepsis depends highly on epidemiological factors.
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      • et al.
      Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome.
      Since 1987, Gram (+) bacteria have become the most common organisms associated with the development of sepsis.
      • Hodgin K.E.
      • Moss M.
      The epidemiology of sepsis.
      • Martin G.S.
      Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes.
      However, the predominant microorganism associated with sepsis varies by region. Baharoon et al. reported Gram (–) bacteria were the most frequently isolated microorganisms among sepsis patients in Saudi Arabia.
      • Baharoon S.
      • Al-Jahdali H.
      • Al Hashmi J.
      • Memish Z.A.
      • Ahmed Q.A.
      Severe sepsis and septic shock at the Hajj: etiologies and outcomes.
      Jaramillo-Bustamante et al. also reported Gram (–) bacteria were the most frequent etiological agent for sepsis among pediatric patients in Colombia.
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      • Fernández-Laverde M.
      • Bareño-Silva J.
      Epidemiology of sepsis in pediatric intensive care units: first Colombian multicenter study.
      In addition, the incidence of fungal organisms associated with sepsis has increased rapidly in recent years.
      • Martin G.S.
      Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes.
      Nevertheless, few studies have addressed the overall mortality from sepsis and the relevant microorganism distribution in mainland China. In this study, we aimed to observe the ecological, epidemiological and microbiological changes of sepsis over time during the first decade of the 21st century in mainland China.

      2. Materials and Methods

      2.1 Mortality data

      For the ecological analysis, the crude sepsis mortality rates were retrieved from the China Health Statistical Yearbook issued by the Ministry of Health of China.

      Ministry of Health of the People's Republic of China. China Health Statistical Yearbook (2008). Identifier: A010610200810002 URL: http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/200809/37759.htm.

      Mortality data were available from the Yearbook for 2003 and 2007. The sepsis mortality rates were stratified by gender, age group, and region (classified as major city, small and medium-sized city, and rural areas).

      2.2 Microbiology data

      The China Academic Journal Full-text Database (CAJ) updated by the China National Knowledge Infrastructure (CNKI) central servers was searched for articles published between 2001 and 2009. CAJ is currently the most comprehensive database of Chinese journals.

      China Knowledge Resource Integrated Database: China Academic Journals Full-text Database. URL: http://oversea.cnki.net/kns55/brief/result.aspx?dbPrefix=CJFD.

      The search terms utilized were “sepsis”[MeSH] AND “blood culture”[MeSH]. The titles and abstracts of 420 citations were initially identified, and irrelevant citations were excluded. Secondly, the full texts were retrieved to identify eligible studies. Hospital-based cross-sectional studies on blood culture examination for patients with suspected sepsis in mainland China were eligible for the analysis. The only exclusion criterion was an observation duration of less than 1 year. Finally, 84 adult and 77 neonatal-pediatric patient studies were included in the analysis. The positivity of a blood culture examination was defined as the percentage of positive microorganisms identified in the blood specimens from hospitalized patients with suspected sepsis. Additionally, the proportions of Gram (+) bacteria, Gram (−) bacteria, and fungus among all identified microorganisms were extracted. The data on adult or neonatal-pediatric patients were retrieved and extracted separately. The eastern, central and western regions of China have different economic conditions and healthcare accessibility.
      • Chen X.Z.
      • Li Y.Y.
      • Hu J.K.
      • Yang K.
      • Liu J.
      • Zhang B.
      • et al.
      Spread and development of laparoscopic surgery for gastric tumors in mainland China: initial experiences.
      Therefore, the epidemiological differences among these three regions of China were analyzed. Due to possible changes in the epidemiology of sepsis related to advances in healthcare accessibility in mainland China over time, the included studies were categorized into three periods: 1990–1999, 2000–2004 and 2005–2009. If the observation duration of a study covered two periods, the period containing the majority of the observation duration was chosen.

