Fungal Diseases Caused by Serious Contamination of Pharmaceuticals and Medical Devices, and Rapid Fungal Detection Using Nano-Diagnostic Tools: A Critical Review

Abstract

Fungal-contaminated compounded pharmaceuticals and medical devices pose a public health problem. This review aimed to provide an organized overview of the literature on that critical issue. Firstly, it was found that compounding pharmacies can produce drugs that are contaminated with fungi, leading to outbreaks of severe fungal diseases. Secondly, inadequate sterile compounding techniques or storage conditions, or exceeding the limit of a fungal count, can result in fungal contamination. Lastly, nanotools can be used to rapidly detect fungi, thus improving fungal diagnostic procedures. To achieve this goal, we have reviewed the published data on PubMed, the CDC, and FDA Web sites, and a literature search was undertaken to identify severe fungal infections associated with compounding pharmacies outside of hospitals, limited by the dates 2003 to 2021. The "Preferred Reporting Items for Critical Reviews" were followed in searching, including, and excluding papers. Fungal outbreaks have been documented due to contaminated pharmaceuticals and medical devices. In 2013, 55 people died from fungal meningitis caused by contaminated steroid injections containing methylprednisolone acetate. Additionally, in 2021, Aspergillus penicillioides contamination was reported in ChloraPrep drugs, which was attributed to the storage conditions that were conducive to the growth of this fungus. These incidents have resulted in severe infectious diseases, such as invasive mycoses, cornea infections, Endophthalmitis, and intestinal and gastric mycosis. By implementing preventive measures and policies, it is possible to avoid these outbreaks. Creating Nano-diagnostics presents a major challenge, where promptly diagnosing fungal infections is required to determine the proper corrective and preventive measures.

Fig. 1

Microscopic examination of Aspergillus sp. displayed long chains conidiospores and a chain of conidia is arranged, with the youngest at the bottom and the oldest at the top. (Photos were taken by Muddukrishnaiah K.)

Fig. 2

Microscopic examination of Penicillium sp. Penicillium conidia on conidiophores. The conidia in long chains of globose shapes, ellipsoids, cylinders or fusiform shapes, and they are arranged in dry chains, divergent or arranged in columns. (Photos were taken by Muddukrishnaiah K.)

Fig. 3

Exophiala spp. microscopical characteristics. Septate hyphae with several annellides and conidiogenous loci bearing elliptical conidia of approximately 2–3 mm or 4–5 mm in diameter. (Photo was taken from Marques et al., 2022)

Fig. 4

Fungal keratitis caused by Fusarium spp. This condition occurs when Fusarium spp. infects the cornea (the clear dome covers colored portion of the eye). (Photo was taken from Szaliński et al., 2021)