Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.
[3] Animal studies have shown that actinomycin-D is corrosive to skin, irritating to the eyes and mucous membranes of the respiratory tract, and highly toxic by the oral route.
Polypeptide antibiotics are produced by all living organisms; largely by bacteria and generally function as natural host defence, presenting new medicinal opportunities.
The re-emergence of colistin use began in the late 1980s, via intravenous injection (IV) methods or inhalation to manage bacterial infections for which no other options are available, such as those caused by P.
[11][12] Bacitracin is a polypeptide antibiotic derived from a bacterium, Bacillus subtilis, and acts against bacteria through the inhibition of cell wall synthesis.
[16] Bacitracin was also trialled in bullous impetigo, an acute blistering infection, however produced ineffective results with no significant difference in success rate in comparison to the placebo trials.
[8] Polymyxins are also distributed as an inhaled medication to treat minor respiratory tract infections due to Pseudomonas, such as cystic fibrosis.
[21] Bleomycin's medical application is as an anti-tumour drug mainly in germinative tumours and Hodgkin's lymphoma, however its use is limited by pulmonary toxicity.
[25] Bleomycin also does not induce myelosuppression with decreased bone marrow activity, or immunosuppression; suppressing the immune responses in patients unlike alternative cytotoxic drugs.
[28] This method of resistance occurrence may account for the inability for polypeptide antibiotics to act on gram-negative bacterium i.e. bacteria with thin peptidoglycan layers, where cases of changes of growth medium produced changes in the outer membrane.
[28] Polypeptide antibiotic resistance eliminates the drug's effectiveness, thus allowing the bacteria to survive, replicate and continue harming to the patient.
[7] Clinical trials and studies with polypeptide antibiotic use during pregnancy are limited, and have produced no definite conclusions of risk to the foetus.
[5] However, use of bacitracin as a topical or ophthalmic medication is considered relatively safe during breastfeeding, due to the skin's low absorption rate of chemicals.
[7] However, cases of anaphylaxis; a severe allergic reaction which can potentially lead to death, have been reported after multiple uses of topical bacitracin on lesions in patients.
[7] Colistin is considered to have high toxicity, mainly having renal and neurological effects, including but not limited to decreased urine secretion, increased urea nitrogen concentrations in the blood and acute tubular necrosis.
[7] Bleomycin use causes side effects ranging from nausea, vomiting, anorexia and fevers, to fatal pulmonary toxicity in 1–2% of cases resulting in death.
Reactive oxygen species produced via the redox reactions that occur due to its mechanism of action involving binding to guanine bases in DNA, which results in reduced membrane stability.
[23] Despite multiple research articles on polypeptide antibiotics, the understanding of their exact mechanism of action and the extent of their toxicity and effects remain unknown.
Thus producing a new challenge, and providing an area for potential future research on polypeptide antibiotic mechanism of actions and how to manipulate them.