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Sodium content of intravenous antibiotic preparations

Sodium content of intravenous antibiotic preparations Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Nina Wang, PharmD 1,2 Phuong Khanh Nguyen, PharmD Christine U. Pham, PharmD Ethan A. Smith, PharmD Brian Kim, PharmD 2,6 Matthew Bidwell Goetz, MD FIDSA 2,6 Christopher J. Graber, MD MPH FIDSA 1. Department of Pharmacy, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA 2. Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA 3. Department of Pharmacy, UCLA Health, Los Angeles, CA 4. Department of Pharmacy Services, Cedars-Sinai Medical Center, Los Angeles, CA 5. Department of Pharmacy, Olive View-UCLA Medical Center, Sylmar, CA 6. David Geffen School of Medicine at UCLA, Los Angeles, CA Corresponding Author: Christopher J. Graber, MD MPH FIDSA Infectious Diseases Section, VA Greater Los Angeles Healthcare System 11301 Wilshire Blvd, 111-F Los Angeles, CA 90073 Email: Christopher.Graber@va.gov Phone: (310) 478-3711 x40275 Fax: (310) 268-4928 Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Dear Editors, We read with great appreciation the recent publication by Frisbee and colleagues , which examines a common and perhaps underappreciated phenomenon seen in clinical practice: concurrent treatment for pneumonia in those admitted for acute decompensated heart failure (ADHF). Recent evidence also suggests that incident cardiac complications, primarily new or worsening heart failure, are frequent in 2,3 those admitted for community-acquired pneumonia (CAP), further complicating the clinical picture . Thus, definitive diagnosis of ADHF vs. CAP can certainly be challenging given the similarity in symptoms and can often lead to overprescribing and excessive treatment burden for both the patient and healthcare system. The authors’ findings that ADHF patients who received intravenous antibiotics had longer lengths of stay, required more diuretics, and were more likely to be readmitted compared with ADHF patients who were not exposed to such therapy serve as a caution against unnecessary intravenous antimicrobial therapy in patients who are at low risk for pneumonia. We believe that an accurate reference for sodium content found in common intravenous antibiotics can serve as a useful tool for antimicrobial stewards in helping convince providers to discontinue antibiotic therapy in ADHF patients who are at low risk for infection. The Supplemental table provided by the authors is intended to serve this purpose. However, there are a few aspects about the data that we would like to clarify: First, sodium restriction is commonly prescribed for patients with heart failure. The amount by which to 4-6 limit sodium may vary, but the guideline-recommended values are described in elemental sodium . It appears that the authors report sodium content from antibiotics used in their study in terms of sodium chloride (e.g. vancomycin, doxycycline, and azithromycin), which would overestimate elemental sodium content present in each antibiotic preparation. For example, if a standard 1 gram dose of vancomycin lacking intrinsic sodium content were prepared in 250mL of normal saline (NS), this particular antibiotic- Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 diluent combination would yield about 900mg of elemental sodium, which contrasts with the 2250mg of sodium reported by the authors. Second, antibiotics are often prepared in diluents that differ in sodium content and volume. Some are available in ready-to-use (RTU) preparations from the manufacturer; others are prepared in varying volumes of dextrose 5% in water (D5W) and NS. For example, with respect to the sodium content reported for linezolid, we are aware of two pre-mixed formulations that are prepared in a NS and a 7,8 dextrose-based solution, containing a sodium content of 1196mg and 