Back to Basics: Revisiting Common EM Controversies

In this post, we will explore the current literature regarding common EM controversies, covering the nature and prevalence of penicillin allergies, the management of skin and soft tissue infections, and the role of NSAIDs for acute pain.

Penicillin allergies in the ED

• Penicillin (PCN) is a Beta-lactam antibiotic discovered in 1928. As of 2010, Beta-lactams (penicillins and cephalosporins) were the top 2 classes of antibacterial drugs sold in the US and 55% of global antibiotic drugs consumed [1].
• With time, patients became allergic to PCN and this relationship was studied by multiple researchers yielding variable results.
• What is the true rate of a PCN allergy?
  • 1-4% of patients taking PCN develop a maculopapular rash, with up to 10% of patients reporting a non-life-threatening reaction (non-Type 1) [2]
  • The accuracy of a reported clinical history of PCN allergy in predicting a positive skin test to PCN is low. Patients with remote or uncertain history of PCN allergy are equally likely to have a positive PCN skin test compared with patients without a history of PCN allergy (approximately 1.7%) [3].
  • A positive skin test is associated with higher incidence of Type 1 allergic reactions (anaphylaxis – more clinically relevant). A negative skin test almost rules out a type 1 reaction (95-98% sensitive) [4]
  • The true rate of PCN allergy was thought to be over-estimated due to mislabeling factors [2]:
    • Prescribing PCNs for viral infections → viral exanthem → rash attributed to PCN rather than viral rash
    • EBV maculopapular rash following amoxicillin prescription
    • Other viral rashes (Cocksackie, Echovirus, HIV)
• The PCN molecule shares a Beta-lactam ring with other Beta-lactam antibiotics (cephalosporins, carbapenem, monobactam).  What about cross-reactivity to other Beta-lactams?
  • Cephalosporins
    • Early studies (1960s) over-reported cross-reactivities due to contaminated models of cephalosporins (made from compounds contaminated with Benzylpenicillin) [6-9]
    • Cross-reactivities ranged from 10-50% in some studies. [6-9]
    • Cross-reactivity was thought to be due to the shared Beta-lactam ring. [6-9]
    • Recent studies using synthetic “clean” cephalosporins show that cross-reactivity is much lower (<10%) and thought to be secondary to side-chain similarities (R1 and R2) [8,9]
      • 1st Gen Cephalosporins have highest risk (0.5-5%) with minimal risk in 2nd/3rd Gen (0.1-2%) [8,9]
  • Carbapenems
    • Cross-reactivity is very low, some studies quoting it at 0.9% and overall <5.2% [6-9]
    • Lowest risk of B-lactams due to difference in side-chain

• Multiple implications from mislabeling PCN allergies and avoiding B-lactams in PCN allergic patients
  • Increased failure rate and inadequate coverage
    • Some studies show higher treatment failure rates in patients reporting PCN allergies who did not receive B-lactam antibiotics for their infections [10,11]
  • Bacterial resistance
    • PCN allergic patients associated with higher rates of C.diff (23%), VRE (30%) and MRSA (14%) thought to be related to antibiotic substitutions [11]
  • Costs
    • Canadian ICU study demonstrated that the use of alternative antibiotics in place of standard beta-lactams incurred an additional cost of $15,672 CAN [11]
    • Study showing increased cost per prescription when substituting another antibiotic secondary to a reported PCN allergy (average 77$ difference) [12]
  • Side effects
    • Higher side effects with Beta-lactam alternatives (Vancomycin and acute kidney injuries, aminoglycosides, quinolones and Cdiff) [13]
• How to approach a PCN allergy in the ED?
  • Taking a detailed history is key to de-labelling PCN allergic patients whenever possible
  • Elements of a good allergy history [14]
    • What exactly were the symptoms?
      • Raised, red, itchy lesions < 24 hrs (hives/urticarial)
      • Swelling of the mouth, eyes, lips or tongue (angioedema)
      • Blisters, ulcers in mucosal areas, skin peeling (SJS, TEN)
      • Respiratory or hemodynamic compromise (anaphylaxis)
      • Joint pains (serum sickness)
      • Other organs like kidneys, lungs, liver (DRESS, Type 4 severe reactions)
    • Timing of the reaction after PCN (minutes, hours, days), was it after the first or multiple doses?
    • How long ago did the reaction happen? (after 10 years of avoidance, only 20% of patients with IgE-mediated PCN allergy will still be allergic)
    • How was the reaction treated? Any epinephrine required?
    • Has patient tolerated similar medications (ampicillin, amoxicillin, cephalexin) since the PCN reaction?

Algorithm on approaching penicillin allergies [14]:

Alternatives to B-lactams in well-defined PCN allergic patients [15]

Take Home Points

1. Cross reactivity from PCN to Cephalosporins is lower than previously published (1st > 2nd > 3rd GEN Cephalosporins)
2. If no features of Type 1 or severe Type 4 reactions (anaphylaxis, angioedema, DRESS, SJS/TEN), can administer Cephalosporins with no expected significant reactions
   • May consider doing a test dose with 10% of dose and close monitoring
3. Adequate documentation and de-labelling false-allergies reduces costs for the system.
4. Use clinical judgment/tools available (algorithms, pharmacists, allergists) to assess risk in patients reporting severe reactions to PCN.

