JP2008079510A - Method for enhancing drug sensitivity of drug-resistant pathogenic microorganisms and method for preventing the appearance of highly drug-resistant bacteria - Google Patents
Method for enhancing drug sensitivity of drug-resistant pathogenic microorganisms and method for preventing the appearance of highly drug-resistant bacteria Download PDFInfo
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- JP2008079510A JP2008079510A JP2006260536A JP2006260536A JP2008079510A JP 2008079510 A JP2008079510 A JP 2008079510A JP 2006260536 A JP2006260536 A JP 2006260536A JP 2006260536 A JP2006260536 A JP 2006260536A JP 2008079510 A JP2008079510 A JP 2008079510A
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Abstract
【課題】
薬剤耐性を持った菌による免疫力のない患者の日和見感染や、手術後の感染など重大な院内感染問題を軽減することを課題とする。
【解決手段】
抗菌性物質存在下に、４０５ｎｍをピークとする４００−４１０ｎｍの波長を有するＬＥＤを照射して、薬剤耐性を有する病原性微生物の当該抗菌性物質に対する感受性を増強する方法、および高濃度の抗菌性物質存在下にＬＥＤを照射して、高度薬剤耐性を有するＭＲＳＡ等の病原性微生物の出現を予防する方法を提供する。
【選択図】なし【Task】
The objective is to alleviate serious nosocomial infection problems such as opportunistic infections in patients without immunity due to drug-resistant bacteria and infections after surgery.
[Solution]
A method of enhancing the sensitivity of a pathogenic microorganism having drug resistance to the antibacterial substance by irradiating an LED having a wavelength of 400-410 nm peaking at 405 nm in the presence of the antibacterial substance, and a high concentration of antibacterial property Provided is a method for preventing the appearance of pathogenic microorganisms such as MRSA having high drug resistance by irradiating an LED in the presence of a substance.
[Selection figure] None
Description
本発明は、抗菌性物質の存在下にＬＥＤ（Ｌｉｇｈｔ Ｅｍｉｔｔｉｎｇ Ｄｉｏｄｅ：光ダイオード）を照射して、薬剤耐性を有する病原性微生物の薬剤感受性を回復し、増強する方法、および高濃度の抗菌性物質存在下にＬＥＤを照射して、高度薬剤耐性を有する病原性微生物の出現を予防する方法に関する。特に、本発明は、セパシア菌、メチシリン耐性黄色ブドウ球菌（ＭＲＳＡ）、緑膿菌、セラチア菌等の細菌の抗生剤に対する感受性を増強する方法に関する。 The present invention relates to a method for recovering and enhancing the drug sensitivity of a pathogenic microorganism having drug resistance by irradiating an LED (Light Emitting Diode) in the presence of the antibacterial substance, and a high concentration of the antibacterial substance The present invention relates to a method for preventing the appearance of pathogenic microorganisms having high drug resistance by irradiating LEDs in the presence. In particular, the present invention relates to a method for enhancing the susceptibility of bacteria such as cepacia, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Serratia bacteria to antibiotics.
現在先進諸国においては、細菌やウイルスなどの多くの病原性微生物に対して有効な抗生剤が開発されており感染症の驚異は低下している。しかし、特定の病原性微生物に対して特定の薬剤を投与し続けると、やがて微生物は当該薬剤に対して耐性を獲得するようになる。近年、このようにして薬剤耐性を持った菌が出現し、日和見感染症や、菌交代症、新規な多剤耐性菌の出現による院内感染症が克服すべき問題となってきている。 In developed countries, antibiotics effective against many pathogenic microorganisms such as bacteria and viruses have been developed, and the wonder of infectious diseases is decreasing. However, if a specific drug is continuously administered to a specific pathogenic microorganism, the microorganism will eventually acquire resistance to the drug. In recent years, bacteria with drug resistance have emerged in this way, and opportunistic infections, fungal substitutions, and nosocomial infections due to the emergence of new multidrug-resistant bacteria have become problems to be overcome.
セフェム系抗生剤を含むベータ・ラクタム剤の多用に対して耐性を獲得したメチシリン耐性黄色ブドウ球菌（ＭＲＳＡ）が発現して社会問題となった後、さまざまな対策研究がなされた。ＭＲＳＡ感染症に対する新規な薬剤組成物として、抗生剤や抗菌剤、例えばアミノグリコシド系抗生剤、グリコペプチド系抗生剤、マクロライド系抗生剤、クロラムフェニコール、フォスホマイシンおよび／またはキノロン系抗菌薬に、フラボノイドを含有させた製剤を開示している（特許文献１）。多剤耐性結核菌による結核感染症の治療や予防効果については、薬剤耐性原生生物感染症患者より採取した血液中のリンパ球を、インターロイキン２等によって増殖・活性化させて主成分とした製剤が有効であることが開示されており（特許文献２）、バンコマイシン等の薬剤耐性菌保菌乃至感染している家畜・家禽・魚介類の感染防除剤としては、乳酸菌、特にエンテロコッカス・フェカリス（Ｅｎｔｅｒｏｃｏｃｃｕｓ ｆａｅｃａｌｉｓ）、エンテロコッカス・フェシウム（Ｅｎｔｅｒｏｃｏｃｃｕｓ ｆａｅｃｉｕｍ）、またはその死菌体、その処理物を有効成分とする薬剤が開示されている（特許文献３）。また、光照射によるＭＲＳＡ耐性菌の殺菌方法としては、室内にフェオフォーバイドのナトリウム塩を含む水溶液を噴霧、散布又は清拭した後、室内に６００〜７００ｎｍの波長を含む光を照射する室内の消毒方法が明かにされている（特許文献４）。光ダイオードによる殺菌方法に関しては、青色発光ダイオードアレイから閃光パルスを発生させて殺菌対象物に照射して殺菌する方法が開示されているが、光源が４６６ｎｍをピークとする４１９−５１９ｎｍの範囲の波長を持つものである（特許文献５）。
しかしながら、薬剤耐性を有する病原性微生物にＬＥＤを照射して、病原性微生物の薬剤感受性を回復し、増強する方法は知られていなかった。本発明は、薬剤耐性を持った菌による免疫力のない患者の日和見感染や、手術後の患部からの感染など重大な院内感染問題を軽減することを課題とし、薬剤耐性を有する病原性微生物の当該抗生剤に対する感受性を増強する方法、および高度薬剤耐性を有する病原性微生物の出現を予防する方法を提供することをその主な課題とする。 However, there has been no known method for irradiating a pathogenic microorganism having drug resistance with an LED to restore and enhance the drug sensitivity of the pathogenic microorganism. An object of the present invention is to alleviate serious nosocomial infection problems such as opportunistic infection of patients without immunity due to drug-resistant bacteria and infection from affected areas after surgery. The main problem is to provide a method for enhancing the sensitivity to the antibiotic and a method for preventing the appearance of pathogenic microorganisms having high drug resistance.
