TEAM POLYMYXIN E
Although polymyxin B can seem like a very appealing alternative, little literature is available detailing the pharmacokinetics of polymyxin B, and there is a dearth of information regarding its pharmacodynamic properties. What we do know from five clinical trials comparing colistin and polymyxin B treatment is there is no difference in mortality.2,3,5-7
In addition, there are particular diseases states where colistin is likely preferred. Colistin is readily converted to its active form in urine and therefore reaches superior urinary concentrations compared with polymyxin B.1
Less than 1% of polymyxin B is recoverable in urine.8
Another benefit of colistin is its ability to be administered via inhalation. Inhalational colistin is currently recommended by the Infectious Diseases Society of America for treatment of hospital acquired- and ventilator associated pneumonia with multi-drug resistant infections.9
Finally, admixtures of polymyxin B require a considerable amount of solution volume, which may make colistin more appealing for those that cannot handle the extra fluid. Depending on patient weight, volumes of 500 to 1000 mL per dose (typically given twice daily) are not uncommon.
Although dosing of colistin is ambiguous at best and an unfortunate amount of interpatient variability exists, a considerable quantity of recent literature has been published to help clarify this issue. A recent study determined that a steady-state concentration of 2 mg/L should meet our targets.10
This study also identified that concentrations greater than 2 mg/L lead to increased incidence and severity of acute kidney injury.10
In addition, studies have suggested no benefit to more aggressive dosing,11
so in the future, it may be possible for us to be able to optimize colistin dosing. Whereas appropriate dosing, especially in renal insufficiency, is still a considerable barrier and a reason why many contemplate polymyxin B, recent literature has at least been able to guide us in the direction of using a 5-mg/kg loading dose and to strongly consider using ideal body weight.12
In addition, a potential scoring system is available to help identify patients most at risk for nephrotoxicity, which may help us customize our dosing in high-risk patients.13
As rampant antibiotic resistance continues to diminish our treatment options, we are more frequently forced to utilize the broadest spectrum and more toxic antibiotics. Recent reports from China documented the emergence of plasmid-mediated colistin resistance (MCR-1),14
and as of November 30, 2016, there have been human isolates of MCR-1 gene–containing organisms in Connecticut, Maryland, New Jersey, New York, and Pennsylvania.15
Animal isolates have also been found in Illinois and South Carolina.15
Optimization of antimicrobial therapy is the fundamental premise in slowing the unavoidable propagation of resistance. Thus, it is imperative to use and dose our polymyxins appropriately. Polymyxin B discernably wins the nephrotoxicity battle and is not a prodrug; administering its active form enables reliable dosing regardless of renal dysfunction and rapid achievement of therapeutic concentrations. However, despite polymyxin B’s multiple benefits, colistin certainly should not be disregarded. Superior urinary concentrations and the ability to administer via inhalation are undoubtedly some of colistin’s strong points. Additionally, more literature has been published that is enabling us to better understand how to appropriately and safely dose colistin.
So, which polymyxin do we choose? As with all clinical conundrums, there is no easy answer and the intellectual debate rages on. Thankfully, new literature on these old drugs continues to be published, and we will undoubtedly further our understanding of these unique antibiotics in the coming years.