114mg, respectively. We surveyed common practices across our institutions and developed a table (Table 1) that addresses the above inconsistencies and incorporates more antibiotics to be a more comprehensive antimicrobial stewardship tool in detailing information on the sodium content intrinsic to these antibiotics and in commonly used diluents. We present our data using standard antibiotic doses and report the total sodium content for various volume-diluent preparations on a per-dose basis. We also provide the “total sodium per day of therapy” as a guide for clinicians to better assess the amount of sodium being administered to their patients relative to the daily sodium restriction recommendations. The package inserts to which we referred are included in Appendix A. In summary, Frisbee et al. revisit an important and challenging area of clinical practice and certainly raise awareness of a potentially useful tool that may further support hospital stewardship programs in the discontinuation of inappropriate antibiotic therapy in patients with heart failure. We wholeheartedly agree that “giving patients at low risk of infection antibiotic therapy ‘just to be safe’” may not actually be safe at all, and we hope that our proposed table will provide a more systematic means to conceptualize sodium content of intravenous antibiotic administration. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 References: 1. Frisbee J, Heidel RE, Rasnake MS. Adverse Outcomes Associated With Potentially Inappropriate Antibiotic Use in Heart Failure Admissions. Open Forum Infect Dis. 2019;6(6):ofz220. 2. Violi F, Cangemi R, Falcone M, et al. Cardiovascular Complications and Short-term Mortality Risk in Community-Acquired Pneumonia. Clin Infect Dis. 2017;64(11):1486-1493. 3. Corrales-medina VF, Musher DM, Wells GA, et al. Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality. Circulation. 2012;125(6):773-81. 4. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240–e327. 5. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16:e1–194. 6. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69. 7. Linezolid (linezolid injection) [package insert]. Lake Forest, IL: Hospira, Inc.; 2019. 8. Linezolid (linezolid injection) [package insert]. East Windsor, NJ: AuroMedics Pharma LLC; 2018. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Table 1. Sodium Content of Intravenous Antibiotic Preparations Intrinsic Intrinsic Total Sodium Usual Total Sodium Total Sodium Total Sodium (mg) per Available Sodium Sodium per Content (mg) in Antibiotic Dose Content in 50mL Content in 100mL Day of Therapy Diluents Content in Vial (or in other Volume of c c d,e (mg) NS (mg) NS (mg) (# of doses) RTU (mg) D5W) (mg) NS -lactams Penicillin G 4 MU RTU, D5W, NS 94 27.2 213.3 390.3 - 2,340 (6) Potassium Penicillin G 4 MU D5W, NS - 154.6 340.1 517.1 - 3,100 (6) Sodium Ampicillin 2,000 NS - 131.6 - 485.6 - 2,910 (6) Ampicillin- 1,500 NS - 115 292 469 - 1,880 (4) Sulbactam 3,000 NS - 230 - 584 - 2,340 (4) Oxacillin 2,000 RTU, D5W, NS 184.8 128 375.8 552.8 - 3,320 (6) Nafcillin 2,000 RTU, D5W, NS 153.2 132.2 415.4 592.4 - 3,550 (6) Piperacillin- 3,375 RTU, D5W, NS 195 162 392.1 569.1 - 2,280 (4) tazobactam 4,500 RTU, D5W, NS 260 216 463.8 640.8 - 2,560 (4) 1,000 RTU, D5W, NS 48 48 225 402 - 1,200 (3) Cefazolin 2,000 RTU, D5W, NS 96 96 - 450 - 1,350 (3) 1,000 RTU, D5W, NS 83 83 294 471 - 470 (1) Ceftriaxone 2,000 RTU, D5W, NS 166 166 410.9 587.9 - 1,180 (2) 1,000 RTU, D5W, NS 54 54 231 408 - 1,220 (3) Ceftazidime 2,000 RTU, D5W, NS 108 108 285 462 - 1,390 (3) 1,000 RTU, D5W, NS 0 0 212.4 389.4 - 1,170 (3) Cefepime 2,000 RTU, D5W, NS 0 0 212.4 389.4 - 1,170 (3) Aztreonam 2,000 RTU, D5W, NS 0 0 - 354 - 1,060 (3) Ertapenem 1,000 NS - 137 349.4 526.4 - 530 (1) 1,000 RTU, NS 290.2 90.2 267.2 444.2 - 1,330 (3) Meropenem 2,000 NS - 180.4 - 534.4 - 1,600 (3) Imipenem 500 D5W, NS - 37.5 - 426.9 - 1,710 (4) Fluoroquinolones/macrolides Ciprofloxacin 400 RTU 0 - - - - 0 (2) Levofloxacin 500 RTU, D5W, NS 0 0 - - 283 (80 mL) 280 (1) Azithromycin 500 D5W, NS - 114 - - 999 (250 mL) 1,000 (1) Anti-MRSA agents 1,000 RTU, D5W, NS 708 0 - - 885 (250 mL) 3,540 (4) Vancomycin 2,000 D5W, NS - 0 - - 1,770 (500 mL) 3,540 (2) Daptomycin 500 NS - 0 212.4 389.4 - 390 (1) Linezolid 600 RTU 114; 1,196 - - - 1,196 (300 mL) 2,390 (2) Ceftaroline 600 D5W, NS - 0 247.8 424.8 - 1,270 (3) Doxycycline 100 D5W, NS - 0 - 389.4 - 780 (2) 600 RTU, D5W, NS 0 0 177 354 - 1,420 (4) Clindamycin 900 RTU, D5W, NS 0 0 177 354 - 1,060 (3) Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Sulfamethoxazole- 1,875- i i D5W - 0 - - - 0 (4) trimethoprim 375 Miscellaneous Metronidazole 500 RTU 326 - - - - 1,300 (4) RTU = Ready-to-Use; D5W = Dextrose 5% in Water; NS = Normal Saline (0.9% NaCl) Values derived from injectable single-dose vial supply; sodium content may vary slightly between manufacturers Intrinsic sodium content of antibiotic plus sodium content in NS; 177mg sodium per 50mL NS; 354mg sodium per 100mL NS; if NS is a recommended solvent for reconstitution per manufacturer, sodium content from the solvent is also included Assumes drug preparation in 100mL NS or other volume of NS/available diluent with appropriate drug concentration per manufacturer; values are rounded to the nearest 10mg Total sodium content per day of therapy considers maximum number of daily doses seen in clinical practice Million units RTU formulations available in both NS (1,196mg sodium) and D5W (114mg sodium) Dose based on 5mg/kg trimethoprim component; weight of 75kg Sodium content from excipients negligible Accepted Manuscript http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

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Oxford University Press
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Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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2328-8957
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10.1093/ofid/ofz508
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Abstract

Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Nina Wang, PharmD 1,2 Phuong Khanh Nguyen, PharmD Christine U. Pham, PharmD Ethan A. Smith, PharmD Brian Kim, PharmD 2,6 Matthew Bidwell Goetz, MD FIDSA 2,6 Christopher J. Graber, MD MPH FIDSA 1. Department of Pharmacy, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA 2. Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA 3. Department of Pharmacy, UCLA Health, Los Angeles, CA 4. Department of Pharmacy Services, Cedars-Sinai Medical Center, Los Angeles, CA 5. Department of Pharmacy, Olive View-UCLA Medical Center, Sylmar, CA 6. David Geffen School of Medicine at UCLA, Los Angeles, CA Corresponding Author: Christopher J. Graber, MD MPH FIDSA Infectious Diseases Section, VA Greater Los Angeles Healthcare System 11301 Wilshire Blvd, 111-F Los Angeles, CA 90073 Email: Christopher.Graber@va.gov Phone: (310) 478-3711 x40275 Fax: (310) 268-4928 Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Dear Editors, We read with great appreciation the recent publication by Frisbee and colleagues , which examines a common and perhaps underappreciated phenomenon seen in clinical practice: concurrent treatment for pneumonia in those admitted for acute decompensated heart failure (ADHF). Recent evidence also suggests that incident cardiac complications, primarily new or worsening heart failure, are frequent in 2,3 those admitted for community-acquired pneumonia (CAP), further complicating the clinical picture . Thus, definitive diagnosis of ADHF vs. CAP can certainly be challenging given the similarity in symptoms and can often lead to overprescribing and excessive treatment burden for both the patient and healthcare system. The authors’ findings that ADHF patients who received intravenous antibiotics had longer