Category: Pharmacology & Therapeutics
Keywords: Sepsis, Antibiotics, CMS, Core Measures (PubMed Search)
Posted: 9/1/2018 by Wesley Oliver
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The Centers for Medicare and Medicaid Services (CMS) require broad spectrum antibiotics to be administered within 3 hours of presentation of sepsis to be in compliance with the sepsis measure.
Not only do the antibiotics that are chosen determine compliance with this measure, but the order in which antibiotics are given can also significantly affect compliance.
According to CMS, for combination antibiotic therapy, both antibiotics must be started within the three hours following presentation; however, they do not need to be completely infused within this time frame.
Combination therapy typically includes a monotherapy antibiotic (see list in detailed information below) plus vancomycin (daptomycin or linezolid could also be used).
So which antibiotic should be given first?
If a monotherapy antibiotic is given first within the 3 hours of presentation, then compliance for the sepsis measure is met. These antibiotics cover a broader range of bacteria and are typically infused over ~30 minutes, which allows plenty of time for your second antibiotic to be initiated.
If vancomycin is given first, compliance with this measure can become difficult. First, vancomycin has a narrower spectrum of activity and is not a monotherapy antibiotic. Second, vancomycin infusion rates range from 1 to 2 hours. Given that antibiotics are usually given after sepsis is flagged, this infusion rate only gives a short period of time for the second antibiotic to be initiated. Thus, vancomycin should almost always be the second antibiotic infused.
In addition, patients may also have limited intravenous access or antibiotics may not be compatible with resuscitation fluids. All of these factors together must be considered when trying to gain compliance with this measure.
Take-Home Point:
Administer monotherapy antibiotics (e.g. piperacillin/tazobactam and cefepime) prior to administering vancomycin in your septic patients to improve compliance with the sepsis measure.
Specifications Manual for National Hospital Inpatient Quality Measures v5.4. The Joint Commission. https://www.jointcommission.org/specifications_manual_for_national_hospital_inpatient_quality_measures.aspx. Updated December 29, 2017. Accessed August 31, 2018.
Category: Pharmacology & Therapeutics
Keywords: Diabetes, DKA (PubMed Search)
Posted: 7/7/2018 by Wesley Oliver
(Updated: 5/28/2023)
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Woodward RS, Flore MC, Machnicki G, Brennan DC. The long-term outcomes and costs of diabetes mellitus among renal transplant recipients: tacrolimus versus cyclosporine. Value Health. 2011;14(4):443-9.
Category: Pharmacology & Therapeutics
Keywords: Fosfomycin, urinary tract infection, cystitis (PubMed Search)
Posted: 3/3/2018 by Wesley Oliver
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Fosfomycin is an antibiotic infrequently used for the treatment of urinary tract infections (UTIs). It has a broad spectrum of activity that covers both gram-positive (MRSA, VRE) and gram-negative bacteria (Pseudomonas, ESBL, and carbapenem-resistant Enterobacteriaceae), which is useful in the treatment of multidrug-resistant bacteria.
Fosfomycin is FDA approved for the treatment of uncomplicated UTIs in women due to susceptible strains of Escherichia coli and Enterococcus faecalis (3g oral as a single dose). Data has also demonstrated that it can be used for complicated UTIs; however, dosing is different in this population (3 g oral every 2-3 days for 3 doses). Fosfomycin is not recommended for pyelonephritis.
The broad spectrum of activity, in addition to only needing a single dose in most cases, makes fosfomycin an attractive option; however, it should be reserved for use in certain circumstances. Fosfomycin should not be considered as a first-line option. It is also more expensive than other medications (~$100/dose) and in countries with high rates of utilization bacteria are developing resistance to fosfomycin. In addition, most outpatient pharmacies do not keep this medication in stock.
Take-Home Point:
Fosfomycin should be reserved for multidrug-resistant UTIs in which other first-line options have been exhausted.
Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5): e103-e120. doi: 10.1093/cid/ciq257.
Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis. 2011;15(11):e732-e739. doi: 10.1016/j.ijid.2011.07.007.
MONUROL [prescribing information]. St. Louis, MO: Forest Pharmaceuticals, Inc; 2007. www.accessdata.fda.gov/drugsatfda_docs/label/2008/050717s005lbl.pdf. Accessed 9/7/2017September 7, 2017.
Oteo J, Bautista V, Lara N, et al; Spanish ESBL-EARS-Net Study Group. Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. J Antimicrob Chemother. 2010;65(11):2459-2463. doi: 10.1093/jac/dkq346.
Raz R. Fosfomycin: an old—new antibiotic. Clin Microbiol Infect. 2012;18(1): 4-7. doi: 10.1111/j.1469-0691.2011.03636.x
Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2014;34(8):845-857. doi: 10.1002/phar.1434.
Vardakas KZ, Legakis NJ, Triarides N, Falagas ME. Susceptibility of contemporary isolates to fosfomycin: a systematic review of the literature. Int J Antimicrob Agents. 2016;47(4):269-285. doi: 10.1016/j.ijantimicag.2016.02.001.
Wankum, Michael, et al. “Fosfomycin Use.” Pharmacy Times, 30 Nov. 2017, www.pharmacytimes.com/publications/health-system-edition/2017/november2017/fosfomycin-use.
Category: Pharmacology & Therapeutics
Keywords: Epinephrine, Asthma (PubMed Search)
Posted: 1/8/2018 by Wesley Oliver
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Patients with severe asthma exacerbations that are unresponsive to inhaled beta-agonists may require the use of epinephrine to control their symptoms. When patients get to this point what route of administration should be used for the administration of epinephrine?
The most recent asthma guidelines (published in 2007) recommend the use of SubQ epinephrine 0.3-0.5 mg every 20 minutes for 3 doses. Drug references typically list SubQ or IM epinephrine 0.01 mg/kg (~0.3-0.5 mg) every 20 minutes as appropriate routes of administration. There is currently no data demonstrating that one route of administration is better than the other in patients with asthma; however, in other disease states, such as anaphylaxis, IM epinephrine is preferred due to the more rapid and reliable absorption over SubQ administration.
Auto-injectors that administer IM epinephrine 0.3 mg are available. These auto-injectors may decrease the risk of medications error; however, they can be expensive. SubQ administration requires the use of a syringe and a vial/ampule of 1 mg/mL epinephrine.
Bottom Line: Either SubQ or IM epinephrine administration is appropriate for patients with severe asthma exacerbations. The preferred method at a given institution will be dictated by historical practice, risk of medication dosing errors, and drug cost.
1. National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7232/
2.Simons FER, Ardusso LRF, Bilo MB, El-Gamal YM, Ledford DK, Ring J, et al. World Allergy Organization Anaphylaxis Guidelines: Summary. J Allergy Clin Immunol. 2011;127(3):587–93. e1-e20.
Category: Pharmacology & Therapeutics
Keywords: Insulin, Hyperkalemia, Dextrose (PubMed Search)
Posted: 11/6/2017 by Wesley Oliver
(Updated: 5/28/2023)
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Strategies for Hyperkalemia Management | |
Stabilize cardiac membrane | Calcium gluconate |
Intracellular movement in skeletal muscles | Albuterol Sodium Bicarbonate Insulin |
Potassium excretion | Loop Diuretics Kayexalate Patiromer (chronic use only) |
Potassium removal | Dialysis |
Insulin mechanism of action for hyperkalemia:
· Binds to skeletal muscle receptors
· Increased activity of the sodium-potassium adenosine triphosphatase and glucose transporter GLUT4
· Glycemic response occurs at lower levels of insulin
· Potassium transport activity increases as insulin levels increase
Patients with insulin resistance due to type-2 diabetes do not become resistant to the kalemic effects of insulin.
