Containment of drug resistance -- combined detection of IL-6 and PCT, future trend

Jan 24, 2019

Infectious diseases are one of the common diseases in emergency departments and many other clinical departments. The unwarranted misuse of antibiotics has led to the emergence of pathogen resistance, which will lead to serious consequences. In the 21st century, precision medicine and evidence-based medicine have proposed to laboratory science how to use non-specific indicators to assist clinical precision diagnosis and treatment of infection. New and old markers such as white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) have successively appeared on the stage.
At present, the most widely used and studied infection markers are procalcitonin (PCT) and C-reactive protein (CRP). While interleukin-6 (IL-6) has various clinical uses, its significance as an infection marker is gradually being studied, paid attention to and more and more clinically applied in the industry.

To curb drug resistance, "IL-6, PCT" tests have their own strengths

PCT is a highly specific indicator of bacterial infection, and its value in bacterial infection has been recognized by many evidence-based medicines.

IL-6 plays a central role in acute inflammatory response and is directly related to inflammatory disease and the degree of infection. "Expert Consensus on Interpretation of Clinical Significance of Infection-Related Biomarkers" (2017) [1] pointed out that IL-6 can be used to assist the early diagnosis of acute infection in the diagnosis of inflammation; IL-6 can be used to evaluate the severity of infection and judge prognosis; Dynamic observation of IL-6 levels also helps to understand the progression of infectious diseases and response to treatment.

PCT combined with IL-6, how much is it worth?

(1) IL-6 is beneficial to the diagnosis of early inflammation
After the inflammatory reaction occurs, IL-6 is the first to be produced, and then induces the production of CRP and PCT.

effect of antibiotic treatment and the judgment of prognosis
(2) The half-life of IL-6 is 1h, which can respond more quickly to the When the infection is not controlled, IL-6 continues to be highly expressed; and once the infection is controlled, IL-6 has a half-life of only 1h, compared with the 19h half-life of CRP and the 24h half-life of PCT, which declines faster after infection control. A larger range is more conducive to early clinical confirmation of efficacy.
The IL-6 index was more sensitive than CRP in early infection, increased earlier, and decreased more rapidly and with greater magnitude in recovery. IL-6 is more sensitive than CRP to weak inflammatory stimuli in the early stages of infection and may provide better differentiation. PCT is more sensitive to systemic infection and more valuable for monitoring antibiotic therapy.
Studies have shown [2] that for patients with initial fever, IL-6 is the best marker of prognosis of patients, significantly better than PCT and CRP. IL-6, PCT and CRP evaluate the area under the ROC curve of survival of patients with initial fever. were 0.807, 0.637 and 0.545, respectively.

Figure 1: ROC curve analysis for evaluating survival of patients with initial fever by the concentrations of IL-6, PCT and CRP

(3) "IP" joint inspection makes it easier to identify G-/G+ bacteria
Studies have shown [3] that the ability of IL-6 to distinguish G-/G+ bacteria is much stronger than that of PCT! If both PCT and IL-6 are significantly elevated, the possibility of G- bacteria infection is high. If PCT is high, but IL-6 is not obvious, the possibility of G+ bacteria should be considered.

Figure 2: CRP, PCT and IL-6 detection results in control group, Gram-positive and negative bacterial bloodstream infection groups

(4) "IP" joint inspection can increase the rate of antibiotic pathogenic inspection in hospitals

The former National Health and Family Planning Commission "Nosocomial Infection Management Quality Control Index" and "Intensive Medicine Specialty Medical Quality Control Index"

(National Health Office Medical Letter [2015] No. 252), microbial culture, PCT, and IL-6 were used as pathogenic test specimens before antibiotic treatment.

(5) "IP" joint inspection is beneficial to the diagnosis of neonatal sepsis
Neonatal PCT has a physiological increase within 48 hours, and it is difficult to determine whether it is infected; while IL-6 has no physiological increase, and the combined detection and diagnosis of PCT is more accurate. The sensitivity of IL-6 is better than that of PCT and CRP, but its specificity is worse than that of PCT. Some studies have shown that the combined detection of PCT+IL-6+CRP, PCT+IL-6 or PCT+CRP in patients with sepsis can help clinically identify patients with early sepsis [4].

Figure 3: Comparison of the sensitivity and specificity of the three detection indicators in the sepsis group (%)

To curb bacterial resistance, the detection of "IL-6 and PCT" has obvious advantages, and it is of great value to help clinics make timely and accurate early diagnosis, early effective treatment, and reduce mortality, while avoiding the abuse of antibiotics and reducing bacterial resistance. As pointed out in the "Expert Consensus on Interpretation of Clinical Application of Infection-Related Biomarkers", "No biomarker is absolutely sensitive and absolutely specific, and a disease cannot be diagnosed solely by the change of a certain biomarker. The patient's clinical manifestations and other laboratory test results can make a correct judgment." At the same time, in the section "Biomarkers of Bacterial Infections that Begin to Be Clinically Applied in Recent Years", the consensus also focused on the introduction of two inflammatory indicators, "procalcitonin (PCT)" and "interleukin-6 (IL-6)". Description: The combined detection of multiple inflammatory indicators, especially the combined detection of bacterial infection biomarkers PCT and IL-6, is useful for the early diagnosis of bacterial infection, the early identification of sepsis, and the monitoring of the development trend of infection. It is a clear development direction for the future!

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