EID/SDD is an approach of giving high-dose aminoglycoside over 30 minutes at an extended interval depending on the renal function (E.g.: 24 hourly, 36 hourly or more). EID is an alternative administration method for SDD when there is more time required to achieve adequate aminoglycoside clearance.

The theoretical benefits of EID / SDD 1, 2 :

• Aminoglycosides display concentration-dependent bactericidal action - that is, higher dose and peak serum concentrations result in more rapid bacterial killing.

• Optimise concentration-dependent bacterial killing by achieving a high peak (>10x MIC).

• Minimize nephrotoxicity by administering larger but less frequent doses and potentially decreasing renal cortical aminoglycoside concentrations.

• Utilize the post-antibiotic effect (PAE) (2-8 hours), defined as a recovery period before organisms can resume growth after drug removal.

• Minimize the development of adaptive resistance by allowing a recovery period during the dosing interval.

SDD is reasonable in most patients, except for 2,3 :

• Pregnancy

• Ascites

• Burns (>20%)

• Endocarditis

• Creatinine clearance <30ml/min

• Dialysis

• Neutropenic patients

• Patients with gram positive infections (such as Staphylococcus, Enterococcus) requiring synergistic effect 

• Heamodynamically unstable

• History of hearing loss/vestibular dysfunction

• Mycobacterium infection

The target reference range may be individualized based on institutional MIC value. 

For children, both peak and trough levels monitoring should be considered in patients demonstrating acute renal function changes or suspicion of treatment failure. Subsequent monitoring should be considered at least once weekly.

Please consult pharmacist for dosage adjustment.

Conventional/traditional dosing includes low doses with frequent administration of aminoglycosides using pharmacokinetic parameters to determine dose and frequency. However, in practice, dose below 7mg/kg for gentamicin at 24 hours interval is frequently used for patients with normal renal function.

The use of conventional dosing is recommended for the indications or populations in which SDD aminoglycosides does not cover (for example staphylococci or enterococci endocarditis).

The target reference range may be individualized based on institutional MIC value. 

Both peak and trough levels monitoring should be considered in patients demonstrating acute renal function changes or suspicion of treatment failure. Subsequent monitoring should be considered at least once weekly.

Vancomycin is a Type III pharmacodynamic properties antibiotic which has mixed properties of time-dependent killing and moderate persistent effects (persistent suppression of bacterial growth following antibiotic exposure). Thus, the optimal dosing of vancomycin is important to ensure adequate antibiotic exposure. The 24h-AUC/MIC ratio is the parameter that correlates with vancomycin efficacy14. The AUC can be estimate using Bayesian software programs (gold standard) or alternative approach involves the use of 2 concentrations (peak and trough) and simple analytic PK equations to estimate AUC values15.

TDM is indicated for all patients expected to receive vancomycin for longer than 48 hours. Some patient groups may require frequent monitoring, such as those in whom changes in vancomycin pharmacokinetics are anticipated over time. At least biweekly monitoring in clinically stable patients16.

CAPD or APD

Intermittent dose (once/day): 

15 - 30mg/kg every 5 - 7 days for CAPD

15 mg/kg every 4 days for APD

Continuous dose (per/L exchange):

Loading: 20–25 mg/kg

Maintenance: 25mg/L

Neonates: 

10 – 20mg/kg every 8 – 48 hours (depending on postmenstrual age, weight, SrCr) 

3 months to < 12 years: 

60 – 80 mg/kg/day in divided doses (q6h for normal renal function) 

≥ 12 years:

60 – 70 mg/kg/day in divided doses (q6-8h for normal renal function)  

References:

1. Drew RH, Hooper DC, Bloom A. Dosing and administration of parenteral aminoglycosides. Uptodate 2 Nov 2023.

2. Aminoglycosides: Recommendations for use, dosing and monitoring. Clinical Guideline Version 3. South Australian expert Advisory Group on Antimicrobial Resistance (SAAGAR), Infection Control Service. 11th Dec 2020. ISBN: 978-1-76083-351-0.

3. Plajer S, Chin P, Vella-Brincat J, Buffery P, Begg E. Gentamicin and renal function: Lessons from 15 years’ experience of a pharmacokinetic service for extended interval dosing of gentamicin. Ther Drug Monitoring 2015; 37: 98-103.

