Sorry I do not understand the difference between ICU and ED! And, in the last 25 years the literature on Aminoglycosides changed! Thanks
________________________________________ From: Silvers MD, Jeffrey H [[email protected]] Sent: Wednesday, September 18, 2013 4:39 PM To: Moine, Pierre; Harkey,Jessica; [email protected] Subject: RE: [Sepsis Groups] Aminoglycoside dosing in severe sepsis/septic shock We are talking about empiric therapy by ED physicians. Not known organisms. Patients presenting to the ED with severe sepsis and shock frequently have unstable renal function. Starting with a higher dose of an aminoglycoside in that environment is hazardous. This is very different than ICU or critically ill surgical patients where clearly there are indications for using aminoglycosides. Dehydration or muscle wasting decreases the apparent volume of distribution. The latter conditions vary widely from patient to patient and from hour to hour in critically ill patients. Hence, it is recommended that a “peak” serum drug level be measured after the initial dose or the first maintenance dose. The following is from the PPID by Mandel. Note that the higher doses of mg/kg in parentheses are for expanded volume patients, the opposite of severe sepsis/septic shock. The daily dose depends on the renal function. Note that Ccr <40 recommends 2.5 mg/kg/day as the dose for euvolemic patients. I suggest 2 mg/kg/day as your first dose in the ED, if used, because the volume of distribution is significantly less in severe sepsis/shock. TABLE 26-12 -- Suggested Once-Daily Dosage Regimens: Gentamicin or Tobramycin*<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0070&appID=NGE> Estimated CrCl[†]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0075&appID=NGE> (mL/min) Dosage Interval (hr) Dose[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> (mg/kg) [cid:[email protected]] (hr) Estimated Serum Level after Drug Administration[§]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0085&appID=NGE> (µg/mL) 1 hr 12 hr 18 hr 24 hr 100 24 5 (7) 2.5 20 (28)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> 1.0 (1.4)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> <1 <1 90 24 5 (7) 3.1 20 (28)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> 2.0 (2.3)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> <1 <1 80 24 5 (7) 3.4 20 (28)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> 2.5 (2.9)[‡]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0080&appID=NGE> <1 <1 70 24 4 (5.5) 3.9 16 2.0 <1 <1 60 24 4 (5.5) 4.5 16 3.0 1.5 <1 50 24 3.5 (5.0) 5.3 14 3.5 1.0 <1 40 24 2.5 (3.5) 6.5 10 3.0 1.5 <1 30 24 2.5 (3.5) 8.4 10 4.0 2.5 1.5 1 hr 24 hr 36 hr 48 hr 20 48 4.0 (5.5) 11.9 16 4.0 2.0 1.0 10 48 3.0 (4.0) 20.4 12 5.0 3.0 2.0 0 (Hemodialysis)[|]<http://www.expertconsultbook.com/expertconsult/p/linkTo?type=bookPage&isbn=978-0-443-06839-3&eid=4-u1.0-B978-0-443-06839-3..00026-6--tn0090&appID=NGE> 48 2.0 (4.0) 69.3 8 7.0 6.0 5.0 Data from Gilbert DN, Lee BL, Dworkin RJ, et al. A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate. Am J Med. 1998;105:182-191; and Gilbert DN, Bennett WM. Use of antimicrobial agents in renal failure. Infect Dis Clin North Am. 1989;3:517-531. CrCl, creatinine clearance; [cid:[email protected]] , half-life. Jeffrey Silvers, M.D. Medical Director of Quality, Eden Medical Center Infectious Diseases specialist From: Moine, Pierre [mailto:[email protected]] Sent: Wednesday, September 18, 2013 9:46 AM To: Silvers MD, Jeffrey H; Harkey,Jessica; [email protected] Subject: RE: [Sepsis Groups] Aminoglycoside dosing in severe sepsis/septic shock Aminoglycosides should be combined with a betalactam for empiric treatment of severe sepsis and septic shock, documented Pseudomonas aeruginosa, Acinetobacter spp, and MDR GNB infections. They should be used high dose once daily (not the FDA recommendations but at least 7 mg/kg for gentamicin and tobramycin, and 20-25 mg/kg for amikacin). The use of extended-interval aminoglycoside dosage regimens in critically ill surgical patients is based on pharmacodynamic endpoints (probability of attaining the target Cmax). Administration of aminoglycosides with the extended-interval dosing scheme has been associated with a lower risk for nephrotoxicity. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. This risk is considered to be even lower when the administration is based on individualized pharmacokinetic monitoring. The subsequent doses may be tailored according to measured plasma aminoglycoside concentrations. In patients with reduced renal function, dosing intervals should be extended in order to reach low trough levels. Aminoglycosides should be anyway discontinued at 2-5 days. Pierre Moine Associate Professor University of Colorado Denver School of Medicine Department of Anesthesiology ________________________________ From: [email protected]<mailto:[email protected]> [[email protected]] On Behalf Of Silvers MD, Jeffrey H [[email protected]] Sent: Tuesday, September 17, 2013 4:26 PM To: Harkey,Jessica; [email protected]<mailto:[email protected]> Subject: Re: [Sepsis Groups] Aminoglycoside dosing in severe sepsis/septic shock I don’t recommend aminoglycosides as empiric therapy in septic shock or severe sepsis, except in rare circumstances. We have lots of alternatives and risk of nephrotoxicity in that situation is very high. If for some reason, that is what the doctor believes should be used, you could give a loading dose of a maximum of 2 mg/kg but no subsequent doses until level obtained. I would not use once daily dosing either. The best option would be to have your infectious disease specialist look at the empiric therapy regimens that the ED doctors are using and make suggestions for them to use in general. A good reference for your doctors: The Sanford Guide to Antimicrobial Therapy 2013. Jeffrey Silvers, M.D. Medical Director of Quality, Eden Medical Center Infectious Diseases specialist From: [email protected]<mailto:[email protected]> [mailto:[email protected]] On Behalf Of Harkey,Jessica Sent: Tuesday, September 17, 2013 10:28 AM To: [email protected]<mailto:[email protected]> Subject: [Sepsis Groups] Aminoglycoside dosing in severe sepsis/septic shock Hello there. I have been having some discussion with our pharmacists on whether or not patients who present to the ED in severe sepsis or septic shock should receive a full dose of an aminoglycoside (when indicated) within the first hour regardless of Cr clearance? The practice of our ED physicians thus far has been to order a full dose, and now we are getting some feedback from pharmacy to reduce the dose per renal function, which seems appropriate with consecutive doses along with monitoring drug levels. I am concerned about delaying administration. For initial empric therapy what are the rest of you doing in such cases? Any literature available for me to share with the pharmacy? Thank you! Jessica Harkey, RN, BSN, CCRN Sepsis Program Coordinator San Joaquin Community Hospital 661-869-6874 [email protected]<mailto:[email protected]> [cid:[email protected]] _______________________________________________ Sepsisgroups mailing list [email protected] http://lists.sepsisgroups.org/listinfo.cgi/sepsisgroups-sepsisgroups.org
