Development of antibiotics

Development of antibiotics
According to World Health Organization (WHO) (2020). The lack of private investment and poor innovation in antibiotic development reduces the efforts in combating drug-resistant infections. Additionally, there is a high need for more development of various antibiotics to help manage multiple infections, for example, the gram negative bacteria that have proved to be difficult in managing. To tackle the current antibiotics shortage, there is a need to develop more potent and efficacious antibiotics to help deal with the myriad of bacterial infections.

Spectrum Coverage

The antibiotic that is to be developed will be named Kleboffecta, which is mainly the type of bacteria that it will be active against, the Klebsiella. The antibiotic will be available as an injectable for severe infections and resistant strains of bacteria and tablet forms. The drug will not have a diluent and must be kept within a temperature of +15 to +28. The injectable is to be administered twice a day with a 12-hour interval for a maximum of 5 days, and then the client is changed to the oral tablet for additional seven days. The dose of the drug will be 100mg administered once a day for a maximum of 7 days. The drug is not allowed to be used for children under the age of 5 years. The drug will have bacteriostatic activity against the Klebsiella strain of bacteria by destroying the polysaccharide capsular formation and synthesis.

Antibiotics are a class of drugs that are used in the treatment of bacterial infections. Most of the antibiotics are either bacteriostatic or bactericidal. The antibiotic that is developed will target gram-negative bacteria. This is because gram-negative bacteria are very resistant to most drugs used in the clinical settings; hence my innovation will target this group of bacteria to reduce this challenge. The specific gram-negative bacteria that the drug will work against will be the Klebsiella. Klebsiella causes various infections, including pneuomanie, meningitis, wound infections, and bold infections (Marques et al., 2019).

Over time, the Klebsiella bacteria have developed resistance to most of the antibiotics used to manage it. This makes it very difficult to determine which type of antibiotic will be effective against a strain of Klebsiella. They are mainly found in the human gut. The infections are common in patients who are getting long treatment with other infections. Having invasive devices like ventilators and intravenous catheters also increases the risk of a Klebsiella infection (Bellich et al., 2019)

It is worth noting that drug-resistant Klebsiella has proved resistant to carbapenems, which is the last line of bacterial drug management, making it difficult to deal with most of this infection. This makes it more enthusing to develop a drug that could target this group of bacteria. The spectrum of coverage will be mainly all strains of Klebsiella (resistant and not resistant). The drug will be lipid-soluble to pass the blood-brain barrier (BBB) with a half-life of 12 hours and excreted through the kidney; hence doses have to be adjusted for those with renal insufficiencies.

Resistance Patterns

The emergence of drug-resistant bacteria has been a significant concern in various clinical settings. To develop the most resistance to this antibiotic, the main pattern will be insufficient empiric therapy and long term use of the drug. Practices like skipping of drug doses and using the drug over a long period will automatically lead to resistance. The developed drug has only to be administered after laboratory testing, indicating that the Klebsiella is resistant, and the patient should not take the drug for more than 45 days consecutively.

The drug is only to be prescribed after all other types of medications active against Klebsiella have proven ineffective. When other medication can be effective against the gram negative bacteria, the use of the drug can reduce the chances of recovery if the client or patient develops the infection later during treatment. The drug is to be administered through directly observed therapy (DOT) for all hospitalized patients. Administration of the drug in alternate days, skipping of doses, and change of time interval before the administration can easily lead to resistance.

The resistance patterns of each antibiotic differ; hence, it is essential to determine the resistance pattern of all the drugs, which will be used to develop strategies to avoid resistance development (Bellich et al., 2019)

Structure of Bacteria

Klebsiella is considered to be non-motile and rod-shaped. They are also opportunistic pathogens belonging mainly to the ESKAPE group of bacteria. They are also proteobacteria and has a prominent polysaccharide capsule. They are also facultative aerobes. It has the following components; capsular polysaccharide (63%), 30% lipopolysaccharide, and 7% protein. The capsule polysaccharide protects the bacteria from harsh conditions and acts as the major virulence factor of Klebsiella pneumoniae. Most of the Klebsiella genus have two types of antigen on the cell surface, namely the O antigen, which is a lipopolysaccharide, and K antigen, which is a capsular polysaccharide. The capsule accounts for the organism’s massive appearance in gram stain and acts as the main conduit for resistance (Marques et al., 2019).

