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1 The first two authors, Zhong-hua Wang and Xue-biao Wei, contributed equally to this work.
Zhong-hua Wang
Footnotes
1 The first two authors, Zhong-hua Wang and Xue-biao Wei, contributed equally to this work.
Affiliations
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
1 The first two authors, Zhong-hua Wang and Xue-biao Wei, contributed equally to this work.
Xue-biao Wei
Footnotes
1 The first two authors, Zhong-hua Wang and Xue-biao Wei, contributed equally to this work.
Affiliations
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Corresponding authors. Shou-hong Wang and Tie-he Qin, Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China; (E-mail address: [email protected]).
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
Corresponding authors. Shou-hong Wang and Tie-he Qin, Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China; (E-mail address: [email protected]).
Department of Geriatric Intensive Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO2 and procalcitonin (PCT) in the early stages of GN bacteria BSI.
Methods
Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients.
Results
A total of 132 patients with BSI were enrolled. The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746–0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745–0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively.
Conclusions
Pcv-aCO2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.
A bloodstream infection (BSI) is a serious systemic infectious disease that often leads to detrimental outcomes. BSI is associated with high mortality and morbidity.
Therefore, early precision anti-infective treatment is particularly important. However, the identification of BSI pathogens still depends on blood culture, which is time consuming and may delay targeted anti-infective treatment.
In recent years, some biomarkers for the early identification of pathogens have been identified, allowing the administration of targeted antibiotics as early as possible. Procalcitonin (PCT) is a helpful biomarker for early diagnosis of sepsis in critically ill patients.
The role of central venous oxygen saturation, blood lactate, and central venous-to-arterial carbon dioxide partial pressure difference as a goal and prognosis of sepsis treatment.
Pcv-aCO2 is defined as partial pressure difference of central venous to arterial carbon dioxide. When tissue perfusion is poor, microcirculation disorder occurs, resulting in a decrease in carbon dioxide clearance rate and an increase in Pcv-aCO2, so Pcv-aCO2 can effectively evaluate the status of microcirculation and tissue perfusion in patients. It is well known that BSI caused by different pathogens have different effects on hemodynamics.
Whether Pcv-aCO2 can be used as a biomarker for the early identification of BSI pathogens is still unclear. The objective of this study was to compare Pcv-aCO2 and serum PCT levels in GN and GP bacteremia groups and to investigate the early diagnostic value of Pcv-aCO2 and PCT in bacterial BSI caused by GN bacteria.
Methods
Patients and samples
This retrospective study was carried out using clinical and routine laboratory data collected at the department of critical care medicine in Guangdong Provincial People’s Hospital between August 2014 and August 2017. The inclusion criterion were as follows: (1) aged >18 years; (2) with systemic inflammatory response syndrome or hypotension; (3) more than one blood culture positive; and (4) a single microorganism was identified in the blood culture. The exclusion criteria were as follows: (1) the patient did not have Pcv-aCO2 and serum PCT levels tested at the time blood was taken for culture; and (2) the patient had a history of a malignant tumor. The study was approved by the research ethics committee of the Guangdong Provincial People’s Hospital (NO. GDREC2016372H). Patients or their relatives in the study provided informed consent to participate in the study.
Study design
The following information was extracted from the medical file of each enrolled patient: (1) clinical and epidemiological data including age, sex, and severity of BSI as evaluated by the Sequential Organ Failure Assessment (SOFA) and Acute Physiology And Chronic Health Evaluation II (APACHE II) scores; (2) biochemical data including the Pcv-aCO2 and PCT levels from the same time as the blood culture. When the patients were diagnosed with BSI, all the dates were collected by one researcher with the use of an electronic case report form and then confirmed by another researcher. Patients were divided into two groups according to blood culture: the GP bacteria group and the GN bacteria group. Pcv-aCO2 levels, serum PCT levels and other variables were compared between the two groups.