      2.3 Statistical analyses

      The 2003 and 2007 mortality rates by age group were initially compared by the Friedman test for multiple subpopulations. The Wilcoxon signed ranks test was used to compare the mortality of two related subpopulations.
      The positivity of the blood culture examinations among tested specimens from patients with suspected sepsis was estimated by meta-analysis to combine eligible studies. Likewise, the proportions of Gram (+) bacteria, Gram (−) bacteria, and fungus among all identified microorganisms from positive blood culture were estimated by meta-analysis using the same approach. All meta-analyses were performed using a random effect model. Subgroup analysis was performed among different regions of China, as well as among different time periods. Additional subgroup analysis was performed among neonatal or pediatric patients. The relative ratios (RRs) and 95% confidence intervals (CIs) of the synthesized positivity of blood cultures or proportion of microorganisms between different subgroups were calculated based on the estimated percentage and the sample size of each subgroup.
      Nonparametric tests were conducted with SPSS 13.0 software (Chicago, U.S.). The meta-analyses were conducted with the statistical software Comprehensive Meta-Analysis 2.0 (Biostat, Englewood NJ, USA). RR and 95% CI was calculated using Microsoft Excel 2010, with the formulas for 95% CI of RR = exp(ln(p1/p2) ± 1.96 * sqrt(1 / (p1 * N1) + 1 / (p2 * N2) – 1 / N1 – 1 / N2)), and p value = 2 * (1 – normsdist(abs(p1 – p2) / sqrt(p1 * (1 – p1) / N1 + p2 * (1 – p2) / N2))). All statistical tests were two sided using an α level of 0.05.

      3. Results

      3.1 Nationwide sepsis mortality

      In the 2003, the crude sepsis mortality gradually increased from major cities to small and medium-sized cities and then to rural areas (Figure 1). Among subgroups, the highest mortality was 0.83 per 100,000 persons among the male population in rural areas. Interestingly, in the 2007, the crude mortality was dramatically decreased in small and medium-sized cities and rural areas. The differences between rural areas and major cities became smaller. In contrast, compared to 2003, the 2007 mortality in the major cities increased among both males and females. Among all subgroups, males had higher sepsis mortality than females, with the only exception being in the 2003 in major cities.
      Figure thumbnail gr1
      Figure 1Nationwide crude mortality (per 100,000 persons) of sepsis in (A) 2003 and (B) 2007.

      3.2 Mortality stratified by age group, gender and region

      The age-specific mortality curves had two peaks in the neonatal-pediatric and the older subpopulations (Figure 2). A sharp decline after one year of age and a sharp rise after 70 years of age could be observed in both the 2003 and the 2007 periods. Between 2003 and 2007, the sepsis mortality among the elderly decreased by approximately half in 2007, but in the <1 year of age subgroup it increased by up to 5 fold (Figure 2). The Friedman test showed significant differences between major cities, small and medium-sized cities, and rural areas in both 2003 (p<0.001) and 2007 (p=0.008).
      Figure thumbnail gr2
      Figure 2Distribution of age-specific crude mortality rates (per 100,000 persons) of sepsis in mainland China in (A) 2003 and (B) 2007.
      In Figure 3, those aged between 1 and 54 years mostly had lower mortality rates than the national average. There were no significant differences between males and females (p>0.05) between any region or time period. Between 2003 and 2007, the sepsis related death decreased significantly in rural males (p=0.033) and females (p=0.005), as well as in males in the small and medium-sized cities (p=0.039), but no significant changes were found in major cities (p>0.05). Interestingly, the dramatic improvement in small and medium-sized cities exceeded the improvements observed in both the rural males (p=0.012) and females (p=0.017).
      Figure thumbnail gr3
      Figure 3Comparisons of age-specific sepsis mortality among different subpopulations. The national averages are referred to those presented in .

