Introduction: Acinetobacter baumannii inactivates β‑lactam antibiotics by hydrolytic or non‑hydrolytic mechanisms that cleave the β‑lactam ring. In recent years, the management of multidrug‑resistant Acinetobacter baumannii infections has emerged as a significant clinical challenge. Patients with such infections often have compromised immune function and multiple comorbidities, necessitating invasive life‑support measures—such as mechanical ventilation, renal replacement therapy, and central venous catheterization—requiring a comprehensive approach to treatment planning. Enhanced surveillance of clinical cases, timely and judicious adjustments to therapeutic regimens, and the exploration of novel strategies for treating multidrug‑resistant Acinetobacter baumannii infections are essential.

　　 Acinetobacter baumannii–related resistance mechanisms

　　 (1) To beta - Mechanisms of resistance to β-lactam antibiotics

　　1) Plasmid-mediated or chromosomal mutations enable bacteria to produce beta -β-lactamase, which inactivates β-lactams via hydrolytic or non-hydrolytic mechanisms beta -β-lactam ring, which inactivates the antibiotic; this is how most pathogenic bacteria resist beta - The primary mechanisms of resistance to β-lactam antibiotics [26, 29]. Metalloenzymes belong to Ambler class B. beta -β-lactamase, classified under Bush functional group 3. Based on metal… beta - Based on the substrate specificity of β-lactamases, they are classified into three subgroups: 3a, 3b, and 3c. The metalloenzymes produced by Acinetobacter that hydrolyze carbapenems belong to subgroup 3a. Currently reported members include IMP‑1, IMP‑2, IMP‑4, IMP‑5, as well as VIM‑1 and VIM‑2 [30, 31]. These enzymes confer resistance to carbapenems, ceftazidime, latamoxef, and other antibiotics, while remaining ineffective against piperacillin and aztreonam. Their activity is not inhibited by inhibitors such as clavulanic acid, but it can be suppressed by ethylenediaminetetraacetic acid (EDTA).

　　2) Carbapenemase (OXA), also known as oxacillinase, is chromosomally mediated. OXA-type enzymes are classified as Ambler class D according to their molecular structure. beta -β-lactamase, classified under Bush’s functional group 2D. Class D OXA-type enzymes can inactivate carbapenem antibiotics, but their hydrolytic activity is significantly lower than that of metallo-β-lactamases [32]. However, with the discovery of the insertion sequence ISAbal, our understanding of OXA-type carbapenemases mediating carbapenem resistance in Acinetobacter baumannii has been refined. Studies have shown that the insertion sequence ISAbal, which is specific to A. baumannii, is often closely associated with genes of the OXA‑23 and OXA‑51 groups; it plays a crucial role in gene transfer and can substantially enhance the expression levels of these resistance genes, thereby conferring resistance to beta - High-level resistance to β-lactam antibiotics [33]. Some OXA enzymes are capable of hydrolyzing broad-spectrum cephalosporins, such as the OXA-type extended‑spectrum enzymes [34], and certain OXA enzymes can also hydrolyze carbapenem antibacterial agents. The first OXA enzyme with carbapenemase activity identified in Acinetobacter baumannii was OXA‑23, discovered in 1985 in a clinical isolate from Scotland, at a time when carbapenems had not yet been introduced into clinical practice. Subsequently, similar enzymes were reported successively in the United Kingdom, Brazil, Polynesia, Singapore, South Korea, and China [27, 34]. It has now been confirmed that the OXA‑51/69‑like group constitutes a set of carbapenemase genes naturally carried on the chromosome of Acinetobacter baumannii [35].

　　3) AmpC type beta - Lactamases, a family of enzymes comprising “serine” cephalosporinases produced by Gram-negative bacilli that are not inhibited by clavulanic acid, belong to Bush group I and Ambler molecular class C. Bacteria of the genus Acinetobacter predominantly produce inducible AmpC-type β-lactamases. beta -β-lactamase. AmpC type beta - β-Lactamase confers resistance to first- through third-generation cephalosporins, cephamycins, aminoglycosides, and anti‑Pseudomonas penicillins, while remaining susceptible to carbapenems, fourth-generation cephalosporins, and fluoroquinolones.

　　4) TEM‑1 and TEM‑2 enzymes belong to Ambler class A and the Bush group 2b. They can efficiently hydrolyze penicillins and first- to third-generation cephalosporins, and some are also capable of hydrolyzing fourth-generation cephalosporins. They are susceptible to carbapenems and cephamycins, and their activity can be inhibited by β‑lactamase inhibitors such as clavulanic acid and sulbactam.

