Recurrent infection of Clostridium difficile in patients over 18 years old may be combatted with Zinplava (bezlotoxumab), an injectable human monoclonal antibody that neutralizes toxin B (an A-B toxin) produced by the bacteria. In general, monoclonal antibodies are antibodies derived from a single B cell clone, allowing them to be specific for a single antigen or epitope. All monoclonal antibodies of a specific type will be identical in every way, including both the constant and variable regions of both the light and heavy chains that together make up the antibody. Monoclonal antibodies are often mass produced in animal models and are used for both therapeutic and immunoassay purposes. The specific mode of action for Zinplava is binding and subsequent neutralization of toxin B that is produced by C. difficile. Zinplava is not, however, a treatment for infection by C. difficile and is only administered in conjunction with antibiotics as a means of preventing recurrent infections in patients with high-risk for recurrence. Clinical trials for Zinplava identified high risk individuals as: being over the age of 65, being immunocompromised, receiving multiple systemic antibacterial drugs, and reporting one or more C. difficile infections within the 6 months prior to the current infection being treated.
Neutralization of toxin B has been found to be clinically significant in reducing recurrent CDI infections, as reported by this NIH article reviewing therapy options for C. difficile infections (CDI). The exact, immunological impact in vivo is not completely verified, however a 2016 NIH study may provide insight into how Zinplava’s neutralization of toxin B helps decrease recurrent infection. The study highlighted the role of toxin B in C. difficile‘s pathogenicity, recognizing it as the likely major actor in providing C. difficile with its pathogenic capability. Evidence for this role stems from toxin B’s role in up-regulating production of IL-8 and interferon gamma to attract neutrophils which are likely responsible for the extreme damage to the mucosa of the intestines, its ability to induce multiple types of apoptosis, and the lack of toxin B negative strains of C. difficile even though toxin A negative strains are present. As such, toxin B impacts the innate immune response by inducing severe inflammation of the colon, among other effects which cause the other symptoms of CDI. Applying Zinplava can help to mitigate that severe inflammation and prevent mucosal damage, which likely contributes to the regeneration of healthy gut microbiota which is important to preventing recurrent infections.
Just as with any drug or foreign substance that enters our body, there are bound to be side effects. The most important and potentially fatal of the side effects associated with Zinplava is heart failure. Specifically, individuals who have been diagnosed with congestive heart failure in the past are at much greater risk for experiencing heart failure when taking Zinplava, leading the FDA to recommend only taking Zinplava “when the benefits outweigh the risks.” Other side effects include all of the following:
- nausea
- headache
- fever
- shortness of breath
- feeling tired
- dizziness
- high blood pressure
Due to the fact that Zinplava is supposed to neutralize toxin B of C. difficile in an effort to dampen its effects, some of these side effects are expected. A neutralized toxin particle will eventually be taken up by a macrophage for degradation. In the event that the toxin enters the blood stream, a phenomenon known as toxemia, the monoclonal antibodies of Zinplava must neutralize it in the blood. This can result in large particles forming within the blood stream, causing an increase in blood pressure leading to headaches, dizziness to do lack of blood flow and potentially shortness of breath if the complex causes a significant blockage. Additionally, nausea likely results from the fact that C. difficile colonizes the lower digestive tract and, as such, Zinplava must migrate to that area in order to work effectively. This influx of materials along with the actions of C. difficile can cause mucosal irritation and nausea.
Keegan's Microbiology Blog 