Part 1: Concerns with Antibiotic Overuse

Three of the most common antibiotic-related unwanted effects seen the ED include:

  1. Their toxic effects
  2. Selection of pathogenic bacteria
  3. Increasing antibiotic resistance

The Magnitude of Antibiotic-Related Toxic Effects

A data-set analysis of almost 110,000 residents in 67 Ontario nursing homes demonstrated that there was a 24% increased risk of antibiotic-related adverse effects in high antibiotic-prescribing nursing homes compared to low ones (Daneman, 2015). Hypersensitivities, being amongst the common adverse reactions to antibiotics, have been responsible for as much as 10% of adverse drug reactions in other studies (Slatore, 2003), and antibiotics have been associated with up to a 5% risk of allergic reactions (Solensky, 2003).

Data from the National Injury Surveillance between 2004 and 2006 shows that 1 in 5 ED visits were due to a drug-related adverse event – representing 142,505 annual emergency visits and 79% of them were allergic reactions (Shehab, 2008).

Antibiotics and Selection of Pathogenic Bacteria

The association of antibiotics and Clostridium difficile infections is familiar to all hospital workers.  Antibiotics alter the microbiota of the gut to favour an environment where pathogenic bacteria can thrive (Baulmer, 2006).  Bacteria other than C. difficile have also been associated with antibiotic-related diarrhea due to this mechanism (Larcombe, 2016).  At The Ottawa Hospital, our internal data shows that our rate of C. difficile infections has risen from 0.32 per 1000 patient days in 2014-15 to 0.42 per 1000 patient days in 2015-16.

Antibiotics and the Proliferation of Antibiotic Resistance

Data from Public Health Ontario (PHO, 2015) show that rates of MRSA have been steadily increasing.  The jurisdiction that has witnessed the highest rise of MRSA rates corresponds to postal code “K” – our home postal code, with a rise of 66% since 2013 (PHO, 2015). Other resistant strains, such as VRE, have shown similar trends (CNSIP, 2015).

The problem of an increasing rate of antibiotic-related unwanted effects is further complicated by stagnation in the development of new antimicrobials.  Since 1969, there have only been two classes of new antibiotics introduced in the market (Conly, 2005) and the number of new antibiotic applications for approval to the FDA is decreasing every year (CDC, 2013).

What is the role of the ED for antibiotic stewardship?

Recent data also demonstrates that there is significant variability in antibiotic prescribing rates across Ontario hospitals, suggesting there is ample room for improvement (Daneman, 2017).  The American College of Emergency Physicians (ACEP) also has a position that “emergency departments take an active role in designing and systematically studying strategies to improve antimicrobial stewardship” (May, 2013).

Next, we present three common clinical scenarios where the role of antibiotics is unfounded or controversial.

Part 2: Three Cases where the Role of Antibiotics is Questionable

Catheter-Associated Asymptomatic Bacteriuria

Within 24 hours of Foley catheter insertion 5 % of patients will have bacterial colonization of their urinary system – this number jumps to 100 % within one month (Hooton, 2010). However, a large prospective study of 1497 patients showed that catheter-associated bacteriuria was associated with symptoms in fewer than 10 % of patients (Tambya, 200).  Table 1 summarizes three of the most important studies that demonstrate antibiotics have a limited role in catheter-associated asymptomatic bacteriuria (CA-ABU).

Table 1. Major Trials for Antibiotics and Catheter-Associated Asymptomatic Bacteriuria

Article Cephalexin for Susceptible Bacteriuria in Afebrile, Long-term Catheterized Patients

JAMA. Warren,1982

Bacteremia and Mortality with Urinary Catheter-Associated Bacteriuria

Infection Control and Hospital Epidemiology. Kzilbach, 2013

A Randomized Trial of Catheter Change and Short Course of Antibiotics for Asymptomatic Bacteriuria in Catheterized ICU Patients

Intensive Care Medicine. Leone, 2007

Population In-patients with CA-ABU. Weekly urine samples for 43 weeks. RCT In-patients with CA-ABU. 444 instances of CA-ABU. Followed 30 days. Retrospective cohort of 9 months ICU patients with CA-ABU. 60 patients. RCT
Intervention Cephalexin for each instance of positive bacteriuria. 17 patients Any antibiotic treatment 3 days of antibiotics and catheter change
Comparison Placebo. 18 patients No antibiotics No antibiotics
Outcome Bacteriuria present in 98.7% of weekly urine specimens of cephalexin group, and 98.2% of placebo group

Cephalexin susceptibility of 36% in cephalexin arm and 75% in placebo arm

Antibiotics odds-ratio of 0.7 ( CI 0.32-1.71) for bacteremia and 0.9 (CI 0.43-1.69) for mortality Rate of bacteriuria at 15 days, urosepsis, and mortality same between both groups


