Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-01-10
2001-05-01
Jones, W. Gary (Department: 1655)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S024320, C536S024300, C536S024330, C435S252100, C435S006120
Reexamination Certificate
active
06225453
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a probe which is useful for detecting and identifying
Klebsiella pneunoniae
, the causative bacteria of infectious diseases, specifically, representative bacteria which cause sepsis, as well as
Klebsiella pneumonia.
BACK GROUND ART
Pathologically, “infection” is defined as an invasion of pathogenic microorganisms (hereinafter referred to as “bacteria”) and an establishment of footholds for the growth in the host organism by the pathogenic microorganisms.
Thereafter, the outbreak of the disease states caused by proliferation of the pathogenic microorganisms in vivo depends upon the relationship between the resistance of the host and the toxicity of the bacteria.
The diseases caused by infection of pathogenic microorganisms are called infectious diseases. Generally, bacteremia in the broad meanings is defined as the cases where the phagocytic abilities of the host cells can not overcome the bacterial proliferative abilities, and the bacteria spread over systemically through the blood flow. Among the bacteremia, the disease state wherein the causative bacteria are discharged into the blood flow persistently or intermittently from a particular focus (infection focus) of the host body, thereby new infection focus is built in another part of the body, resulting in the serious systemic symptoms is called sepsis. Particularly, when the body defense mechanisms against the infection are deteriorated due to the underlying disease and the therapeutic treatment for such disease, especially in the disease state of malignant tumor, leukemia, collagen disease or the like, the infection may often lead to sepsis, then even to the shock state, then DIC (disseminated intravascular coagulation), ARDS (adult respiratory distress syndrome) and the like, finally to the death.
Thus, there is a demand for the improvement of the method for rapid diagnosis of the infectious disease because the accurate diagnosis at an early stage of the infection is necessary, which is extremely crucial for the appropriate therapeutic treatment.
Further, when the host suffers from the infectious disease, the phagocytes such as neutrophils, monocytes and macrophages primarily play defensive roles in the tissues in vivo, while the dominantly proliferated bacteria are exited from the phagocytic cells into the host blood flow, then the bacteria will make appearance in the blood.
In the conventional diagnostic procedure, it is mandatory to: (1) analyze the clinical symptoms; (2) culture the specimen for the proliferation of the causative bacteria; (3) identify the causative bacteria isolated from the specimen; and (4) check the shock state of the patient, and then the therapeutic strategy is determined after these items are sufficiently examined. For determinative diagnosis, the causative bacteria must be detected and identified accurately from the specimen such as blood, then the therapeutic treatment should be conducted by administering appropriate antibiotics and the like for killing the identified bacteria. In particular, the possibility of the presence of the drug-resistant strain as well as possible induction of the replacement of bacteria should be considered well, therefore, it is very important to isolate and identify a pathogen, and to select suitable drugs at an early stage based on the drug sensitivity test of the pathogen.
Many of the causative bacteria of sepsis are members of gram-negative rods, and among all of these bacteria, aerobic gram-negative rods such as Pseudomonas, Klebsiella and
Escherichia coli
account for 60 to 70%. Especially,
Klebsiella pneumoniae
is the representative of the causative bacteria of sepsis.
On the other hand,
Klebsiella pneumonia
is a kind of pneumonia which is caused by
Klebsiella pneumoniae
. This pneumonia is characterized by the production of a lot of viscous capsule matter, and the occurrence of the resistant bacteria against the drugs, thus, the prognoses may be unfavorable, often leading to death with complication of septic shock.
Bacteremia including sepsis is a disease state wherein the bacteria exit into the blood, and a large dose of the antibiotics effective for the causative bacteria are administered for the therapeutic treatment thereof. Whereas, since antibiotics generally deteriorate several functions of the organs such as liver, administration of the anti-bacterial agents having no effectiveness to the patient in a critical condition should be avoided at most. Therefore, the rapid and accurate method to identify the causative bacteria has been desired in the clinical field.
As above mentioned, the basis of the therapeutic treatment of the bacteremia including sepsis is to administer proper antibiotics at an earliest stage. In order to accomplish such a rapid treatment, the causative bacteria must be elucidated first. In general, identification of the causative bacteria is conducted by culturing the blood sample from a patient suspected as suffering from bacteremia in the bottle with a culture bottle method, and then culturing the sample as a specimen which showed a positive signal in this method on a selection medium. However, in accordance with such a procedure, at least two separate bottles, containing medium for aerobic bacteria and another for anaerobic bacteria are required. Moreover, a long term culture is necessary and indigenous bacteria on skin may be contaminated in the sample. Additionally, in cases of the diagnosis of the patients who had already been treated with a large dose of antibiotics when the possible bacteremia was suspected, the growth and proliferation of the bacteria may be prevented even if the bacteria are present in the specimen. Accordingly, the feasibility of successful culture of the bacteria from such specimen may become extremely low.
Furthermore, alternative subroutine methods developed heretofore may include: an instrumental analysis method of constituents of bacteria and metabolic products from bacteria (See Yoshimi Benno, “Quick identification of bacteria with gas chromatography”,
Rinsho Kensa
, Vol. 29, No.12 pp.1618-1623, November 1985, Igaku Shoin.); a method utilizing a specific antibody (See Japanese Patent Provisional Publication No.60-224068.); and a hybridization method utilizing a specificity of DNA (Japanese Patent Provisional Publication No. 61-502376), however, any of which requires the steps for separation of the bacteria, as well as the steps for culturing and growing the bacteria.
On the other hand, an established method based on the function of the phagocyte in the infectious diseases has been proposed, wherein a stained smear of buffy coat in which leukocytes in the blood sample are concentrated is examined under an optical microscope. Generally speaking, the detection rate of bacteria in buffy coat specimens from adult bacteremia patients is 30% at most, which is similar to that in blood specimens from earlobes, however, it was reported that in case that the patients are newborn children, the bacteria could be detected in seven cases in ten (70%). Therefore, information concerning the presence of bacteria in peripheral blood obtained by a microscopic prospection on a smear can provide an important guiding principle for the therapeutic treatment.
The above mentioned conventional methods necessitate the pretreatment which requires at least three to four days in total, containing one to two days for the selective isolation of bacteria from a specimen, one day for proliferating cultivation, and one or more days for operation of fixation, and the culture thereof should be continued in practice until the bacteria grow enough, therefore, the pretreatment may require one week or more days. In addition, any bacteria other than the causative bacteria may be contaminated during the culture step in some cases, and such contaminants may not be distinguished from the causative bacteria.
More importantly, as mentioned above, because many of the causative bacteria in the specimen to be proliferated and detected have been incorporated into phagocytes, and are al
Abe Kanako
Keshi Hiroyuki
Matsuhisa Akio
Ueyama Hiroshi
Fuso Pharmaceutical Industries Ltd.
Goldberg Jeanine
Jones W. Gary
Marshall O'Toole Gerstein Murray & Borun
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