Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Abstract

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

Functional Analysis of the Acinetobacter baumannii XerC and XerD Site-Specific Recombinases: Potential Role in Dissemination of Resistance Genes

“…The common presence of these Xer modules (XerC/D binding sites–resistance gene–XerC/D binding sites) led to the proposal that these elements play an important role in the horizontal dissemination of resistance genes [ 19 , 21 , 22 , 23 , 24 , 25 , 26 ]. The interest in the Xer modules was enhanced because many of them include carbapenemase genes like bla OXA24/40 -like, which confer A. baumannii , a member of the ESKAPE group of bacteria [ 27 ], the ability to resist some of the last-line antibiotics [ 21 , 22 , 23 , 24 , 25 , 28 ]. Xer modules have also been recently found in bacteria other than Acinetobacter and including genes other than bla OXA24/40 -like.…”

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors inAcinetobacter baumannii

“…Acinetobacter baumannii has emerged as an important pathogen due to its ability to resist multiple antibiotics, persist in hospital settings, and cause a wide variety of infections such as pneumonia, bacteremia, urinary tract infections, skin and soft-tissue infections, and meningitis (1)(2)(3)(4). The acquisition of resistance to carbapenems by certain strains (carbapenem-resistant Acinetobacter baumannii, CRAB) increased the problematic nature of this pathogen (5), which has been qualified as an "urgent" threat in a recent report by the Centers for Disease Control and Prevention (6).…”

A Diverse Panel of Clinical Acinetobacter baumannii for Research and Development

“…A key component in the success of A. baumannii has been its remarkable ability to develop antibiotic resistance through mutation (15,16), gene amplification (17), or horizontal acquisition of resistance genes (18,19). Of particular concern is the emergence of carbapenem-resistant A. baumannii (CRAB), resulting in infections treatable only with "last-line" antibiotics (4,7,20,21). For example, notwithstanding its nephrotoxicity, colistin (polymyxin E) is considered the last-line drug for treating infections caused by CRAB, but colistin-resistant strains have been isolated (22)(23)(24).…”