Skip to content

Polymyxin B in ICU patients: A concise Lecture in 10 minutes

  • by

Polymyxin B is an old antibiotic which was Developed in 1940s. In recent years, it is being used as a last resort therapy for Gram-negative multidrug-resistant (MDR) and extremely drug resistant (XDR) infections.

Hello friends polymix in b is an old antibiotic which was developed in 1940s in recent years it is being used as a last resort therapy for gram-negative mdr infections and also xdr infections so in this short lecture i am going to cover its brief pharmacology indications and evidence base regarding the clinical efficacy in mdr infections chemically it consists of

A positively charged peptide ring and a tripeptide side chain with a fatty acid tail tail helps in attachment and entry through bacterial membrane how does it act let’s understand polymix in b binds to the negatively charged lipopolysaccharide on the outer cell membrane of gram-negative bacteria interactions of cationic polymix in b and anionic lipopolysaccharide

Displace the positively charged cations like calcium and magnesium which are stabilizer of lipopolysaccharide cell membrane lead to instability of cell membrane once inside the bacterial cell polymex in b stops the cellular respiration that is bacterial respiration and secondly the polymex scenes are reported to have potent anti-antitoxin activity so this is

About the mechanism of action now regarding the range of bacteria it can kill it acts against most of the gram-negative aerobic basili including acetobacter pseudomonas klebsiella and androbacter species which are all important nosocomial pathogens however several pathogens poses intrinsic resistance to the polymexians which we must not forget such as proteus

Providencias racia niseria chromobacterium and bulgold area and all gram positive and anaerobic in organisms also resistant to polymix in b despite wide clinical use the understanding of formula kinetics of polymex in b has not been very great polymix in b is administered intravenously as sulphate salt which is an active compound and has high protein binding and

Large volume of distribution of about 42 liters after iv injection it spreads very fast and well do all tissues especially gi respiratory biliary and soft tissues however the penetration of polymix in b into csf is not well described despite large volume of distribution the elimination is rather fast with half life of about 9 to 12 hours and eliminated predominantly

By a non-renal mechanism so typically less than 5 percent of an intravenous dose of polymex in b is excreted in urine unchanged therefore renal based dose reduction is not relevant for polymix in b if a decrease in creatinine clearance occurs during the therapy the polymex indeed daily those should not be decreased particularly in a patient with a life-threatening

Or deep-seated infection or if the pathogens mic is more than one milligram per liter on sensitivity pattern being a large non-dilatable molecule polymex in b does not require dose modification in patients on renal replacements rapidly if you compare with cholesterol polymix in b is really safe whereas cholesterol is administered as product and most of it gets

Cleared via kidney so cholesterol requires a significant dose adjustment in renal impairment the dose is 15 000 to 25 000 units per kg divided into two roses even in renal dysfunction do not decrease the dose lower than 15 000 units per kg for better bacterial effects so for an adult patient use 15 lakhs per day in two divided doses of 7.5 lakh unit iv the dose

More than 20 lakhs per unit per day may cause real impairment that that one you should remember csf penetration may not be great so for the intrathecal dose you have to use 50 000 od for three days then 50 000 alternate day for at least two weeks after the cultures of csf are negative and sugar content has returned to normal can we use innational root in mdr

Web cases yes but there is limited literature for the utility of aerosolized polymix in b but clinical studies are there and those described was 2.5 milligram per kg that is 25 000 unit per kg per day i may still wait for few more studies to come before i would use in my patients however guidelines give only weak recommendations for aerosolization of polymix

In b the main side effect of polymaxines are nephrotoxicity and neurotoxicity in case of polymix in b the neural toxicity is the most common most uh significant side effect patients who are at particular risk are mystery and gravis patient who require increased doses of neural stigma other adverse effects includes paresthesia dizziness taxi and nestoria in less

Than 10 cases hyper sensitivity may also occur coming to the indications of polymix in b as we all know it is our antibiotic choice as a last resort to combat mdgam negative infections in icu this should be guided by cultures and sensitivity testing and mic values so now let’s talk about the evidence base for clinical efficacy of polymath cmb so acinatobacter

Bomini is a major killer in icu patients especially due to its multi-drug resistance property and capacity to form a biofilm findings from a mexican study demonstrate 100 percent susceptibility of high leader mdr bombing eye to polymix in b which suggests superior efficacy of polymix in b against mdr and biofilm producing a bombing isolates limb at all evaluated

Three antibiotics polymix in b riphampisin antigen cyclin alone and in combination in such infections in 31 mdr isolates all were susceptible to polymix in b but if they used the monotherapy no antibiotic had bacterial activity but in combination polymix in b and families in had highest bactericidal activity that was about 42 percent in another study birth at

All evaluated activity of polymix in b in combination with the meeping european name portion cyclin and they found that polymix in b plus kappa p m combination was most effective against k nemoni and androbacter caloric compared to digital combination in a retrospective study in 276 patient elias at all explored the impact of dose of polymix in b on mortality

So they found that the modality rate was 60.5 percent septic shock use of mechanical ventilation charleston’s comorbidity score and age was independent predictors of mortality polymix in b in a dose of 200 mg per day and above was associated with significant lower mortality but 200 me 200 mg means 20 lakhs unit this dose had higher risk of severe renal impairment

So you have to look for other risk factors in such patients who may develop renal dysfunction apart from using the polymix in b in larger doses more than 200 mg per day so another study is there which was performed in multiple drug registering negative respiratory tract infections patient required retrospective analysis of 25 critical patient they all received 29

Days of course your 21 20 courses were received main pathogens were isolated were uh acetobacter bombing eye and pseudomonas aeruginosa the clinical cure rate was very high 76 percent and concluded that polymaxine b in combination with other antimicrobials can be considered as reasonable and safe treatment options for mdi gram negative destructive tract infection

Though this was an old study but that was the study which always have been quoted to use the polymix in b for such infections in such particular group of patients so that’s all in summary i can say that kinetics of polymix in b is to requires research its role in resistance and severe infection as combination therapy has been proven and still require more data

Those may be reduced in aki or ckd depending upon not lower than 15 lakh unit per day in favor of better microbiological clearance combination should be papered over monotherapy in mdr infections as we can also see in success 2021 guideline which i just uploaded the video on uh sepsis 2021 guidelines some time back and every opportunity to save this drug as last

Resort rather than the overuse because we have very few antibiotics left in pipeline and the research pipeline is quite an empty thank you so much for your attention

Transcribed from video
Polymyxin B in ICU patients: A concise Lecture in 10 minutes By Dr Mohd Saif Khan