Month: February 2015

VRE: A Very Real Emergency Medicine Problem

by empharmd, posted in EM PharmD Blog

With increasing prevalence of antimicrobial resistance among bacteria coupled with the lack of novel antimicrobial development, multi-drug resistant bacteria will continue to be problematic [1]. Due to this increased prevalence, it is likely that even in the emergency department, we will see more and more patients with prior cultures or past medical history documentation of multi-drug resistant bacteria, such as vancomycin resistant Enterococcus (VRE). Once we are aware of this information, how should this affect our decision making for treatment of these patients?

To help address this, assessment of the following clinical questions may be useful:

1)   Is my patient likely to be ill from VRE?

Enterococcus is a common colonizing agent of the gastrointestinal tract and may also colonize the genitourinary tract as well as the skin [2]. As a result, care should be taken to determine colonization versus infection if VRE has been isolated.

In non-critically ill emergency medicine patients, examining for the presence of VRE risk factors may help to guide therapy. Some common risk factors include: [2]

    • Recent administration of antibiotics (including but not limited to cephalosporins, clindamycin and metronidazole likely due to selective pressure for Enterococcus species) 
    • Recent or prolonged hospitalization or stay in a health care facility 
    • Compromised immune systems (hematologic malignancy, organ transplant) 
    • High severity of illness 

In patients who are likely to be ill due to VRE, treatment should be started with an agent likely to be active against the VRE at the site of the infection.

2)   How sick is my patient? 

In critically ill patients with a past medical history positive for VRE, it is prudent to cover the patient for this organism until proven otherwise. There are no specific recommendations for VRE bacteremia in general; however, the 2009 clinical practice guidelines recommend either intravenous linezolid or daptomycin for the treatment of intravenous catheter-related bacteremia secondary to VRE [3].

3)   Do I have culture data? 

Past cultures isolated from previous infections may or may not be what is currently making the patient ill. For serious illness such as bacteremia or endocarditis, consideration of past culture data may be acceptable for select patients such as those who are sent in from an outside facility with recent culture data or a recent hospital visit where current cultures were obtained. For example, if a patient was seen last week with a urinary tract infection from VRE and is now presenting with symptoms of urosepsis, depending upon the clinical picture it may be reasonable to use the culture data from the prior week to base clinical decisions (see Table 1 below for treatment options).

For the more common infection of VRE cystitis, more treatment options may be available. Ideally, we will be able to choose the most narrow, tolerable, and cost-effective antimicrobial coverage for our patients.

Table 1: VRE Treatment Options [2-6]
Infection Type
Ampicillin Sensitive VRE
Ampicillin Resistant VRE
Uncomplicated Urinary Tract Infections
(PO therapy only listed)
 – Ampicillin or Amoxicillin
 – Nitrofurantoin
 – Fosfomycin
 – Doxycycline
 – Nitrofurantoin
 – Fosfomycin
 – Doxycycline
 – Linezolid (if no other treatments are sensitive)
Complicated Urinary Tract Infections  & Systemic VRE Infection
 – Ampicillin + Aminoglycoside
 – Daptomycin
 – Linezolid
 – Quinupristin-dalfopristin*

*Limited activity against Enterococcus faecalis and poor patient tolerability
Table 2: Medication Dosing Regimens for VRE Based on Type and Source of Infection
Indication
Medication
Dose‡
Duration
Uncomplicated Urinary Tract Infections
(PO therapy only listed)
Ampicillin
250-500 mg PO q6 hours
20-28 doses
Amoxicillin
250-500 mg PO q8 hours
15-21 doses
Nitrofurantoin
100 mg PO q12 hours
10 doses
Fosfomycin
3 g PO
1 dose
Doxycycline
100 mg PO q12 hours
10-14 doses
Complicated Urinary Tract Infections  & Systemic VRE Infection
Ampicillin
Gentamicin
2 gm IV q4 hours
1 mg/kg IV q8 hours
Duration depends upon location and severity of infection
Daptomycin
8-12 mg/kg q24 hours
Linezolid
600 mg IV/PO 12 hours
Quinupristin-dalfopristin
7.5 mg/kg IV q8 hours
Adapted from from Chambers HF, Elipoulos GM, Gilbert DN, Saags MS, eds. The Sanford Guide to Antimicrobial Therapy, 44th ed. Sperryville, VA: Antimicrobial Therapy; 2014.