本発明者等は、薬剤耐性を有する病原性微生物に対し、抗生剤存在下でＬＥＤを照射すると、当該抗生剤の効力が回復し高まったことを見出し、本発明を完成させた。 The inventors of the present invention have found that when a pathogenic microorganism having drug resistance is irradiated with an LED in the presence of an antibiotic, the efficacy of the antibiotic is recovered and increased, and the present invention has been completed.
すなわち、本発明は以下の（１）〜（１２）を提供する。 That is, the present invention provides the following (1) to (12).
（１）ＬＥＤを照射して、薬剤耐性を有する病原性微生物の抗菌性物質に対する感受性を増強する方法。 (1) A method of enhancing the sensitivity of a pathogenic microorganism having drug resistance to an antibacterial substance by irradiating an LED.
（２）抗菌性物質存在下にＬＥＤを照射して、薬剤耐性を有する病原性微生物の当該抗菌性物質に対する感受性を増強する方法。 (2) A method of enhancing the sensitivity of a pathogenic microorganism having drug resistance to the antibacterial substance by irradiating the LED in the presence of the antibacterial substance.
（３）前記ＬＥＤが４０５ｎｍをピークとする４００−４１０ｎｍの波長を有するものである上記（１）または（２）に記載の感受性を増強する方法。 (3) The method for enhancing sensitivity according to (1) or (2) above, wherein the LED has a wavelength of 400 to 410 nm having a peak at 405 nm.
（４）薬剤耐性を有する病原性微生物に対し、４０５ｎｍの波長を有するＬＥＤを用い、強度２〜１０ｍＷ／ｃｍ２の光を１６〜５０時間照射することを特徴とする上記（１）〜（３）のいずれかに記載の感受性を増強する方法。
(4) The above-mentioned (1) to (3), wherein a pathogenic microorganism having drug resistance is irradiated with light having an intensity of 2 to 10 mW /
（５）薬剤耐性を有する病原性微生物が、大腸菌、黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌（ＭＲＳＡ）、緑膿菌、肺炎桿菌、腸内細菌エンテロバクテリア、プロテウス菌、サルモネラ・チフス菌、サルモネラ菌、シトロバクター菌、赤痢菌、腸炎ビブリオ菌、肺炎球菌、ヘリコバクター・ピロリ菌、古草菌、セレウス菌、セラチア菌、化膿レンサ球菌、アシネトバクテリア菌、インフルエンザ菌、セパシア菌、腸球菌、表皮ブドウ球菌、カタル球菌、B群レンサ球菌、バクテロイド属菌等の細菌、または白癬菌、表在性真菌、石膏状小胞子菌、アスペルギルス菌、カンジダ菌、クリプトコッカス菌、ノルカジア菌、ムコール菌、瘢風菌等の真菌、またはＱベータファージ、Ｍ１３バクテリオファージ、インフルエンザウイルス、肝炎ウイルス、ヘルペスウイルス（ＨＳＶ）、水痘帯状疱疹ウイルス（ＶＺＶ）、エイズウイルス（Ｈｕｍａｎ Ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ Ｖｉｒｕｓ：ＨＩＶ）等のウイルスから選ばれるものである上記（１）〜（４）のいずれかに記載の感受性を増強する方法。 (5) Pathogenic microorganisms having drug resistance are Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Klebsiella pneumoniae, enterobacteria enterobacteria, Proteus, Salmonella typhi, Salmonella, Citrobacter, Shigella, Vibrio parahaemolyticus, pneumococci, Helicobacter pylori, archaea, cereus, serratia, pyogenes streptococci, acinetobacteria, influenza, cepacia, enterococci, staphylococcus epidermidis Bacteria such as Cataract, Group B Streptococcus, Bacteroides, etc., or Ringworm, Superficial Fungi, Plaster Microspore, Aspergillus, Candida, Cryptococcus, Norcadia, Mucor, Scarlet, etc. Fungus, or Q beta phage, M13 bacteriophage, influenza virus, hepatitis The sensitivity according to any one of (1) to (4) above, which is selected from viruses such as viruses, herpesvirus (HSV), varicella-zoster virus (VZV), AIDS virus (Human Immunodefectivity Virus: HIV) and the like. How to strengthen.
（６）抗菌性物質が、ペニシリン系、セフェム系、カルバペネム系、モノバクタム系からなるベータ・ラクタム系抗生剤、アミノグリコシド系抗生剤、マクロライド系抗生剤、テトラサイクリン系抗生剤、クロラムフェニコール系抗生剤、リンコマイシン系抗生剤、グリコペプチド系抗生剤、サルファ剤抗生剤、キノロン系抗生剤等の抗生剤、または洗剤、消毒薬、漂白剤、植物由来の抗菌性物質、または光触媒による抗菌作用物質から選ばれるものである上記（１）〜（５）のいずれかに記載の感受性を増強する方法。 (6) Antibacterial substances include beta-lactam antibiotics, aminoglycoside antibiotics, macrolide antibiotics, tetracycline antibiotics, chloramphenicol antibiotics consisting of penicillins, cephems, carbapenems and monobactams From antibiotics, lincomycin antibiotics, glycopeptide antibiotics, sulfa antibiotics, quinolone antibiotics, or detergents, disinfectants, bleaches, plant-derived antibacterial substances, or photocatalytic antibacterial substances The method for enhancing sensitivity according to any one of the above (1) to (5), which is selected.
