WO2024005275A1

WO2024005275A1 - Method for evaluating antibiotic susceptibility in human body using strem-1

Info

Publication number: WO2024005275A1
Application number: PCT/KR2022/017165
Authority: WO
Inventors: 이재혁
Original assignee: 서울대학교병원
Priority date: 2022-06-29
Filing date: 2022-11-03
Publication date: 2024-01-04

Abstract

A method for evaluating antibiotic susceptibility in a human body using sTREM-1 is provided. The evaluation method can determine in vivo antibiotic susceptibility by measuring a blood concentration of soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) in blood collected from a human body administered with antibiotics for infectious diseases.

Description

Method for evaluating antibiotic susceptibility in the human body using STREM-1

The present invention relates to a method for evaluating antibiotic susceptibility in the human body, and more specifically, to a method for evaluating antibiotic susceptibility in the human body using sTREM-1.

Sepsis is a fatal infectious disease in which a local infection caused by bacteria at a wound or inflamed area progresses into a systemic inflammatory response. Sepsis is a disease with a very high mortality and morbidity rate if it is not recognized quickly and treated appropriately, and is the most important cause of death in intensive care units.

In the case of sepsis caused by bacterial infection, it is recommended to quickly administer antibiotics within 1 hour. Since it is known that the mortality rate increases by approximately 7.5% for each hour of delay in antibiotic administration, rapid administration of antibiotics is the most effective way to reduce the mortality rate of sepsis patients.

Meanwhile, according to many papers, the initial administration of inappropriate antibiotics can actually worsen the patient's condition, so selection of appropriate antibiotics is also an important part of patient treatment. Although it is desirable to administer appropriate antibiotics targeting the causative pathogen, antibiotics are mostly selected empirically and administered to patients based on the patient's demographic characteristics, underlying disease, and infection site. The appropriateness of the empirically selected antibiotic can be confirmed from changes in the patient's condition over the next few days, or can be confirmed by performing in vitro antibiotic sensitivity testing when the pathogen is identified through culture testing.

Here, in the case of existing culture tests, the identification ability or yield rate for the causative bacteria of infectious diseases is very low, about 20-40%, and it takes 3 to 5 days, up to a week or more, to obtain test results, so it is used in emergency diseases such as sepsis. Adjusting or changing antibiotics through culture tests is clinically very difficult.

Accordingly, after extensive research and effort, the inventor of the present application developed a biomarker that can evaluate antibiotic susceptibility through reactions in the human body and completed the present invention.

The problem to be solved by the present invention is to provide a method for evaluating antibiotic susceptibility in the human body using sTREM-1.

The problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below. will be.

The method for assessing antibiotic susceptibility according to an embodiment of the present invention to achieve the above problem is to measure antibiotic susceptibility in the human body (in Includes methods for evaluating in vivo antibiotic susceptibility.

The infectious disease may be sepsis.

2 - 4 hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 30 - 320 ng/mL and 390 - 1580 ng/mL, it is classified as a susceptible antibiotic and a resistant antibiotic, respectively. can be judged.

2 hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 80 - 260 ng/mL and 390 - 970 ng/mL, the antibiotic is judged to be susceptible and resistant, respectively. You can.

Four hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 30 - 320 ng/mL and 510 - 1580 ng/mL, the antibiotic is judged to be susceptible and resistant, respectively. You can.

Details of other embodiments are included in the detailed description and drawings.

As described above, the method for evaluating antibiotic susceptibility in the human body according to the present invention has the following excellent effects.

sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells-1) is previously known as an inflammatory marker and its expression level is known to increase in the serum of patients with inflammatory diseases. In contrast, in the present invention, sTREM-1 is not used as an inflammatory marker, but rather as an evaluation tool for in vivo antibiotic susceptibility.

Since sTREM-1 used in the antibiotic susceptibility evaluation of the present invention has a short half-life of about 2 hours and responds characteristically to bacterial infection, it was confirmed that the blood concentration of sTREM-1 varies significantly within a short period of time depending on the appropriateness of the antibiotic. It has been done. For example, by measuring the blood concentration of sTREM-1 within 2 to 5 hours after administering any antibiotic to a patient with an infectious disease, it is possible to evaluate whether the antibiotic is susceptible or resistant to the antibiotic. Therefore, the method for evaluating antibiotic susceptibility in the human body according to the present invention can evaluate antibiotic suitability in a shorter time compared to antibiotic susceptibility testing through existing culture.

