The emergence of the mcr-9 gene is quite remarkable.Use of colistin to treat Acinetobacter baumannii infections has led to the development of resistant bacterial strains. They have also developed resistance to the antimicrobial compounds LL-37 and lysozyme, produced by the human immune system. This cross-resistance is caused by gain-of-function mutations to the pmrB gene, a phosphoethanolamine transferase (similar to mcr-1) located on the bacterial chromosome.Not all resistance to colistin and some other antibiotics is due to the presence of resistance genes. Heteroresistance, the phenomenon wherein apparently genetically identical microbes exhibit a range of resistance to an antibiotic, has been observed in some species of Enterobacter since at least 2016 and was observed in some strains of Klebsiella pneumoniae in 2017–2018. In some cases this phenomenon has significant clinical consequences. Inherently resistant
Variable resistance
Aeromonas
Vibrio
Prevotella
Fusobacterium
Escherichia coli

Adverse reactions
The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves), but this may reflect the very high doses given, which are much higher than the doses currently recommended by any manufacturer and for which no adjustment was made for pre-existing renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen. Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and it has been used for extended periods up to six months with no ill effects.
Muller and retinal pigment epithelium cells normally release immunosuppressive factors, but certain combinations of cytokines may stimulate retinal pigment epithelium cells to release factors encouraging inflammation.Generally, mild intraocular inflammation results in a small, discrete, evanescent lesions. Larger dots, having less discrete borders, are the result of high intensity intraocular inflammation. In essence, an immune response with the normal amount and appropriate cytokine release will result in small white dots and a misregulated response eventually will produce scarring of the retinal tissue. Treatment is required in the latter case to combat loss of vision. The white dots usually disappear naturally. Corticosteroids have been shown to speed up this process. The differences in the immune response of each patient may contribute to the differences seen between the white dot syndromes. Distinct diseases
Due to the number of common features among the multiple syndromes, many suggest that the white dot syndromes are not distinct and represent a spectrum of one disease. Gass described the AZOOR complex which consists of multiple evanescent white dot syndrome, nultifocal choroiditis, punctate inner choroiditis, acute idiopathic blind spot enlargement, acute macular neuroretinopathy, acute annular outer retinopathy, and acute zonal occult outer retinopathy. He suggested these diseases represent one disease due to common factors such as a high occurrence in females, unexplained visual field loss, and reduced electroretinographic amplitudes. Reddy et al. conducted a study on the blind spots in multifocal choroiditis, punctate inner choroiditis, multiple evanescent white dot syndrome, and diffuse subretinal fibrosis syndrome. Clinical and electroretinographic evidence suggested the diseases are distinct.