The exact cause is unknown. It may be due to virus reservoirs in tissues that are not reached by the medication, or reinfection. In May 2022, Pfizer suggested repeating the treatment, but the FDA said there has been no evidence of benefit.In a 2022 US case report of 10 people with rebound while the Omicron variant has been circulating, viral load during relapse was comparable to levels during initial infection and high enough to cause secondary transmission. Also, sequencing of SARS CoV2 in three patients showed that rebound was a relapse with the same strain as it was not due to a mutation during treatment nor an infection with a different viral strain. As of September 2022, it is unknown how common rebound is among people after Paxlovid treatment, but study author David Ho thinks it is not uncommon. Besides him, President Joe Biden, First Lady Jill Biden, Anthony Fauci and Peter Hotez are known to have experienced rebound. As of September 2022, Pfizer is studying the phenomenon in a new trial it calls EPIC-SR (standard risk) while the omicron variant is circulating.As of July 2022, no Paxlovid drug resistant SARS CoV2 has been observed in clinical context. The engineering of a nirmaltrevir-resistant chimera of Vesicular Stomatitis Virus under laboratory conditions was published without formal peer review in July 2022. Manufacturing
Pfizer selected its largest oral tablet factory in Freiburg as the launch facility for the manufacturing of the co-packaged medication.
Destruction of deeper tissues, and deformity and loss of function in the affected limbs may occur in later stages. It tends to occur in one foot. Mycetoma due to bacteria has similar clinical features. Causes
Eumycetoma is a type of mycetoma caused by fungi. Mycetoma caused by bacteria from the phylum Actinomycetes is different. Both have similar clinical features.The most common fungi causing white discharge is Pseudallescheria boydii. Other causative agents of non-black grain eumycetoma include Acremonium and Fusarium species.Black discharge tends to be caused by species from the genera Madurella, Pyrenochaeta, Exophiala, Leptosphaeria and Curvularia. The most common species are Madurella mycetomatis and Trematospheria grisea (previously called Madurella grisea). Mechanism
The disease is acquired by entry of the fungal spores from the soil through a breach in the skin produced by minor trauma like a thorn prick. The disease then spreads to deeper tissues and also forms sinus tracts leading to skin surface. Mature lesions are characterised by a grainy discharge from these sinuses. These discharges contain fungal colonies and are infective. Spread of infection internally through blood or lymph is uncommon.Infections that produce a black discharge mainly spread subcutaneously. In the red and yellow varieties deep spread occurs early, infiltrating muscles and bones but sparing nerves and tendons, which are highly resistant to the invasion.Botryomycosis, also known as bacterial pseudomycosis, produces a similar clinical picture and is caused usually by Staphylococcus aureus. Other bacteria may also cause botryomycosis.