Conventional antibiotic susceptibility testing is usually performed in vitro by culturing bacteria in a medical laboratory and exposing them to antibiotics, but the present invention provides a method for evaluating antibiotic susceptibility in vivo. For example, according to the present invention, after administering any antibiotic to a patient with an infectious disease, the blood concentration of sTREM-1 is measured in blood collected from the patient and the appropriateness of the antibiotic is judged based on the concentration, so the appropriateness of the antibiotic can be checked. can be judged accurately.

Initially, antibiotics are empirically administered to patients with infectious diseases, but according to the present invention, the appropriateness of the antibiotic can be quickly evaluated and the antibiotics preemptively adjusted according to the results, thereby improving the patient's prognosis. In addition, many clinicians have always felt burdened about the appropriateness of empirically prescribed antibiotics, but the method for evaluating antibiotic susceptibility in the human body according to the present invention can relieve this psychological burden. In addition, according to the present invention, the appropriateness of antibiotics can be confirmed within a few hours, preventing the abuse of a wide range of antibiotics and creating a safer society by reducing the occurrence of resistant bacteria.

Figure 1 is a diagram showing an experimental method of a porcine bacteremia model according to an embodiment of the present invention.

Figures 2A to 2F are graphs measuring hemodynamic changes over time.

Figures 3A to 3E are graphs measuring changes in fluid administration and vasopressor usage over time.

Figures 4a to 4f are graphs measuring changes in blood cell count over time.

Figures 5A to 5F are graphs measuring relevant values to evaluate organ failure by the porcine bacteremia model of the present invention.

Figures 6a to 6f are graphs comparing trends in SOFA scores in the porcine bacteremia model of the present invention.

Figure 7 is a diagram showing blood culture test results over time.

Figures 8A to 8K are graphs measuring blood concentrations of various biomarkers over time.

The present invention will be described in more detail based on examples and experimental examples. However, these examples and experimental examples are only intended to aid understanding of the present invention, and the scope of the present invention is not limited by these examples.

The method for assessing antibiotic susceptibility according to an embodiment of the present invention is to measure the blood concentration of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells-1) in blood collected from a human body administered antibiotics for infectious diseases. You can determine your antibiotic susceptibility (in vivo antibiotic susceptibility). Here, the infectious disease may be bacteremia or sepsis.

Specifically, 2 to 4 hours after antibiotic administration, if the blood concentration of sTREM-1 in blood collected from the human body is measured to be 30 to 320 ng/mL, it can be judged to be a susceptible antibiotic, and 390 to 1580 ng/mL. If measured in mL, it can be judged to be a resistant antibiotic.

More specifically, 2 hours after antibiotic administration, if the blood concentration of sTREM-1 in blood collected from the human body is measured to be 80 - 260 ng/mL, it can be judged to be a susceptible antibiotic, and 390 - 970 ng/mL. If measured as , it can be judged as a resistant antibiotic.

More specifically, 4 hours after antibiotic administration, if the blood concentration of sTREM-1 in blood collected from the human body is measured to be 30 - 320 ng/mL, it can be judged to be a susceptible antibiotic, and 510 - 1580 ng/mL. If measured as , it can be judged as a resistant antibiotic.

실시예 1. 돼지 균혈증 모델Example 1. Porcine bacteremia model

In this example, to confirm hemodynamic changes and biomarker changes according to antibiotic sensitivity in gram-negative sepsis, a preclinical <porcine bacteremia model> induced by intravenous administration of ESBL-producing E. coli was used. used. The pig bacteremia model consists of a <susceptible antibiotic treatment group> administered a susceptible antibiotic (ertapenem) against ESBL-producing E. coli, and a <resistant antibiotic treatment group> administered a resistant antibiotic (ceftriaxone) against ESBL-producing E. coli. > was assigned.

<1-1> Experiment settings

This experiment was approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University Bundang Hospital (protocol number: BA-2104-317-029-03), and all animals were used by the National Institutes of Health. They were managed in accordance with Health's 'Guide for the Care and Use of Laboratory Animals'.