lengths of stay, required more diuretics, and were more likely to be readmitted compared with ADHF patients who were not exposed to such therapy serve as a caution against unnecessary intravenous antimicrobial therapy in patients who are at low risk for pneumonia. We believe that an accurate reference for sodium content found in common intravenous antibiotics can serve as a useful tool for antimicrobial stewards in helping convince providers to discontinue antibiotic therapy in ADHF patients who are at low risk for infection. The Supplemental table provided by the authors is intended to serve this purpose. However, there are a few aspects about the data that we would like to clarify: First, sodium restriction is commonly prescribed for patients with heart failure. The amount by which to 4-6 limit sodium may vary, but the guideline-recommended values are described in elemental sodium . It appears that the authors report sodium content from antibiotics used in their study in terms of sodium chloride (e.g. vancomycin, doxycycline, and azithromycin), which would overestimate elemental sodium content present in each antibiotic preparation. For example, if a standard 1 gram dose of vancomycin lacking intrinsic sodium content were prepared in 250mL of normal saline (NS), this particular antibiotic- Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 diluent combination would yield about 900mg of elemental sodium, which contrasts with the 2250mg of sodium reported by the authors. Second, antibiotics are often prepared in diluents that differ in sodium content and volume. Some are available in ready-to-use (RTU) preparations from the manufacturer; others are prepared in varying volumes of dextrose 5% in water (D5W) and NS. For example, with respect to the sodium content reported for linezolid, we are aware of two pre-mixed formulations that are prepared in a NS and a 7,8 dextrose-based solution, containing a sodium content of 1196mg and 114mg, respectively. We surveyed common practices across our institutions and developed a table (Table 1) that addresses the above inconsistencies and incorporates more antibiotics to be a more comprehensive antimicrobial stewardship tool in detailing information on the sodium content intrinsic to these antibiotics and in commonly used diluents. We present our data using standard antibiotic doses and report the total sodium content for various volume-diluent preparations on a per-dose basis. We also provide the “total sodium per day of therapy” as a guide for clinicians to better assess the amount of sodium being administered to their patients relative to the daily sodium restriction recommendations. The package inserts to which we referred are included in Appendix A. In summary, Frisbee et al. revisit an important and challenging area of clinical practice and certainly raise awareness of a potentially useful tool that may further support hospital stewardship programs in the discontinuation of inappropriate antibiotic therapy in patients with heart failure. We wholeheartedly agree that “giving patients at low risk of infection antibiotic therapy ‘just to be safe’” may not actually be safe at all, and we hope that our proposed table will provide a more systematic means to conceptualize sodium content of intravenous antibiotic administration. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 References: 1. Frisbee J, Heidel RE, Rasnake MS. Adverse Outcomes Associated With Potentially Inappropriate Antibiotic Use in Heart Failure Admissions. Open Forum Infect Dis. 2019;6(6):ofz220. 2. Violi F, Cangemi R, Falcone M, et al. Cardiovascular Complications and Short-term Mortality Risk in Community-Acquired Pneumonia. Clin Infect Dis. 2017;64(11):1486-1493. 3. Corrales-medina VF, Musher DM, Wells GA, et al. Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality. Circulation. 2012;125(6):773-81. 4. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240–e327. 5. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16:e1–194. 6. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69. 7. Linezolid (linezolid injection) [package insert]. Lake Forest, IL: Hospira, Inc.; 2019. 8. Linezolid (linezolid injection) [package insert]. East Windsor, NJ: AuroMedics Pharma LLC; 2018. Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Table 1. Sodium Content of Intravenous Antibiotic Preparations Intrinsic Intrinsic Total Sodium Usual Total Sodium Total Sodium Total Sodium (mg) per Available Sodium Sodium per Content (mg) in Antibiotic Dose Content in 50mL Content in 100mL Day of Therapy Diluents Content in Vial (or in other Volume of c c d,e (mg) NS (mg) NS (mg) (# of doses) RTU (mg) D5W) (mg) NS -lactams Penicillin G 4 MU RTU, D5W, NS 94 27.2 213.3 390.3 - 2,340 (6) Potassium Penicillin G 4 MU D5W, NS - 154.6 340.1 517.1 - 3,100 (6) Sodium Ampicillin 2,000 NS - 131.6 - 485.6 - 2,910 (6) Ampicillin- 1,500 NS - 115 292 469 - 1,880 (4) Sulbactam 3,000 NS - 230 - 584 - 2,340 (4) Oxacillin 2,000 RTU, D5W, NS 184.8 128 375.8 552.8 - 3,320 (6) Nafcillin 2,000 RTU, D5W, NS 153.2 132.2 415.4 592.4 - 3,550 (6) Piperacillin- 3,375 RTU, D5W, NS 195 162 392.1 569.1 - 2,280 (4) tazobactam 4,500 RTU, D5W, NS 260 216 463.8 640.8 - 2,560 (4) 1,000 RTU, D5W, NS 48 48 225 402 - 1,200 (3) Cefazolin 2,000 RTU, D5W, NS 96 96 - 450 - 1,350 (3) 1,000 RTU, D5W, NS 83 83 294 471 - 470 (1) Ceftriaxone 2,000 RTU, D5W, NS 166 166 410.9 587.9 - 1,180 (2) 1,000 RTU, D5W, NS 54 54 231 408 - 1,220 (3) Ceftazidime 2,000 RTU, D5W, NS 108 108 285 462 - 1,390 (3) 1,000 RTU, D5W, NS 0 0 212.4 389.4 - 1,170 (3) Cefepime 2,000 RTU, D5W, NS 0 0 212.4 389.4 - 1,170 (3) Aztreonam 2,000 RTU, D5W, NS 0 0 - 354 - 1,060 (3) Ertapenem 1,000 NS - 137 349.4 526.4 - 530 (1) 1,000 RTU, NS 290.2 90.2 267.2 444.2 - 1,330 (3) Meropenem 2,000 NS - 180.4 - 534.4 - 1,600 (3) Imipenem 500 D5W, NS - 37.5 - 426.9 - 1,710 (4) Fluoroquinolones/macrolides Ciprofloxacin 400 RTU 0 - - - - 0 (2) Levofloxacin 500 RTU, D5W, NS 0 0 - - 283 (80 mL) 280 (1) Azithromycin 500 D5W, NS - 114 - - 999 (250 mL) 1,000 (1) Anti-MRSA agents 1,000 RTU, D5W, NS 708 0 - - 885 (250 mL) 3,540 (4) Vancomycin 2,000 D5W, NS - 0 - - 1,770 (500 mL) 3,540 (2) Daptomycin 500 NS - 0 212.4 389.4 - 390 (1) Linezolid 600 RTU 114; 1,196 - - - 1,196 (300 mL) 2,390 (2) Ceftaroline 600 D5W, NS - 0 247.8 424.8 - 1,270 (3) Doxycycline 100 D5W, NS - 0 - 389.4 - 780 (2) 600 RTU, D5W, NS 0 0 177 354 - 1,420 (4) Clindamycin 900 RTU, D5W, NS 0 0 177 354 - 1,060 (3) Accepted Manuscript Downloaded from https://academic.oup.com/ofid/advance-article-abstract/doi/10.1093/ofid/ofz508/5645185 by DeepDyve user on 06 December 2019 Sulfamethoxazole- 1,875- i i D5W - 0 - - - 0 (4) trimethoprim 375 Miscellaneous Metronidazole 500 RTU 326 - - - - 1,300 (4) RTU = Ready-to-Use; D5W = Dextrose 5% in Water; NS = Normal Saline (0.9% NaCl) Values derived from injectable single-dose vial supply; sodium content may vary slightly between manufacturers Intrinsic sodium content of antibiotic plus sodium content in NS; 177mg sodium per 50mL NS; 354mg sodium per 100mL NS; if NS is a recommended solvent for reconstitution per manufacturer, sodium content from the solvent is also included Assumes drug preparation in 100mL NS or other volume of NS/available diluent with appropriate drug concentration per manufacturer; values are rounded to the nearest 10mg Total sodium content per day of therapy considers maximum number of daily doses seen in clinical practice Million units RTU formulations available in both NS (1,196mg sodium) and D5W (114mg sodium) Dose based on 5mg/kg trimethoprim component; weight of 75kg Sodium content from excipients negligible Accepted Manuscript

Journal

Open Forum Infectious DiseasesOxford University Press

Published: Dec 1, 2019

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