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Strategies for Surviving the IV Fluid Shortage: Antibiotic IV to PO Conversions & First Dose via IV Push

2017-12-15T14:12:42+00:00

Hurricane Maria ravaged Puerto Rico almost 3 months ago, destroying factories that manufacture and distribute medications and related supplies. Healthcare facilities across the nation are now experiencing a critical shortage of small-volume intravenous (IV) fluids, which impacts the supply of IV antimicrobials. With no end in sight, ED providers can protect the quality of patient care by considering 2 strategies: IV to PO conversion and first-dose antimicrobials via IV push.

IV to PO: What You Should Know

Every healthcare team member has a role in IV to PO stewardship. Clinicians should consider if a PO medication is equally effective prior to prescribing an IV therapy. Pharmacists can make PO recommendations during order verification. Nurses can consider a patient’s ability to tolerate a PO medication. Patient education is also crucial as some patients expect IV therapies when in an ED.

Some diagnoses warrant empiric IV antibiotics, and a there is no clinically appropriate PO alternative. Examples (not a complete list) include:

  • Meningitis
  • Endocarditis
  • Severe intra-abdominal infections
  • High-risk neutropenic fever
  • History of multi-drug resistant organisms with no PO antibiotic options

Additionally, the following situations generally exclude patients from receiving PO medications:

  • Hemodynamically instability
  • Severe vomiting or diarrhea within past 24 hours
  • Non-functional GI tract (e.g. obstruction, malabsorption, or bleed)
  • Aspiration risk (e.g. altered mental status or impaired swallowing apparatus)
  • Patient is not tolerating at least a clear liquid diet or tube feeds
  • Medication cannot be administered through a feeding tube

That being said, it is possible to treat certain infections with PO medications from the start of a patient’s ED course such as:

  • Urinary tract infections
  • Certain skin and soft tissue infections
  • Low-risk community-acquired pneumonia

Anecdotally, these are the “big 3” common offenders of empiric IV antibiotics in the ED when a PO alternative is often appropriate. For example, IV azithromycin is typically diluted to a concentration of 2 mg/mL (500 mg in 250 mL bag) and infused over 30-60 minutes. The PO tablet, however, is absorbed rapidly from the GI tract and distributed to the lung. Not only would PO treatment conserve IV fluids, but it would reduce ED length of stay.

Other potential benefits of IV to PO conversion include:

  • Decreasing the risk of infection via IV placement
  • Decreasing the risk of phlebitis
  • Promoting patient comfort
  • Promoting early ambulation
  • Decreasing nursing workload

When IV Equals PO

These antimicrobials have excellent absorption and/or bioavailability and are efficacious independent of enteral or parenteral route1:

* Reduced at high pH

^ Sulfamethoxazole/Trimethoprim

Antimicrobial Bioavailability
Azithromycin 34-52%
Clindamycin ~90%
Ciprofloxacin 50-85%
Doxycycline >90%*
Fluconazole >90%
Isavuconazole 98%
Levofloxacin 99%
Linezolid ~100%
Metronidazole >95%
Moxifloxacin 90%
Rifampin >90%
TMP/SMX^ 90-100%
Voriconazole 96%

To Push or Not To Push

IV push antibiotic administration eliminates the need for small-volume IV fluids and reduces time to administration. Antimicrobials that are safe to administer via IV push are typically those with low osmolality and minimal rates of injection-related phlebitis. A trick of the trade for IV push antibiotics has been previously described on EM:RAP (subscription podcast), and we expand on the previously published table below.2–9

Note: it is important to reconstitute these antimicrobials in sterile water for injection (SWFI) to minimize osmolality. Reconstitution with NS or D5W may cause significant phlebitis.

Antimicrobial

Reconstitution or Concentration

IV Push Rate
Aztreonam 1 g + 10 mL SWFI 3-5 minutes
Cefazolin 1 g + 10 mL SWFI 3 minutes
Cefepime

1 g + 10 mL SWFI

2 g + 10-20 mL SWFI

3 minutes
Cefotetan 1 g + 10 mL SWFI 3 minutes
Cefoxitin 1 g + 10 mL SWFI 3 minutes
Ceftazidime 1 g + 10 mL SWFI 3 minutes
Ceftriaxone

1 g + 10 mL SWFI

2 g + 20 mL SWFI

3 minutes
Cefuroxime 1.5 g + 20 mL SWFI 3 minutes
Daptomycin 500 mg + 10 mL SWFI 2 minutes
Ertapenem 1 g + 10 mL SWFI 5 minutes
Gentamicin 40 mg/mL 3 minutes
Meropenem

500 mg vial + 10 mL SWFI

1 g + 20 mL SWFI

3-5 minutes
Tobramycin 40 mg/mL 3 minutes

Special Case: Beta-Lactam Antibiotics

Although the ED is an ideal environment for many IV push antibiotics, the bactericidal activity of beta-lactams is more time-dependent than concentration. This means that the most appropriate dosing strategy for this drug class maximizes the duration of antibiotic exposure.