<1-2> Animal preparation

Eleven domestic male pigs (44 ± 3.5 kg) were used in this study (Cronex, Seoul, Korea). Anesthesia was induced in pigs by intramuscular administration of a mixture of zolazepam/tiletamine (Zoletil, 5 mg/kg; Virbac, Carros, France) and xylazine (Rompun, 5 mg/kg; Elanco, Greenfield, IN). Pigs were monitored with a 3-lead electrocardiography monitor, pulse oximeter, and rectal temperature probe (IntelliVue, Patient Monitor MP20, Philips, Amsterdam, Netherlands).

A 7-Fr endotracheal tube applied to a mechanical ventilator (Drager Fabius GS, Lubeck, Germany) with an appropriate concentration (2-3%) of inhalational anesthesia (Sevoflurane; Baxter Inc., Deerfield, IL, USA). Intubation was performed. Artificial respiration was performed with a tidal volume of 6 mL/kg, fraction of inspired oxygen of 0.21, positive end-expiratory pressure of 5 cmH ₂ O, and respiratory rate of 12-15/min. It was set to control mode. To maintain the arterial blood oxygen partial pressure PaO ₂ above 65 mmHg and the arterial blood carbon dioxide partial pressure PaCO ₂ at 40-45 mm Hg, mechanical ventilation was additionally adjusted.

For invasive blood pressure monitoring and repetitive blood sampling, a 6-Fr arterial catheter (Merit Medical, South Jordan, UT, USA) was inserted into the femoral artery using ultrasound. A Swan-Ganz catheter (Model 131HF, 7 Fr; Edwards Lifesciences, Irvine, CA, USA) was inserted into the right jugular vein to monitor cardiac output and pulmonary capillary wedge pressure (PCWP). ) was inserted into. Additionally, a central venous catheter (ARROW CVC; Teleflex, Morrisville, NC, USA) was inserted into the left jugular vein for intravenous administration of fluids and vasopressors. Suprapubic cystostomy was performed, and a Foley catheter was inserted to monitor urine output. After the above aseptic procedure, blood samples containing cultures were obtained from the arterial catheter.

<1-3> Induction of porcine bacteremia model

Figure 1 is a diagram showing an experimental method of a porcine bacteremia model according to an embodiment of the present invention. As shown in Figure 1, to induce the porcine bacteremia model, ESBL (extended-spectrum β-lactamase)-producing Escherichia coli (5.0 × 10 ⁹ CFU, strain: BAA-196, ATCC, Manassas, VA, USA) was used. It was diluted in 1000 mL of normal saline and injected intravenously into the subject for 1 hour (the starting point of bacterial injection corresponds to “Pre” in Figure 1). After complete injection of bacteria (corresponding to “0h” in Figure 1), six pigs were assigned the antibiotic ceftriaxone (2 g, Cerixone, Chong Kun Dang, Seoul, Korea), and five pigs were assigned the antibiotic Ertapenem (2 g, Invanz, MSD, Whitehouse Station, NJ, USA) was assigned. One hour after bacterial injection and collection of blood samples were completed, antibiotics were administered to subjects as previously assigned (corresponding to “1h” in Figure 1).

Pigs were monitored for up to 7 hours after completion of bacterial infusion, with the primary goal being to maintain mean arterial pressure (MAP) above 65 mmHg. Balanced crystalloid solution (Plasma Solution A, HK inno. N, Seoul, Korea) was administered when mean arterial pressure (MAP) was less than 65 mmHg. Consisting of norepinephrine, vasopressin, and epinephrine when cumulative fluid exceeds 30 mL/kg or the target mean arterial pressure (MAP) is not reached with bolus fluid. Vasopressors were administered sequentially.

<1-4> Measurement and calculation

Hemodynamic parameters such as arterial blood pressure, heart rate (HR), lead II electrocardiographic variables, pulse oximetry variables, pulmonary arterial pressure, and central venous pressure. Variables were continuously acquired and recorded hourly. Cardiac output was measured every hour using the thermodilution technique and the median value was calculated. Using blood samples obtained via femoral artery catheter, P/F ratio (ratio of partial pressure of oxygen to fraction of inspired oxygen), electrolyte and lactate variables (Nova CCX; Nova, Waltham, MA, USA), and complete blood count. Arterial blood gas analysis including (Hemavet 950FS; Drew Scientific Inc, Miami Lakes, FL, USA) and chemistry panel tests (albumin, creatinine, and bilirubin; VetScan; Abaxis, Union City, CA, USA) were performed at baseline. , performed at 1 hour, 3 hours, 5 hours, and 7 hours. Based on hemodynamic and laboratory variables, the sequential organ failure assessment score (SOFA score) was calculated to evaluate organ failure and prognosis.