      3.3 Sepsis among adult patients

      The overall positivity of blood culture examination was 10.6% based on 71 studies in adult patients (Table 1). Compared to eastern China, the positivity was mildly but significantly higher in central China, and lower in western China. Between 2005 and 2009, the positivity tended to decline over time.
      Table 1Meta-analysis on positivity of blood culture examinations among adult patients with suspected sepsis.
      SubsetNo. of StudiesSum of SpecimensSynthesized positivity (%)RR for synthesized positivity
      Total71237,71410.6 (9.8–11.6)
      Region
       Eastern China45137,54610.6 (9.5–11.9)Ref
       Central China1670,06411.3 (9.7–13.2)1.07 (1.04–1.09)*
       Western China1030,1049.5 (7.1–12.7)0.90 (0.86–0.93)*
      Period of sampling
       1990–1999738,04410.4 (8.2–13.0)Ref
       2000–200445148,66511.0 (9.9–12.2)1.06 (1.02–1.09)*
       2005–20091951,0059.9 (8.1–12.0)0.95 (0.92–0.99)*
      Abbreviation: RR, relative ratio. * p<0.05.
      The proportions of Gram (+) bacteria, Gram (−) bacteria, and fungus were 47.2%, 44.5%, and 6.4%, respectively, among identified microorganisms based on 84 studies (Table 2). No significant difference was found between the proportions of Gram (+) and Gram (−) bacteria. Compared to eastern China, central China had a significantly higher proportion of Gram (+) bacteria, but lower proportions of Gram (−) bacteria and fungus. In western China, the proportion of Gram (+) was lower than in eastern China, but that of Gram (−) bacteria was higher. Additionally, the proportions did not change significantly over time.
      Table 2Meta-analysis on proportion of microbiological patterns among identified microorganisms from adult patients.
      SubsetNo. of StudiesSum of identified microorganismsSynthesized proportion (%)RR for synthesized proportion
      Gram (+)Gram (–)FungusGram (+)Gram (–)Fungus
      Total8432,37747.2 (43.9–50.5)44.5 (41.6–47.5)6.4 (5.6–7.3)
      Region
       Eastern China5418,90844.7 (41.3–48.0)46.3 (43.3–49.4)7.2 (6.2–8.3)RefRefRef
       Central China2010,23660.6 (54.7–66.3)34.4 (29.8–39.2)4.3 (3.1–5.8)1.36 (1.33–1.39)*0.74 (0.72–0.77)*0.60 (0.54–0.66)*
       Western China103,23333.9 (25.9–43.0)56.4 (46.0–66.2)7.3 (4.2–12.4)0.76 (0.72–0.80)*1.22 (1.18–1.26)*1.01 (0.89–1.16)
      Period of sampling
       1990–1999115,09550.5 (41.7–59.4)43.3 (35.2–51.8)5.4 (3.4–8.4)RefRefRef
       2000–20045221,31245.9 (41.9–49.9)44.7 (41.1–48.4)7.0 (5.9–8.4)0.91 (0.88–0.94)*1.03 (1.00–1.07)1.30 (1.14–1.47)*
       2005–2009215,97048.7 (40.6–56.9)44.7 (37.7–51.9)5.5 (4.3–7.0)0.96 (0.93–1.00)1.03 (0.99–1.08)1.02 (0.87–1.19)
      Abbreviation: RR, relative ratio. * p<0.05.

      3.4 Sepsis among neonatal and pediatric patients

      Based on 41 studies in neonatal-pediatric patients, the overall positivity of blood culture examination was 17.0% and 13.3% for neonatal and pediatric patients with suspected sepsis, respectively (Table 3). The positivity of the pediatric patients was significantly lower than that of the neonatal patients. The positivity in western and central China was significantly higher than in eastern China. Additionally, the positivity in both pediatric and neonatal patients decreased over time.
      Table 3Meta-analysis on positivity of blood culture examinations among neonatal and pediatric patients with suspected sepsis.
      SubsetNo. of StudiesSum of SpecimensSynthesized positivity (%)RR for synthesized positivity
      Patient type
       Neonatal30132,20017.0 (13.6–21.0)Ref
       Pediatric1135,79913.3 (9.7–18.1)0.78 (0.76–0.81)*
      Region
       Eastern China2286,55613.1 (10.5–16.2)Ref
       Central China927,68317.2 (13.1–22.4)1.31 (1.27–1.35)*
       Western China1053,76023.8 (14.4–36.8)1.82 (1.78–1.86)*
      Period of sampling
       1990–19991260,07419.6 (15.2–25.0)Ref
       2000–20041558,36815.0 (10.0–21.9)0.77 (0.75–0.78)*
       2005–20091232,61613.4 (9.6–18.4)0.68 (0.66–0.71)*
      Abbreviation: RR, relative ratio. * p<0.05.
      The proportions of Gram (+) bacteria, Gram (−) bacteria, and fungus among neonatal patients were 77.4%, 21.1%, and 0.8%, respectively, based on 58 studies (Table 4). Gram (+) bacteria were the predominant microorganisms followed by Gram (−) bacteria. The percentage of blood cultures positive for fungus was significantly lower in neonatal and pediatric patients than in adult patients. However, among pediatric patients, the proportion of Gram (+) bacteria was mildly but significantly decreased, while that of Gram (−) bacteria was increased as compared to adult patients.
      Table 4Meta-analysis on proportion of microbiological patterns among identified microorganisms from neonatal and pediatric patients.
      SubsetNo. of StudiesSum of identified microorganismsSynthesized proportion (%)RR for synthesized proportion
      Gram (+)Gram (–)FungusGram (+)Gram (–)Fungus
      Patient type
       Neonatal5820,03777.4 (74.2–80.4)21.1 (18.3–24.2)0.8 (0.5–1.1)RefRefRef
       Pediatric196,10973.2 (66.4–79.1)24.6 (18.5–32.0)0.9 (0.5–1.4)0.95 (0.93–0.96)*1.17 (1.11–1.23)*1.13 (0.83–1.53)
      Region
       Eastern China3913,49575.7 (71.9–79.2)22.1 (18.9–25.7)0.9 (0.6–1.4)RefRefRef
       Central China217,52475.8 (68.3–82.0)23.0 (16.8–30.8)0.5 (0.3–1.0)1.00 (0.98–1.01)1.04 (0.99–1.10)0.56 (0.39–0.80)*
       Western China175,12778.6 (73.0–83.2)20.4 (15.9–25.9)0.7 (0.4–1.3)1.04 (1.02–1.06)*0.92 (0.87–0.98)*0.78 (0.54–1.13)
      Period of sampling
       1990–19992612,00271.9 (67.0–76.3)25.7 (21.3–30.6)0.8 (0.5–1.3)RefRefRef
       2000–2004256,20277.8 (73.7–81.4)21.1 (17.6–25.1)0.7 (0.4–1.1)1.08 (1.06–1.10)*0.82 (0.78–0.87)*0.88 (0.61–1.25)
       2005–2009174,53279.2 (69.5–86.4)19.7 (12.9–29.0)0.9 (0.5–1.8)1.10 (1.08–1.12)*0.77 (0.72–0.82)*1.13 (0.78–1.62)
      Abbreviation: RR, relative ratio. * p<0.05.
      There were no significant geographical differences in the proportion of microorganisms (Table 4), with the only exception that fungal sepsis was lower in central China than in eastern China. Moreover, the proportion of Gram (+) bacteria was significantly increased over time, while that of Gram (−) bacteria was decreased.