Hypoglycemia following insulin administration for hyperkalemia:
· Occurs 1-3 hours post dose, even with initial bolus of dextrose
· The amount of glucose is insufficient to replace the glucose utilized in response to the administered dose of insulin
· Insulin’s half-life is increased in ESRD leading to longer duration of action
A systematic review of 11 studies regarding insulin dosing for hyperkalemia:
· 22 patients (18%) experienced hypoglycemia
· Studies that only gave 25 grams (1 amp) of dextrose had the highest incidence of hypoglycemia (30%)
Tips:
· Consider insulin dose reduction in patients with renal failure
· Use an order set to ensure patients receive appropriate POC glucose monitoring to detect delayed onset of hypoglycemia
· Dextrose 50% (25 grams) should be given to all patients with pre-insulin BG <350 mg/dL
Subsequent PRN dextrose 50% (25 grams) should be used to maintain BG >100 mg/dL after insulin administration
References:
1. Sterns RH, Grieff M, Bernstein PL. Treatment of hyperkalemia: something old, something new. Kidney International 2016;89(3):5460554.
2. Harel Z, Kamel KS (2016) Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review. PLoS ONE 11(5): e0154963. doi:10.1371/journal.pone.0154963
Category: Pharmacology & Therapeutics
Keywords: Ureteral stones, Alpha-blockers (PubMed Search)
Posted: 9/2/2017 by Wesley Oliver
(Updated: 5/28/2023)
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Alpha-blockers (tamsulosin, alfuzosin, doxazosin, and terazosin) are antagonists of alpha1A-adrenoreceptors, which results in the relaxation of ureteral smooth muscle. Current evidence suggests alpha-blockers may be useful when ureteral stones are 5-10 mm; however, there is no evidence to support the use of alpha-blockers with stones <5 mm. Patients with ureteral stones >10 mm were excluded from studies utilizing these medications.
The size of most ureteral stones will be unknown due to the lack of need for imaging able to measure stone size. Given that the median ureteral stone size is <5 mm, most patients will not benefit from the use of an alpha-blocker.
Also, keep in mind that the data for adverse events with alpha-blockers used for ureteral stones is limited and that these medications have a risk of hypotension.
Ferre RM et al. Tamsulosin for ureteral stones in the emergency department: a randomized, controlled trial. Ann Emerg Med 2009.
77 patients
Ibuprofen + oxycodone + tamsulosin vs. ibuprofen + oxycodone
Stone expulsion at 14 days: Tamsulosin group=77.1% vs. Standard therapy=64.9%
-Difference=12% (95% CI: -8.4-32.8%)
No clinically/statistically significant differences
Pickard R et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015.
1,136 patients
Tamsulosin vs. nifedipine vs. placebo
No further intervention at 4 weeks: Tamsulosin=81% vs. Nifedipine=80% vs. Placebo=80%
No clinically/statistically significant differences
Furyk JS et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016.
403 patients
Tamsulosin vs. placebo
Stone passage at 28 days: Tamsulosin=87% vs. Placebo=81.9%
-Difference=5% (95% CI: -3-13%)
Found difference in subgroup analysis of large stones (5-10 mm)
-Tamsulosin=83.3% vs. Placebo=61%
-Difference=22.4% (95% CI: 3.1-41.6%)
No other clinically/statistically significant differences
Hollingsworth JM et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016.
Meta-analysis of 55 trials
No benefit in patients with smaller stones (<5 mm): RR=1.19 (95% CI: 1.00-1.98)
Benefit in patients with larger stones (5-10 mm): RR=1.57 (95% CI: 1.39-1.61)
1.) Ferre RM, Wasielewski JN, Strout TD, Perron AD. Tamsulosin for ureteral stones in the emergency department: a randomized, controlled trial. Ann Emerg Med 2009;54:432-9.
2.) Furyk JS, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med 2016;67:86-95.
3.) Hollingsworth JM, Canales BK, Rogers MAM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ 2016;355:i6112.
4.) Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015;386:341-9.