Acinetobacter, a gram-negative coccobacillus, is a significant infectious agent in hospitals worldwide. Antimicrobial peptides such as the polymyxins are often the last resort antibiotic used to treat these infections. Whilst Acinetobacter strain can develop resistance to polymyxins, whether this gives strains resistance to other cationic antimicrobials is not fully understood.
In this study, we examined the susceptibility of 16 Australian clinical isolates of Acinetobacter to different cationic antimicrobials, including polymyxins (polymyxin B and colistin), the antimicrobial peptides melimine, Mel4, LL-37 and lactoferricin, as well as the cationic disinfectants polyhexamethylene biguanide (PHMB), Chlorhexidine (CHX) and polyquaternium-1 (PQ-1). The minimum inhibitory concentration of strains were determined.
There were diverse susceptibility patterns among the strains. All strains had a high MICs towards lactoferricin, with MICs ranging from 62.5 to >500 μg/ml. Some polymyxin-sensitive strains were also sensitive to other cationic antimicrobials, with minimum inhibitory concentrations (MICs) ranging from 1.95 to 15.62 μg/ml for Mel4 and melimine, and MICs ranging from 7.8 to 62 μg/ml for LL37. A polymyxin-resistant strain had relatively high MICs of 125 and 250 μg/ml with Mel4 and melimine but relatively low MICs with the cationic disinfectants. Interestingly, the polymyxin-resistant mutant strain of A. baumannii ATCC 19606, with MICs of 1,250 and >2,500 μg/ml against polymyxin B and colistin, respectively, had relatively low MICs for melimine, Mel4 and disinfectants with MICs values of 25μg/ml (melimine), 12.5 μg/ml (Mel4 and PQ-1) and 6.25 μg/ml (PHMB and CHX).
The results show diverse susceptibility patterns of Acinetobacter spp. towards cationic antimicrobials, implying distinct mechanisms of susceptibility and evolution. Inconsistent cross susceptibility also indicates a differential or LPS-independent mechanism of action for cationic antimicrobials in polymyxin-resistant strains. Future studies will evaluate the mechanisms of actions of different cationic antimicrobials and the mechanisms of resistance in Acinetobacter species.