      4. Discussion

      In the ecological analysis, the nationwide average mortality was lower than 1 per 100,000 persons in mainland China during the first decade of the 21st century. The sepsis mortality in small and medium-sized cities and rural areas declined significantly over time, but there was a slight increase in the mortality in major cities. The mortality of the elderly with sepsis declined, but that of neonates with sepsis increased dramatically, especially among male neonates. In the epidemiological study review, the overall positivity of the blood cultures were 17.0%, 13.3% and 10.6% among neonatal, pediatric and adult patients with suspected sepsis, respectively. Among identified microorganisms, the proportions of Gram (+) and (–) bacteria were not significantly different among adult patients, while Gram (+) bacteria were predominant among neonatal and pediatric patients and increased over time. Geographical differences among the proportions existed across mainland China. Sepsis with fungus was rare but increased in prevalence from neonatal to adult patients.
      Sepsis, especially severe sepsis, is a common and major cause of admission to the intensive care unit and is also an expensive and frequently fatal condition.
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      Likewise, in mainland China, we also find this correlation between age and mortality from sepsis. Among adults, the sepsis mortality starts to rise from 55 years of age, dramatically increases from 75 years of age onward, and finally reaches the peak in the ≥85 age group.
      Elder nonsurvivors of sepsis die earlier during hospitalization, while elder survivors more frequently require skilled nursing or rehabilitative care after hospitalization.
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      Therefore, health care resource prioritization and polarization may be one reason for the difference in sepsis mortality rates between elderly and younger adult populations. In mainland China, the crude mortality did not differ between geographic regions (east, central and west China), but it did differ between urban and rural areas in 2003. A possible reason for this finding could be the difference in economic and health care resource development between rural and urban areas. However, the dramatic decline in the mortality in small and medium-sized cities and rural areas might also be attributed to the “Surviving Sepsis Campaign” that issued the first national guidelines for treatment of multiple organ dysfunction syndrome and severe sepsis in 2007.

      Research Group of Major Project Granted by Beijing Municipal Sciences and Technology Commission “The Diagnosis and Treatment of MODS: the effect of integrated traditional and Western medicine on mortality”. Protocols for treatment of multiple organ dysfunction syndrome/severe sepsis combined of traditional Chinese medicine and Western medicine. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2007;19(10):577–9. (in Chinese).