（７）薬剤耐性を有する病原性微生物の、抗菌性物質存在下における、当該抗菌性物質に対する感受性が下記の組み合わせから選ばれるものである上記（１）〜（４）のいずれかに記載の感受性を増強する方法。
１）セパシア菌のエリスロマイシン、ゲンタマイシン、クロラムフェニコール、テトラサイクリンに対する感受性、または、
２）ＭＲＳＡのアンピシリン、テトラサイクリンに対する感受性、または、
３）緑膿菌のクロラムフェニコール、テトラサイクリンに対する感受性、または、
４）セラチア菌のエリスロマイシンに対する感受性。
(7) The sensitivity according to any one of (1) to (4) above, wherein the sensitivity of the pathogenic microorganism having drug resistance to the antibacterial substance in the presence of the antibacterial substance is selected from the following combinations: How to strengthen.
1) sensitivity of cepacia to erythromycin, gentamicin, chloramphenicol, tetracycline, or
2) sensitivity of MRSA to ampicillin, tetracycline, or
3) Susceptibility of Pseudomonas aeruginosa to chloramphenicol, tetracycline, or
4) Sensitivity of Serratia to erythromycin.
（８）上記（１）に記載の病原性微生物の抗菌性物質に対する感受性を増強する方法であって、高濃度の抗菌性物質存在下にＬＥＤを照射して、高度薬剤耐性を有する病原性微生物の出現を予防する方法。 (8) A method for enhancing the susceptibility of a pathogenic microorganism according to (1) to an antibacterial substance, wherein the LED is irradiated in the presence of a high concentration of the antibacterial substance and has a high drug resistance. To prevent the emergence of.
（９）前記ＬＥＤが４０５ｎｍをピークとする４００−４１０ｎｍの波長を有するものである上記（８）に記載の病原性微生物の出現を予防する方法。 (9) The method for preventing the appearance of pathogenic microorganisms according to (8) above, wherein the LED has a wavelength of 400 to 410 nm having a peak at 405 nm.
（１０）高度薬剤耐性を有する病原性微生物に対し、４０５ｎｍの波長を有するＬＥＤを用い、強度２〜１０ｍＷ／ｃｍ２の光を１６〜５０時間照射することを特徴とする上記（８）または（９）に記載の病原性微生物の出現を予防する方法。
(10) The above (8) or (9), wherein a pathogenic microorganism having high drug resistance is irradiated with light having an intensity of 2 to 10 mW /
（１１）高度薬剤耐性を有する病原性微生物が、ＭＲＳＡである上記（８）〜（１０）のいずれかに記載の病原性微生物の出現を予防する方法。 (11) The method for preventing the appearance of the pathogenic microorganism according to any one of (8) to (10), wherein the pathogenic microorganism having high drug resistance is MRSA.
（１２）高濃度の抗菌性物質がオフロキサシン、セファゾリン、セフォチアム、セファメタゾール、フロモキセフ、またはイミペネムから選ばれるものである上記（８）〜（１１）のいずれかに記載の病原性微生物の出現を予防する方法。 (12) Appearance of the pathogenic microorganism according to any one of the above (8) to (11), wherein the high-concentration antibacterial substance is selected from ofloxacin, cefazoline, cefotiam, cephamethazole, flomoxef, or imipenem. How to prevent.
本発明により、薬剤耐性を有する病原性微生物の感受性が増強するため、手術後の日和見感染や院内感染等による危険性を弱めることが可能である。更に、高濃度の抗菌性物質で処理するため耐性菌が出現しやすい状況において、ＬＥＤを照射することにより、耐性菌の出現を予防することが可能になる。 According to the present invention, since the susceptibility of pathogenic microorganisms having drug resistance is enhanced, it is possible to reduce the risk due to opportunistic infection and nosocomial infection after surgery. Furthermore, since treatment with a high concentration of antibacterial substance makes it possible to prevent the appearance of resistant bacteria by irradiating the LED in a situation where resistant bacteria are likely to appear.
本発明は、ＬＥＤを照射して、薬剤耐性を有する病原性微生物の抗菌性物質に対する感受性を増強する方法である。 The present invention is a method for enhancing the sensitivity of a pathogenic microorganism having drug resistance to an antibacterial substance by irradiating an LED.
本発明で使用するＬＥＤは、赤色ダイオード、緑色ダイオード、青色ダイオード、白色ダイオード、紫外色ダイオードが挙げられる。近紫外波長（３５０−４１０ｎｍ）を有するダイオードが効果的であり、４０５ｎｍをピークとする４００−４１０ｎｍの波長を有する近紫外ダイオード（以後４０５ｎｍＬＥＤという）が人体や環境への影響を考慮するときもっとも適切である。 Examples of the LED used in the present invention include a red diode, a green diode, a blue diode, a white diode, and an ultraviolet diode. A diode having a near-ultraviolet wavelength (350-410 nm) is effective, and a near-ultraviolet diode having a wavelength of 400-410 nm with a peak at 405 nm (hereinafter referred to as 405 nm LED) is most appropriate when considering the influence on the human body and the environment. It is.
ＬＥＤの耐性菌に照射する光強度は、好ましくは、１００μＷ〜１００ｍＷ／ｃｍ２であるが、最も好ましいのは、２〜１０ｍＷ／ｃｍ２である。照射対象物への照射方法は、照射装置の構造や対象物の形状・存在する環境によって異なる。人をはじめとする動物や植物などを対象とする場合には、近接（５〜２０ｃｍ）もしくは対象物から２００ｃｍまでの間隔にして行う。
The light intensity applied to the LED resistant bacteria is preferably 100 μW to 100 mW /
薬剤感受性試験は、次のように行う。図１に示すように、検査対象菌を適切な固形培地上に塗布し、その上に試験する薬剤を含む濾紙を定着させる。カバーをした後、適切な培養温度で菌を増殖させる。このとき、薬剤の濾紙に近い培地には高濃度の薬剤が滲出し、濾紙から遠くになるに従いその薬剤濃度は低下する。検査対象菌の増殖不可能な薬剤濃度のところで、成育阻止円が形成される。その成育阻止円の半径により、検査対象菌のその薬剤に対する感受性（耐性）度が計測される。また、このときにＬＥＤ光を照射すると、ＬＥＤ光による薬剤感受性変化を比較・測定することが出来る。 The drug sensitivity test is performed as follows. As shown in FIG. 1, the test bacteria are applied on a suitable solid medium, and a filter paper containing the drug to be tested is fixed thereon. After covering, the bacteria are grown at an appropriate culture temperature. At this time, a high concentration of the drug oozes out from the medium close to the filter paper for the drug, and the drug concentration decreases as the distance from the filter paper increases. A growth inhibition circle is formed at a drug concentration at which the test bacteria cannot grow. The degree of sensitivity (resistance) of the bacterium to be tested to the drug is measured by the radius of the growth inhibition circle. Moreover, when LED light is irradiated at this time, the drug sensitivity change by LED light can be compared and measured.
