Combined drug sensitive test data processing method, device and equipment and storage medium

Abstract

The invention relates to the technical field of data processing, and discloses a combined drug sensitive test data processing method, device and equipment and a storage medium, and the method comprises the following steps: obtaining a combined drug sensitive plate optical density value matrix output by a microplate reader and a set growth inhibition threshold; based on the optical density value matrix of the combined drug sensitive plate and the growth inhibition threshold, respectively judging the growth state corresponding to each hole in the combined drug sensitive plate; calculating a corresponding partial bacteriostatic concentration index according to the hole with the growth state in growth inhibition; and determining the combined effect of the two drugs based on the calculated minimum partial bacteriostatic concentration index. According to the invention, the accuracy and reliability of the combined drug sensitive test result can be improved.

Description

Technical Field

[0001] The present invention relates to the technical field of data processing, and in particular to a method, device, equipment and storage medium for processing combined drug sensitivity test data. Background Art

[0002] The combined drug sensitivity test is a key tool for evaluating the effectiveness of the combined action of multiple antibiotics against specific pathogens. The gold standard for the combined drug sensitivity test is the checkerboard dilution method, but it is cumbersome to operate, relies on manual judgment of test results, has many defects, and is difficult to be routinely carried out in ordinary laboratories.

[0003] At present, the deficiencies of manually interpreting the results of the combined drug sensitivity test by the checkerboard dilution method are mainly reflected in the following two aspects: First, the objectivity relying on experience and technical level is poor. Different testers may have different interpretation standards and preferences, resulting in problems with result standardization; Second, subjective judgment is prone to introduce errors. It is difficult for the naked eye to accurately identify subtle differences, increasing the possibility of result errors. For example, for some antibacterial drugs (bacteriostatic drugs), when 80% of bacterial growth is inhibited, it is judged as no growth (clear), but at this time, the content in the corresponding well on the combined drug sensitivity plate may be between absolute clarity and absolute turbidity, so different personnel may have deviations in interpretation.

[0004] This situation has greatly hindered the application and development of the combined drug sensitivity test and restricted the improvement of scientific research and clinical efficacy. There is an urgent need for an objective, accurate and repeatable method for interpreting the results of the combined drug sensitivity test to improve the reliability and credibility of test results. Summary of the Invention

[0005] In view of this, the present invention provides a method, device, equipment and storage medium for processing combined drug sensitivity test data to solve the problem of the accuracy of interpreting the results of the combined drug sensitivity test.

[0006] In a first aspect, the present invention provides a method for processing combined drug sensitivity test data, the method comprising:

[0007] Obtaining a matrix of optical density values of a combined drug sensitivity plate output by an enzyme-linked immunosorbent assay (ELISA) reader and a set growth inhibition threshold;

[0008] Based on the matrix of optical density values of the combined drug sensitivity plate and the growth inhibition threshold, respectively determining the growth state corresponding to each well on the combined drug sensitivity plate;

[0009] For the wells with a growth state of growth inhibition, calculating the corresponding fractional inhibitory concentration index;

[0010] Based on the calculated minimum fractional inhibitory concentration index, determining the combined effect of the two drugs.

[0011] In an alternative embodiment, determining the growth state corresponding to each well on the combined drug sensitivity plate based on the combined drug sensitivity plate OD value matrix and the growth inhibition threshold includes:

[0012] For the first well on the combined drug sensitivity plate, obtain the OD value corresponding to the first well based on the combined drug sensitivity plate OD value matrix;

[0013] If the OD value corresponding to the first well is less than the growth inhibition threshold, determine that the growth state of the first well is growth inhibition.

[0014] In an alternative embodiment, after obtaining the OD value corresponding to the first well on the combined drug sensitivity plate based on the combined drug sensitivity plate OD value matrix, it further includes:

[0015] If the OD value corresponding to the first well is greater than or equal to the growth inhibition threshold, determine whether the OD value corresponding to the first well is less than the target OD value; wherein, the target OD value is the OD value corresponding to the well with both drug concentrations being zero in the combined drug sensitivity plate OD value matrix;

[0016] If the OD value corresponding to the first well is less than the target OD value, determine that the growth state corresponding to the first well is growth restriction;

[0017] If the OD value corresponding to the first well is greater than or equal to the target OD value, determine that the growth state corresponding to the first well is growth unrestricted.

[0018] In an alternative embodiment, after determining the growth state corresponding to each well on the combined drug sensitivity plate based on the combined drug sensitivity plate OD value matrix and the growth inhibition threshold, it further includes:

[0019] Draw a combined drug sensitivity spectrum diagram based on the growth state corresponding to each well on the combined drug sensitivity plate.

[0020] In an alternative embodiment, calculating the corresponding fractional inhibitory concentration index for the well with the growth state of growth inhibition includes:

[0021] For the second well on the combined drug sensitivity plate with the growth state of growth inhibition, obtain the concentrations of the two drugs in the second well;

[0022] Obtain the minimum inhibitory concentrations of the two drugs;

[0023] Calculate the corresponding fractional inhibitory concentration index for the second well based on the minimum inhibitory concentrations of the two drugs and the concentrations of the two drugs in the second well.

