Carbapenem-Resistant Acinetobacter baumannii: Virulence Factors, Molecular Epidemiology, and Latest Updates in Treatment Options

Abstract

Acinetobacter baumannii is a Gram-negative, non-motile pathogen commonly associated with healthcare settings. It is capable of causing severe infections, particularly in immunocompromised and critically ill individuals, and is linked to poor clinical outcomes. Infections caused by carbapenem-resistant A. baumannii (CRAB) represent a major public health concern due to limited treatment options and high resistance rates. Several virulence determinants contribute to CRAB's pathogenicity, including capsular exopolysaccharide (CPS), lipopolysaccharide (LPS), lipooligosaccharide (LOS), efflux pumps, outer membrane proteins (OMPs), pili, metal acquisition systems, two-component regulatory systems (TCSs), and secretion systems (SSs). The dominant resistance mechanism in CRAB involves the production of carbapenemases, most notably oxacillinase-23 (OXA-23) and metallo-β-lactamases (MBLs) such as Verona integron-encoded MBL (VIM) and New Delhi MBL (NDM). Accurate identification of these resistance mechanisms is crucial for guiding effective antimicrobial therapy. Potential treatment options include older agents like polymyxins, ampicillin-sulbactam, high-dose carbapenems, tigecycline, and minocycline, along with newer antimicrobials such as eravacycline, cefiderocol, and aztreonam-avibactam. This review aims to explore the virulence mechanisms and molecular pathogenesis of CRAB, while also presenting recent developments in its epidemiology and available antimicrobial therapies.

Keywords: antimicrobial agents; antimicrobial treatment; carbapenem-resistant Acinetobacter baumannii; molecular epidemiology; virulence factors.

Figure 1

The major antibiotic resistance mechanisms in CRAB strains.

Figure 2

Two-dimensional structures of antimicrobial agents including (a) colistin (polymyxin class) (2D structure of colistin; C₅₂H₉₈N₁₆O₁₃; https://pubchem.ncbi.nlm.nih.gov/compound/44144393) [251,252]; (b) ampicillin–sulbactam (2D structure of ampicillin–sulbactam; C₂₅H₃₁N₃O₉S₂; https://pubchem.ncbi.nlm.nih.gov/compound/18541918) [253] (penicillins class-β-lactamase inhibitor) [252], (c) tigecycline (2D structure of tigecycline; C₂₉H₃₉N₅O₈; https://pubchem.ncbi.nlm.nih.gov/compound/54686904) [254] (glycylcyclines class) [252], (d) Fosfomycin (2D structure of fosfomycin; C₃H₇O₄P; https://pubchem.ncbi.nlm.nih.gov/compound/446987) [255] (organic phosphonic acids class) [252], (e) plazomicin (2D structure of plazomicin; C₂₅H₄₈N₆O₁₀; https://pubchem.ncbi.nlm.nih.gov/compound/42613186) [256] (aminoglycosides class) [252], (f) eravacycline (2D structure of eravacycline; C₂₇H₃₁FN₄O₈; https://pubchem.ncbi.nlm.nih.gov/compound/54726192) [257] (tetracyclines class) [252], (g) cefiderocol (2D structure of cefiderocol; C₃₀H₃₄ClN₇O₁₀S₂; https://pubchem.ncbi.nlm.nih.gov/compound/77843966) [258] (cephalosporins class) [252], (h) temocillin (2D structure of temocillin; C₁₆H₁₈N₂O₇S₂; https://pubchem.ncbi.nlm.nih.gov/compound/171758) [259] (carboxylic acids class) [252], (i) ceftolozane–tazobactam (2D structure of ceftolozane–tazobactam; C₃₃H₄₄N₁₆O₁₇S₄; https://pubchem.ncbi.nlm.nih.gov/compound/172973390) [260] (cephalosporins class-β-lactamase inhibitor) [252], (j) meropenem–vaborbactam (2D structure of meropenem–vaborbactam; C₂₉H₄₁BN₄O₁₀S₂; https://pubchem.ncbi.nlm.nih.gov/compound/86298703) [261] (carbapenems class-β-lactamase inhibitor) [252], and (k) ceftazidime–avibactam (2D structure of ceftazidime–avibactam; C₂₉H₃₃N₉O₁₃S₃; https://pubchem.ncbi.nlm.nih.gov/compound/90643431) [262] (cephalosporins class-non-β-lactam β-lactamase inhibitor) [252] against CRAB isolates (https://www.ncbi.nlm.nih.gov/; https://go.drugbank.com//drugs; accessed on 27 June 2025).