The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a member of the polymyxin class of antibiotics, such as commercially available natural products antibiotics, e.g., polymyxins B and polymyxins E (colistin and its pro-drug colistin methane sulfonate (CMS)) and synthetic or semi-synthetic derivatives and analogs, e.g., SPR206, MRX-8 and QPX9003 and polymyxin-like antibiotics, e.g., Pol7306

The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a member of the polymyxin class of antibiotics, such as commercially available natural products antibiotics, e.g., polymyxins B and polymyxins E (colistin and its pro-drug colistin methane sulfonate (CMS)) and synthetic or semi-synthetic derivatives and analogs, e.g., SPR206, MRX-8 and QPX9003 and polymyxin-like antibiotics, e.g., Pol7306

The present invention provides a compound of formula (I), and its use in methods of treatment, including the treatment of bacterial infections. Methods for the preparation of the compound of formula (I) are also provided. The compound of formula (I) has the structure shown below, where —R.sup.6 and —R.sup.7 are each together with the carbonyl group and nitrogen alpha to the carbon to which it is attached an amino acid residue, except that R.sup.6 together with the carbonyl group and nitrogen alpha to the carbon to which it is attached is not a phenylalanine, leucine or valine residue and/or —R.sup.7 together with the carbonyl group and nitrogen alpha to the carbon to which it is attached is not a leucine, iso-leucine, phenylalanine, threonine, valine or nor-valine residue, and -T, -A.sup.1, -A.sup.2, -A.sup.3 and —R.sup.10 are as discussed in the application:

##STR00001##

The present invention provides a compound of formula (I), and its use in methods of treatment, including the treatment of bacterial infections. Methods for the preparation of the compound of formula (I) are also provided. The compound of formula (I) has the structure shown below, where —R.sup.6 and —R.sup.7 are each together with the carbonyl group and nitrogen alpha to the carbon to which it is attached an amino acid residue, except that R.sup.6 together with the carbonyl group and nitrogen alpha to the carbon to which it is attached is not a phenylalanine, leucine or valine residue and/or —R.sup.7 together with the carbonyl group and nitrogen alpha to the carbon to which it is attached is not a leucine, iso-leucine, phenylalanine, threonine, valine or nor-valine residue, and -T, -A.sup.1, -A.sup.2, -A.sup.3 and —R.sup.10 are as discussed in the application:

##STR00001##

The invention provides a polymyxin compound of formula (I) and salts, solvates and protected forms thereof, pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds and compositions in methods of treatment, such as methods for the treatment of microbial infections. The compounds of formula (I) are represented thus: ##STR00001## wherein —R.sup.15 is a group: ##STR00002## and —R.sup.16 is hydrogen; —R.sup.17 is hydrogen -L- is a covalent bond or methylene; and —Ar is optionally substituted aryl. The groups —X—, —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, and —R.sup.8 are as defined herein.

The invention provides a polymyxin compound of formula (I) and salts, solvates and protected forms thereof, pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds and compositions in methods of treatment, such as methods for the treatment of microbial infections. The compounds of formula (I) are represented thus: ##STR00001## wherein —R.sup.15 is a group: ##STR00002## and —R.sup.16 is hydrogen; —R.sup.17 is hydrogen -L- is a covalent bond or methylene; and —Ar is optionally substituted aryl. The groups —X—, —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, and —R.sup.8 are as defined herein.

A polymyxin B component or salts thereof, and a preparation and application thereof. The polymyxin B component includes six α,γ-diaminobutyric acids respectively at positions 1, 3-5 and 8-9, two threonine residues at positions 2 and 10, a phenylalanine residue at position 6 and a leucine residue at position 7 linked in sequence. The threonine residue at position 10 is linked to the α,γ-diaminobutyric acid at position 4 by an amido bond, and the α,γ-diaminobutyric acid at position 1 is linked to 6-methyloctyl-2-enoyl.

A polymyxin B component or salts thereof, and a preparation and application thereof. The polymyxin B component includes six α,γ-diaminobutyric acids respectively at positions 1, 3-5 and 8-9, two threonine residues at positions 2 and 10, a phenylalanine residue at position 6 and a leucine residue at position 7 linked in sequence. The threonine residue at position 10 is linked to the α,γ-diaminobutyric acid at position 4 by an amido bond, and the α,γ-diaminobutyric acid at position 1 is linked to 6-methyloctyl-2-enoyl.

There is provided a range of novel compounds. These novel compounds may demonstrate abroad spectrum antibacterial and antifungal activity. These compounds may be active against the emerging polymyxin resistant bacteria. These compounds may also be useful when used in conjunction with other pharmaceutically active agents.

There is provided a range of novel compounds. These novel compounds may demonstrate abroad spectrum antibacterial and antifungal activity. These compounds may be active against the emerging polymyxin resistant bacteria. These compounds may also be useful when used in conjunction with other pharmaceutically active agents.