‡Dosing for adult patients, not adjusted based on renal function
¶Dosing for Macrobid formulation

In conclusion, the “big gun” antibiotics of daptomycin or linezolid may not always be the go-to choice for VRE in the ED. Based on the suspected source of the infection and prior culture data when available, more narrow treatment with ampicillin or nitrofurantoin for example may be acceptable, easier to administer, and more cost-effective as treatment options in select patients.
References:
  1. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: No ESKAPE! An update from the Infectious Disease Society of America. Clin Infect Dis. 2009;48:1-12.
  2. Patel R, Gallaher JC. Vancomycin-resistant Enterococcal bacteremia pharmacotherapy. Ann Pharmacother. 2015;49(1):69-85.
  3. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravenous catheter-related infection: 2009 update by the Infectious Disease Society of America. Clin Infect Dis. 2009;49:1-45.
  4. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: Diagnosis, antimicrobial therapy, and management of complications: A statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Disease Society of America. Circulation 2005;111:e394-e434.
  5. Heintz BH, Halilovic J, Christensen CL. Vancomycin-resistant Enterococcal urinary tract infections. Pharmacotherapy.2010;30(11):1136-49.
  6. Murray BE. Vancomycin-resistant Enterococcal infections. N Engl J Med. 2000;342(10):710-21.

Jill Logan, Pharm.D., BCPS (@EMPharm)

Emergency Medicine Clinical Pharmacist
Baltimore Washington Medical Center
Reviewed by: Craig Cocchio, Pharm.D., BCPS and Nadia Awad, Pharm.D., BCPS 

Throwback Drug Thursday: Sus-Phrine, An Aqueous Formulation of Epinephrine

by Nadia I. Awad, posted in EM PharmD Blog

Note: This is the introduction of a series of posts on Emergency Medicine PharmD called “Throwback Drug Thursdays” (#TBDT). It will feature medications that were once available for routine use in the emergency department, but are no longer on the market.  

I work with some awesome providers within my emergency department, many of whom have been practicing for quite some time. Sometimes, they will reminisce back to their time during residency, especially the interesting cases they encountered during their training. One day, we were talking about the management of status asthmaticus, and one of my physicians stated that during her residency, she routinely used a medication called Sus-Phrine, and described how efficacious it was in managing these patients. I mentioned that I never heard of any product called Sus-Phrine. Of course, I got teased (with reactions along the lines of “Finally! We stumped her on something!”), but I did a little digging, and was quite surprised to find out specific details related to this medication, which is none other than a rather interesting formulation of epinephrine.

Well, if you thought the concentrations of epinephrine in currently available formulations are prone to errors, as discussed in this post here and here, then it’s no small wonder how some people will react when they learn that this product existed in a concentration of 1:200. Yes, that’s right…1:200.
When the product was first introduced in the 1950s, one of its claims to fame in terms of administration was that as opposed to an intramuscular injection (such as the gluteal muscle) with a relatively large needle, as was the case for decades before this product was released, it could be administered subcutaneously with a needle of any gauge, including a tuberculin-type needle. 
Before Sus-Phrine made it to the market, epinephrine was commonly prepared in either peanut oil or gelatin, which posed many problems in terms of its preparation and administration. This was especially true in times of extreme cold weather where the product would often coagulate, which proved to be challenging when drawing up the product into a syringe for administration. The stability and pharmacokinetic properties of the product was more predictable due to the aqueous nature of the product (contained as a suspension made of phenol, sodium thioglycollate, and glycerin in distilled water).
Another one of the purported advantages of Sus-Phrine was the fact that its duration of action was generally six to ten hours, minimizing the need for repeat administration as was necessary for previous preparations of epinephrine. The onset of action following administration of Sus-Phrine occurred within 10 to 20 minutes.
The recommended dosing strategy of Sus-Phrine was a bit of a doozy as well: 0.005 mL/kg. Initial doses in pediatric and adult patients generally not exceeding 0.15 mL and 0.3 mL, respectively, which was somewhat convenient as the product was commercially available in a vial size of 0.3 mL. It was used as a therapeutic adjunct in the management of status asthmaticus, urticaria, and angioedema for quite some time, but production of Sus-Phrine discontinued in the early 1990s.  
Small wonder how practices related to managing such conditions as status asthmaticus and angioedema and formulations of epinephrine have evolved over the past several decades. It is a bit ironic how we have come full circle with epinephrine in terms of preferred route of administration, dosing, and duration of action with available formulations. It certainly makes me appreciate what we can learn all the more from those who are seasoned in practice. And I will never again be puzzled the next time I hear about Sus-Phrine in a conversation.
References:
Naterman HL. Ephinephrine base suspended in water with thioglycolate. J Allergy 1953; 24:60.
Unger AH, Unger L. Prolonged epinephrine action. Ann Allergy 1952; 10:128-130.
Jenkins CM. A clinical study of Sus-Phrine, an aqueous epinephrine suspension for sustained action. J Natl Med Assoc 1953; 45:120-122.
Ben-Zvi Z, Lam C, Hoffman J, et al. An evaluation of the initial treatment of acute asthma. Pediatrics 1982; 70:348-353.
Ben-Zvi Z, Lam C, Spohn WA, et al. An evaluation of repeated injections of epinephrine for the initial treatment of acute asthma. Am Rev Respir Dis 1983; 127:101-105.

Kornberg AE, Zuckerman S, Welliver JR, et al. Effect of injected long-acting epinephrine in addition to aerosolized albuterol in the treatment of acute asthma in children. Pediatr Emerg Care 1991; 7:1-3.