[0024] In an alternative embodiment, the obtaining of the minimum inhibitory concentrations of the two drugs includes:

[0025] Obtaining the first minimum inhibitory concentrations of the two drugs input by the user;

[0026] Based on the optical density value matrix of the combined drug susceptibility plate, respectively determining the second minimum inhibitory concentrations of the two drugs;

[0027] If the second minimum inhibitory concentration is inconsistent with the first minimum inhibitory concentration, then perform a weighted sum of the minimum inhibitory concentration and the second minimum inhibitory concentration to obtain the minimum inhibitory concentration.

[0028] In an alternative embodiment, the determining of the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index includes:

[0029] If the minimum fractional inhibitory concentration index is greater than a first preset threshold, then determine that the combined effect of the two drugs is an antagonistic effect;

[0030] If the minimum fractional inhibitory concentration index is less than or equal to the first preset threshold and greater than a second preset threshold, then determine that the combined effect of the two drugs is an indifferent effect;

[0031] If the minimum fractional inhibitory concentration index is less than or equal to the second preset threshold and greater than a third preset threshold, then determine that the combined effect of the two drugs is an additive effect;

[0032] If the minimum fractional inhibitory concentration index is less than or equal to the third preset threshold, then determine that the combined effect of the two drugs is a synergistic effect.

[0033] In a second aspect, the present invention provides a combined drug susceptibility test data processing device, and the device includes:

[0034] A first acquisition module, configured to acquire the optical density value matrix of the combined drug susceptibility plate output by the microplate reader and a set growth inhibition threshold;

[0035] A judgment module, configured to respectively judge the growth states corresponding to each well on the combined drug susceptibility plate based on the optical density value matrix of the combined drug susceptibility plate and the growth inhibition threshold;

[0036] A calculation module, configured to calculate the corresponding fractional inhibitory concentration index for the wells with a growth inhibition state;

[0037] A determination module, configured to determine the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index.

[0038] In a third aspect, the present invention provides a computer device, including: a memory and a processor, which are communicatively connected to each other. The memory stores computer instructions, and the processor executes the computer instructions to perform the combined drug susceptibility test data processing method according to the first aspect or any corresponding embodiment thereof.

[0039] In a fourth aspect, the present invention provides a computer-readable storage medium, on which computer instructions are stored. The computer instructions are used to cause a computer to execute the combined drug susceptibility test data processing method according to the first aspect or any corresponding embodiment thereof.

[0040] In a fifth aspect, the present invention provides a computer program product, including computer instructions, which are used to cause a computer to execute the combined drug susceptibility test data processing method according to the first aspect or any corresponding embodiment thereof.

[0041] The combined drug susceptibility test data processing method, device, equipment and storage medium provided in this embodiment automatically judge the growth state corresponding to each well on the combined drug susceptibility plate based on the combined drug susceptibility plate optical density value matrix and the growth inhibition threshold respectively; then, for the wells with the growth state of growth inhibition, calculate the corresponding fractional inhibitory concentration index; finally, based on the calculated minimum fractional inhibitory concentration index, determine the combined effect of the two drugs. It avoids the problem that it is difficult to ensure the accuracy of manually interpreting the results of the combined drug susceptibility test, improves the accuracy and reliability of the test results, and also significantly improves the result interpretation efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the related art, the following will briefly introduce the drawings required for use in the description of the specific embodiments or the related art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0043] Figure 1 is a flowchart of the combined drug susceptibility test data processing method according to an embodiment of the present invention;

[0044] Figure 2 is a flowchart of another combined drug susceptibility test data processing method according to an embodiment of the present invention;

[0045] Figure 3 is a schematic diagram of a 96-well plate after combined drug susceptibility test incubation according to an embodiment of the present invention;

[0046] Figure 4 is a schematic diagram of the microplate reader readings of a 96-well plate for combined drug susceptibility test according to an embodiment of the present invention;

[0047] Figure 5 is a schematic diagram of a combined drug susceptibility spectrum according to an embodiment of the present invention;

[0048] Figure 6 is a structural block diagram of a combined drug susceptibility test data processing device according to an embodiment of the present invention;

[0049] Figure 7 is a schematic diagram of the hardware structure of a computer device according to an embodiment of the present invention. Detailed implementation manners

[0050] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0051] According to an embodiment of the present invention, an embodiment of a combined drug susceptibility test data processing method is provided. It should be noted that the steps shown in the flowchart of the accompanying drawings can be executed in a computer system such as a set of executable computer instructions, and although the logical order is shown in the flowchart, in some cases, the steps shown or described can be executed in a different order than here.

[0052] In this embodiment, a combined drug susceptibility test data processing method is provided, which can be used in various computer devices. Figure 1 is a flowchart of a combined drug susceptibility test data processing method according to an embodiment of the present invention, as Figure 1 shown, and the process includes the following steps:

[0053] Step S101, obtain the combined drug susceptibility plate optical density value matrix output by the microplate reader and the set growth inhibition threshold.

[0054] Specifically, the optical density (OD) value can be an OD 600 value matrix, and the OD 600 value refers to the optical density value measured at a wavelength of 600 nanometers. The growth inhibition threshold can be, for example, 0.06.