Skin and Soft Tissue Infections (SSTIs)

• SSTIs and abscesses are among the top presentations to the ED with over 3 million visits annually in the US [16]
• Incision and drainage (I+D) is mainstay of treatment for abscesses as per the 2014 IDSA guidelines below [17]

• Review of multiple ED resources and IDSA guidelines show differing approaches with respect to abscess management:
  • Antibiotics
    • Most resources do not recommend routine antibiotic prescription for mild abscesses [17, 18]
    • Antibiotics are recommended under certain circumstances [17]:
      • Severe or extensive disease (using clinical judgment)
      • Rapid progression in presence of associated signs/symptoms of systemic illness (SIRS)
      • Associated comorbidities or immunosuppression
      • Extremes of age
      • Abscess in area difficult to drain (face, hand, genitalia)
      • Associated septic phlebitis
      • Lack of response to I+D alone
    • If treating with Abx, course of 5-10 days with an agent that has MRSA coverage (doxycycline, clindamycin, Septra); if high risk of MRSA [17]
  • Incision + Drainage
    • Conventional straight line technique vs. Loop (novel technique using two small incisions at edge of abscess and a loop to maintain drainage, repositioned BID and self-removed by patient within 10-14 days)
      • Conventional I+D is quick, easy, and traditionally taught in medical training (including straight line, ellipse, etc).
      • Some studies support the LOOP technique as having improved cosmesis, decreased need for wound care/follow-ups, decreased costs to system, less painful, and more tolerated by pediatric population [19-23]
        • Link to LOOP technique video: https://www.youtube.com/watch?v=gw7tA1B9Aos)
      • Few RCTs comparing conventional vs. Loop I+D techniques showed non-inferiority in adults and pediatric populations. However, data is limited to single-centre/small sample size. Loop technique is promising but stronger data is required before making a recommendation for it [19-23]
  • Irrigation
    • Most emergency physicians irrigate abscesses although not much data is available to guide this practice [24]
    • One study showed similar failure rates between irrigation (up to 100cc of NS) vs. non-irrigation group of adults with similar-size abscesses [24]
    • Overall, consensus is to irrigate, but to what extent is unclear
  • Packing
    • Traditionally done and thought to prevent premature closure of the wound and abscess recurrence
    • New studies show that packing may be painful and unnecessary [25-27]
      • Pediatric ED population RCT comparing packed vs. non-packed showed similar failure rates [25]
      • Adult ED population RCT comparing packed vs. non-packed showed similar failure rates but higher pain and higher narcotic use in the packed group [26]
      • Cochrane review (2 RCTs) comparing packing vs. non-packing in perianal abscesses showed no difference in wound healing time or pain as well as no influence in secondary outcomes (recurrence, incontinence, return to work, resource use) [27]

Take Home Points

1. Mainstay of abscess management remains an I+D (use technique that you prefer, make a large incision – i.e: “don’t skimp on it”)
2. Irrigation may or may not make a difference
3. Packing is not always necessary, especially for smaller abscesses
4. Prescribe antibiotics only in high risk cases (5-7 days is usually sufficient)

NSAIDs for acute pain

• NSAIDs are among the top analgesic choice for treating moderate-severe acute pain in the ED [28-29]
• Oral (Ibuprofen, Naproxen) vs. parenteral (IV/IM Toradol) NSAIDs debate ongoing for decades [28]
• Evidence overwhelmingly shows no difference in analgesic effect between the two routes. However, many emergency physicians continue to use parenteral NSAIDs with the misconception that it is more “powerful and effective” than their oral counterparts [29,30]
• The idea that administering a drug parenterally infers an additional placebo “needle effect” is a myth that has been disproven by multiple RCTs [30-32]
• Providing parenteral (IM/IV) NSAIDs when not indicated is potentially harmful (more painful IM route) with no added benefits to oral NSAIDs [32]
• Reserve parenteral NSAIDs to cases where oral administration is contraindicated (i.e: NPO, decreased LOC, nausea/vomiting, ileus)
• Why care about parenteral vs. oral in the ED?
  • Side effects
    • Parenteral Toradol has higher COX-1 selectivity (coefficient of 2.5 vs. 0.5 in Naproxen/Advil) → more GI side effects [33]
    • Risk of GI side effects (including hemorrhage) proportional to dose given [29-33]
    • Single dose of parenteral Toradol interferes with platelet function (worsens bleeding in post-op patients) [29-33]
  • Costs
    • As an example, at The Ottawa Hospital, a parenteral dose of Toradol vs. oral equivalent (Advil/Naproxen) is 18-28 x more expensive [34]
• Ketorolac and ceiling effect?
  • IV: Post-op studies showing IV Ketorolac at low doses (7.5 mg – 10 mg) was as effective as larger doses (15-30 mg) at providing analgesia [35, 36]
  • IM: Cancer-pain studies showing 10 mg similar to 30 mg IM in relief of pain [37,38]
  • Emergency Department study in 2017 [39]
    • IV Ketorolac 10 mg vs. 15 mg vs. 30 mg were all equally effective in acute pain reduction at 30 mins

Take Home points

1. Unless contraindicated, using oral NSAIDs is recommended over parenteral NSAIDs. Advil or Naproxen are adequate starting options.
2. If prescribing NSAIDs, ensure no contraindications and do not prescribe for a long duration. Consider prophylactic PPIs for patients with high risk or history of peptic ulcer disease / GI side effects. Avoid NSAIDs in the following population:
   • Over age 65
   • History of peptic ulcer disease
   • Taking corticosteroids, anticoagulants, or ASA
3. If using parenteral (IV/IM) NSAIDs, consider starting with lower doses (i.e: Ketorolac 10-15 mg/dose) especially in the elderly (age >65)