ReviewEmerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology
Introduction
The emergence and spread of bacteria resistant to multiple antibiotics and at the origin of severe infections is currently of great concern. This is particularly true for nosocomial pathogens isolated in hospitals, where these superbugs may compromise advanced medicine, including surgery, transplantation, efficient treatment of immunocompromised and haematological patients, etc. Among the increasingly reported and commonly identified multidrug-resistant or even pandrug-resistant bacteria, the lactose-non-fermenting Gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa occupy an important place. These bacterial species are quick to become multidrug-resistant owing to their additional intrinsic resistance mechanisms. They are responsible for hospital-acquired infections (bloodstream, urinary tract, pulmonary and device-related infections) and are frequently isolated from immunocompromised patients hospitalised in the intensive care unit. Resistance to multiple antibiotic classes, and notably to the β-lactam cephalosporins and carbapenems, is on the rise worldwide. In this review, the emerging antibiotic resistance mechanisms in A. baumannii and P. aeruginosa are highlighted, with a special focus on the most prescribed antimicrobial agents, i.e. β-lactams, aminoglycosides and fluoroquinolones.
Section snippets
Extended-spectrum β-lactamases (ESBLs)
The class A ESBLs confer resistance to expanded-spectrum cephalosporins and are inhibited in vitro by clavulanic acid and tazobactam [1]. They have been extensively identified in members of the Enterobacteriaceae family but are also reported from non-fermenters.
Broad resistance to aminoglycosides
Aminoglycosides are used in the treatment of a broad range of life-threatening infections. The activity of aminoglycosides depends on binding to a highly conserved motif of 16S rRNA. Mechanisms of aminoglycosides resistance include decreased outer membrane permeability, active efflux and amino acid substitutions in ribosomal proteins, whereas the most common resistance mechanism is enzymatic leading to modification of the drug. Methylation of 16S ribosomal RNA has recently been demonstrated to
Broad resistance to fluoroquinolones
In Gram-negative organisms, acquisition of resistance to quinolones may be related to chromosomal mutations in genes encoding the topoisomerases or to mutations in the efflux pump regulation systems. In addition, plasmid-mediated quinolone resistance genes (coding for the Qnr proteins) have been identified in Enterobacteriaceae. These acquired Qnr proteins have not been identified in non-fermenters. In P. aeruginosa and A. baumannii, a single mutation in the gyrA gene encoding DNA gyrase is
Resistance to tigecycline
Tigecycline, a semisynthetic derivative of minocycline, has a peculiar mechanism of action and overcomes the widely distributed tet gene-encoded resistance mechanism known to confer resistance to tetracycline. Tigecycline shows good activity towards Gram-negative pathogens that may produce a large array of resistance mechanisms, including ESBLs and carbapenemases [296]. The activity of tigecycline against A. baumannii is overall good, and successful results have been reported clinically [296].
Resistance to colistin
During the past decade, we have witnessed a renewal of clinical interest in polymyxins (colistin) owing to two concomitant facts: (i) the emergence of carbapenem-, cephalosporin- and aminoglycoside-resistant Gram-negative isolates; and (ii) the paucity of novel marketed antibiotic molecules. Actually, polymyxins remain most often active against these multidrug-resistant isolates [303]. Emergence of colistin resistance in relation to increased usage is worrisome since polymyxins are the last
Concluding remarks
Increasing rates of bacterial resistance among non-fermenters are threatening the effectiveness of antibiotics used as last-resort therapeutic options. In A. baumannii and P. aeruginosa, acquisition of resistance traits to these molecules is becoming more and more frequent, leading to multidrug and pandrug resistance. The last years have shown that: (i) most of the broad-spectrum resistance patterns identified in Enterobacteriaceae may be also identified in P. aeruginosa and A. baumannii; (ii)
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