Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Abstract

Increasing antibiotic resistance in multidrug-resistant (MDR) Gram-negative bacteria (MDR-GNB) presents significant health problems worldwide, since the vital available and effective antibiotics, including; broad-spectrum penicillins, fluoroquinolones, aminoglycosides, and β-lactams, such as; carbapenems, monobactam, and cephalosporins; often fail to fight MDR Gram-negative pathogens as well as the absence of new antibiotics that can defeat these "superbugs". All of these has prompted the reconsideration of old drugs such as polymyxins that were reckoned too toxic for clinical use. Only two polymyxins, polymyxin E (colistin) and polymyxin B, are currently commercially available. Colistin has re-emerged as a last-hope treatment in the mid-1990s against MDR Gram-negative pathogens due to the development of extensively drug-resistant GNB. Unfortunately, rapid global resistance towards colistin has emerged following its resurgence. Different mechanisms of colistin resistance have been characterized, including intrinsic, mutational, and transferable mechanisms. In this review, we intend to discuss the progress over the last two decades in understanding the alternative colistin mechanisms of action and different strategies used by bacteria to develop resistance against colistin, besides providing an update about what is previously recognized and what is novel concerning colistin resistance.

Antimicrobials as Single and Combination Therapy for Colistin-Resistant Pseudomonas aeruginosa at a University Hospital in Thailand

“…However, none of the CoR-PA strains in our study carried the mcr-1 gene. These results differed from previous reports in which CoR-PA strains were mcr-1-positive [11,14,26]. Moreover, we did not explore LPS modification or loss, or the overexpression of efflux pumps.…”

Plasmid mediated colistin resistant mcr-1 and co-existence of OXA-48 among Escherichia coli from clinical and poultry isolates: first report from Nepal

“…The emergence and spread of CRE has obliged clinicians to use colistin—a drug notorious for its toxicity [ 29 ]. Colistin is the last resort drugs for these resistant isolates [ 30 ]. Increasingly over the recent years, morbidity, mortality and the economic consequences associated with colistin resistance are reported [ 31 ].…”

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

“…Loss of the OprD porin (usually mediated by the inactivation of the OprD gene through deletions, mutations, or insertions) has been reported as one of the principal mechanisms of carbapenem resistance in Pseudomonas [182]; in addition, imipenem selects for porin-deficient mutants in 1 out of 5 patients treated with this drug [183]. On the other hand, the overproduction of the OprH porin (which is the smallest porin of P. aeruginosa), coupled with cation-starvation, has been described in isolates with increased MICs to polymyxins and aminoglycosides [184].…”