Top 10 Antibiotic Mistakes in the ED

Overview:

Antibiotics are one of the center pillars of medical management both within and outside of the emergency department (ED). Diagnostic momentum and treatment is established early within a patient’s presentation and is typically initiated in the ED. This places a particular responsibility on us both to initiate adequate treatment for our patients, which is appropriately broad and disease-specific, but also to keep with appropriate antibiotic stewardship.

EMRA*Caster Alex Kaminsky sits down with Dr. Bryan Hayes, ED clinical pharmacist to discuss pearls and pitfalls regarding antibiotic use in the ED - meanwhile dispelling common antibiotic myths and misconceptions along the way.

Key Points:

1. Verify penicillin and cephalosporin “allergies” when listed in electronic health record (EHR)

• Most patients do not have a true allergy.
  • Likely closer to 10% have a true hypersensitivity; even lower for anaphylaxis.
    • Anaphylaxis: penicillins (0.004-0.015%) and cephalosporins (0.0001-0.1%) -- Cephalosporin is higher than penicillin! (Idsoe 1968, Kelkar 2001)
  • Patients with allergies listed within the EHR have overall worse complications, longer hospital length of stay, and higher all-cause mortality than those who do not.
    
    Resources: Macy 2014, MacFadden 2016

2. Cross reactivity of cephalosporin allergies with penicillin allergy is LOW

• Not due to the beta-lactam ring; more likely due to side-chain reactivity.
  • Typically limited to first- and second-generation cephalosporins
  • More likely a unique allergy to that particular generation cephalosporin

Bryan: "The high cross reactivity [commonly cited at 10%] found in the early studies probably was caused, at least in part, by contamination of the study drugs with penicillin during the manufacturing process. Before the 1980s, pharmaceutical companies used Acremonium (formally called Cephalosporium) to create both penicillins and cephalosporins."

"Furthermore, the authors of the early studies loosely defined 'allergy' and did not account for the fact that penicillin-allergic patients have an increased risk of adverse reactions to any medication."

• Specific allergy to amoxicillin or ampicillin = avoid: cephalexin, cefaclor, cefadroxil, cefprozil
• Carbapenem allergy and penicillin?
  • Less than 1% (Atanaskovic-Markovic 2009, Atanaskovic-Markovic 2008, Romano 2007, Romano 2006, Wall 2014, Kula 2014, Frumin 2009).
• Consider a “test dose” of 10% of typical antibiotic dose.
  
  Resources: Shenoy 2019, Campagna 2012, Pichichero 2014

3. Use oral medications instead of intravenous (IV) when possible

• Many of our meds have GOOD oral bioavailability (Stevens 2014, MacGregor 1997)

Bryan: “Even 1 dose of IV antibiotics in the ED can lead to an increased risk of antibiotic-associated diarrhea and C. diff.” (Haran 2014, Belforti 2016).

4. Avoid single-dose vancomycin to “cover” prior to discharge

• Single dose will not reach therapeutic levels
• IDSA guidelines
  • non-purulent = coverage against Streptococcus species (eg, cephalosporins)
  • purulent = coverage for Staphylococcus species including MRSA (eg, doxycycline, trimethoprim-sulfamethoxazole [TMP-SMX], vancomycin).

Bryan: “Even loading with 30 mg/kg in the ED only achieves therapeutic levels 34% of the time." (Rosini 2015)

5. When using vancomycin, use appropriate loading dose

• Load with 15-20 mg/kg (actual body weight, max 2 g)
  • Critically ill 25-30 mg/kg

Bryan: “Doses > 20 mg/kg in the ED do not increase risk of nephrotoxicity, even in the setting of preexisting kidney disease." (Rosini 2016, Marvin 2019)

            Caveat: Vancomycin/Zosyn combo is significantly more difficult on kidneys

Resources: Heil 2018, Rybak 2009, Liu 2011, Denetclaw 2015

6. Avoid ‘double covering’ for gram-negative infections

• Exception: Consideration for critically ill patients on vents or in septic shock

Resources: (Tamma 2012, Johnson 2011, Paul 2014)

7. Consider accidental underdosing in critically ill patients, particularly obese

Bryan’s Bonus pearl: Second doses of antibiotics in the ED pose a different, yet equally important challenge. With long boarding times, subsequent doses get missed or delayed (Leisman 2017). An in-depth discussion of this issue: Importance of Second Antibiotic Doses in ED Sepsis Patients from PharmERToxGuy blog.

8. Investigate past cultures

6-12 months; We know antibiotic choice matters with respect to mortality (Garnacho-Montero 2003, Zilberberg 2014, Garnacho-Montero 2015). So, it is important to avoid empiric antibiotics for which there is recent documented resistance.

9. Consider important drug-drug interactions

Huge List — To name a few:

1. Warfarin - major interaction: moxifloxacin, metronidazole, TMP-SMX; moderate interaction: azithromycin, ciprofloxacin, doxycycline, levofloxacin (Seamans 2018)
2. Sulfonylureas - TMP-SMX inhibits metabolism = hypoglycemia. Levofloxacin and ciprofloxacin can also have this issue (Schelleman 2010).
3. Methadone - QT prolongation with fluoroquinolones
4. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, potassium-sparing diuretics - Increased hyperkalemia risk with TMP-SMX (Antoniou 2010, Fralick 2014)
5. Ethanol - The interaction with metronidazole may be less clinically significant than we think (EMPharmD blog 2014)

Bonus Myth Buster: Antibiotics, other than rifampin, generally do not interact with hormonal contraception (Simmons 2018).

10. Consider important adverse effects

• Fluoroquinolones, Fluoroquinolones, Fluoroquinolones …
  • Two great summaries of the fluoroquinolones adverse effects from EMPharmD blog and ALiEM blog. The risk rarely outweighs the benefit even in critically ill patients, as summarized on the EMCrit blog. Unless contraindications exist to first-line therapies, fluoroquinolones should generally be reserved for second-line (FDA Safety Alert 2018).

Risk of C. diff in order by antibiotic class: clindamycin, fluoroquinolones, cephalosporins, penicillins, macrolides, TMP-SMX (Brown 2013, Deshpande 2013)

11. Antimicrobial stewardship

ED pharmacists are key clinicians who help optimize antibiotics and decrease time to antibiotic administration in sepsis patients (Flynn 2014, DeFratus 2013).

“Antimicrobial stewardship efforts in the ED should target high-impact areas: antibiotic prescribing for nonindicated respiratory tract conditions, such as bronchitis and sinusitis; overtreatment of asymptomatic bacteriuria; and using two antibiotics (double coverage) for uncomplicated cases of cellulitis or abscess.” (Pulia 2018)