Blood samples (20 mL) for culture were collected at baseline, 0 hours, 1 hour, 3 hours, 5 hours, and 7 hours and cultured in paired aerobic and anaerobic blood culture bottles (BD BACTEC; Becton Dickinson, Franklin Lakes, NJ; USA) was injected. A pair of blood culture bottles were then transferred without delay to the microbiology laboratory's blood culture system (BD BACTEC FX; Becton Dickinson, Franklin Lakes, NJ, USA). Final blood culture reports were obtained from the Department of Laboratory Medicine microbiology laboratory.

For cytokine analysis, additional blood samples (10 ml) were collected in EDTA tubes (BD Vacutainer Systems; Becton Dickinson, Franklin Lakes, NJ. USA) at baseline, 1 hour, 3 hours, 5 hours, and 7 hours. did. The collected blood samples were centrifuged at 3000 rpm for 15 minutes, and the upper layer of plasma was separated and stored in a deep freezer at -70°C until analysis. Using an ELISA (enzyme-linked immunosorbent assay) kit, cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10), CRP (C-reactive protein), and procalcitonin , presepsin, heparan sulfate, syndecan, and sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells-1) levels were measured.

<1-5> Statistical analysis

Variables are described as median and interquartile range. Two-way RM ANOVA was performed to compare variable trends between the two treatment groups. P values less than 0.05 were considered significant. Statistical analysis and graph generation were performed using Prism 9.2 (GraphPad Software Inc., San Diego, CA, USA).

실시예 2. 실험 결과Example 2. Experimental results

After administering ESBL-producing E. coli to the pigs, the pig's condition was monitored for up to 7 hours. Five pigs administered antibiotics (ertapenem) were classified as <susceptible antibiotic treatment group>, and six pigs administered antibiotics (ceftriaxone) were classified as <resistant antibiotic treatment group>.

<2-1> Hemodynamic changes

Figures 2A to 2F are graphs measuring hemodynamic changes over time. Specifically, Figure 2a is a graph measuring mean arterial pressure (MAP) over time. Figure 2b is a graph measuring heart rate (HR) over time. Figure 2c is a graph measuring cardiac output over time. Figure 2d is a graph measuring stroke volume over time. Figure 2e is a graph measuring systemic vascular resistance (SVR) over time. Figure 2f is a graph measuring PCWP (pulmonary capillary wedge pressure) over time.

There was no significant difference in hemodynamic variables between the susceptible and resistant antibiotic treated groups during the first 7 hours after antibiotic administration.

<2-2> Changes in fluid administration and vasopressor usage

Figures 3A to 3E are graphs measuring changes in fluid administration and vasopressor usage over time. Specifically, Figure 3a is a graph showing the amount of fluid per hour required to maintain average arterial pressure above 65 mmHg over time. Figure 3b is a graph showing the cumulative amount of fluid required to maintain average arterial pressure above 65 mmHg over time. Figure 3c is a graph showing the dose of norepinephrine vasopressor required to maintain average arterial pressure above 65 mmHg over time. Figure 3d is a graph showing the dosage of vasopressin vasopressor required to maintain average arterial pressure above 65 mmHg over time. Figure 3e is a graph showing the dosage of epinephrine vasopressor required to maintain average arterial pressure above 65 mmHg over time.

For the amount of fluid (Figures 3a and 3b) and the dose of vasopressors (Figures 3c, 3d and 3e) required to maintain mean arterial pressure above 65 mmHg, there were no significant differences between the two treatment groups over time. There wasn't.