本発明における「感受性」とは、例えば、病原微生物であるＡ菌に対して、ある抗菌性物質Ｂが有効であるとき、Ａ菌は抗菌性物質Ｂに対して感受性があると言い、「感受性を増強する」とは、Ａ菌に対する抗菌性物質Ｂの効果を高めることを意味する。 “Sensitivity” in the present invention means that, for example, when a certain antibacterial substance B is effective against a bacterium A which is a pathogenic microorganism, the A bacterium is sensitive to the antibacterial substance B. “To enhance” means to enhance the effect of the antibacterial substance B against A bacteria.
本発明における「薬剤耐性を有する病原性微生物」とは、薬剤（抗菌性物質）に対して抵抗性を持ち、薬剤が効かない、あるいは効きにくくなった病原性微生物を指し、細菌、真菌、ウイルスが含まれる。 The “pathogenic microorganism having drug resistance” in the present invention refers to a pathogenic microorganism having resistance to a drug (antibacterial substance) and ineffective or less effective for the drug. Is included.
細菌としては、大腸菌（Ｅｓｃｈｅｒｉｃｈｉａ ｃｏｌｉ）、黄色ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ）、メチシリン耐性黄色ブドウ球菌（ｍｅｔｈｉｃｉｌｌｉｎ−ｒｅｓｉｓｔａｎｔ Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ：ＭＲＳＡ）、緑膿菌（Ｐｓｅｕｄｏｍｏｎａｓ ａｅｒｕｇｉｎｏｓａ）、肺炎桿菌（Ｋｌｅｂｓｉｅｌｌａ ｐｎｅｕｍｏｎｉａｅ）、腸内細菌エンテロバクテリア（Ｅｎｔｅｒｏｂａｃｔｅｒ ｃｌｏａｃａｅ）、プロテウス菌（Ｐｒｏｔｅｕｓ、Ｐｒｏｖｉｄｅｎｃｉａ、Ｍｏｒｇａｎｅｌｌａ）、サルモネラ・チフス菌（Ｓａｌｍｏｎｅｌｌａ ｔｙｐｈｉｍｕｒｉｕｍ）、サルモネラ菌（Ｓａｌｍｏｎｅｌｌａ ｅｎｔｅｒｉｔｉｄｉｓ）、シトロバクター菌（Ｃｉｔｒｏｂａｃｔｅｒ ｆｒｅｕｎｄｉｉ）、赤痢菌（Ｓｈｉｇｅｌｌａ ｄｙｓｅｎｔｅｒｉａｅ）、腸炎ビブリオ菌（Ｖｉｂｒｉｏ ｐａｒａｈａｅｍｏｌｙｔｉｃｕｓ）、肺炎球菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｐｎｅｕｍｏｎｉａｅ）、ヘリコバクター・ピロリ菌（Ｈｅｌｉｃｏｂａｃｔｅｒ ｐｙｌｏｒｉ）、古草菌（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ）、セレウス菌（Ｂａｃｉｌｌｕｓ ｃｅｒｅｕｓ）、セラチア菌（Ｓｅｒｒａｔｉａ ｍａｒｃｅｓｃｅｎｓ）、化膿レンサ球菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｐｙｏｇｅｎｅｓ）、アシネトバクテリア菌（Ａｃｉｎｅｔｏｂａｃｔｅｒ ｃａｌｃｏａｃｅｔｉｃｕｓ）、インフルエンザ菌（Ｈａｅｍｏｐｈｉｌｕｓ ｉｎｆｌｕｅｎｚａｅ）、セパシア菌（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ）、腸球菌（Ｅｎｔｅｒｏｃｏｃｃｕｓ）、 表皮ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ｅｐｉｄｅｒｍｉｄｉｓ）、カタル球菌（Ｍｏｒａｘｅｌｌａ（Ｂｒａｎｈａｍｅｌｌａ）ｃａｔａｒｒｈａｌｉｓ）、B群レンサ球菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ａｇａｌａｃｔｉａｅ）およびバクテロイド菌（Ｂａｃｔｅｒｏｉｄｅｓ ｆｒａｇｉｌｉｓ）等をあげることができる。 Examples of the bacterium include Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonasella pneumoniae, Bacterial Enterobacteria (Proteus, Providencia, Morganella), Salmonella typhimurium, Salmonella enteritidis (Citrobacter), Citrobacter (Citrobacter) acter freundii), Shigella dysenteriae, Vibrio parahaelus mylyticus, Streptococcus pneumoniae, Helicobacter pylori (Helicobacter pylum) Serratia marcescens, Streptococcus pyogenes, Acinetobacter calcoaceticus, Haemophilus influenzae, Pseudomonia epacia), enterococci (Enterococcus), Staphylococcus epidermidis (Staphylococcus epidermidis), Moraxella catarrhalis (Moraxella (Branhamella) catarrhalis), B streptococci (Streptococcus agalactiae) and Bacteroides bacteria (Bacteroides fragilis) or the like can be mentioned.
真菌としては、白癬菌（Ｔｒｉｃｈｏｐｈｙｔｏｎ ｍｅｎｔａｇｒｏｐｈｙｔｅｓ）、表在性真菌（Ｅｐｉｄｅｒｍｏｐｈｙｔｏｎ ｆｌｏｃｃｏｓｕｍ）、石膏状小胞子菌（Ｍｉｃｒｏｓｐｏｒｕｍ ｇｙｐｓｅｕｍ）、アスペルギルス菌（Ａｓｐｅｒｇｉｌｌｕｓ）、カンジダ菌（ｃａｎｄｉｄａ ａｌｂｉｃａｎｓ）、クリプトコッカス菌（Ｃｒｙｐｔｏｃｏｃｃｕｓ）、ノルカジア菌、ムコール菌（ｍｕｃｏｒｍｙｃｏｓ）および瘢風菌等をあげることができる。 Examples of fungi include Trichophyton mentagrophytes, Superficial fungi (Epidermophyton floccusum), Microsporum gypsum, Aspergillus (c), Candida (c), Candida (c) Examples thereof include fungi, mucormycos, and scabs.
