Original Research

The Safety and Efficacy of AUC/MIC-Guided vs Trough-Guided Vancomycin Monitoring Among Veterans

Fed Pract. 2023 January;40(1):28-33 | doi:10.12788/fp.0346

References

1. Gallagher J, MacDougall C. Glycopeptides and short-acting lipoglycopeptides In: Antibiotics Simplified. Jones & Bartlett Learning; 2018.

2. 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. doi:10.1093/ajhp/zxaa036

3. Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9(1):9-14. doi:10.1517/14740330903413514

4. Poston-Blahnik A, Moenster R. Association between vancomycin area under the curve and nephrotoxicity: a single center, retrospective cohort study in a veteran population. Open Forum Infect Dis. 2021;8(5):ofab094. Published 2021 Mar 12. doi:10.1093/ofid/ofab094

5. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82-98. doi:10.2146/ajhp080434

6. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925-942. doi:10.2165/00003088-200443130-00005

7. Gyamlani G, Potukuchi PK, Thomas F, et al. Vancomycin-Associated Acute Kidney Injury in a Large Veteran Population. Am J Nephrol. 2019;49(2):133-142. doi:10.1159/000496484

8. Neely MN, Kato L, Youn G, et al. Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing. Antimicrob Agents Chemother. 2018;62(2):e02042-17. Published 2018 Jan 25. doi:10.1128/AAC.02042-17

9. Prabaker KK, Tran TP, Pratummas T, Goetz MB, Graber CJ. Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. J Hosp Med. 2012;7(2):91-97. doi:10.1002/jhm.946

10. Patel N, Stornelli N, Sangiovanni RJ, Huang DB, Lodise TP. Effect of vancomycin-associated acute kidney injury on incidence of 30-day readmissions among hospitalized Veterans Affairs patients with skin and skin structure infections. Antimicrob Agents Chemother. 2020;64(10):e01268-20. Published 2020 Sep 21. doi:10.1128/AAC.01268-20

11. Acute Kidney Injury Work Group. Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2(suppl 1):1-138.

12. Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014;77:50-57. doi:10.1016/j.addr.2014.05.016

For AUC/MIC-guided TDM the C_max levels were ideally drawn 1 to 2 hours after vancomycin infusion and C_min levels were ideally drawn 30 minutes before the next dose. First-order pharmacokinetic equations were used to estimate the AUC/MIC.¹² If the timing of a vancomycin level was inappropriate, actual levels were extrapolated based on the timing of the blood draw compared with the ideal C_min or C_max time. Extrapolated levels were used for both trough-guided and AUC/MIC-guided TDM groups when appropriate. Vancomycin levels were excluded if they were drawn during the vancomycin infusion.

Study participant age, sex, race, weight, baseline estimated glomerular filtration (eGFR) rate, baseline sCr, concomitant nephrotoxic medications, duration of vancomycin course, indication of vancomycin, and acuity of illness based on indication were collected. sCr levels were collected from the initial day vancomycin was ordered through 72 hours following completion of a vancomycin course to evaluate for AKI. Patients’ charts were reviewed for the use of the following nephrotoxic medications: nonsteroidal anti-inflammatories, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aminoglycosides, piperacillin/tazobactam, loop diuretics, amphotericin B, acyclovir, intravenous contrast, and nephrotoxic chemotherapy (cisplatin). The category of concomitant nephrotoxic medications was also collected including the continuation of a home nephrotoxic medication vs the initiation of a new nephrotoxic medication.

Statistical Analysis

The primary endpoint of the incidence of vancomycin-induced AKI was compared using a Fisher exact test. The secondary endpoint of the percentage of trough levels or AUC/MICs in the therapeutic, subtherapeutic, and supratherapeutic range were compared using a student t test. The secondary endpoint of first level or AUC/MIC within goal range was compared using a χ² test. Continuous baseline characteristics were reported as a mean and compared using a student t test. Nominal baseline characteristics were reported as a percentage and compared using the χ² test. P values < .05 were considered statistically significant.

RESULTS

This study included 97 patients, 43 in the AUC/MIC group and 54 in the trough group.

Baseline characteristics were similar between the study groups (Table 1). Patients in the AUC/MIC group used more newly started nephrotoxins (P = .03) and the trough group had more acutely ill patients (P = .02).

One (2%) patient in the AUC/MIC group and 2 (4%) patients in the trough group experienced vancomycin-induced AKI (P = .10) (Table 2).

Ten (23%) patients in the AUC/MIC group and 8 (15%) in the trough group had overall AKI (P = .29). Eight patients in the AUC/MIC group and 5 in the trough group were found to have AKI with the use of concomitant nephrotoxins as a potential alternative cause of AKI. One patient in the AUC/MIC group had documented hypotension and 1 in the trough group had documented dehydration as possible causes of AKI. The incidence of the initial AUC/MIC or trough level within the therapeutic range was 56% (n = 24) in the AUC/MIC group and 35% (n = 19) in the trough group (P = .04). The percentage of AUC/MICs vs trough levels in the therapeutic range (57% vs 35%) was statistically significant (P = .02).

References

1. Gallagher J, MacDougall C. Glycopeptides and short-acting lipoglycopeptides In: Antibiotics Simplified. Jones & Bartlett Learning; 2018.

2. 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. doi:10.1093/ajhp/zxaa036

3. Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9(1):9-14. doi:10.1517/14740330903413514

4. Poston-Blahnik A, Moenster R. Association between vancomycin area under the curve and nephrotoxicity: a single center, retrospective cohort study in a veteran population. Open Forum Infect Dis. 2021;8(5):ofab094. Published 2021 Mar 12. doi:10.1093/ofid/ofab094

5. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82-98. doi:10.2146/ajhp080434

6. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925-942. doi:10.2165/00003088-200443130-00005

7. Gyamlani G, Potukuchi PK, Thomas F, et al. Vancomycin-Associated Acute Kidney Injury in a Large Veteran Population. Am J Nephrol. 2019;49(2):133-142. doi:10.1159/000496484

8. Neely MN, Kato L, Youn G, et al. Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing. Antimicrob Agents Chemother. 2018;62(2):e02042-17. Published 2018 Jan 25. doi:10.1128/AAC.02042-17

9. Prabaker KK, Tran TP, Pratummas T, Goetz MB, Graber CJ. Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. J Hosp Med. 2012;7(2):91-97. doi:10.1002/jhm.946

10. Patel N, Stornelli N, Sangiovanni RJ, Huang DB, Lodise TP. Effect of vancomycin-associated acute kidney injury on incidence of 30-day readmissions among hospitalized Veterans Affairs patients with skin and skin structure infections. Antimicrob Agents Chemother. 2020;64(10):e01268-20. Published 2020 Sep 21. doi:10.1128/AAC.01268-20

11. Acute Kidney Injury Work Group. Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2(suppl 1):1-138.

12. Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014;77:50-57. doi:10.1016/j.addr.2014.05.016

The Safety and Efficacy of AUC/MIC-Guided vs Trough-Guided Vancomycin Monitoring Among Veterans

References

Statistical Analysis

RESULTS

Pages

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