In recent years, there has been a sudden influx of patients with fevers and chills,suspected to be suffering from bacterial infections, who fail to improve even with the strongest antibiotic treatments. Between 2020 and 2021, such cases nearly doubled causing deadly outbreaks.
After multiple investigations and laboratory tests, this mystery infection has been deemed a multidrug-resistant fungal infection rather than a bacterial infection. This discovery has made quite a stir in the medical community leading to the CDC terming it a 'serious global health threat'. These fungi are now named "superbugs" as they are resistant to several antifungal drugs causing a delay in treatment.
Back in 2009, the "superbug" Candida Auris, a type of yeast, killed almost one-third of those it infected. It lingered on surfaces for weeks. C.Auris had been first discovered in Japan and ever since then outbreaks and discovery of new strains had increased exponentially.
Usually, fungi are easy to treat and are treated with or with a combination of the four main classes of antifungal drugs: the polyenes, azoles, allylamines and echinocandins. However, fungi like C. Auris, today, are slowly developing resistance against these drugs and in some cases against all of them, making it difficult to efficiently treat these diseases. Symptoms include high fever, chills, pain and fatigue. Such symptoms are quite easy to miss and thereby cause treatment delays, which prove to be fatal. The only way to prevent the contraction of the infection is by improving the hygienic standards of hospitals as they tend to occur in cluster outbreaks in healthcare settings.
Apart from C.Auris, other fungi superbugs include Aspergillus fumigatus and Candida glabrata. These infections, although not similar in symptoms, do have similar mortality rates as C.Auris, render common antifungal drugs useless, and are of utmost importance to the medical community. Fungi are slowly evolving to become stronger than ever before, which is well demonstrated by the recent case of a disease caused by Chondrostereum purpureum in Kolkata, India that marked the first time in which such a deadly plant fungus affected humans.
The primary reason for our lack of research on antifungals is because these infections have been historically pushed aside because of their tendency to only infect the immunocompromised and vulnerable population, shifting the focus to bacterial infections which usually infect people without regard to their immunity status. However, as more vulnerable people are affected, it is imperative that we provide the best treatment available to them. And to do so, we need to ramp up our efforts towards the goal of efficient drugs against these diseases.
However, it isn't easy to develop these antifungals as fungi come with a plethora of challenges. Any new innovation has been slow in the medical community in terms of antifungals ever since the first echinocandins were approved 20 years ago. Fungi are eukaryotes and are way more closely related to humans than other microbes thus making it difficult to develop drugs that won't negatively affect human cells. In short, the compounds that can kill fungal cells can also kill human cells. Even today, the four classes of antifungals come with drawbacks and potential side effects including fever, heart inflammation, kidney problems and liver toxicity. Antifungal drugs work by targeting the unique structures and processes of fungi depending on which class of drug, each has a different mechanism to work.
Additionally, many patients with these invasive fungal infections are diagnosed with bacterial/viral infections. Oftentimes, they are prescribed with antibiotics that further deteriorate their health and worsen the fungal infection, causing defects in the antifungal immune response, specifically in the gut as it disrupts the microbiome, promotes fungal overgrowth and weakens the immune system.
Furthermore, it is important to understand the potential repercussions of these superbugs Healthcare, in many countries, is already expensive and when diseases like these emerge (with very few treatment routes), it hampers the lives of many patients, hurdling them with debt. 15% of the population is susceptible to these invasive fungal infections and proper treatment is necessary, but that can easily burn holes in the pockets of patients. Additionally, fungal infections not only affect humans but also plants, which yield terrible economic losses. Today, fungi destroy ⅓ of crops, annually. Drug-resistant fungi can amplify these impacts. The lives of animals also seem grim in the hands of these fungi, as they threaten the extinction of many animal species. In the future, there are even chances of thermal-intolerant fungi mutating further to be able to sustain at mammalian temperatures making fungi even a bigger threat to us.
Nevertheless, all hope is not lost, despite the low commercial demand of these drugs, they are necessary for the vulnerable and high risk population. Research on developing drugs is ongoing and the future seems bright. Some of the drugs on trial currently include Olorofilm which is currently ongoing their Phase II trials. If this is approved, it can potentially treat aspergillosis and other infections— preventing us from another “The Last of Us” plot line.