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.
Highlights
Antimicrobial resistance (AMR) continues to pose a serious public health threat worldwide, and rates of AMR continue to rise in many parts of the world [1,2]
Cefepime was combined with some novel β-lactam β-lactamase inhibitors (BLBLI), due to its high potency, its stability against AmpC enzymes, and its chemical structure making it easier to protect from β-lactamases, including some class D carbapenemases (e.g., OXA-48)
This study showed the potent activity of this combination against P. aeruginosa strains, with diverse resistance mechanisms such as Pseudomonas-derived cephalosporinase (PDC) variants, OprD mutations, increased MexAB-OprM/MexXY-OprM efflux pump expressions, and Klebsiella pneumoniae carbapenemase (KPC), GES, or VIM carbapenemases [264]
Summary
Antimicrobial resistance (AMR) continues to pose a serious public health threat worldwide, and rates of AMR continue to rise in many parts of the world [1,2]. Because of the significant differences in the molecular epidemiology of carbapenem-resistant Gram-negative bacteria (CR-GNB) and the lack of new antibiotics in many countries, treatment approaches for infections caused by these pathogens differ significantly worldwide. 20–25% of CMS administered is typically converted into active colistin [20] It generally takes >36 h to achieve the target serum concentration, even with a loading dose [20]. A recent systematic review and meta-analysis mostly containing observational studies reported that the administration of a colistin loading dose in patients being treated with high maintenance dosage regimens significantly increased the rate of microbiological eradication, but did not provide any benefit for clinical cure, mortality, or nephrotoxicity risk [29]. An additional dose of colistin corresponding to 10% of the baseline dose is required per hour of dialysis to compensate for loss in dialysis
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