ウイルスとしては、大腸菌に感染するファージウイルスであるＱベータファージや、Ｍ１３バクテリオファージの他、インフルエンザウイルス、肝炎ウイルス、ヘルペスウイルス（Ｈｅｒｐｅｓ Ｓｉｍｐｌｅｘ Ｖｉｒｕｓ：ＨＳＶ）、水痘帯状疱疹ウイルス（Ｖａｒｉｃｅｌｌａ Ｚｏｓｔｅｒ Ｖｉｒｕｓ：ＶＺＶ）、およびエイズウイルス（Ｈｕｍａｎ Ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ Ｖｉｒｕｓ：ＨＩＶ）等をあげることができる。 As viruses, Q beta phage which is a phage virus that infects Escherichia coli, M13 bacteriophage, influenza virus, hepatitis virus, herpes virus (Herpes Simplex Virus: HSV), varicella zoster virus (VZV) And AIDS virus (Human Immunodefense Virus: HIV) and the like.
本発明で使用する抗菌性物質とは、抗生剤、抗真菌剤および抗ウイルス剤、洗剤、消毒薬、漂白剤、植物由来の抗菌性物質、光触媒による抗菌作用物質をいう。特に、細菌、真菌、ウイルス等の病原性微生物が耐性を有する抗生剤、抗真菌剤および抗ウイルス剤を指す。 The antibacterial substance used in the present invention refers to antibiotics, antifungal and antiviral agents, detergents, disinfectants, bleaching agents, plant-derived antibacterial substances, and antibacterial substances using photocatalysts. In particular, it refers to antibiotics, antifungals and antivirals to which pathogenic microorganisms such as bacteria, fungi and viruses are resistant.
抗生剤としては、ベータ・ラクタム系抗生剤のペニシリン系抗生剤として、オキサシリン（ＭＰＩＰＣ）、ベンジルペニシリン（ＰＣＧ）アンピシリン（ＡＢＰＣ）、ピペラシン（ＰＩＰＣ）、アモキシシリン、メチシリン等を、セフェム系抗生剤として、セファゾリン（ＣＥＺ）、セフォチアム（ＣＴＭ）、セフメタゾール（ＣＭＺ）、フロモキセフ（ＦＭＯＸ）、セフォペラゾン（ＣＰＺ）、スルバクタム・セフォペラゾン（ＳＢＴ／ＣＰＺ）、セフォタキシム（ＣＴＸ）、セフタジジム（ＣＡＺ）、セフピロム（ＣＰＲ）、セフェピム（ＣＦＰＭ）、セフォゾプラン（ＣＺＯＰ）等を、カルバペネム系抗生剤として、イミペネム（ＩＰＭ）、パニペネム（ＰＡＰＭ）、メロペネム（ＭＥＰＭ）等を、モノバクタム系抗生剤として、アズトレオナム（ＡＺＴ）、カルモナム（ＣＲＭＮ）等を、また、アミノグリコシド系抗生剤として、ゲンタマイシン（ＧＭ）、トブラマイシン（ＴＯＢ）、アミカシン（ＡＭＫ）、アルベカシン（ＡＢＫ）、ストレプトマイシン、カナマイシン等を、マクロライド系抗生剤としてエリスロマイシン（ＥＭ）、テトラサイクリン系抗生剤としてミノサイクリン（ＭＩＮＯ）、リンコマイシン系抗生剤としてクリンダマイシン（ＣＬＤＭ）、およびクロラムフェニコール系抗生剤をあげることができる。さらに、グリコペプチド系抗生剤として、バンコマイシン（ＶＣＭ）やテイコプラニン（ＴＥＩＣ）、キノロン系抗生剤として、オフロキサシン（ＯＦＬＸ）やレボフロキサシン（ＬＶＦＸ）、またサルファ剤系抗生剤等をあげることができる。 As antibiotics, beta-lactam antibiotics, penicillin antibiotics, oxacillin (MPIPC), benzylpenicillin (PCG) ampicillin (ABPC), piperacin (PIPC), amoxicillin, methicillin, etc. as cephem antibiotics, Cefazolin (CEZ), Cefotiam (CTM), Cefmetazole (CMZ), Flomoxef (FMOX), Cefoperazone (CPZ), Sulbactam Cefoperazone (SBT / CPZ), Cefotaxim (CTX), Cefazidime (CAZ), Cefopirome (CPR), (CFPM), cefozopran (CZOP), etc. as carbapenem antibiotics, imipenem (IPM), panipenem (PAPM), meropenem (MEPM), etc. as monobactam antibiotics Leonam (AZT), carmonam (CRMN), etc., and aminoglycoside antibiotics such as gentamicin (GM), tobramycin (TOB), amikacin (AMK), arbekacin (ABK), streptomycin, kanamycin, etc., macrolide antibiotics As the agent, erythromycin (EM), minocycline (MINO) as the tetracycline antibiotic, clindamycin (CLDM) as the lincomycin antibiotic, and chloramphenicol antibiotic can be mentioned. Furthermore, examples of the glycopeptide antibiotic include vancomycin (VCM) and teicoplanin (TEIC), and examples of the quinolone antibiotic include ofloxacin (OFLX), levofloxacin (LVFX), and sulfa antibiotics.
抗真菌剤としては、アンフォテリシンＢ等のポリエンマクロライド系、およびフルシトシン等のピリミジン誘導体、およびミコナゾール、クロトリマゾール、ビホナゾール等のイミダゾール系、およびフルコナゾール、イトラコナゾール等のトリアゾール系等の抗真菌剤をあげることができる。 Examples of antifungal agents include polyene macrolides such as amphotericin B, pyrimidine derivatives such as flucytosine, imidazoles such as miconazole, clotrimazole, and bifonazole, and triazoles such as fluconazole and itraconazole. be able to.
