iNtODEWORLD | New Approach against Emerging Gram(-) Bacteria
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Highly Serious

Gram negative bacterial infections

True infectious control problems come from Gram negative bacteria, while Gram positive bacterial infections, even with multiple drug resistant ones, can be controlled by using multiple antibiotics (either administered in combined single dosages or in separate stages). Gram negative bacteria have a different cell wall structure and react differently to antibiotics than Gram positive bacteria. For this reason, dealing with Gram negative bacterial infections demands separate treatment drugs.

Most of the antibiotics developed after 1945 were for Gram positive bacterial infections. Since the 1970s, development for Gram negative bacterial infections has been continuing. Nevertheless, a targeted, safe and effective treatment drug for Gram negative bacteria hasn’t yet arrived.

Carbapenem is the current drug of choice for the treatment of Gram negative bacterial infections. While it is a broad-spectrum antibiotic effective against both Gram positive and Gram negative bacteria, it is intended to be a drug of last resort and not to be used indiscriminately. Despite this warning, Carbapenem resistant strains have been reported.

ANTIBIOTICS

For Gram negative bacterial infection treatment

Carbapenem

Aminoglycoside

Fluoroquinolone

Imipenem

Meropenem

Doripenem

Amikacin

Gentamicin

Tobramycin

Ciprofloxacin

Levofloxacin

IMPORTANCE OF GRAM NEGATIVE BACTERIA

In the expanding medical perspective

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MULTIPLE DRUG RESISTANT ACINETOBACTER BAUMANNII

Residential Acinetobacter baumannii usually associated with respiratory tract, urinary tract, skin and soft tissue and bloodstream infections and multidrug resistant Acinetobacter baumannii is difficult to treat.

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PSEUDOMONAS AERUGINOSA

Generally benign in normal healthy people, but can be an opportunistic pathogen in persons suffering from various diseases. Infections can occur in damaged tissues caused by burn or surgery, and also in a respiratory tract or eye. Especially in cystic fibrosis and immuno-depressed patients; or in patients with fatal septicemia, endocarditis, peritonitis, malignant external otitis, chronic inflammatory otitis media, or spinal cord osteomyelitis.

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MULTIPLE DRUG RESISTANT ENTEROBACTERIACEAE

Encompass Escherichia, Salmonella, and Enterobacter cloacae are major pathogens which cause intestinal diseases or food poisoning: Enterobacter cloacae is a major pathogen of nosocomial infections which can cause pneumonia and incur death after septicemia.

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CARBAPENEM RESISTANT KLEBSIELLA PNEUMONIAE

Residential bacteria in the oral cavity and intestine can lead to a nosocomial and opportunistic infection. Common infections include a respiratory tract infection (leading to gastroenteritis), urinary tract infections, cerebromeningitis, septicemia and acute pneumonia.

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Symptoms of infection with N. gonorrhoeae differ, depending on the site of infection. Note also that 10% of infected males and 80% of infected females are asymptomatic. Men who have had a gonorrhea infection have a significantly increased risk of having prostate cancer. Infection of the genitals can result in a purulent (or pus-like) discharge from the genitals, which may be foul-smelling. Symptoms may include inflammation, redness, swelling, and dysuria N. gonorrhoeae can also cause conjunctivitis, pharyngitis, proctitis or urethritis, prostatitis, and orchitis

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According to 2008 NHSN (National Healthcare System Network) data, 13% of E. coli and Klebsiella infections, 17% of Pseudomonas infections, and 74% of Acinetobacter baumannii infections were of Multiple Drug Resistant Gram negative bacteria. Almost all of these infectious pathogens were reported to be Carbapenem resistant strains.

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Resistance to the three representative antibiotics for Gram negative infection treatment- Carbapenem, Aminoglycosides and Fluoroquinolone- has already spread amongst the Acinetobacter and Pseudomonas strains.

WORLDWIDE DRUG DEVELOPMENT STATUS

  • Innovative drug development is urgently needed since there is no appropriate treatment alternative against Gram negative superbugs.
  • Recently, a limited number of new drugs having been developed for use in treating Gram negative bacterial infections. For example, Zerbaxa was approved in 2014 and Avycaz in 2015.
  • Currently, the market frequently rewards companies that can bring forth novel treatments with either exclusivity arrangements or simple market dominance. This endgame motivates many companies to research and develop drugs for use in novel Gram negative bacterial infection treatments.
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iNtRON’S NEW DRUG DEVELOPMENT TARGETING GRAM NEGATIVE BACTERIA

  • iNtRON is securing a bacteriophage library specific to Acinetobacter, Paseudomonas, Enterobacteriaceae, and Using their genetic information, iNtRON is developing advanced Endolysin (itlysin) as an innovative next generation antibiotic alternative.
  • The Endolysins can be applied in an effective method to treat Biofilms, which are densely packed communities of microbial cells that grow on living or inert surfaces and surround themselves with a self-produced matrix of extracellular polymeric substance (EPS).

CANDIDATE ENDOLYSINS TARGETING GRAM NEGATIVE BACTERIA

Characteristics of Candidate Endolysins

  • NPA-EL200 – developed using the genetic information of an E. coli bacteriophage and degrades the peptidoglycan linkages found in Salmonella, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia;
  • NPA-TL200 – developed using the genetic information of an E. coli bacteriophage and degrades the peptidoglycan linkages found in Salmonella, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia;
  • NPA-SJ200 – developed using the genetic information of an Salmonella bacteriophage and degrades the peptidoglycan linkages found in Salmonella, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia;
  • SEL-2 – developed using the genetic information of an Salmonella bacteriophage and degrades the peptidoglycan linkages found in Salmonella, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia;
  • NPA-CH200 – developed using the genetic information of an E. coli bacteriophage and degrades the peptidoglycan linkages found in Salmonella, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia.
iNtODEWORLD, Inc is the US subsidiary of iNtRON Biotechnology, Inc.