[0055] The process of the combined drug susceptibility test includes:

[0056] 1. Select drugs: Refer to relevant guidelines, literature, and the combined medication experience of clinicians to select different drug combinations. Prepare checkerboard dilution modules respectively, and increase the recognition by marking different colors or significant identifiers. Perform serial dilutions with twofold dilutions at 2 - 3 concentration gradients above and below the minimum inhibitory concentration (MIC) value of different drug resistance breakpoints as the center, and form a 6×6 checkerboard for the combination of two drugs. Clinically, a set or multiple sets of drug combination joint susceptibility tests can be personalized according to the actual situation of the isolated strains of different patients.

[0057] 2. Prepare the bacterial suspension: Culture the bacteria to be tested until the logarithmic growth phase, and then prepare a bacterial suspension with an appropriate concentration (usually 0.5 McFarland turbidity unit, containing approximately 1 - 2×10 8 CFU / mL).

[0058] 3. Set up the test groups:

[0059] Single drug group: Use each drug separately.

[0060] Combined medication group: Mix two or more drugs in different proportions and use them.

[0061] Control group: Include a positive control (bacterial suspension without drugs) and a negative control (culture medium without bacteria).

[0062] 4. Inoculation and incubation: Add the bacterial suspension to the liquid medium containing drugs. Then incubate under appropriate conditions (such as 37°C). In the embodiment of the present invention, in the incubation step, a microplate shaker is used for incubation at 35°C to accelerate bacterial growth, and the results can be read in 4 - 6 hours. Compared with the previous 18 - 24 hours for reading results, it can significantly accelerate the reporting time, which is of great significance for the preemptive treatment of critically ill infected patients who need to perform joint susceptibility tests.

[0063] Step S102: Based on the light density value matrix of the joint susceptibility plate and the growth inhibition threshold, respectively determine the growth state corresponding to each well on the joint susceptibility plate.

[0064] In some optional specific implementation manners, step S102, that is, the step of respectively determining the growth state corresponding to each well on the joint susceptibility plate based on the light density value matrix of the joint susceptibility plate and the growth inhibition threshold, includes:

[0065] Step S1021: For the first well on the joint susceptibility plate, obtain the light density value corresponding to the first well based on the light density value matrix of the joint susceptibility plate.

[0066] Step S1022, if the optical density value corresponding to the first well is less than the growth inhibition threshold, determine that the growth state of the first well is growth inhibition (I).

[0067] In some other alternative specific embodiments, after step S1021, that is, after obtaining the optical density value corresponding to the first well on the combined drug susceptibility plate based on the combined drug susceptibility plate optical density value matrix, the following further includes:

[0068] Step S1023, if the optical density value corresponding to the first well is greater than or equal to the growth inhibition threshold, determine whether the optical density value corresponding to the first well is less than the target optical density value; wherein, the target optical density value is the optical density value corresponding to the well on the combined drug susceptibility plate optical density value matrix where the concentrations of both drugs are zero. The target optical density value can also be defined as the unrestricted growth threshold (UnrC).

[0069] Step S1024, if the optical density value corresponding to the first well is less than the target optical density value, determine that the growth state corresponding to the first well is growth restricted (L).

[0070] Step S1025, if the optical density value corresponding to the first well is greater than or equal to the target optical density value, determine that the growth state corresponding to the first well is growth unrestricted (U).

[0071] Human visual assessment is often affected by various factors, such as fatigue, mood, experience differences, etc., which may all lead to inconsistent judgment criteria and the generation of errors. In the embodiments of the present invention, the growth state of bacteria in each well on the combined drug susceptibility plate is automatically judged according to the optical density value corresponding to each well, and the optical density value is detected by an enzyme-linked immunosorbent assay instrument. Such an interpretation method can significantly improve the objectivity and standardization level of the interpretation results, effectively avoid the subjective deviation and inconsistency brought by the naked-eye observation of different personnel, and ensure that more accurate and reliable results can be obtained for each test.

[0072] In addition, the growth inhibition threshold can be set by the joint interpretation of multiple experienced senior technicians, thereby further eliminating the deviation of different personnel and ensuring the accuracy of the interpretation results.

[0073] In some alternative specific embodiments, after step S102, that is, after respectively judging the growth state corresponding to each well on the combined drug susceptibility plate based on the combined drug susceptibility plate optical density value matrix and the growth inhibition threshold, the following further includes:

[0074] Draw a combined drug susceptibility spectrum diagram based on the growth state corresponding to each well on the combined drug susceptibility plate.

[0075] Specifically, different colors are used in the combined drug susceptibility spectrum diagram to represent different growth states.

[0076] In the embodiments of the present invention, based on the growth states corresponding to the respective wells on the combined drug susceptibility plate, a combined drug susceptibility spectrogram is drawn, so as to visually display the inhibitory effect of the drug combination on the growth of microorganisms.

[0077] Step S103: For the wells with a growth inhibitory state, calculate the corresponding fractional inhibitory concentration index (FIC).

[0078] In some optional specific embodiments, step S103, that is, for the wells with a growth inhibitory state, calculating the corresponding fractional inhibitory concentration index, includes:

[0079] Step S1031: For the second well on the combined drug susceptibility plate with a growth inhibitory state, obtain the concentrations of the two drugs in the second well.