抗ウイルス剤としては、ジドブジン、スタブジン、デラビルジン、イドクスウリジン、アシクロビル、ファムシクロビル、ガンシクロビル、アマンタジン、リマンタジン等があげられるが、ウイルスは、病原性微生物の中では、最も形態変異を起こしやすい生物であるため、多くの薬剤が短期間で耐性になり効果を失う。 Antiviral agents include zidovudine, stavudine, delavirdine, idoxuridine, acyclovir, famciclovir, ganciclovir, amantadine, rimantadine, etc., but viruses are the organisms most likely to undergo morphological variation among pathogenic microorganisms. Therefore, many drugs become resistant in a short period and lose their effect.
ＬＥＤを照射することにより、抗生剤存在下で、薬剤耐性を有する病原性微生物の当該抗生剤に対する感受性の増強は、下記の組み合わせにおいて見出されるものである。すなわち、大腸菌のカナマイシン、ストレプトマイシン等のアミノグルコシド系抗生剤、アンピシリン等のペニシリン系抗生剤、クロラムフェニコール、テトラサイクリン系抗生剤に対する感受性、あるいはＭＲＳＡのメチシリン、アンピシリン、クロキサシン、オキサシリン等のペニシリン系抗生剤、セフェム系抗生剤、テトラサイクリン系抗生剤に対する感受性、あるいは緑膿菌のカンバペネム抗生剤、テトラサイクリン系抗生剤、クロラムフェニコールに対する感受性、あるいは肺炎桿菌のセフタジジム、セフォタキシム等のセフェム系抗生剤に対する感受性、あるいは腸内細菌エンテロバクテリアのセフェム系抗生剤に対する感受性、あるいはシトロバクター菌のセフェム系抗生剤に対する感受性、あるいは肺炎球菌のペニシリン系抗生剤に対する感受性、あるいはセラチア菌のペニシリン系抗生剤、セフェム系抗生剤、カルバペネム抗生剤、エリスロマイシンに対する感受性、セパシア菌のエリスロマイシン、ゲンタマイシンに対する感受性、あるいは化膿レンサ球菌のペニシリン系抗生剤、マクロライド系抗生剤に対する感受性等である。 By irradiating the LED, in the presence of the antibiotic, the enhancement of the sensitivity of the pathogenic microorganism having drug resistance to the antibiotic is found in the following combinations. That is, sensitivity to aminoglucoside antibiotics such as kanamycin and streptomycin of Escherichia coli, penicillin antibiotics such as ampicillin, chloramphenicol, tetracycline antibiotics, or penicillin antibiotics such as MRSA methicillin, ampicillin, cloxacin, oxacillin, etc. Susceptibility to Cephem antibiotics, cephem antibiotics, tetracycline antibiotics, Pseudomonas aeruginosa cambapenem antibiotics, tetracycline antibiotics, chloramphenicol, or Klebsiella pneumoniae ceftazidime, cefotaxime, etc. Or enterobacterial enterobacteria susceptibility to cephem antibiotics, or Citrobacter susceptibility to cephem antibiotics, or Streptococcus pneumoniae penicillin Sensitivity to herbicides, Sericia penicillin antibiotics, cephem antibiotics, carbapenem antibiotics, erythromycin sensitivity, cepacia erythromycin, gentamicin sensitivity, or Streptococcus penicillin antibiotics, macrolide antibiotics Sensitivity to the agent.
本発明はまた、高濃度の抗菌性物質存在下にＬＥＤを照射して、高度薬剤耐性を有する病原性微生物の出現を予防する方法である。高度薬剤耐性を有する病原性微生物とは、高濃度で使用された抗菌性物質に対し、薬剤耐性を強く持つようになった病原性微生物のことをいう。高度薬剤耐性を有する病原性微生物としては、ＭＲＳＡ、緑膿菌、セパシア菌、セラチア菌があげられ、病原性微生物が耐性を有する抗菌性物質としては、オフロキサシン、セファゾリン、セフォチアム、セファメタゾール、フロモキセフ、またはイミペネム等があげられる。上記の抗菌性物質の存在下に、ＬＥＤを照射することにより、高度薬剤耐性を有する病原性微生物の感受性が高まり、出現を予防することができるが、特に著しい効果を現す組み合わせは、ＭＲＳＡのオフロキサシンに対する感受性であり、オフロキサシン存在下でＭＲＳＡの出現を予防することができる。 The present invention is also a method for preventing the appearance of pathogenic microorganisms having high drug resistance by irradiating LEDs in the presence of a high concentration of antibacterial substances. A pathogenic microorganism having a high drug resistance refers to a pathogenic microorganism having a strong drug resistance against an antibacterial substance used at a high concentration. Examples of pathogenic microorganisms having high drug resistance include MRSA, Pseudomonas aeruginosa, Sephacia and Serratia, and antibacterial substances to which pathogenic microorganisms are resistant include ofloxacin, cefazoline, cefotiam, cephamethazole, flomoxef. Or imipenem. Irradiation with an LED in the presence of the above antibacterial substance increases the susceptibility of pathogenic microorganisms having high drug resistance and can prevent their appearance, but a combination that exhibits a particularly remarkable effect is the MRSA ofloxacin. And can prevent the appearance of MRSA in the presence of ofloxacin.
以下、本発明を更に詳しく説明するため、実施例を挙げるが本発明はこれに限定されない。 Hereinafter, examples will be given to describe the present invention in more detail, but the present invention is not limited thereto.
１）使用菌株
試験に用いた菌株は、メチシリン感受性黄色ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ：ＭＳＳＡ）を、メチシリン耐性黄色ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ：ＭＲＳＡ）、緑膿菌Ｐｓｅｕｄｏｍｏｎａｓ ａｅｒｕｇｉｎｏｓａ ＰＡＯ１、セパシア菌（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ）およびセラチア菌Ｓｅｒｒａｔｉａ ｍａｒｃｅｓｃｅｎｓを用いた。
1) Strain used The strains used in the test were methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa pA, sepa The Serratia marcescens was used.