Measurements of Pcv-aCO2 and PCT levels
Arterial and central venous blood gas analysis were routinely measured at the same time as blood was taken for culture within 6 h of suspected bloodstream infection during the hospital course. The Pcv-aCO2 level was obtained by the simultaneous analyses of arterial and central venous blood gas with a Radiometer ABL800 blood gas analyzer (Radiometer, Denmark). Serum PCT was measured with the Kryptor immunoassay (Elecsys BRAHMS PCT, Shanghai, China) in the Department of the Clinical Laboratory Center of Guangdong Provincial People's Hospital.
Statistical analyses
Statistical analyses were performed using SPSS software version 24.0 (SPSS Inc., Chicago, Illinois, USA). The continuous variables are presented as the mean ± SD and were compared using Student's t-test or analysis of variance (ANOVA) when normally distributed. Otherwise, they were compared by the Wilcoxon rank-sum test and are presented as the median and interquartile range (IQR). The discrete variables were expressed as counts (%) and compared using χ2 or Fisher's exact tests. Receiver operating characteristic (ROC) curve analysis was used to evaluate Pcv-aCO2 and PCT as markers of clinical success. A P value < 0.05 was considered statistically significant.
Results
A total of 132 patients including 75 GP bacteria BSI and 57 GN bacteria BSI patients were enrolled in the study (Fig. 1). The baseline characteristics in the GP and GN bacteria groups are shown in Table 1. The proportions of sex, age and past disease history were similar in both groups. The SOFA (12.21 ± 3.87 vs 9.68 ± 3.37 p = 0.001) and APACHE Ⅱ scores (28.61 ± 6.48 vs 25.07 ± 5.61 p = 0.001) were higher in the GN group than in the GP group. Regarding the concurrent foci of infection, there was no significant difference in the proportion of pneumonia and abdominal infection between the two groups. The proportions of urinary tract infection (10.67 vs 24.56 p = 0.034) and skin and soft tissue infection (14.67 vs 3.51 p = 0.033) in the GP group were lower and higher than those in the GN group, respectively.
The most common GP bacterial species were Staphylococcus species, including Staphylococcus aureus, coagulase-positive Staphylococcus haemolyticus and Enterococcus species. The three most common GN bacterial species were Escherichia coli, Klebsiella pneumoniae, and nonfermentative GN bacilli including Acinetobacter baumannii and Pseudomonas aeruginosa (Table 2).
TABLE 2Pathogen distribution of bloodstream infection.
The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels at the onset of BSI were significantly higher in the GN group than in the GP group (Fig. 2). The corresponding ROC curve was constructed to measure the overall diagnostic value. Pcv-aCO2 and PCT have similar diagnostic value for BSI caused by GN bacteria (Fig. 3). The area under the ROC curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746–0.900). Considering a Pcv-aCO2 cutoff value of 6.70 mmHg, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745–0.890), and the optimal cutoff value was 12.6 ng/mL; The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 89.19% and 74.73%, respectively.
FIGURE 2The differences between the GN and GP groups in Pcv-aCO2 and serum PCT levels: A, Pcv-aCO2 levels in the two groups: the Pcv-aCO2 levels were significantly higher in the GN group than in the GP group (p < 0.001); B, PCT levels in the two groups: the PCT levels were significantly higher in the GN group than in the GP group (p < 0.001). Abbreviations: GN, gram-negative; GP, gram-positive; Pcv-aCO2, central venous-to-arterial carbon dioxide difference; PCT, procalcitonin.
The present study demonstrated that the levels of Pcv-aCO2 and PCT were higher in BSI caused by GN bacteria than by GP bacteria. The Pcv-aCO2 and PCT can improve the accuracy of early diagnosis of BSI caused by GN bacteria.
BSI represents a common complication among critical patients and is a leading cause of morbidity and mortality.
BSI may have serious adverse outcomes without timely and effective treatment. Studies have shown that the correct use of antibiotics in patients with severe infection is important for reducing mortality and morbidity.
However, the pathogens of BSI is mainly determined by time-consuming blood culture, which making it difficult to identify pathogens in the early stage. Moreover, due to the small number of pathogenic microorganisms in circulating blood, the extensive requirements for culture conditions for specific pathogens, and the use of antibiotics before blood culture, the positivity rate of blood culture is not high, which may eventually lead to delayed use of targeted antibiotics.