[0080] Step S1032: Obtain the minimum inhibitory concentrations of the two drugs.

[0081] Step S1033: Based on the minimum inhibitory concentrations of the two drugs and the concentrations of the two drugs in the second well, calculate the fractional inhibitory concentration index corresponding to the second well.

[0082] Specifically, the calculation formula for the fractional inhibitory concentration index corresponding to the second well is:

[0083]

[0084] Where ca and cb are the concentrations of the two drugs corresponding to the second well.

[0085] In some optional specific embodiments, step S1032, that is, obtaining the minimum inhibitory concentrations of the two drugs, includes:

[0086] Step S10321: Obtain the first minimum inhibitory concentrations MicA and MicB of the two drugs input by the user. The first minimum inhibitory concentrations MicA and MicB of the two drugs can be the minimum inhibitory concentrations used for manual judgment based on the combined drug susceptibility plate.

[0087] Step S10322: Based on the combined drug susceptibility plate optical density value matrix, respectively determine the second minimum inhibitory concentrations cMicA and cMicB of the two drugs.

[0088] That is, the minimum inhibitory concentrations of two drugs are automatically interpreted according to the optical density value matrix of the combined drug susceptibility plate. For example, for the wells on the combined drug susceptibility plate where the optical density value is less than the growth inhibition threshold and the concentration of the first drug is zero, the concentration when the concentration of the second drug is the lowest is used as the minimum inhibitory concentration of the second drug.

[0089] In other embodiments, the minimum inhibitory concentration of the drug can also be determined according to the growth state of each well judged as described above. For example, for the wells with a growth state of growth inhibition and a concentration of the first drug of zero, the concentration when the concentration of the second drug is the lowest is used as the minimum inhibitory concentration of the second drug.

[0090] Step S10323, if the second minimum inhibitory concentration is inconsistent with the first minimum inhibitory concentration, then the minimum inhibitory concentration and the second minimum inhibitory concentration are weighted and summed to obtain the minimum inhibitory concentration.

[0091] Among them, the weight value of the second minimum inhibitory concentration can be greater than the weight value of the first minimum inhibitory concentration. Specifically, the consistency of the minimum inhibitory concentrations of the two drugs is judged separately. If only the minimum inhibitory concentration of one of the drugs is inconsistent, then only the first minimum inhibitory concentration and the second minimum inhibitory concentration corresponding to the inconsistent drug need to be weighted and summed.

[0092] Of course, if the second minimum inhibitory concentration is consistent with the first minimum inhibitory concentration, then the minimum inhibitory concentrations of the two drugs can be directly obtained without correction.

[0093] In the embodiments of the present invention, in addition to obtaining the minimum inhibitory concentrations MicA and MicB of the two drugs input by the user, the minimum inhibitory concentrations of the two drugs are automatically interpreted according to the optical density value matrix of the combined drug susceptibility plate, and compared with the minimum inhibitory concentrations MicA and MicB of the two drugs input by the user. Finally, the final minimum inhibitory concentration is adjusted or determined according to the comparison result. Thereby, the interpretation accuracy can be optimized and the influence of subjective factors on the test results can be reduced.

[0094] In other specific embodiments, if the first minimum inhibitory concentration and the second minimum inhibitory concentration of one of the drugs are inconsistent, or the first minimum inhibitory concentration and the second minimum inhibitory concentration of both drugs are inconsistent, then the second minimum inhibitory concentration can be directly determined as the minimum inhibitory concentration.

[0095] In other specific embodiments, it is also possible to automatically interpret the minimum inhibitory concentrations of the two drugs by a machine according to the optical density value matrix of the combined drug susceptibility plate or automatically determine the minimum inhibitory concentrations of the two drugs according to the growth state of each well judged as described above without manual interpretation of the minimum inhibitory concentrations of the two drugs.

[0096] Step S104: Determine the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index.

[0097] In some optional specific embodiments, Step S104, that is, determining the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index, includes:

[0098] Step S1041: If the minimum fractional inhibitory concentration index is greater than the first preset threshold, determine that the combined effect of the two drugs is an antagonistic effect. The first preset threshold can be, for example, 2.0.

[0099] Step S1042: If the minimum fractional inhibitory concentration index is less than or equal to the first preset threshold and greater than the second preset threshold, determine that the combined effect of the two drugs is an indifferent effect. The second preset threshold can be, for example, 1.0.

[0100] Step S1043: If the minimum fractional inhibitory concentration index is less than or equal to the second preset threshold and greater than the third preset threshold, determine that the combined effect of the two drugs is an additive effect. The third preset threshold can be, for example, 0.5.

[0101] Step S1044: If the minimum fractional inhibitory concentration index is less than or equal to the third preset threshold, determine that the combined effect of the two drugs is a synergistic effect.

[0102] In addition, the concentrations of the two drugs in the well corresponding to the minimum fractional inhibitory concentration index can be determined as the optimal combined concentration of the two drugs.

[0103] In summary, the embodiments of the present invention can finally obtain the verified minimum inhibitory concentrations cMicA and cMicB, the optimal combined concentration of the two drugs, the final fractional inhibitory concentration index (i.e., the minimum fractional inhibitory concentration index), the combined effect determination result, and the combined drug susceptibility spectrum diagram.

