Drug related hypersensitivity to Penicillin

By on August 14, 2017

Penicillin was discovered by Ernest Duchesne in 1896 and Alexander Fleming by isolating the antibiotic substance from the fungus Penicillium chrysogenum. The fungus produces this antibiotic when its food resources are limited as a mechanism to kill bacteria. It is used in the treatment of a variety of infections (such as scarlet fever, skin, ear and throat infection, pneumonia, rheumatic fever, chorea). The structure of penicillin consists of a thiazolidine ring connected to a beta-lactam ring, which is attached to a side chain. It is derived from 6 amino penicillin acid and differs from other structures in terms of their side chain structure (Mestrovic, 2016). The integrity of the thiazolidine beta-lactam ring is essential for the integrity and stability of Penicillin. It can be produced by the down streaming process; however, in that case, the products produced are impure which require filtration process to separate the microbial cell from the growth medium.

Structure of Penicillin
Structure of Penicillin

Role of penicillin

In the course of an infection, when taken, Penicillin interferes with the synthesis of bacterial cell wall leading to its eventual disruption. The antibiotic effect of the drug is dependent on the nature of the side chain acid. As can be seen in the below figure, Penicillin inhibits the trans-peptidase catalyzed reaction; the lack of trans-peptidase may cause inhibition of cell wall synthesis. This hinders the formation of cross-links essential for cell wall integrity, resulting in the blockade of the cell wall synthesis. The antibiotic binds to the microorganisms and interferes with the synthesis of the cell wall of the microbes thus, leading to the death of the microorganism (Tripathi, 2008). The use of penicillin is so common that allergic reactions will occur because of sensitization from its use. In case of hypersensitivity, penicillin allergy can lead to two clinical reactions, namely acute reactions and sub-acute reactions mediated by IgE and IgG antibodies respectively. Acute reactions are initiated within few minutes due to IgE leading to sudden anaphylaxis along with hypotension, bronchospasm, urticaria and angioedema. However, a sub-acute reaction occurs due to IgG and can include urticaria, fever and or arthritis (Kucers & Bennett, 1987).

Penicillin's mode of action
Penicillin’s mode of action

Diagnostic procedures of penicillin allergy

Penicillin allergy is among the most common drug allergy with a prevalence of 8-12% across the globe. Prevalence is higher among individuals receiving healthcare opportunities, female and ageing population (Macy & Ho, 2012). The symptoms include nausea, vomiting, itching, rashes shortness of breath and anaphylaxis.

Skin sensitivity tests are important to determine the safety of the drug, wherein a positive skin test indicates the presence of IgE antibodies which excludes the use of Penicillin and other β-lactam antibiotics. Further, high specificity was shown by in-vitro testing method (Demoly et al., 2014). Oral amoxicillin challenge is an effective and safe method to determine the IgE mediated penicillin allergy. There are many types of research to determine the effectiveness of diagnostic tools and procedures for the diagnosis of penicillin allergy which are easy and inexpensive. According to a report, researchers aim to improve their scanning devices with new photonic technologies, wherein diagnosis is via reading a compact disc-like laser cartridge containing pre-loaded beta-lactam reagent which will recognize IgE, an antibody in the blood of an allergic patient and a second tracer antibody. This technique is 100 times more efficient than the others; when a patient’s blood sample runs across the cartridge, the device will send the signal depending on the level of the hypersensitivity (K, 2016).

Furthermore, Penicillin remains the most common drug allergy which is reported to affect nearly 8-10% of the world population. Managing the penicillin allergy involves spreading awareness, knowledge of signs and symptoms. This article has discussed the mode of action of the drug and described acute and sub-acute reactions of drug hypersensitivity. The most commonly used diagnostic test is based on skin sensitivity, however, newer technologies have been developed to stem the prevalence of this drug allergy.

References

  • Albin, S., & Agarwal, S. (2014). Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population. Allergy and Asthma Proceedings, 35(6), 489–94. https://doi.org/10.2500/aap.2014.35.3791.
  • Demoly, P., Adkinson, N. F., Brockow, K., Castells, M., Chiriac, A. M., Greenberger, P. A., Thong, B. Y.-H. (2014). International Consensus on drug allergy. Allergy, 69(4), 420–437. https://doi.org/10.1111/all.12350.
  • Kucers A, Bennett N.M. The use of antibiotics: a comprehensive review with clinical emphasis. Philadelphia: Lipincott; 1987.
  • Walter, K. (2016, October). Rapid Allergy Detector Helps Avoid Penicillin Deaths. RandD Magazine, 1. Retrieved from http://www.rdmag.com/article/2016/10/rapid-allergy-detector-helps-avoid-penicillin-deaths.
  • Mestrovic, T. (2016, December). News Paper Article. News Medical Life Sciences, p. 1. Retrieved from http://www.news-medical.net/health/What-is-Penicillin.aspx.
  • New bio-photonic device aims to take drug hypersensitivity detection into new era. (2016, October). News Medical Life Sciences, p. 1. Europe. Retrieved from http://www.news-medical.net/news/20161020/New-bio-photonic-device-aims-to-take-drug-hypersensitivity-detection-into-new-era.aspx.
  • Solanki, G., Mathur, R., & Solanki, R. (2014). A Review of Penicillin Allergies. International Journal of Pharmacy Review and Research, 4(2), 1–3. Retrieved from www.ijprr.com/File_Folder/97-99.pdf.
  • Solensky, R., Khan, D. A., Contributors, W., Bernstein, I. L., Bloomberg, G. R., Castells, M. C., … Chicago, E. M. (n.d.). Drug Allergy: An Updated Practice Parameter Preface Glossary Executive Summary Algorithm for Disease Management of Drug Hyper- sensitivity Annotations for Disease Management of Drug Hyper- sensitivity. ANAI, 105, 259–273.e78. https://doi.org/10.1016/j.anai.2010.08.002.
  • Solensky, R., Khan, D. A., Contributors, W., Bernstein, I. L., Bloomberg, G. R., Castells, M. C., … Chicago, E. M. (2010). Drug Allergy: An Updated Practice Parameter Preface Glossary Executive Summary Algorithm for Disease Management of Drug Hyper- sensitivity Annotations for Disease Management of Drug Hyper- sensitivity. ANAI, 105, 259–273.e78. https://doi.org/10.1016/j.anai.2010.08.002.
  • Tripathi, K. D. (2008). Essentials of medical pharmacology. (M. Tripathi, Ed.) (Sixth). New Delhi: Jaypee Bros. Retrieved from https://docs.google.com/file/d/0BxvjJ4mG_bfYT1h4Z1FnalhfVWs/edit?pli=1.

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