The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: a multicenter prospective registry-based observational study.
The infections caused by GN bacteria result in higher levels of PCT than those resulting from infections caused by GP bacteria and fungi, and the PCT level can provide guidance for the choice of antibiotics;
Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to gram-negative bacteria.
In fact, PCT also plays an important role in the initial identification of pathogens in patients with BSI. Our study showed that serum PCT levels were significantly higher in the GN group than in the GP group, which is similar to previous research.
The reason for the apparent increase in PCT level caused by GN bacteria may be related to activation of signaling pathways by endotoxins. Therefore, PCT is a useful indicator for the identification of pathogens in patients with BSI and provides important clues for the early selection of appropriate antibiotic regimens.
In this study, we first found that the Pcv-aCO2 level in patients with BSI caused by GN bacteria was significantly higher than that caused by GP bacteria. This may be due to different pathogen infections cause different circulation disorders,
Lipopolysaccharide (LPS) from the cellular wall of Gram-negative bacteria, also known as endotoxin, is a key molecule in the pathogenesis of sepsis and septic shock. Preface.
Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock.
Weil et al. found that Pcv-aCO2 was significantly elevated in patients who underwent cardiac arrest, which is clearly associated with poor tissue perfusion.
Pcv-aCO2 is not consistent with the changes in cardiac output in patients with septic shock, suggesting that changes in the Pcv-aCO2 level are related not only to cardiac output but also to the tissue oxygen supply and demand balance.
During early fluid resuscitation in septic shock patients, the improvement in Pcv-aCO2 is closely related to the prognosis and can be used as an indicator of adequate fluid resuscitation.
The high ratio of Pcv-aCO2 to arterial-central venous oxygen partial pressure is associated with poor lactate clearance and is an independent predictor of ICU death in septic shock patients.
The prognostic value of central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio in septic shock patients with central venous O2 saturation≥80.
High central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio is associated with poor lactate clearance in septic patients after resuscitation.
Since Pcv-aCO2 can reflect tissue perfusion and oxygen metabolism, it can be used as an indicator of BSI severity and pathogen identification. In this study, the level of Pcv-aCO2, SOFA score and APACHEⅡ score in GN bacteria group was significantly higher than in GP bacteria group. Furthermore, we evaluated the diagnostic value of Pcv-aCO2 and PCT for BSI caused by GN bacteria with a ROC curve. Pcv-aCO2 and PCT have similar predictive value for the diagnosis of bloodstream infection caused by GN bacteria. We found that they can provide clues for the identification of pathogens in the early stage of BSI and improve the diagnostic efficiency of BSI caused by GN bacteria.
Conclusions
Pcv-aCO2 and PCT levels were higher in the GN group than in the GP group. They have similar and high diagnostic value for the early diagnosis of GN bacteria BSI.
The authors declare that they have no competing interests.
Funding
The study was supported by Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (Grant No. 2021001 and 20221003), the Medical Science and Technology Foundation of Guangdong Province (Grant No. A2017602), Science and Technology Projects of Guangzhou (Grant No. 201903010097) and the National Clinical Key Specialty Subject Construction Project (Grant Nos. 2012-649 and 2013-544).
References
McNamara J.F.
Righi E.
Wright H.
et al.
Long-term morbidity and mortality following bloodstream infection: a systematic literature review.
The role of central venous oxygen saturation, blood lactate, and central venous-to-arterial carbon dioxide partial pressure difference as a goal and prognosis of sepsis treatment.
The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: a multicenter prospective registry-based observational study.
Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to gram-negative bacteria.
Lipopolysaccharide (LPS) from the cellular wall of Gram-negative bacteria, also known as endotoxin, is a key molecule in the pathogenesis of sepsis and septic shock. Preface.
Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock.
The prognostic value of central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio in septic shock patients with central venous O2 saturation≥80.
High central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio is associated with poor lactate clearance in septic patients after resuscitation.
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