UMEM Educational Pearls

 

Background:

· Empiric broad spectrum antibiotic therapy is a mainstay of the management of critically ill patients with septic shock.

· Vancomycin is widely used for the coverage of potential MRSA infection

• PROS: cheap, widely available, relatively widespread tissue penetration when given IV, and is generally well-tolerated

• CONS: has a complicated dosing regimen requiring specifically-timed serum concentration sampling and subsequent dose changes, frequently subtherapeutic, carries a risk of AKI especially when used concomitantly with piperacillin/tazobactam,¹ as it commonly is during empiric therapy for septic shock.         

· Continuous infusion of vancomycin has been repeatedly demonstrated to reach target serum concentrations faster, maintain consistent serum vancomycin levels better, with fewer serum concentration sampling required, and less overall vancomycin required to do so, in both adult and pediatric populations.^2-5

 

Current Article: 

Flannery AH, Bissell BD, Bastin MT, et al. Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: a Systematic Review and Meta-Analysis. Crit Care Med. 2020;48(6):912-8.

· Systematic review and meta-analysis of 11 studies for a total of 2123 patients

· Comparing continuous versus intermittent vancomycin infusion.

· Primary outcome of AKI, secondary outcome of mortality

· Found a reduction in the incidence of AKI in the continuous infusion cohort:

• OR 0.47 (95% CI 0.34-0.65) even when taking into account trough levels /area under the curve concentrations and the severity of AKI examined by the individual studies.

· No association between infusion strategy and mortality

 

Considerations:

· Initial loading dose used in most of the studies (15 mk/kg) probably underdosed, current recommendation for 25mg/kg initial loading dose⁷ (which is not even always effective by itself)⁸ (Reardon)

· Continuous infusion may be difficult with limited IV access

· AKI associated with increased hospital stay, costs, mortality (although didn’t pan out in study) – worth preventing if possible.

 

Take Home:

· Give a 25-30mk/kg loading dose of vancomycin in critically ill patients with suspicion of MRSA to achieve target serum concentrations sooner.

· Continuous vancomycin is a viable option and could be considered in ED boarders, especially if there is concern for impending renal injury.

 

References

1.     Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL. Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis. Crit Care Med. 2018;46(1):12?20. doi:10.1097/CCM.0000000000002769

2.     Taheri M, Dadashzadeh S, Shokouhi S, Ebrahimzadeh K, Sadeghi M, Sahraei Z. Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion. Iran J Pharm Res. 2018;17(Suppl2):195?205. 

3.     Gwee A, Cranswick N, McMullan B, et al. Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled Trial. Pediatrics. 2019;143(2):e20182179. doi:10.1542/peds.2018-2179 

4.     Vuagnat A, Stern R, Lotthe A, et al. High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion. J Clin Pharm Ther. 2004;29(4):351?357. doi:10.1111/j.1365-2710.2004.00572.x 

5.     Hong LT, Goolsby TA, Sherman DS, et al. Continuous infusion vs intermittent vancomycin in neurosurgical intensive care unit patients. J Crit Care. 2015;30(5):1153.e1?1153.e11536. doi:10.1016/j.jcrc.2015.06.012 

6.     Flannery AH, Bissell BD, Bastin MT, et al. Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: a Systematic Review and Meta-Analysis. Crit Care Med. 2020;48(6):912-8.

7.     Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020 Mar 19. doi: 10.1093/ajhp/zxaa036

8.     Álvarez O, Plaza-Plaza JC, Ramirez M, et al. Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients. Antimicrob Agents Chemother. 2017;61(8):e00280-17. doi: 10.1128/AAC.00280-17