A recent systematic review and meta-analysis that included 3,401 patients receiving piperacillin/tazobactam therapy found that a prolonged infusion was associated with decreased mortality and improved clinical cure when compared to intermittent dosing.10 Therefore, it is reasonable to limit IV push administration of beta-lactam antibiotics to first doses in the ED. Fluid conservation efforts can continue by preparing subsequent doses as concentrated solutions in 20-60 mL syringes and using syringe pumps for prolonged infusions. Additionally, some beta-lactams can be compounded in large-volume IV fluids and administered as continuous infusions.

Final Thoughts

There are potential silver linings during critical medication and IV fluid shortages, including the opportunities to:

  • Highlight treatment practices for which there is minimal supportive data
  • Study the clinical and operational outcomes of alternative treatment strategies
  • Gain experience using other effective medications (e.g. ketamine during previous etomidate shortage)
  • Provide team-based care, working closely with nurses and pharmacists to select patients best suited for PO therapies

Final note: Be sure to thank your nurses, pharmacy technicians, central pharmacists, information technology specialists, administrators, and others who are instrumental in operationalizing drug shortage efforts!

Updated 12/15/17 to include oral Sulfamethoxazole/Trimethoprim use.

1.
Azithromycin, Clindamycin, Ciprofloxacin, Doxycycline, Fluconazole, Isavuconazole, Linezolid, Levofloxacin, Metronidazole, Moxifloxacin, Rifampin, Voriconazole. Lexi-Comp Online . http://online.lexi.com/crlsql/servlet/crlonline. Published 2017. Accessed November 10, 2017.
2.
Nowobilski-Vasilios A, Poole S. Development and preliminary outcomes of a program for administering antimicrobials by i.v. push in home care. Am J Health Syst Pharm. 1999;56(1):76-79. [PubMed]
3.
Garrelts J, Smith D, Ast D, Peterie J. A comparison of the safety, timing and cost-effectiveness of administering antibiotics by intravenous bolus (push) versus intravenous piggyback (slow infusion) in surgical prophylaxis. Pharmacoeconomics. 1992;1(2):116-123. [PubMed]
4.
Norrby S, Newell P, Faulkner K, Lesky W. Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem. J Antimicrob Chemother. 1995;36 Suppl A:207-223. [PubMed]
5.
Garrelts J, Ast D, LaRocca J, Smith D, Peterie J. Postinfusion phlebitis after intravenous push versus intravenous piggyback administration of antimicrobial agents. Clin Pharm. 1988;7(10):760-765. [PubMed]
6.
Loewenthal M, Dobson P. Tobramycin and gentamicin can safely be given by slow push. J Antimicrob Chemother. 2010;65(9):2049-2050. [PubMed]
7.
Wiskirchen D, Housman S, Quintiliani R, Nicolau D, Kuti J. Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers. Pharmacotherapy. 2013;33(3):266-274. [PubMed]
8.
Roberts GW, Harbi GA, Khalessi-Rad M. Immediate Post-Administration Safety of Bolus Gentamicin. ournal of Pharmacy Practice and Research. 2012;42:200-203. doi: 2012
9.
Butterfield-Cowper J, Burgner K. Effects of i.v. push administration on β-lactam pharmacodynamics. Am J Health Syst Pharm. 2017;74(9):e170-e175. [PubMed]
10.
Rhodes NJ, Liu J, O’Donnell JN. Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients:Results of a Systematic Review and Meta-Analysis. Crit Care Med. 2017. doi: 10.1097
Jenny Koehl, PharmD, BCPS

Jenny Koehl, PharmD, BCPS

Clinical Pharmacist
Department of Emergency Medicine
Massachusetts General Hospital
Erin McCreary, PharmD, BCPS

Erin McCreary, PharmD, BCPS

Education and Development Coordinator
Infectious Disease Clinical Pharmacist
UW Health