Acinetobacter baumannii resistant to everything: what should we do?

Abstract

associated with the interplay between decreased outer membrane permeability and constitutive expression of some efflux pumps; (ii) the acquisition of genetic elements such as resistance islands, which may carry up to 45 resistance genes or insertion sequence elements—these latter elements can be inserted upstream from some chromosomal genes and can contribute to the expression of these genes, such as blaADC or blaOXA-51, encoding a chromosomal cephalosporinase and a carbapenemase, respectively, and in addition, mutations in genes related to the overexpression of efflux pumps (AdeABC and AdeIJK) can generate multiresistance, as these efflux pumps normally have different substrates; and (iii) the ability to survive in the environment, most likely associated with biofilm production, which can contribute to the acquisition of either mutations or genetic elements [2,3]. All the above-mentioned features lead to the development of multidrug-resistant, extended-drug-resistant and pan-drug-resistant A. baumannii strains. Therefore, not many alternatives are available to treat the infections caused by pan-resistant A. baumannii strains. The drugs currently available, which show a lower percentage of resistant clinical isolates, are colistin and tigecycline. Colistin has been used in several studies to treat infections caused by multidrug-resistant A. baumannii, with suboptimal results. To improve its efficacy, recent pharmacokinetic/pharmacodynamic data have led to the suggestion that the colistin dosage should be optimized with an initial loading dose, to enable therapeutic concentrations to be reached more rapidly [4]. Tigecycline has shown good in vitro activity against A. baumannii; however, few data, none of them definitive, have been reported from noncomparative studies concerning its efficacy in A. baumannii infections. Moreover, rapid appearance of resistance has occurred during the treatment, most likely associated with the overexpression of AdeABC and/or other efflux pumps. Among the possible combination therapies for the treatment of multidrug-resistant A. baumannii infections, rifampin plus colistin has been evaluated in ventilator-associated pneumonia and bacteraemia. Once more, the results have been discordant, and it may be stressed that a high dose of rifampin must be used; moreover, to avoid the appearance of rifampin resistance during the treatment, it is necessary to ensure, in the case of empirical therapy, that the drug combined with rifampin is active against the A. baumannii strains causing infections in a particular setting. The problematic situation generated by A. baumannii has not been reflected in the development of new antibacterial agents against this microorganism. The last drugs developed, such as doripenem, ceftobiprole and ceftalorine, do not show activity against A. baumannii resistant to carbapenems