Questions continue to come up about how to initially dose antibiotics in severe sepsis or septic shock. Use the following as a guide for individualizing therapy...
What is the optimal time to start antibiotics? Exact timing is debated, but keep aiming for early antibiotic administration. For further information see note, Update your SEPSIS protocols and Optimize INITIAL antibiotic dosing in septic patients.
Should different initial doses be used? There's no proof that higher initial antibiotic doses improve patient outcomes. BUT standard doses may lead to inadequate levels in up to 84% of severely septic patients. This is possibly due to an increase in volume of distribution, especially during fluid resuscitation.
Consider vancomycin loading doses to reach target levels faster. If your hospital uses smaller doses of beta-lactams more frequently, consider a higher first dose, such as meropenem 1 to 2 g ONCE followed by 500 mg IV q6hr (We suggest loading dose of 2 g meropenem, administered over 30 min, with the next dose 6 hr later). Think about a "bolus" for first doses of extended infusion beta-lactams for higher levels sooner. For example, give pip/tazo (Tazocin, Pipra-Taz) 4.5 g ONCE over 30 minutes, then start infusing over four hours or more.
When should antibiotics be renally adjusted? We're used to adjusting antibiotic doses in patients with renal insufficiency. But ACUTE kidney injury patients may not need immediate renal adjustments due to a temporary increase in nonrenal clearance. Plus, renal function can improve rapidly with fluids. Consider modifying your renal adjustment policy for severely septic patients with acute renal insufficiency. Suggest waiting 24 hours to adjust doses in many of these patients and reassess daily.
Point out that risks of underdosing beta-lactams are usually greater than risks of overdosing. Be aware of potential underdosing in patients on continuous dialysis. Dosing references may not reflect newer machines and filters. Check local resistance patterns, antibiograms and patient history to further individualize therapy. Schedule which antibiotic to give first if IV access is limited. Choose based on broadest spectrum, infection site, and bactericidal activity.
REFERENCES
-
Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. Available at: https://ccforum.biomedcentral.com/articles/10.1186/cc9091
Abdul-Aziz MH, Lipman J, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Dulhunty J, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Roberts JA; DALI Study Group. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. J Antimicrob Chemother. 2016 Jan;71(1):196-207. Available at: https://pubmed.ncbi.nlm.nih.gov/26433783
Matzke GR, Aronoff GR, Atkinson AJ Jr, Bennett WM, Decker BS, Eckardt KU, Golper T, Grabe DW, Kasiske B, Keller F, Kielstein JT, Mehta R, Mueller BA, Pasko DA, Schaefer F, Sica DA, Inker LA, Umans JG, Murray P. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011 Dec;80(11):1122-37. Available at: https://www.kidney-international.org/article/S0085-2538(15)54984-3/fulltext