<2-3> Changes in blood cell count

Figures 4a to 4f are graphs measuring changes in blood cell count over time. Specifically, Figure 4a is a graph measuring hemoglobin (Hb) levels over time. Figure 4b is a graph measuring total white blood cell (WBC) count over time. Figure 4c is a graph measuring the number of neutrophils over time. Figure 4d is a graph measuring the number of lymphocytes over time. Figure 4e is a graph measuring the number of monocytes over time. Figure 4f is a graph measuring the number of platelets over time.

For hemoglobin levels (Figure 4a), there were no significant differences between the two treatment groups over time. There were no significant differences between the two treatment groups over time for neutrophil count (Figure 4c), lymphocyte count (Figure 4d), monocyte count (Figure 4e), and total white blood cell count (Figure 4b). Platelet counts in both treatment groups decreased as a result of sepsis progression with no significant difference over time (Figure 4F).

<2-4> Changes in blood chemistry tests

Figures 5A to 5F are graphs measuring relevant values to evaluate organ failure by the porcine bacteremia model of the present invention. Specifically, Figure 5a is a graph measuring lactate over time. Figure 5b is a graph measuring creatinine over time. Figure 5c is a graph measuring bilirubin over time. Figure 5d is a graph measuring urine output over time. Figure 5e is a graph measuring the P/F ratio over time. Figure 5f is a graph measuring albumin over time.

As sepsis progresses due to bacterial infusion, lactate (Figure 5a), creatinine (Figure 5b), and bilirubin (Figure 5c) increase, while urine output (Figure 5d), P/F ratio (Figure 5e), and albumin (Figure 5f) ) decreased. However, there were no significant differences between the two treatment groups in lactic acid, creatinine, bilirubin, urine volume, P/F ratio, and albumin.

<2-5> Comparison of SOFA scores

Based on hemodynamic and laboratory data, central nervous system (CNS)-free SOFA scores were assessed to reflect objective response. Figures 6a to 6f are graphs comparing trends in SOFA scores in the porcine bacteremia model of the present invention. Specifically, Figure 6a is a graph showing the total SOFA score over time. Figure 6b is a graph showing the SOFA score for the respiratory system over time. Figure 6c is a graph showing SOFA scores for coagulation over time. Figure 6d is a graph showing the SOFA score for the liver over time. Figure 6e is a graph showing the SOFA score for cardiovascular (cardiovascular) over time. Figure 6f is a graph showing SOFA scores for renal over time.

As shown in Figure 6A, total SOFA scores increased after bacterial administration. After 2 hours, it was confirmed that the total SOFA score of the resistant antibiotic treatment group (ceftriaxone) was higher than that of the susceptible antibiotic treatment group (ertapenem) due to the respiratory SOFA score, but there was no statistical significance. Therefore, there was no significant difference between the two treatment groups in the trends of the total SOFA score and the SOFA score of each area.

<2-6> Blood culture test

Blood samples were collected at baseline (Pre: E. coli infusion started), 0 hours (E. coli infusion completed), 1 hour, 3 hours, 5 hours, and 7 hours, and blood culture tests were performed. Figure 7 is a diagram showing blood culture test results over time.

As shown in Figure 7, no bacteria were identified in both treatment groups in blood culture tests prior to E. coli injection. E. coli was identified in all samples at the time of completion of E. coli injection (0h) and up to 1 hour after completion of injection (1h). One hour after antibiotic administration (i.e., 2 hours after E. coli injection), blood culture tests showed that all groups treated with susceptible antibiotics (ertapenem) were negative, and all groups treated with resistant antibiotics (ceftriaxone) were confirmed positive. .

<2-7> Changes in various biomarkers

Additional blood samples were taken at baseline (Pre), 1 hour, 3 hours, 5 hours, and 7 hours to measure levels of various biomarkers. Figures 8A to 8K are graphs measuring blood concentrations of various biomarkers over time. Specifically, Figure 8a is a graph measuring the blood concentration of TNF-α over time. Figure 8b is a graph measuring the blood concentration of IL-1β over time. Figure 8c is a graph measuring the blood concentration of IL-6 over time. Figure 8d is a graph measuring the blood concentration of IL-8 over time. Figure 8e is a graph measuring the blood concentration of IL-10 over time. Figure 8f is a graph measuring the blood concentration of CRP (C-reactive protein) over time. Figure 8g is a graph measuring the blood concentration of procalcitonin over time. Figure 8h is a graph measuring the blood concentration of presepsin over time. Figure 8i is a graph measuring the blood concentration of heparan sulfate over time. Figure 8j is a graph measuring the blood concentration of syndecan over time. Figure 8k is a graph measuring the blood concentration of sTREM-1 over time.

