Antibacterial spectrum<unk>  has been effective in treating infections caused by Pseudomonas, Escherichia, and Klebsiella species. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms: * Escherichia coli: 0.12–128 μg/ml * Klebsiella pneumoniae: 0.25–128 μg/ml * Pseudomonas aeruginosa: ≤0.06–16 μg/ml For example,<unk>  in combination with other drugs is used to attack P. aeruginosa biofilm infection in lungs of patients with cystic fibrosis. Biofilms have a low-oxygen environment below the surface where bacteria are metabolically inactive, and<unk>  is highly effective in this environment. However, P. aeruginosa reside in the top layers of the biofilm, where they remain metabolically active. This is because surviving tolerant cells migrate to the top of the biofilm via pili and form new aggregates via quorum sensing. Administration and dosage Forms Two forms of<unk>  are available commercially:<unk>  sulfate and<unk> ethate sodium<unk>  methanesulfonate sodium,<unk>  sulfomethate sodium).<unk>  sulfate is cationic;<unk> ethate sodium is anionic.<unk>  sulfate is stable, whereas<unk> ethate sodium is readily hydrolysed to a variety of methanesulfonated derivatives.<unk>  sulfate and<unk> ethate sodium are eliminated from the body by different routes. With respect to Pseudomonas aeruginosa,<unk> ethate is the inactive prodrug of<unk> . The two drugs are not interchangeable. *<unk> ethate sodium may be used to treat Pseudomonas aeruginosa infections in patients with cystic fibrosis, and it has come into recent use for treating multidrug-resistant Acinetobacter infection, although resistant forms have been reported.<unk> ethate sodium has also been given intrathecally and intraventricularly in Acinetobacter baumannii and Pseudomonas aeruginosa meningitis and ventriculitis Some studies have indicated that<unk>  may be useful for treating infections caused by carbapenem-resistant isolates of Acinetobacter baumannii. *<unk>  sulfate may be used to treat intestinal infections, or to suppress colonic flora.<unk>  sulfate is also used in topical creams, powders, and otic solutions. *<unk>  A (polymyxin E1) and<unk>  B (polymyxin E2) can be purified individually to research and study their effects and potencies as separate compounds. Dosage<unk>  sulfate and<unk> ethate sodium may both be given intravenously, but the dosing is complicated. The different labeling of the parenteral products of<unk>  methanesulfonate in different parts of the world was noted by Li et al.<unk> ethate sodium manufactured by Xellia (Colomycin injection) is prescribed in international units, whereas<unk> ethate sodium manufactured by Parkdale Pharmaceuticals (Coly-Mycin M Parenteral) is prescribed in milligrams of<unk>  base: * Colomycin 1,000,000 units is 80 mg<unk> ethate; * Coly-mycin M 150 mg<unk>  base is 360 mg<unk> ethate or 4,500,000 units. Because<unk>  was introduced into clinical practice over 50 years ago, it was never subject to the regulations that modern drugs are subject to, and therefore there is no standardised dosing of<unk>  and no detailed trials on pharmacology or pharmacokinetics. The optimal dosing of<unk>  for most infections is therefore unknown. Colomycin has a recommended intravenous dose of 1 to 2 million units three times daily for patients weighing 60 kg or more with normal renal function. Coly-Mycin has a recommended dose of 2.5 to 5 mg/kg<unk>  base a day, which is equivalent to 6 to 12 mg/kg<unk> ethate sodium per day. For a 60 kg man, therefore, the recommended dose for Colomycin is 240 to 480 mg of<unk> ethate sodium, yet the recommended dose for Coly-Mycin is 360 to 720 mg of<unk> ethate sodium. Likewise, the recommended "maximum" dose for each preparation is different (480 mg for Colomycin and 720 mg for Coly-Mycin). Each country has different generic preparations of<unk> , and the recommended dose depends on the manufacturer. This complete absence of any regulation or standardisation of dose makes intravenous<unk>  dosing difficult for the physician.<unk>  has been used in combination with rifampicin; evidence of in vitro synergy exists, and the combination has been used successfully in patients. There is also in vitro evidence of synergy for<unk> ethate sodium used in combination with other antipseudomonal antibiotics.<unk> ethate sodium aerosol (Promixin; Colomycin Injection) is used to treat pulmonary infections, especially in cystic fibrosis. In the UK, the recommended adult dose is 1–2 million units (80–160 mg) nebulised<unk> ethate twice daily. Nebulized<unk>  has also been used to decrease severe exacerbations in patients with chronic obstructive pulmonary disease and infection with Pseudomonas aeruginosa. Resistance Resistance to<unk>  is rare, but has been described. , no agreement exists about how to define<unk>  resistance. The uses a MIC cut-off of 2 mg/l, whereas the British Society for Antimicrobial Chemotherapy sets a MIC cutoff of 4 mg/l or less as sensitive, and 8 mg/l or more as resistant. No standards for describing<unk>  sensitivity are given in the United States. The first known<unk> -resistance gene in a plasmid which can be transferred between bacterial strains is mcr-1. It was found in 2011 in China on a pig farm where<unk>  is routinely used and became publicly known in November 2015. The presence of this plasmid-borne gene was confirmed starting December 2015 in South-East Asia, several European countries, and the United States. It is found in certain strains of the bacteria Paenibacillus polymyxa. India reported the first detailed<unk> -resistance study, which mapped 13<unk> -resistant infections recorded over 18 months. It concluded that pan-drug-resistant infections, particularly those in the bloodstream, have a higher mortality. Multiple other cases were reported from other Indian hospitals. Although resistance to polymyxins is generally less than 10%, it is more frequent in the Mediterranean and South-East Asia (Korea and Singapore), where<unk>  resistance rates are increasing.<unk> -resistant E. coli was identified in the United States in May 2016. Use of<unk>  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<unk>  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 *Brucella *Burkholderia cepacia *Chryseobacterium indologenes *Edwardsiella *Elizabethkingia meningoseptica *Francisella tularensis spp. * Gram-negative cocci *Helicobacter pylori *Moraxella catarrhalis *Morganella spp. *Neisseria gonorrhoeae and Neisseria meningitidis *Proteus *Providencia *Serratia * Some strains of Stenotrophomonas maltophilia Variable resistance * Aeromonas * Vibrio * Prevotella * Fusobacterium * Escherichia coli
Colistin
Resistin
Meropenem
Vancomycin
Ertapenem
Fosfomycin
Teicoplanin
Ciprofloxacin