２）培地及び器材
液体培地：ＬＢ−Ｂｒｏｔｈ（Ｌｅｎｎｏｘ）（ｎａｃａｌａｉ ｔｅｓｑｕｅ）
固形培地：ミュラーヒントン寒天培地−Ｎ「ニッスイ」（日水製薬株式会社製）
薬剤感受性ディスク：ＳＮディスク、ＳＮディスク−Ｋ（日水製薬株式会社製）
４０５ｎｍＬＥＤ照射装置：（小糸製作所製）
その他の器材：ニッスイ角シャーレ２号、滅菌綿棒（日水製薬株式会社製）
2) Medium and equipment liquid medium: LB-Broth (Lennox) (nacalai tesque)
Solid medium: Mueller Hinton agar medium-N “Nissui” (manufactured by Nissui Pharmaceutical Co., Ltd.)
Drug sensitivity disk: SN disk, SN disk-K (manufactured by Nissui Pharmaceutical Co., Ltd.)
405 nm LED irradiation device: (manufactured by Koito Manufacturing Co., Ltd.)
Other equipment: Nissui Square Petri dish No. 2, sterile cotton swab (manufactured by Nissui Pharmaceutical Co., Ltd.)
３）薬剤感受性ディスク
ＳＮディスクおよびＳＮディスク−Ｋ（日水製薬株式会社）を用いた。抗菌性物質としては、オキサシリン（ＭＰＩＰＣ）、ベンジルペニシリン（ＰＣＧ）アンピシリン（ＡＢＰＣ）、ピペラシン（ＰＩＰＣ）、セファゾリン（ＣＥＺ）、セフォチアム（ＣＴＭ）、セフメタゾール（ＣＭＺ）、フロモキセフ（ＦＭＯＸ）、セフォペラゾン（ＣＰＺ）、スルバクタム・セフォペラゾン（ＳＢＴ／ＣＰＺ）、セフォタキシム（ＣＴＸ）、セフタジジム（ＣＡＺ）、セフピロム（ＣＰＲ）、セフェピム（ＣＦＰＭ）、セフォゾプラン（ＣＺＯＰ）、イミペネム（ＩＰＭ）、パニペネム（ＰＡＰＭ）、メロペネム（ＭＥＰＭ）、アズトレオナム（ＡＺＴ）、カルモナム（ＣＲＭＮ）、ゲンタマイシン（ＧＭ）、トブラマイシン（ＴＯＢ）、アミカシン（ＡＭＫ）、アルベカシン（ＡＢＫ）、ミノサイクリン（ＭＩＮＯ）、エリスロマイシン（ＥＭ）、クリンダマイシン（ＣＬＤＭ）、バンコマイシン（ＶＣＭ）、テイコプラニン（ＴＥＩＣ）、オフロキサシン（ＯＦＬＸ）、レボフロキサシン（ＬＶＦＸ）を使用した。
3) Drug sensitivity disk SN disk and SN disk-K (Nissui Pharmaceutical Co., Ltd.) were used. Antibacterial substances include oxacillin (MPIPC), benzylpenicillin (PCG) ampicillin (ABPC), piperacin (PIPC), cefazolin (CEZ), cefotiam (CTM), cefmetazole (CMZ), flomoxef (FMOX), cefoperazone (CPZ) , Sulbactam cefoperazone (SBT / CPZ), cefotaxime (CTX), ceftazidime (CAZ), cefpirom (CPR), cefepime (CFPM), cefozopran (CZOP), imipenem (IPM), panipenem (PAPM), meropenem (PM) Aztreonam (AZT), Carmonam (CRMN), Gentamicin (GM), Tobramycin (TOB), Amikacin (AMK), Arbekacin (ABK), Minocycline (MINO) Erythromycin (EM), clindamycin (CLDM), vancomycin (VCM), teicoplanin (TEIC), ofloxacin (OFLX), was used levofloxacin (LVFX).
４）培養方法
ＬＢ−Ｂｒｏｔｈに接種した使用菌をＯ／Ｎで培養し、新しいＬＢ−Ｂｒｏｔｈに再度接種し対数増殖期の菌を生理食塩水でＯＤ６００ｎｍ＝０．０５に調節した菌液をミュラーヒントン寒天培地−Ｎ ８０ｍｌを固めたニッスイ角シャーレ２号に滅菌綿棒に菌液をよく浸し、余分な菌液は試験管の管壁で除き図２の様に菌液を塗布した。その上に試験する８種類の薬剤を含む濾紙を定着させた。カバーをした後、同じ角シャーレを２枚作成しＬＥＤを照射するものと、照射しないものに分け、２４時間照射容器で培養した。
4) Cultivation method The used bacteria inoculated into LB-Broth is cultured with O / N, then inoculated again into new LB-Broth, and the bacterial solution in which the logarithmic growth period bacteria are adjusted to OD 600 nm = 0.05 with physiological saline is Mueller. The bacterial solution was thoroughly immersed in a sterilized cotton swab in a Nissui square dish No. 2 in which 80 ml of Hinton agar medium-N was hardened, and the excess bacterial solution was removed at the tube wall of the test tube, and the bacterial solution was applied as shown in FIG. A filter paper containing 8 kinds of drugs to be tested was fixed thereon. After covering, two identical petri dishes were prepared and divided into those that were irradiated with LED and those that were not irradiated, and cultured in an irradiation container for 24 hours.
５）ＬＥＤの照射実験
ＬＥＤ照射装置を含むシャーレ（ＬＥＤを照射するもの、しないもの）は、３２リットル（内寸約３２０ｍｍ×４２５ｍｍ×２３０ｍｍ）のプラスチック容器内に置いて照射実験を行った。（図３、図４）本照射装置で１０ｍＡの電流、４０５ｎｍＬＥＤで１３０ｍｍの距離から２４時間照射した。照射容器の外部温度は約２９℃で４０５ｎｍＬＥＤ照射表面は約３４℃で、同容器内の４０５ｎｍＬＥＤの照射されない空間の温度は約２９℃であった。４０５ｎｍＬＥＤを照射しない角シャーレはこの空間に置いた。ＬＥＤを照射するシャーレには培地の乾燥を防止する目的でシャーレの縁から約１ｍｍの隙間をもたせサランラップで覆った。
5) LED irradiation experiment The petri dish including the LED irradiation device (one that irradiates the LED, one that does not irradiate the LED) was placed in a 32 liter (inner dimensions about 320 mm x 425 mm x 230 mm) plastic container for an irradiation experiment. (FIGS. 3 and 4) Irradiation was performed for 24 hours from a current of 10 mA with this irradiation apparatus and a distance of 130 mm with a 405 nm LED. The external temperature of the irradiation container was about 29 ° C., the surface irradiated with the 405 nm LED was about 34 ° C., and the temperature of the non-irradiated space of the 405 nm LED in the container was about 29 ° C. An angular petri dish that did not irradiate a 405 nm LED was placed in this space. The petri dish irradiated with the LED was covered with a Saran wrap with a gap of about 1 mm from the edge of the petri dish for the purpose of preventing the culture medium from drying.