[0104] The combined drug susceptibility test data processing method provided in this embodiment automatically determines the growth state corresponding to each well on the combined drug susceptibility plate based on the combined drug susceptibility plate optical density value matrix and the growth inhibition threshold; then, for the wells with the growth state of growth inhibition, calculate the corresponding fractional inhibitory concentration index; finally, determine the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index. It avoids the problem that the accuracy of manually interpreting the results of the combined drug susceptibility test is difficult to guarantee, improves the accuracy and reliability of the test results, and significantly improves the result interpretation efficiency.

[0105] The algorithm corresponding to the combined drug susceptibility test data processing method provided in the embodiments of the present invention can be run through the Fic_find.R program in the R language, and the OD measured by the microplate reader 600Automatically interpret the combined effect of drugs. The program runs in the R version 4.3.1 environment and depends on R language packages such as dplyr, readxl, and pheatmap. Through precise numerical analysis, the embodiments of the present invention can correct the visual errors in the experiment, systematically evaluate the combined effect between drugs, and generate a result visualization chart.

[0106] In this embodiment, a method for processing combined drug sensitivity test data is provided, which can be used in various computer devices. Figure 2 It is a flowchart of the method for processing combined drug sensitivity test data according to the embodiments of the present invention, as Figure 2 shown, and the process specifically includes:

[0107] First, input the experimental data, including the initial minimum inhibitory concentrations (MicA and MicB) of two drugs judged manually and the OD 600 value matrix (OD) of the combined drug sensitivity plate output by the microplate reader. Subsequently, automatically interpret and correct the minimum inhibitory concentrations (cMicA, cMicB) of the two drugs according to the OD matrix, and compare and adjust them with the input initial minimum inhibitory concentrations (MicA and MicB). This step aims to optimize the interpretation accuracy and reduce the influence of subjective factors on the experimental results. After the correction is completed, define the OD 600 value of the wells in the OD matrix where the concentrations of both drugs are zero as the unrestricted growth threshold (UnrC), and set 0.06 as the growth inhibition threshold. By comparing the OD 600 values of each well with the above two thresholds, determine the growth state of each well, which is specifically divided into three categories: growth inhibition (I), growth restriction (L), and unrestricted growth (U). Subsequently, draw a combined drug sensitivity spectrum diagram based on this to visually display the inhibition of the drug combination on microbial growth.

[0108] After completing the growth state judgment, further calculate the current Fic value (cFic) for each well determined to be growth inhibited (I). The calculation formula for the Fic value is:

[0109]

[0110] where ca and ca are the concentrations of the two drugs corresponding to this well. Among all the cFic values, select the minimum value as the final Fic value, and determine the combined effect of the two drugs based on this value. The specific criteria are: when the Fic value is less than or equal to 0.5, it is judged as "synergistic effect"; when it is between 0.5 and 1.0, it is "additive effect"; when it is between 1.0 and 2.0, it is "no effect"; when it is greater than 2.0, it is "antagonistic effect".

[0111] Finally, the algorithm will comprehensively output the results including the verified minimum inhibitory concentration (cMic), the optimal combined concentration of the two drugs, the final Fic value, the combined effect determination result, and the combined drug susceptibility spectrum diagram.

[0112] In this embodiment, a method for processing combined drug susceptibility test data is provided, which can be used in various computer devices, such as mobile phones, tablets, etc. The specific method is as follows:

[0113] Analyze the combined effect of drug A and drug B through a combined drug susceptibility test. Figure 3 It is a schematic diagram of the situation after incubation in a 96-well plate. First, verify the Mic value. Specifically, in the wells with a drug B concentration of 0, the concentration of drug A gradually increases. Manually judge the Mic value according to the turbidity and clarity of the well contents on the 96-well plate ( Figure 3 as shown). (Turbid wells indicate bacterial growth, and clear wells indicate no bacterial growth). In addition, for the Figure 3 96-well plate shown, after reading by an enzyme-linked immunosorbent assay (ELISA) reader, the output OD 600 value is as Figure 4 shown. The machine sequentially compares the OD 600 value of each well with the set growth inhibition threshold (I = 0.060) to judge the growth state in the well (less than the growth inhibition threshold is judged as no bacterial growth, and greater than the growth inhibition threshold is judged as having bacterial growth). The results show that when the concentration of drug A reaches 64, the corresponding well is judged to be in a growth inhibition state, which is consistent with the manual judgment result and does not need to be adjusted. Similarly, the Mic value of drug B is automatically judged, and the judgment result is slightly different from the manual result. Finally, the automatic judgment result is used as the standard, and the Mic value is adjusted to 32. Then, by judging the OD 600 value matrix of the combined drug susceptibility plate, for each well judged to be in a growth inhibition state, calculate its current Fic value, that is, the cFic value, according to the calculation method of Fic, and report the minimum cFic value as Fic. The concentrations of the two drugs corresponding to the well position are the optimal combined concentrations. In this embodiment, the obtained Fic value is 0.375. At this time, the concentrations of drug A and drug B are 16 and 4 respectively, that is, at this concentration combination, the two drugs can achieve the best antibacterial effect. According to the combined effect determination standard, an Fic value less than or equal to 0.5 belongs to "synergistic effect", indicating that the combined use of the two drugs can significantly enhance the antibacterial effect at this concentration, far better than the effect of using the two drugs alone.

