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ABSTRACT
Introduction: Living in the ‘era of antibiotic resistance’ and facing the threat of an ‘end to antibiotics’, physicians in the last decade have revived use of colistin, since the available literature at the clinical level was poor and limited
Areas covered: Herein, the authors present the current available knowledge regarding colistin, i.e. in vitro activity and interactions, current pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, as well as toxicity issues, whereas the recently published newer plasmid mediated mcr-1 resistance gene is reviewed and discussed.
Expert opinion: As proven in a big number of studies and despite their retrospective design, it is surmized that for carbapenemase producing K. pneumoniae, colistin should be given in combination with another active in vitro antibiotic and preferably meropenem/doripenem whenever the relevant minimum inhibitory concentration is ≤8 mg/L. However, colistin monotherapy seems adequate for infections caused by A. baumannii and P. aeruginosa. Based on current knowledge on PK/PD, appropriate dosage schedules are discussed in detail. The worldwide fear of the spread of the plasmid mediated mcr-1 colistin resistance gene is prevailing which, if not limited, the real catastrophy of a life-saver antibiotic will follow soon.
Article highlights
Colistin, a polypeptide antibiotic of 1950s, was abandoned in 1970s due to reported cases of nephrotoxicity and was re-introduced in clinical practice in the 2000s due to the emerging increase of MDR Gram-negative pathogens in combination with the deficit of newer antimicrobial. It is systemically administrated in the form of colistin methanesulfonate (CMS) which is hydrolyzed to colistin that exhibits antibacterial activity. With the introduction of new assays that distinguish CMS from colistin, more accurate dosage schedules have been implied with the application of a loading dose and maintenance dose with longer intervals.
Colistin has a very narrow spectrum of activity, including MDR and XDR Gram-negative bacteria. It is inactive against Proteus spp., Providencia spp., Serratia spp, Gram positive and anaerobes.
In vitro interactions have led to synergistic results mainly with rifampicin and carbapenems against A. baumannii and P. aeruginosa. In carbapenemase producing K.pneumoniae synergy has been found with previous antimicrobial regimens and with tigecycline. The synergistic results of colistin with antimicrobials with Gram-positive activity, against A. baumannii is an unorthodox combination.
Clinical efficacy varies and although based mainly on retrospective studies, colistin should be given for carbapenemase producing K.pneumoniae in combination with another active in vitro antibiotic and preferably meropenem/doripenem whenever the relevant MIC is ≤8mg/L. However, colistin could be administrated as monotherapy for infections caused by A. baumannii and P. aeruginosa. However, randomized prospective clinical studies are warranted.
The most common adverse effect are nephrotoxicity and neurotoxicity.
The emergence of plasmid-mediated colistin resistance mcr-1 gene is a real threat due to worldwide spread in animals, human isolates, food and environmental samples, mostly in Escherchia coli.
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Declaration of interest
M Souli has received funding for research from Achaogen. H Giamarellou has received funding for research from Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.