６）結果
ＬＥＤ光を照射による薬剤感受性変化について、図５にはセラチア菌、セパシア菌、ＭＲＳＡ菌についての実際の実験結果を、図６には、セパシア菌、ＭＲＳＡ菌、緑膿菌、セラチア菌についての感受性評価を示した。
6) Results Regarding drug sensitivity change by irradiation with LED light, FIG. 5 shows actual experimental results for Serratia, Sephacia and MRSA, and FIG. 6 shows Sephacia, MRSA, Pseudomonas and Serratia. The sensitivity evaluation for was shown.
１）使用菌株
メチシリン耐性黄色ブドウ球菌（Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ：ＭＲＳＡ）を試験に用いた。
1) Strain used Methicillin-resistant Staphylococcus aureus (MRSA) was used for the test.
２）培地および器材感受性ディスク
実施例1で使用したものと同じものを使用した。
2) Medium and equipment sensitive disc The same one as used in Example 1 was used.
３）薬剤感受性ディスク
ＳＮディスクおよびＳＮディスク−Ｋ（日水製薬株式会社）を用いた。抗菌性物質としては、オキサシリン（ＭＰＩＰＣ）、ベンジルペニシリン（ＰＣＧ）アンピシリン（ＡＢＰＣ）、セファゾリン（ＣＥＺ）、セフォチアム（ＣＴＭ）、セフメタゾール（ＣＭＺ）、フロモキセフ（ＦＭＯＸ）、イミペネム（ＩＰＭ）、ゲンタマイシン（ＧＭ）、アルベカシン（ＡＢＫ）、ミノサイクリン（ＭＩＮＯ）、エリスロマイシン（ＥＭ）、クリンダマイシン（ＣＬＤＭ）、バンコマイシン（ＶＣＭ）、テイコプラニン（ＴＥＩＣ）、オフロキサシン（ＯＦＬＸ）を使用した。
3) Drug sensitivity disk SN disk and SN disk-K (Nissui Pharmaceutical Co., Ltd.) were used. Antibacterial substances include oxacillin (MPIPC), benzylpenicillin (PCG) ampicillin (ABPC), cefazolin (CEZ), cefotiam (CTM), cefmetazole (CMZ), flomoxef (FMOX), imipenem (IPM), gentamicin (GM) Arbekacin (ABK), Minocycline (MINO), Erythromycin (EM), Clindamycin (CLDM), Vancomycin (VCM), Teicoplanin (TEIC), Ofloxacin (OFLX) were used.
４）培養方法およびＬＥＤ照射実験は実施例１と同様に行った。 4) The culture method and the LED irradiation experiment were performed in the same manner as in Example 1.
５）結果
図７に示すように、高濃度でＭＲＳＡが耐性を有するセファゾリン（ＣＥＺ）、セフォチアム（ＣＴＭ）、セフメタゾール（ＣＭＺ）、フロモキセフ（ＦＭＯＸ）、イミペネム（ＩＰＭ）、オフロキサシン（ＯＦＬＸ）で、生育抑制効果を著しかったことにより、抗菌性物質存在下、ＬＥＤ照射により高度薬剤耐性菌の出現を予防できることが明らかになった。
5) Results As shown in FIG. 7, growth with high concentrations of MRSA resistant cefazolin (CEZ), cefotiam (CTM), cefmetazole (CMZ), flomoxef (FMOX), imipenem (IPM), ofloxacin (OFLX) Due to the remarkable inhibitory effect, it became clear that the appearance of highly drug-resistant bacteria can be prevented by LED irradiation in the presence of antibacterial substances.
本発明の薬剤耐性を有する病原性微生物にＬＥＤを照射して、病原性微生物の薬剤感受性を回復し、増強する方法を利用することにより、薬剤耐性を持った菌による免疫力のない患者の日和見感染や、手術後の患部からの感染など重大な院内感染問題を軽減することができる。特に高濃度に使用する薬剤に対するＭＲＳＡの出現を抑制することができることは、社会的に極めて有用である。 By optimizing the pathogenic microorganisms of the present invention by irradiating the pathogenic microorganisms with LEDs to restore and enhance the drug susceptibility of the pathogenic microorganisms, opportunistic patients who have no immunity due to drug-resistant bacteria Serious hospital infection problems such as infection and infection from affected areas after surgery can be reduced. In particular, the ability to suppress the appearance of MRSA for drugs used at high concentrations is extremely useful to society.
Claims (12)
１）セパシア菌のエリスロマイシン、ゲンタマイシン、クロラムフェニコール、テトラサイクリンに対する感受性、または、
２）ＭＲＳＡのアンピシリン、テトラサイクリンに対する感受性、または、
３）緑膿菌のクロラムフェニコール、テトラサイクリンに対する感受性、または、
４）セラチア菌のエリスロマイシンに対する感受性。 The method for enhancing sensitivity according to any one of claims 1 to 4, wherein the sensitivity of the pathogenic microorganism having drug resistance to the antibacterial substance in the presence of the antibacterial substance is selected from the following combinations.
1) sensitivity of cepacia to erythromycin, gentamicin, chloramphenicol, tetracycline, or
2) sensitivity of MRSA to ampicillin, tetracycline, or
3) Susceptibility of Pseudomonas aeruginosa to chloramphenicol, tetracycline, or
4) Sensitivity of Serratia to erythromycin.
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|---|---|---|---|---|
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