For inflammatory cytokines, including TNF-α (Figure 8A), IL-1β (Figure 8B), IL-6 (Figure 8C), IL-8 (Figure 8D), and IL-10 (Figure 8E), both treatment groups. No significant differences were identified between the two.

For clinical biomarkers such as CRP (Figure 8f), procalcitonin (Figure 8g) and presepsin (Figure 8h), no significant differences were identified between the two treatment groups.

In the case of heparan sulfate (Figure 8i) and syndecan (Figure 8j), which constitute the endothelial glycocalyx layer, no significant differences were identified between the two treatment groups.

In the case of sTREM-1 shown in Figure 8k, the blood concentration increased from 1 hour after completion of bacterial injection, and a significant difference was confirmed between the two treatment groups over time (P < 0.0001 between times, P = 0.0036 between groups, P = 0.0001 between times × groups). In particular, a significant difference was observed between the two treatment groups 2 hours after antibiotic administration (i.e., 3 hours after bacterial injection) (P = 0.0239, Sidak's multiple comparisons).

Specifically, as a result of measuring the blood concentration of sTREM-1 2 hours after antibiotic administration (i.e., 3 hours after E. coli administration), it was measured to be 80 - 260 ng/mL in the susceptible antibiotic-treated group, and in the resistant antibiotic-treated group. For the treatment group, it was measured at 390-970 ng/mL.

Additionally, as a result of measuring the blood concentration of sTREM-1 4 hours after antibiotic administration (i.e., 5 hours after E. coli administration), it was measured to be 30 - 320 ng/mL in the susceptible antibiotic-treated group, and in the resistant antibiotic-treated group. In the case of , it was measured at 510-1580 ng/mL.

According to the E. coli-induced bacteremia pig model of the present invention, the blood concentration of sTREM-1 was confirmed to have a significant difference within a short period of time after antibiotic treatment between the susceptible antibiotic treatment group and the resistant antibiotic treatment group.

sTREM-1 is an amplifier of the innate immune response whose membrane-bound form (TREM-1) is expressed in neutrophils, mature monocytes, and macrophages. Lipopolysaccharide stimulation induces upregulation of TREM-1 in monocytes and neutrophils, which then releases the soluble form of TREM-1 in the blood through cleavage of the membrane-bound receptor. Activation of TREM-1 creates neutrophil extracellular trap (NET) structures, and inhibition of TREM-1 reduces NET release, resulting in endothelial cell activation and vascular dysfunction. ) leads to a decrease in In the present invention, based on the short half-life of sTREM-1 (about 2 hours), antibiotic treatment of susceptibility to bacteremia could prevent further release of sTREM-1, thereby lowering the level of sTREM-1 after antibiotic treatment.

Although embodiments of the present invention have been described above with reference to the attached drawings, those skilled in the art will understand that the present invention can be implemented in other specific forms without changing the technical idea or essential features. You will be able to understand it. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

Claims

A method of evaluating in vivo antibiotic susceptibility by measuring the blood concentration of sTREM-1 in blood collected from a human body administered antibiotics for infectious diseases.
According to paragraph 1,

A method for evaluating antibiotic susceptibility in the human body, wherein the infectious disease is sepsis.
According to paragraph 1,

2 - 4 hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 30 - 320 ng/mL and 390 - 1580 ng/mL, it is classified as a susceptible antibiotic and a resistant antibiotic, respectively. A method for evaluating antibiotic susceptibility in the human body, characterized in that it is determined.
According to paragraph 1,

2 hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 80 - 260 ng/mL and 390 - 970 ng/mL, the antibiotic is judged to be susceptible and resistant, respectively. A method for evaluating antibiotic susceptibility in the human body, characterized in that.
According to paragraph 1,

Four hours after administration of the antibiotic, if the blood concentration of sTREM-1 in the blood collected from the human body is measured to be 30 - 320 ng/mL and 510 - 1580 ng/mL, the antibiotic is judged to be susceptible and resistant, respectively. A method for evaluating antibiotic susceptibility in the human body, characterized in that.