[0114] Figure 5The combined drug sensitivity spectrum diagram shown intuitively displays the growth status under different concentration combinations from the color distribution: red represents unrestricted growth (U), yellow represents restricted growth (L), and green represents complete growth inhibition (I). The point marked with an asterisk in the figure corresponds to the combination of drug A at a concentration of 16 and drug B at a concentration of 4, which is located in the green area, indicating that complete growth inhibition has been successfully achieved under this combination.

[0115] In summary, the results of this embodiment clearly show that the combined use of drug A and drug B at appropriate concentrations has a significant synergistic effect, can achieve a strong antibacterial effect at a lower concentration, thus effectively optimizing the dosage design, reducing the single drug usage, and providing a quantitative basis for clinical combined drug use.

[0116] In this embodiment, a combined drug sensitivity test data processing device is also provided. This device is used to implement the above-mentioned embodiments and preferred implementation manners, and those that have been described will not be repeated. As used hereinafter, the term "module" can be a combination of software and / or hardware that can achieve a predetermined function. Although the devices described in the following embodiments are preferably implemented in software, implementation in hardware, or a combination of software and hardware is also possible and contemplated.

[0117] This embodiment provides a combined drug sensitivity test data processing device, as Figure 6 shown, including:

[0118] A first acquisition module 601, configured to acquire the combined drug sensitivity plate optical density value matrix output by the microplate reader and the set growth inhibition threshold;

[0119] A judgment module 602, configured to respectively judge the growth status corresponding to each well on the combined drug sensitivity plate based on the combined drug sensitivity plate optical density value matrix and the growth inhibition threshold;

[0120] A calculation module 603, configured to calculate the corresponding fractional inhibitory concentration index for the wells with the growth status of growth inhibition;

[0121] A determination module 604, configured to determine the combined effect of the two drugs based on the calculated minimum fractional inhibitory concentration index.

[0122] In some alternative implementation manners, the judgment module 602 includes:

[0123] An optical density value acquisition unit, configured to acquire the optical density value corresponding to the first well on the combined drug sensitivity plate based on the combined drug sensitivity plate optical density value matrix for the first well on the combined drug sensitivity plate;

[0124] A first growth status determination unit, configured to determine that the growth status of the first well is growth inhibition if the optical density value corresponding to the first well is less than the growth inhibition threshold.

[0125] In some alternative embodiments, the determination module 602 further includes:

[0126] A determination unit, configured to determine whether the optical density value corresponding to the first well is less than a target optical density value if the optical density value corresponding to the first well is greater than or equal to the growth inhibition threshold; wherein, the target optical density value is the optical density value corresponding to the well in the optical density value matrix of the combined drug susceptibility plate where the concentrations of both drugs are zero.

[0127] A second growth state determination unit, configured to determine that the growth state corresponding to the first well is growth restricted if the optical density value corresponding to the first well is less than the target optical density value.

[0128] A third growth state determination unit, configured to determine that the growth state corresponding to the first well is growth unrestricted if the optical density value corresponding to the first well is greater than or equal to the target optical density value.

[0129] In some alternative embodiments, the combined drug susceptibility test data processing device further includes:

[0130] A plotting module, configured to plot a combined drug susceptibility spectrum diagram based on the growth states corresponding to the respective wells on the combined drug susceptibility plate.

[0131] In some alternative embodiments, the calculation module 603 includes:

[0132] A concentration acquisition unit, configured to acquire the concentrations of the two drugs in the second well for which the growth state on the combined drug susceptibility plate is growth inhibition.

[0133] A minimum inhibitory concentration acquisition unit, configured to acquire the minimum inhibitory concentrations of the two drugs.

[0134] A calculation unit, configured to calculate the fractional inhibitory concentration index corresponding to the second well based on the minimum inhibitory concentrations of the two drugs and the concentrations of the two drugs in the second well.

[0135] In some alternative embodiments, the minimum inhibitory concentration acquisition unit is specifically configured to acquire the first minimum inhibitory concentrations of the two drugs input by the user; respectively determine the second minimum inhibitory concentrations of the two drugs based on the optical density value matrix of the combined drug susceptibility plate; if the second minimum inhibitory concentration is inconsistent with the first minimum inhibitory concentration, then perform a weighted sum of the minimum inhibitory concentration and the second minimum inhibitory concentration to obtain the minimum inhibitory concentration.

[0136] In some alternative embodiments, the determining module 604 is specifically configured to: if the minimum fractional inhibitory concentration index is greater than a first preset threshold, determine that the combined effect of the two drugs is an antagonistic effect; if the minimum fractional inhibitory concentration index is less than or equal to the first preset threshold and greater than a second preset threshold, determine that the combined effect of the two drugs is an irrelevant effect; if the minimum fractional inhibitory concentration index is less than or equal to the second preset threshold and greater than a third preset threshold, determine that the combined effect of the two drugs is an additive effect; and if the minimum fractional inhibitory concentration index is less than or equal to the third preset threshold, determine that the combined effect of the two drugs is a synergistic effect.