　　5) Alterations in penicillin-binding proteins and outer membrane porins. Acinetobacter is resistant to… beta - The permeability of β-lactams is only 1%–3% of that of Escherichia coli; therefore, its outer membrane is resistant to beta - β-lactamase–producing antibiotics serve as a barrier, and resistance at clinically relevant levels is rarely achieved through reduced permeability alone. Carbapenem‑resistant Acinetobacter species, including those resistant to imipenem and meropenem, have been identified, except… beta In addition to β-lactamase activity, alterations in penicillin-binding proteins and a reduction or loss of outer membrane porin expression have also been observed [36].

　　 (2) Resistance to other antimicrobial agents

　　Acinetobacter resistance to aminoglycoside antibiotics is primarily mediated by the production of three classes of aminoglycoside-modifying enzymes: acetyltransferases (AAC), phosphotransferases (APH), and nucleotidyltransferases (ANT) [37]. Resistance to quinolones arises from mutations in the gyrA and ParC genes, which alter the structure of DNA gyrase; another contributing factor is the downregulation of intracellular drug concentrations mediated by efflux pump systems. Currently, two mechanisms underlie Acinetobacter baumannii resistance to tetracycline antibiotics: TatA and TatB, which are specific transposon‑mediated efflux pumps [38].

　　 Control and Treatment of Nosocomial Infections Caused by Multidrug-Resistant Acinetobacter baumannii

　　(1) Control of Ambient Environmental Pollution

　　Acinetobacter baumannii is widely distributed in hospital environments and on human skin, factors that are of critical importance in outbreaks of this pathogen. The organism can be transmitted via the hands of healthcare workers; proper hand hygiene, the use of gloves, and the application of disinfectant‑containing or alcohol‑based soaps are highly effective in controlling nosocomial infections. Strengthening environmental surveillance, implementing rigorous disinfection and isolation measures, are essential for controlling hospital‑acquired infections caused by multidrug‑resistant A. baumannii [39, 40].

　　(II) In Vitro Antimicrobial Activity Assay Against Acinetobacter baumannii

　　The results of in vitro antibacterial activity assays provide the best guidance for the treatment of Acinetobacter baumannii infections. Studies have shown that sulbactam exhibits intrinsic activity against A. baumannii, but it does not enhance the activity of other… beta - The mechanism of action of β-lactam antibiotics [41]. Quinolone combination beta - β‑Lactams and imipenem in combination with aminoglycosides have demonstrated synergistic effects against imipenem‑susceptible strains [42]. Polymyxin B exhibits synergy with imipenem, meropenem, azithromycin, rifampicin, trimethoprim–sulfamethoxazole (SMZ‑TMP), and ampicillin/sulbactam [43]. These findings suggest that combination antibiotic therapy for multidrug‑resistant Acinetobacter baumannii is more effective than monotherapy and may help suppress the emergence of new resistance mechanisms [44].

　　 Clinical Experience in the Use of Antimicrobial Agents for Treating Acinetobacter baumannii

　　While in vitro susceptibility testing of antimicrobial agents is undoubtedly important, in actual clinical practice, antibiotic selection should not be based solely on these results. Both prospective and retrospective studies have demonstrated that sulbactam therapy achieves favorable outcomes—with a cure rate of 67.5%—in cases of meningitis, pneumonia, peritonitis, surgical wound infections, and urinary tract infections caused by multidrug‑resistant Acinetobacter baumannii (imipenem‑resistant) [45]. A U.S. study indicated that piperacillin–sulbactam can be used to treat infections with imipenem‑resistant A. baumannii, with a daily dose of at least 6 g for severe nosocomial infections [46]. Additionally, reports suggest that polymyxin E, when combined with other antimicrobials such as imipenem, piperacillin–sulbactam, aztreonam, quinolones, and aminoglycosides, yields good therapeutic results in multidrug‑resistant A. baumannii infections, particularly ventilator‑associated pneumonia, with 76% of cases showing favorable responses [47]. The efficacy of polymyxin B in treating multidrug‑resistant A. baumannii—including endocarditis, meningitis, pneumonia, urinary tract infections, and catheter‑related infections—has been well established; however, monotherapy may promote the emergence of new resistance mechanisms. Consequently, current guidelines recommend combining 2–3 antibiotics to treat multidrug‑resistant A. baumannii, which not only enhances antimicrobial activity but also helps reduce the development of resistant strains [48].

　　 Conclusion

　　In recent years, the treatment of multidrug‑resistant Acinetobacter baumannii infections has become a major clinical challenge. To date, there remain very few antibiotics that demonstrate robust antibacterial activity against such infections. Moreover, patients with A. baumannii infections often have compromised immune function and multiple comorbidities, necessitating invasive life‑support measures—such as mechanical ventilation, renal replacement therapy, and central venous catheterization. Consequently, it is essential to adopt a comprehensive approach to therapeutic decision‑making, strengthen clinical surveillance, promptly and appropriately adjust treatment regimens, and explore novel strategies for managing multidrug‑resistant A. baumannii infections.

　　Source: Critical Care Medicine Branch of the Chinese Medical Association