The Role of Colistin in the Era of New β-Lactam/β-Lactamase Inhibitor Combinations

Abstract

With the current crisis related to the emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB), classical treatment approaches with so-called “old-fashion antibiotics” are generally unsatisfactory. Newly approved β-lactam/β-lactamase inhibitors (BLBLIs) should be considered as the first-line treatment options for carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections. However, colistin can be prescribed for uncomplicated lower urinary tract infections caused by CR-GNB by relying on its pharmacokinetic and pharmacodynamic properties. Similarly, colistin can still be regarded as an alternative therapy for infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) until new and effective agents are approved. Using colistin in combination regimens (i.e., including at least two in vitro active agents) can be considered in CRAB infections, and CRE infections with high risk of mortality. In conclusion, new BLBLIs have largely replaced colistin for the treatment of CR-GNB infections. Nevertheless, colistin may be needed for the treatment of CRAB infections and in the setting where the new BLBLIs are currently unavailable. In addition, with the advent of rapid diagnostic methods and novel antimicrobials, the application of personalized medicine has gained significant importance in the treatment of CRE infections.

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

“…After liver transplantation, the risk of bacterial infections fluctuates over time, and clinicians should be aware of the differences between early infections (<1 month) with a high risk of community-acquired infections and latent infections in which the risk of opportunistic infections and hospital-acquired pathogens increases with prolonged immunosuppression and hospitalization ( Figure 1 ) [ 116 , 117 , 118 , 119 , 120 ].…”

Colistin Monotherapy versus Colistin plus Sitafloxacin for Therapy of Carbapenem-Resistant Acinetobacter baumannii Infections: A Preliminary Study

“…These factors have a significant effect on clinical outcomes, including clinical improvement and all-cause mortality. Moreover, since patients with CR A. baumannii infections frequently have other concurrent infections (i.e., bacteria or fungi), the relative contributions of CR A.baumanni infections versus other infections on the clinical outcomes and mortality are difficult to determine [ 27 ].…”

Next-Generation Polymyxin Class of Antibiotics: A Ray of Hope Illuminating a Dark Road

“…The activity of colistin and polymyxin B against Stenotrophomonas maltophilia exists but is variable [ 29 , 30 ]. For acquired polymyxin resistance mechanisms in CRE, CRAB, and CRPA, detailed information can be found in a previous review [ 24 ]. It is important to note that some Gram-negative species have natural resistance against polymyxins, including Brucella , Legionella , Campylobacter , Vibrio cholera , Proteus spp., Providencia spp., some Aeromonas spp., Chromobacterium spp., Edwardsiella spp., Serratia marcescens , Morganella morganii , Burkholderia mallei , and Burkholderia cepacia .…”

“…Likewise, mutations in OmpK35 and OmpK36 porins elevate the MIC values of imipenem-cilastatin-relebactam and some class A GES-type carbapenemase derivatives may confer resistance to this agent [ 23 ]. The evolving nature of AMR in GNB requires the development of antibiotics from various classes with different mechanisms of action [ 24 ]. Notwithstanding that the size and complexity of existing polymyxins make it difficult, next-generation polymyxins are being developed to reduce toxicity, increase efficacy, and to overcome resistance.…”