Optimizing Infection Biomarkers to Optimize Diagnosis and Treatment of Infectious Diseases

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Infectious diseases are a serious public health problem and an important factor causing human death. As long as most infectious diseases are timely and accurately diagnosed and given scientific and reasonable treatment, it is possible to completely cure them in a relatively short period of time. The detection of infection-related biomarkers is of great help in the auxiliary diagnosis of infectious diseases, judging prognosis, determining the course of anti-infection treatment and continuous monitoring, and can even help to distinguish the pathogens that cause infection to a certain extent.

Recently, at the media interview of "expert consensus on the interpretation of clinical significance of infection related biomarkers" (hereinafter referred to as "consensus") held in Nanjing, Professor Xie Lixin, director of Respiratory Department of PLA General Hospital, Professor Shi Yi, director of Respiratory Disease Research Institute of Nanjing General Hospital of PLA, and Professor Zhou Yongli, director of laboratory center of Zhejiang Provincial People's Hospital, interpreted the contents of the consensus from different angles.

PCT and IL-6-assisted diagnosis and treatment of infectious diseases

"For infectious diseases, we can not only rely on symptoms, signs and imaging findings to make judgments, but also optimize infection-related biomarkers, which are of great significance for identifying infection and non-infection, dynamically evaluating the severity and prognosis of the disease, and guiding the rational use of antibiotics." Professor Xie Lixin pointed out, "The characteristics that a good infection marker should have include: high sensitivity, which can change significantly in the early stage of infection and is not affected by non-infectious factors; high specificity, which can distinguish pathogen types and identify whether it is bacterial Infection; Able to assist in assessing the severity and prognosis of infection, monitoring treatment response, and guiding the use of antibacterial drugs."

The traditional biological markers of bacterial infection include peripheral blood white blood cell (WBC), erythrocyte sedimentation rate (ESR), neutrophil alkaline phosphatase (NAP) score, endotoxin level and so on, which have different limitations, such as many influencing factors, low specificity, relatively complicated operation and limited clinical value. C- reactive protein (CRP) is a widely used biomarker of bacterial infection. As a sensitive indicator of inflammation, CPR detection is rapid and convenient, and its increase is positively correlated with the severity of infection or inflammation. CRP detection can also help to distinguish between bacterial infection and viral infection.

It is worth noting that in recent years, procalcitonin (PCT) and interleukin 6(IL-6) have gradually been applied in clinical practice, and have broad application prospects. Professor Shi Yi pointed out: "PCT, as an important biomarker of bacterial infection commonly used in clinical practice, has great reference significance; the relative advantage of IL-6 detection lies in the early detection of acute infection."

PCT is a functional protein, an intermediate product in the synthesis of calcitonin, and a propeptide substance of calcitonin without hormonal activity. The Consensus pointed out that PCT has high clinical value in the early diagnosis of severe bacterial infections, judging the severity of the disease, prognosis, evaluating the efficacy of anti-infection, guiding the application of antibacterial drugs, and has high diagnostic value for systemic and local infections. It is an important tool for judging sepsis.

A meta-analysis of 30 clinical trials confirmed that PCT can effectively assist in the early diagnosis of sepsis. The experimental data showed that when the cut-off value of PCT was 1.1 μg/L, the sensitivity of early identification of sepsis was 77% and the specificity was 79%. In addition, PCT is often normal or slightly elevated in focal bacterial infections and can assist in the diagnosis of focal bacterial infections. At the same time, the level of PCT can effectively reflect the severity of bacterial infection, and its concentration is positively correlated with the severity of systemic bacterial infection.

In judging the prognosis of sepsis patients and assisting in guiding antibiotic treatment, studies have confirmed that after effective anti-infection treatment, the PCT level in the circulation of sepsis patients can be reduced by 50% after 24 hours, and the degree of reduction is positively correlated with the increase of patient survival rate, while the PCT level continues to increase or remain high, indicating poor prognosis. PCT detection combined with clinical information can further clarify the necessity of antibiotic treatment and optimize the antibiotic use process, dynamic monitoring of PCT level can assist antibiotic treatment, and its test results can be used as an indication for starting antibiotic treatment and a standard for judging the efficacy of antibiotics, thus significantly reducing the exposure time of antibiotics with good safety.

IL-6 is an important inflammatory mediator involved in sepsis and other infections, which is released in the blood soon after infection, and can be used as an indicator of the degree of infection. The "Consensus" pointed out that in the inflammatory response, the increase in IL-6 is earlier than other cytokines, and also earlier than CRP and PCT. It peaks at 2 hours and lasts for a long time, so it can be used to assist in the early diagnosis of acute infection.

The Consensus emphasizes that no biomarker is absolutely sensitive and absolutely specific. A disease cannot be diagnosed solely by the change of a certain biomarker. Only by combining and referring to the patient's clinical manifestations and other laboratory test results can it be made. Correct judgment. Professor Shi Yi pointed out: "Multi-index joint detection will be the future development trend, which can improve the early diagnosis rate and prognostic value of infectious diseases." PCT combined with IL-6 detection for the auxiliary diagnosis of bacterial infection can avoid the error of single index to judge the type of infection, help clinicians to quickly determine the treatment plan and improve the success rate of treatment.

Biomarkers rely on detection methods to achieve clinical value

"Good biomarkers require good testing methods to achieve their clinical value, and the clinical use of PCT and IL-6 needs to be strongly supported by precise testing methods. This Consensus reflects clinical needs and points the way for the development of infection biomarker testing and quality control technology in the laboratory." Professor Zhou Yonglie said, "When selecting a testing system, controlling the total error and the traceability of calibration products are the keys to the accuracy of the testing results. At the same time, we should pay attention to the performance verification of the testing system and do a good job in quality control."

The Consensus points out that Roche diagnostic Elecsys BRAHMS PCT is one of the commonly used PCT tests at home and abroad. It uses electrochemiluminescence technology to make the test results highly consistent and traceable. It only needs 18 microliters of sample and can achieve a detection range of 0.02 ng/ml to 100 ng/ml within 18 minutes. At the same time, it has excellent intra-and inter-batch precision, which is suitable for all Roche diagnostic immunoassay platforms and can achieve highly consistent test results. Combined with Elecsys IL-6 detection, it is helpful for clinicians to detect infection early, realize differential diagnosis, curative effect monitoring and prognosis evaluation, and then improve the treatment decision-making and the success rate of infectious disease treatment.