Sulbactam for carbapenem-resistant Acinetobacter baumannii infections: a literature review

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is characterized as a critical priority pathogen with restricted therapeutic options. To date, the most effective antimicrobial treatment against this difficult-to-treat bacterial strain has not been established. Sulbactam is a β-lactamase inhibitor with intrinsic activity against this pathogen, however, as a β-lactam, it can be hydrolysed by β-lactamases produced by A. baumannii. High-dose, extended-infusion treatment with sulbactam can overcome this hydrolysis by β-lactamases and is considered an effective therapeutic strategy against CRAB. The aim of this review is to analyse primary and secondary research studies that compare sulbactam-based with other regimens, such as polymyxin-containing regimens, tigecycline-containing regimens and other antimicrobial combinations against CRAB infections, especially ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) and bacteraemia. Our findings suggest that results are conflicting, mostly because of high heterogeneity among studies. However, in most studies, sulbactam-based regimens have demonstrated comparable, and in several studies more favourable results in contrast to other antimicrobial treatments with respect to clinical cure and mortality in CRAB-associated pneumonia, yet without reaching statistical significance in most cases. The auspicious novel β-lactam/β-lactamase inhibitor combination sulbactam/durlobactam is also discussed, although real-world clinical data regarding its efficacy in CRAB infections are still scarce. More randomized controlled trials comparing sulbactam-based with other regimens are warranted to determine the most effective antimicrobial combination against CRAB infections. Nevertheless, current data suggest that sulbactam could play a major role in this combination treatment.

Figure 1.

The rationale behind the use of high-dose sulbactam against CRAB infections. (a) Conventional-dose therapy with sulbactam may not be effective against CRAB, as this molecule can be hydrolysed by class A, ADC-type class C, OXA-type class D β-lactamases, and MBLs, which can be produced by CRAB isolates. As a result, sulbactam molecules cannot reach their targets, i.e. PBP1a, PBP1b and PBP3. (b) High-dose, extended-infusion therapy allows more sulbactam molecules to reach their PBP targets, as they overcome the hydrolysis by β-lactamases. Binding to PBPs leads to interruption of bacterial cell wall formation and consequently, to bacterial death. Figure created with BioRender.com.