Case

A 48-year-old man presents to your ED complaining of a two-day history of a warm, painful, reddened area on his right shin. It started with a minor abrasion earlier in the week. He has no significant past medical history and no known drug allergies. There is no evidence of an abscess on examination, and his labs and vital signs are normal. He is diagnosed with uncomplicated cellulitis, and you plan to send him home with a five-day course of cephalexin but are thinking about giving him a “one for the road” single dose of IV cefazolin before he leaves.

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Question

What is the risk of emergency department patients developing antibiotic-associated diarrhea (AAD) with an IV dose of antibiotics prior to discharge?

Background

We all know that diarrhea is a common side effect of antibiotic therapy. The incidence reported in the literature is between 5 percent and 39 percent.¹ Clostridium difficile infection (CDI) is one of the most concerning types of AAD and has been increasing.²

A number of factors are known to increase the risk of AAD/CDI.³ These include the type of antibiotic used and the duration of therapy. While almost all antibiotics can cause AAD and CDI, the cephalosporins, broad-spectrum penicillins, and clindamycin are more often the cause.

There are some patient factors also thought to be associated with AAD/CDI. These are age greater than 65 years, comorbidities, and a history of AAD.

Relevant Article

Haran JP, Hayward G, Skinner S, et al. Factors influencing the development of antibiotic associated diarrhea in ED patients discharged home: risk of administering IV antibiotics. Am J Emerg Med. 2014;32(10):1195-1199.

• Population: Adult patients from three EDs.
  • Patients were excluded if they had diarrhea or C. difficile in the previous four weeks, had received an antibiotic in the previous four weeks, or were admitted to the hospital.
• Intervention: IV antibiotics as part of their ED visit and discharged home with a prescription for antibiotics.
• Comparison: Patients who were not given IV antibiotics as part of their ED visit and discharged home with a new prescription for antibiotics.
• Outcomes:
  • Primary outcome was the development of AAD (three or more loose stools per day for at least two days).
  • Secondary outcome was the development of CDI (AAD that led to a diagnosis of CDI confirmed by a positive C. difficile toxin A assay).
• Authors’ Conclusions: “Intravenous antibiotic therapy administered to ED patients before discharge was associated with higher rates of AAD and with two cases of CDI. Care should be taken when deciding to use broad-spectrum IV antibiotics to treat ED patients before discharge home.”
• Key Results: There were 247 patients included in the study. The most common infection being treated was a skin/soft tissue infection.
  • Primary outcome of antibiotic-associated diarrhea:
    • 45/247 (18 percent) odds ratio 2.73 (95 percent CI, 1.38–5.43)
    • 25.7 percent IV group versus 12.3 percent oral group
    • Absolute difference of 13.4 percent
    • Number needed to harm=7
  • Secondary outcome of C. difficile infection:
    • 2/247 (1 percent)

The rate of AAD increased with the duration of antibiotic therapy. Clindamycin, vancomycin, cephalosporins, penicillins, and macrolides were associated with the highest rates of AAD; quinolones and doxycycline had the lowest rates.

More than a quarter (28 percent) of patients who developed AAD stopped taking their antibiotic, and 16 percent had a follow-up health care visit because of diarrheal symptoms.

EBM Commentary

This was a small observational trial that demonstrated 26 percent of patients given IV antibiotics in the ED developed AAD. This was an absolute increase of 13 percent over those patients given oral antibiotics only and fits well into the range of 5–39 percent previously described in the literature.

The primary outcome was patient-oriented but didn’t necessarily take into account all potential confounders (history of constipation and current medications that could have affected gastrointestinal motility or the development of diarrhea/constipation).

It was unclear if the primary outcome was accurately measured to minimize bias. Patients were asked about the development of AAD with a survey four weeks after finishing antibiotic therapy. This introduces potential recall bias.

Despite its limitations, this study provides important information about potential risks of an intervention that has yet to demonstrate any benefit in a patient population well enough to go home on a course of oral antibiotics.

In addition, if 28 percent of patients who develop AAD after a dose of IV antibiotics stop taking the antibiotics early due to the side effects, this could have implications for both the patient and may contribute to the eventual development of antimicrobial resistance.

Bottom Line

Giving IV antibiotics in the ED to patients well enough to go home on oral antibiotics is not without harm. This small observational study shows IV antibiotics are associated with an increased risk of AAD in this patient population.

Case Resolution

You decide not to give a dose of IV cefazolin and send the patient home with a five-day course of cephalexin for his cellulitis as recommended by the Infectious Diseases Society of America.⁴

Thanks to Meghan Groth, the emergency medicine pharmacy specialist at the University of Vermont Medical Center, for her help with this review.

Remember to be skeptical of anything you learn, even if you learned it on The Skeptics Guide to Emergency Medicine.

References

1. Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med. 2002;346(5):334-339.
2. Ghose C. Clostridium difficile infection in the twenty-first century. Emerg Microbes Infec. 2013;2(9):1-8.
3. McFarland LV. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea. Dig Dis. 1998;16(5):292-307.
4. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis 
and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52.