      Subsequently, the guidelines were disseminated in mainland China to improve the outcomes of critically ill patients, including sepsis patients.
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      Particularly, we have found that the mortality of neonates with sepsis increased in mainland China, which requires additional study. In a cross-sectional study from the Shanghai area in China, the proportion of neonate and pediatric patients admitted to pediatric intensive care units with sepsis was as high as 14.5%.

      Collaborative Group for the Study of Sepsis in PICUs in Shanghai Area. Hospital epidemiology, management and outcome of pediatric sepsis and severe sepsis in 4 PICUs in Shanghai. Zhonghua Er Ke Za Zhi 2012;50(3):172–7. (in Chinese).

      Among those with sepsis, 38.8% and 30.5%, respectively, suffered from severe disease and then died.

      Collaborative Group for the Study of Sepsis in PICUs in Beijing Area. Clinical study on sepsis in 2 pediatric intensive care units in Beijing. Zhonghua Er Ke Za Zhi 2012;50(3):178–83. (in Chinese).

      In another study from Beijing, China, pediatric sepsis had the characteristics of high morbidity, mortality and cost, and patients younger than 3 years were more susceptible to developing sepsis in pediatric intensive care units as compared to those aged 3 years and above.
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      • Laopaiboon M.
      • et al.
      Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health.
      The decreasing positivity of blood culture examination from the 1990s to the 2000s may be attributed to the improved awareness among physicians of testing blood cultures for suspected sepsis. The geographic differences in the blood culture positivity may also partially reflect the differences in the awareness of the need to perform blood culture between eastern, central and western China. In particular, in western China, the blood culture positivity among neonatal-pediatric patients with suspected sepsis was 1.8 times that in eastern China. Increased use of blood culture examination is potentially associated with early diagnosis of sepsis and timely alteration of antibiotics. Western China is a relatively less developed region of mainland China and, thus, the accessibility of healthcare and abundance of medical resources is relatively limited compared to eastern China. This finding highlights the necessity of improving access to healthcare in western China.
      Additionally, empirical treatment for sepsis should be based on local patterns of antibiotic resistance until the etiologic agent has been identified.
      • Simonsen K.A.
      • Anderson-Berry A.L.
      • Delair S.F.
      • Davies H.D.
      Early-onset neonatal sepsis.
      However, the microbiology among adult patients with sepsis is almost of equal risk between Gram (+) and Gram (−) bacteria in mainland China; thus, the empirical treatment should be largely dependent on the original site of infection. The microbiology in mainland China is different from the experiences from other countries.
      • Hodgin K.E.
      • Moss M.
      The epidemiology of sepsis.
      • Martin G.S.
      Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes.
      • Baharoon S.
      • Al-Jahdali H.
      • Al Hashmi J.
      • Memish Z.A.
      • Ahmed Q.A.
      Severe sepsis and septic shock at the Hajj: etiologies and outcomes.
      In particular, Gram (+) bacteria were the predominant microorganisms among neonatal or pediatric patients with sepsis, and the proportion of Gram (+) bacteria has tended to increase over time. According to a report by Jaramillo-Bustamante et al.,
      • Jaramillo-Bustamante J.C.
      • Marín-Agudelo A.
      • Fernández-Laverde M.
      • Bareño-Silva J.
      Epidemiology of sepsis in pediatric intensive care units: first Colombian multicenter study.
      these bacteria should be a strong indication for empirical antibiotic treatment with a relatively narrow spectrum targeting Gram (+) bacteria. Additionally, sepsis with fungus was found to be relative rare in mainland China, especially among neonatal or pediatric patients, and its proportion remained stable over time. Moreover, the risk of fungal sepsis was found to be associated with age. The proportion of fungal sepsis among adult patients was 8-fold that of neonatal patients. This finding indicates that positive antifungal treatment for highly suspected fungal sepsis in adult patients needs to be considered in cases of absent or questionable blood culture results.
      In summary, the sepsis mortality declined in small sized cities and rural areas, but increased slightly in major cities in mainland China during the first decade of the 21st century. The mortality among the elderly declined but increased among neonates. The positivity of blood culture remained relatively stable among suspected sepsis patients. The proportion of Gram (+) bacteria was significantly higher than that of Gram (−) bacteria among neonates with sepsis, but the proportions were equal among adults.
      Conflicts of interest: None declared.
      Funding: National Natural Science Foundation of China (No. 81301866).
      Data sharing: The reference list of literatures identified from the China Academic Journal Full-text Database (CAJ) was unpublished. These extra data is available by emailing Dr. Xin-Zu Chen ( [email protected] ).

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