Isolation of colistin-resistant Hafnia alvei

Colistin belongs to the polymyxins, a group of polypeptide antibiotics which includes polymyxins A, B, C, D and colistin (polymyxin E). Of these, only polymyxins B and E have been employed for therapy of human infections (Gales et al, 2001; Kasiakou et al, 2005; Tan & Ng, 2006). Colistin is mainly administered as colistin sulphomethate sodium; the active drug is then released after hydrolysis and removed by glomerular filtration (Muyembe et al, 1973). Bactericidal activity is due to binding of cell membrane phospholipids and subsequent rapid permeability changes, leading to leakage of cell contents. Interestingly, this process is not dependent on bacterial metabolic activity (Gales et al, 2001; Kasiakou et al, 2005; Tan & Ng, 2006). Colistin emerged in the early 1960s (Catchpole et al, 1997; Kasiakou et al, 2005) as an alternative for treatment of multidrug-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa infections, but due to its neurotoxicity (neuromuscular blockade, dizziness, nausea, convulsions, coma) and nephrotoxicity (Gales et al, 2001; Jones et al, 2005; Kasiakou et al, 2005; Tan & Ng, 2006) it was displaced in the 1970s by the less toxic aminoglycosides, carboxypenicillins and cephalosporins. Clinical use of colistin has therefore been limited to use in oral non-absorbable compounds, nebulized formulations, and topical preparations for therapy of otitis, conjunctivitis and skin infections (Jones et al, 2005; Tan & Ng, 2006). For this reason, our knowledge of colistin is limited. It exerts activity against Gram-negative bacteria [including extended-spectrum b-lactamase (ESBL)-producing bacteria] (Catchpole et al, 1997), except for Proteus spp., Serratia spp., Providencia spp., Burkholderia pseudomallei and Neisseria spp., which are known to be intrinsically resistant to colistin. Also, Gram-positive and anaerobic organisms show intrinsic polymyxin resistance (Kasiakou et al, 2005; Li et al, 2005; Markou et al, 2003). In addition, resistant P. aeruginosa, Adnetobacter, Edwardsiella tarda, Enterobacter, Klebsiella and Salmonella strains have been reported (Catchpole et al, 1997; Kasiakou et al, 2005; Muyembe et al, 1973; Shimizu et al, 1977). Interestingly, cross-resistance with antimicrobials other than polypeptide compounds has not been described so far. Recently, the paucity of novel antibiotics against multidrug-resistant organisms has renewed interest in the possible use of polymyxin E.