Efficient removal of colistin A and B in critically ill patients undergoing CVVHDF and sorbent technologies

Abstract

Background Colistin pharmacokinetics data are scarce regarding patients undergoing renal replacement therapy (RRT), or even absent as in patients treated with sorbent technologies potentially capable of removing colistin by extensive absorption on many polymeric materials.Methods Twelve septic shock patients with acute kidney injury (AKI) undergoing RRT [continuous venovenous hemodiafiltration (CVVHDF) n = 7, coupled-plasma filtration adsorption-HF (CPFA-HF) n = 4, hemoperfusion n = 1] treated with colistin methanesulfonate at a dose of 4.5 9 106 U bid were studied. Colistin A (Col-A) and colistin B (Col-B) concentrations on plasma and effluent at time 0, 0.2, 1, 3, 6, 12, 24 and 48 h were determined by the liquid chromatography-tandem mass spectrometry method.Results With CVVHDF the sieving coefficient was lower for Col-A, peaked early (0.40 for Col-A at 10 min, and 0.59 for Col-B at 3 h) and declined after 48 h (0.22 and 0.30 for Col-A and Col-B, respectively). Colistin's filter clearance showed a similar pattern, with the highest clearance value of 18.7 ml/min for Col-B at 1 h. With CPFA-HF after the cartridge the Col-A and Col-B levels were negligible (\0.2 mg/l) or not detectable. The sum of the effluent and cartridge clearances reached values of 30 and 40 ml/min for Col-A and Col-B, respectively. With hemoperfusion the postcartridge concentrations for Col-A and Col-B were about 30 % lower than those determined precartridge. Conclusions During CPFA-HF and CVVHDF, the extent of colistin removal is high, and patients should receive an unreduced dosage. However, due to risk of accumulation in longterm administration colistin plasma levels determination is recommended. Key WordsColistin sieving coefficient _ Colistin extracorporeal removal _ CVVHDF _ Coupled plasmafiltration adsorption _ Hemoperfusion Introduction Colistin (polymyxin E), a re-emerged antibiotic for multidrug-resistant gram-negative bacterial infections [1][2][3][4], is an antibiotic mixture containing more than 30 components differing in aminoacid and fatty-acid residue composition. The two major components of the mixture are colistin A (polymyxin E1) and colistin B (polymyxin E2) [4]. Colistin A and B have a discrete neuro-and nephrotoxicity [5][6][7][8]. To reduce colistine nephro-and neurotoxicity, the drug is currently administered intravenously as sodium colistimethate (CMS), an inactive prodrug which is hydrolyzed in vivo to the active colistin base moiety [2][3][4]. The risk of colistin nephrotoxicity proved to be clinically significant after 14 days administration [5]; it appeared to be linked to its cumulative dosage [6], was associated with advancing age and receipt of concurrent nephrotoxic agents [7], and was predicted by the plasma colistin level [8].Pharmacokinetics and pharmacodynamics of colistin are complex, and data are relatively scarce for critically ill patients with acute kidney injury (AKI) undergoing continuous venovenous hemodiafiltration (CVVHDF) or hemodialysis, which provide inconstant clearance of colistin i...

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

“…Colistin methanesulfonate and formed colistin are efficiently cleared by intermittent and continuous renal support modalities; less information is available for SLED than for shorter forms of IHD and CRRT . Supplementary doses of CMS are needed for patients receiving IHD or SLED.…”

“…Colistin methanesulfonate and formed colistin are efficiently cleared by intermittent and continuous renal support modalities; less information is available for SLED than for shorter forms of IHD and CRRT. 6,33,[70][71][72][73][74][75][76][77] Supplementary doses of CMS are needed for patients receiving IHD or SLED. IHD, SLED, and CRRT, each removes~10% of colistin an hour necessitating replacement of 10% of the daily dose per hour on these modalities.…”

Hemodialysis with High Cut-Off Hemodialyzers in Patients with Multi-Drug Resistant Gram-Negative Sepsis and Acute Kidney Injury: A Retrospective, Case-Control Study

“…Adequacy and dose adjustment of antibiotic therapy during CRRT are important issued, and several reports in literature warn against that the risk of underdosage. For instance, the extracorporeal drug removal for antibiotics used against MDR gram-negative infections has been established in literature [32] . Despite the appropriateness of antibiosis being retrospectively addressed in our study, the retrospective nature of this study prevented us from obtaining data on antibiotic concentrations during CRRT treatments.…”

A Guide to Understanding Antimicrobial Drug Dosing in Critically Ill Patients on Renal Replacement Therapy

“…A further study reported relatively high SA during CVVHDF (0.42 for colistin A and 0.48 for colistin B) with a high extent of colistin removal, suggesting the dose should not be reduced (89). In patients with septic shock and AKI undergoing coupled plasma filtration-adsorption/CVVHDF or hemoperfusion with polymyxin B fiber cartridges, colistin removal was high, especially in the case of coupled plasma filtration-adsorption/CVVHDF; however, the short duration of hemoperfusion probably resulted in very little impact on total-body colistin content (90). Regarding PK of colistin during IHD, a case report analyzed the variations in colistin plasma levels in 2 patients with pneumonia from multidrug-resistant Gram-negative bacteria and AKI undergoing 4-h IHD; 2 million IU q12h has been suggested as the most appropriate dose in patients undergoing daily IHD (91).…”