[0137] The further function descriptions of the above-mentioned various modules and units are the same as those in the corresponding foregoing embodiments, and will not be elaborated herein.

[0138] The combined drug susceptibility test data processing device in this embodiment is presented in the form of functional units. Here, the unit refers to an ASIC (Application Specific Integrated Circuit) circuit, a processor and a memory that execute one or more software or fixed programs, and / or other devices that can provide the above functions.

[0139] An embodiment of the present invention further provides a computer device having the above-mentioned Figure 6 combined drug susceptibility test data processing device.

[0140] Please refer to Figure 7 , Figure 7 which is a schematic structural diagram of a computer device provided by an alternative embodiment of the present invention. As shown in Figure 7 , the computer device includes: one or more processors 10, a memory 20, and interfaces for connecting various components, including a high-speed interface and a low-speed interface. Each component communicates with each other using different buses and can be installed on a common motherboard or installed in other ways as needed. The processor can process instructions executed within the computer device, including instructions stored in the memory or on the memory to display graphical information of the GUI on an external input / output device (such as a display device coupled to the interface). In some alternative embodiments, if necessary, multiple processors and / or multiple buses can be used together with multiple memories and multiple memories. Similarly, multiple computer devices can be connected, and each device provides some necessary operations (for example, as a server array, a set of blade servers, or a multi-processor system). Figure 7 In

[0141] The processor 10 can be a central processing unit, a network processor, or a combination thereof. Among them, the processor 10 can further include a hardware chip. The above-mentioned hardware chip can be an application-specific integrated circuit, a programmable logic device, or a combination thereof. The above-mentioned programmable logic device can be a complex programmable logic device, a field-programmable gate array, a generic array logic, or any combination thereof.

[0142] Among them, the memory 20 stores instructions executable by at least one processor 10, so that the at least one processor 10 executes the method shown in the above embodiments.

[0143] The memory 20 can include a program storage area and a data storage area. Among them, the program storage area can store an operating system and application programs required for at least one function; the data storage area can store data created according to the use of the computer device, etc. In addition, the memory 20 can include a high-speed random access memory, and can also include a non-transitory memory, such as at least one disk storage device, a flash memory device, or other non-transitory solid-state storage devices. In some alternative embodiments, the memory 20 can optionally include a memory remotely provided relative to the processor 10, and these remote memories can be connected to the computer device through a network. Examples of the above network include but are not limited to the Internet, an enterprise intranet, a local area network, a mobile communication network, and combinations thereof.

[0144] The memory 20 can include a volatile memory, for example, a random access memory; the memory can also include a non-volatile memory, for example, a flash memory, a hard disk, or a solid-state drive; the memory 20 can also include a combination of the above types of memories.

[0145] The computer device further includes an input device 30 and an output device 40. The processor 10, the memory 20, the input device 30, and the output device 40 can be connected through a bus or other means. Figure 7 Taking connection through a bus as an example.

[0146] The input device 30 can receive input digital or character information, and generate key signal inputs related to the user settings and function control of the computer device, such as a touch screen, a keypad, a mouse, a trackpad, a touchpad, a pointing stick, one or more mouse buttons, a trackball, a joystick, etc. The output device 40 can include a display device, an auxiliary lighting device (for example, an LED), and a tactile feedback device (for example, a vibration motor), etc. The above display device includes but is not limited to a liquid crystal display, a light-emitting diode, a display, and a plasma display. In some alternative embodiments, the display device can be a touch screen.

[0147] The computer device further includes a communication interface for the computer device to communicate with other devices or communication networks.

[0148] Embodiments of the present invention also provide a computer-readable storage medium. The method according to the embodiments of the present invention can be implemented in hardware, firmware, or be implemented as computer code that can be recorded on a storage medium, or be implemented as computer code that is originally stored in a remote storage medium or a non-transitory machine-readable storage medium and downloaded through a network and will be stored in a local storage medium, so that the method described herein can be stored in such software processing on a storage medium using a general-purpose computer, a dedicated processor, or programmable or dedicated hardware. Among them, the storage medium can be a magnetic disk, an optical disk, a read-only memory, a random access memory, a flash memory, a hard disk, or a solid-state drive, etc.; further, the storage medium can also include a combination of the above types of memories. It can be understood that a computer, a processor, a microprocessor controller, or programmable hardware includes a storage component that can store or receive software or computer code, and when the software or computer code is accessed and executed by the computer, the processor, or the hardware, the method shown in the above embodiments is implemented.

[0149] A part of the present invention can be applied as a computer program product, for example, computer program instructions, which, when executed by a computer, can call or provide the method and / or technical solution according to the present invention through the operation of the computer. Those skilled in the art should be able to understand that the forms in which computer program instructions exist in a computer-readable medium include, but are not limited to, source files, executable files, installation package files, etc. Correspondingly, the ways in which computer program instructions are executed by a computer include, but are not limited to: the computer directly executes the instruction, or the computer compiles the instruction and then executes the corresponding compiled program, or the computer reads and executes the instruction, or the computer reads and installs the instruction and then executes the corresponding installed program. Here, the computer-readable medium can be any available computer-readable storage medium or communication medium accessible by the computer.