4. Pérez-Blanco, JS; Sáez, Fernández, EM; Calvo, MV; Lanao,JM; Martín-Suárez, A. Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin. Pharmaceutics 2021,13, 264.

5. Bland CM, Pai, MP, Lodise TP. Reappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing. Pharmacotherapy 2018;38(12):1229–1238.

6. Pacifici GM, Marchini G. Clinical Pharmacology of Amikacin in Infants and Children. Clin Med Invest, 2020, 5: 1-14.

7. Zhuang L, He Y, Xia H et al. Gentamicin dosing strategy in patients with end-stage renal disease receiving haemodialysis: evaluation using a semi-mechanistic pharmacokinetic/pharmacodynamic model. J Antimicrob Chemother 2016 Apr;71(4):1012-21.

8. Eschenauer, GA, Lam, SW, Mueller, BA. Dose Timing of Aminoglycosides in Hemodialysis Patients: A Pharmacology View. Seminars in Dialysis—Vol 29, No 3 (May–June) 201, 204–213.

9. He S, Cheng Z, Xie F. Population Pharmacokinetics and Dosing Optimization of Gentamicin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy. Drug Design, Development and Therapy 2022:16 13–22.

10. Roger C, Wallis SC, Muller L, et al. Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy. Antimicrob Agents Chemother. 2016. 60:4901–4909.

11. Kojya S, Shiohira H, Sunagawa Yet al. Therapeutic Drug Monitoring in Peritoneal Dialysis: A Case of Nontuberculous Mycobacterium Catheter-Related Infection Treated with Amikacin. Clin Case Rep. 2020;8:995–998.

12. Smeltzer BD, Shcwartzman MS, Bertino JSJ. AmikacinPharmacokineticsduring Continuous Ambulatory Peritoneal Dialysis. Antimicrob Agents Chemother. 1988. 32: 236-240.

13. Farkas A, Oikonomou K, Ghanbar M, et al. Population Pharmacokinetics of Intraperitoneal Gentamicin and the Impact of Varying Dwell Times on Pharmacodynamic Target Attainment in Patients with Acute Peritonitis Undergoing Peritoneal Dialysis. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0167921.

14. Lodise TP, Rosenkranz SL, Finnemeyer M et al. The emperor’s new clothes: prospective observational evaluation of the association between initial vancomycin exposure and failure rates among adult hospitalized patients with MRSA bloodstream infections (PROVIDE) [published online ahead of print June 3, 2019]. Clin Infect Dis. doi.10.1093/cid/ciz460.

15. 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;77(11):835-864. https://doi.org/10.1093/ajhp/zxaa036

16. Reuter et al. Optimal Practice for Vancomycin Therapeutic Drug Monitoring: Position Statement From the Anti-infectives Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit  Volume 44, Number 1, February 2022.

17. van Hal SJ, Paterson DL, Lodise TP. Systematic review and metaanalysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57:734–744.

18. SHC Vancomycin Dosing Guide. Stanford Health Care, Pharmacy Department Policies and Procedures. Last Approval: 03/2023

19. Ables M, Welch RW, Walley B. Development and Assessment of Vancomycin Dosing Utilizing AUC/MIC Protocol in Patients With End-Stage Renal Disease (ESRD) on Intermittent Hemodialysis (IHD). J Pharm Pract. 2023 Sep 16:8971900231198927. doi: 10.1177/08971900231198927. Epub ahead of print. PMID: 37715731

20. Susan J. Lewis and Bruce A. Mueller. Evaluation and Development of Vancomycin Dosing Schemes to Meet New AUC/MIC Targets in Intermittent Hemodialysis Using Monte Carlo Simulation Techniques. The Journal of Clinical Pharmacology / Vol 61 No 2 2021.

21. WACHS Specialised Medication – Intravenous Vancomycin in Adults Guideline. Date of Last Review: March 2020

22. Li PK-T, Chow KM, Cho Y, et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment. Peritoneal Dialysis International. 2022;42(2):110-153. doi:10.1177/08968608221080586

23. Cardiff Critical Care Standard Operating Procedures. Vancomycin version 1.0. Issue date 06/07/2021