In Klebsiella pneumoniae, the capsule is separated into two layers and is also differentiated by a bundle of fibers. In the inner layer of the capsule, the fibers stand perpendicularly to the outer cell membrane surface. The outer layers are aligned to form a fine network structure. Additionally, the strains of Klebsiella pneumoniae have been shown to generate fimbriae (type 3) (Bellich et al., 2019)

Disease Processes

The primary disease process that will be elucidated is that of Klebsiella pneuomaniae. This is one of the common causes of nosocomial infections. Klebsiella always causes infections when it moves out of the gut and invades other places in the body. The diseases include urinary tract infections, pneumonia, septicemia, and soft tissue injuries. The virulence factor mainly causes the severity and differences in the diseases. Most medical machines and interventions like catheters increase the risk of a person being invaded with the Klebsiella bacteria. When the bacteria access the lungs, bloodstream, wounds, brain, and the urinary tract, it causes severe infections. The main aim of the drug will be to avoid the multiplication of the bacteria and limits its motility to ensure that it doesn’t affect various body systems or organs (Marques et al., 2019).

Hypothesis

Hypothesis 1: Bacteria acquiring new property or behavior makes the antibiotics to be ineffective.

Bacteria always acquire new behavior when exposed to different kinds of drugs or environments. This may lead to the bacteria changing their structure, shape membranes, and morphology to adapt to the new environments. This will make the drugs’ mechanism of action ineffective, hence not treating the disease caused by the particular bacteria (Dik et al., 2018)

Hypothesis 2: Poor adherence to the treatment course, therapy, and instructions make antibiotics ineffective.

When the right doses are not taken at the right time and frequency, the antibiotic will not reach the required distribution level in the body or the point of efficacy; hence, this will not be exerted its mechanism of action thoroughly, therefore not treating the disease, as in Tomczyk et al. (2018)

Hypothesis 3: the destruction of the drug’s composition by the gut enzymes makes the drug ineffective.

Some drugs are destroyed in acidic or alkaline environments; hence if the drugs pass through these mediums, then their composition, the structure will be altered, rendering the whole drug ineffective and not reaching its target point of cation hence being unable to treat the disease as in Tomczyk et al. (2018).

References

Bellich, B., Ravenscroft, N., Rizzo, R., Lagatolla, C., D’Andrea, M. M., Rossolini, G. M., & Cescutti, P. (2019). Structure of the capsular polysaccharide of the KPC-2-producing Klebsiella pneumoniae strain KK207-2 and assignment of the glycosyltransferases functions. International journal of biological macromolecules, 130, 536-544.

Dik, D. A., Fisher, J. F., & Mobashery, S. (2018). Cell-wall recycling of the Gram-negative bacteria and the nexus to antibiotic resistance. Chemical reviews, 118(12), 5952-5984.

Marques, C., Menezes, J., Belas, A., Aboim, C., Cavaco-Silva, P., Trigueiro, G., … & Pomba, C. (2019). Klebsiella pneumoniae causing urinary tract infections in companion animals and humans: population structure, antimicrobial resistance and virulence genes. Journal of Antimicrobial Chemotherapy, 74(3), 594-602.

Partridge, S. R., & Tsafnat, G. (2018). Automated annotation of mobile antibiotic resistance in Gram-negative bacteria: the Multiple Antibiotic Resistance Annotator (MARA) and database. Journal of Antimicrobial Chemotherapy, 73(4), 883-890.

Tomczyk, S., Whitten, T., Holzbauer, S. M., & Lynfield, R. (2018). Combating antibiotic resistance: a survey on the antibiotic-prescribing habits of dentists. General dentistry, 66(5), 61-68.

World Health Organization (2020, January 17). Lack of new antibiotics threatens global efforts to contain drug-resistant infections. https://www.who.int/news-room/detail/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections

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