[0150] Although the embodiments of the present invention have been described in conjunction with the accompanying drawings, those skilled in the art can make various modifications and variations without departing from the spirit and scope of the present invention, and such modifications and variations all fall within the scope defined by the appended claims.

Claims

1. A combined drug sensitivity test data processing method, characterized in that: The method comprises: Obtain the optical density value matrix of the combined drug sensitivity plate output by the microplate reader and the set growth inhibition threshold; Based on the optical density value matrix of the combined drug-sensitive plate and the growth inhibition threshold, respectively judging the growth state corresponding to each well on the combined drug-sensitive plate; For the wells whose growth state is growth inhibition, calculating the corresponding partial inhibition concentration index; The combined effect of the two drugs was determined based on the calculated minimum partial inhibitory concentration index.

2. The method according to claim 1, characterized in that: The step of judging the growth status of each hole on the combined drug-sensitive plate based on the optical density value matrix of the combined drug-sensitive plate and the growth inhibition threshold comprises: For the first well on the combined drug-sensitive plate, obtaining an optical density value corresponding to the first well based on the optical density value matrix of the combined drug-sensitive plate; If the optical density value corresponding to the first hole is less than the growth inhibition threshold, it is determined that the growth state of the first hole is growth inhibition.

3. The method according to claim 2, characterized in that After obtaining the optical density value corresponding to the first hole on the combined drug-sensitive plate based on the optical density value matrix of the combined drug-sensitive plate, the method further includes: If the optical density value corresponding to the first well is greater than or equal to the growth inhibition threshold, then determining whether the optical density value corresponding to the first well is less than a target optical density value; wherein the target optical density value is the optical density value corresponding to the wells in the optical density value matrix of the combined drug sensitivity plate where the concentrations of both drugs are zero; If the optical density value corresponding to the first hole is less than the target optical density value, determining that the growth state corresponding to the first hole is growth restricted; If the optical density value corresponding to the first hole is greater than or equal to the target optical density value, it is determined that the growth state corresponding to the first hole is unrestricted growth.

4. The method according to claim 3, characterized in that After respectively judging the growth state corresponding to each well on the combined drug-sensitive plate based on the optical density value matrix of the combined drug-sensitive plate and the growth inhibition threshold, the method further includes: Based on the growth status corresponding to each well on the combined drug sensitivity plate, a combined drug sensitivity spectrum is drawn.

5. The method according to claim 1, characterized in that: The step of calculating the corresponding partial inhibition concentration index for the wells whose growth state is growth inhibition includes: For the second well on the combined drug-sensitive plate whose growth state is growth inhibition, obtaining the concentrations of the two drugs in the second well; Obtain the minimum inhibitory concentration of the two drugs; Based on the minimum inhibitory concentrations of the two drugs and the concentrations of the two drugs in the second well, a partial inhibitory concentration index corresponding to the second well is calculated.

6. The method according to claim 5, characterized in that The step of obtaining the minimum inhibitory concentration of the two drugs comprises: Get the first minimum inhibitory concentration of the two drugs input by the user; Based on the optical density value matrix of the combined drug sensitivity plate, the second minimum inhibitory concentration of the two drugs is determined respectively; If the second minimum inhibitory concentration is inconsistent with the first minimum inhibitory concentration, a weighted sum is performed on the minimum inhibitory concentration and the second minimum inhibitory concentration to obtain the minimum inhibitory concentration.

7. The method according to any one of claims 1 to 6, characterized in that The method of determining the combined effect of the two drugs based on the calculated minimum partial inhibitory concentration index includes: If the minimum partial inhibitory concentration index is greater than a first preset threshold, determining that the combined effect of the two drugs is an antagonistic effect; If the minimum partial inhibitory concentration index is less than or equal to the first preset threshold value and greater than the second preset threshold value, the combined effect of the two drugs is determined to be an irrelevant effect; If the minimum partial inhibitory concentration index is less than or equal to the second preset threshold value and greater than the third preset threshold value, it is determined that the combined effect of the two drugs is additive; If the minimum partial inhibitory concentration index is less than or equal to the third preset threshold, the combined effect of the two drugs is determined to be a synergistic effect.

8. A combined drug sensitivity test data processing device, characterized in that: The device comprises: The first acquisition module is used to obtain the optical density value matrix of the combined drug sensitivity plate output by the microplate reader and the set growth inhibition threshold; A judgment module, used to judge the growth status corresponding to each well on the combined drug-sensitive plate based on the optical density value matrix of the combined drug-sensitive plate and the growth inhibition threshold; A calculation module, for calculating the corresponding partial inhibition concentration index for the wells whose growth state is growth inhibition; The determination module is used to determine the combined effect of the two drugs based on the calculated minimum partial inhibitory concentration index.

9. A computer device, characterized in that: include: A memory and a processor, wherein the memory and the processor are communicatively connected to each other, the memory stores computer instructions, and the processor executes the combined drug sensitivity test data processing method according to any one of claims 1 to 7 by executing the computer instructions.

10. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores computer instructions, and the computer instructions are used to enable a computer to execute the combined drug sensitivity test data processing method according to any one of claims 1 to 7.

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