  • No difference in rates of bacteriuria in antibiotic vs. placebo arms.
  • Antibiotics associated with increased rate of antibiotic resistance
  • Limited by:
    • Small sample size
  • No effect on rate of bacteremia or mortality
  • Large sample size but limited by:
    • Retrospective
    • Inpatient population
    • High-rate of mortality (21%)
  • No difference in patient outcomes with antibiotic treatment
  • Limited by:
    • ICU population
    • Small sample size
    • No standard antibiotic regimen

In spite of evidence showing no meaningful benefit from antibiotic treatment in CA-ABU, a recent study showed the downstream effects that antibiotic mis-prescribing can have in the ED (Kiyatkin, 2016). In their retrospective study, 59% of patients had antibiotics inappropriately initiated in the ED, and in those cases 80% of them had them inappropriately continued by the in-patient consultant.

Uncomplicated Pulpitis

Pulpitis is a common dental ailment resulting in over 6,000 ED visits in the Champlain LHIN (OOHA, 2017).  Multiple dental societies have published recommendations and guidelines suggesting the indications for antibiotics in dental pain, which include (SDCEP, 2013):

  1. Fever
  2. Trismus
  3. Worsening swelling
  4. Obvious signs of cellulitis

Table 2 summarizes the two most important trials questioning the role of antibiotics in uncomplicated dental pain.

Table 2. Major Trials for Antibiotics and Uncomplicated Pulpitis

Article Effect of Systemic Penicillin on Pain in Untreated Irreversible Pulpitis

Endodontics. Nagle, 2000

Efficacy of Penicillin for Dental Pain without Overt Infection

Academic Emergency Medicine. Runyon, 2004

Population Emergency patients with irreversible pulpitis  Emergency patients with irreversible pulpitis
Intervention Penicillin 500 mg po Q6H x 7 days. 20 patients Penicillin. 98 patients (34 lost to follow up)
Comparison Placebo. 20 patients Placebo. 97 patients (27 lost to follow up)
Outcome Same scores for sum pain intensity, total ibuprofen taken, and percentage of patients with vital teeth Infection rate 6- 7 % in both groups. No difference in visual analog pain scores


  • First RCT in an emergency setting with patient-centred outcomes
  • No difference in pain between antibiotics and placebo
  • Limited by:
    • Small sample size
    • No adverse events reported
    • Infection was not an outcome
  • RCT with larger sample size in relevant population showing no benefit from antibiotics
  • Limited by:
    • No adverse events reported
    • 31 % lost to follow up rate

Uncomplicated Diverticulitis

There has been a shift in the understanding of the pathophysiology of diverticulitis, whereby most frameworks emphasize the role of inflammation, gut microbiota imbalances, colon motility, and visceral hypersensitivity as crucial elements in the disease (Strate, 2012).  Most expert bodies have not updated their guidelines with regards the role of antibiotics in uncomplicated diverticulitis, however the American Gastroenterology Association in 2015 downgraded the recommendation for antibiotics to one of “selective use” (Stollman, 2015).

Table 3 summarizes the two most impactful RCTs that challenge the role of antibiotics in uncomplicated diverticulitis.

Table 3. Major Trials for Antibiotics and Uncomplicated Diverticulitis

Article Randomized Clinical Trial of Antibiotics in Acute Uncomplicated Diverticulitis

British Journal of Surgery. Chabok, 2012

Randomized Clinical Trial of Observational versus Antibiotic Treatment For a First Episode of CT-Proven Uncomplicated Acute Diverticulitis

British Journal of Surgery. Daniels, 2017

  •  Sweden and Iceland. Open multi-centre RCT
  • 623 patients with uncomplicated diverticulitis
  • 10 hospitals across 7 years
  • RCT: 22 clinical sites in Netherlands
  • 528 patients with left-sided acute uncomplicated diverticulitis
Intervention Antibiotics x 7 days (cephalosporin + flagyl, carbapenem, or pip-tazo)

311 patients (22 lost to follow up)

Amox-clav (95 % of patients ) or cipro/flagyl (5%)

268 patients (10 lost to follow up)

Comparison  IV fluids. 399 patients (19 lost to follow up)  IV fluids. 263 patients (6 lost to follow up)
Outcomes  No difference in complication rate, emergency surgeries, hospital stay, or recurrent diverticulitis  No difference in time to recovery, proportion without recovery, readmission, complications, recurrence, or mortality
13 % of patients in observation group sent home directly


First RCT to address this question, with a substantial sample size, showing no benefit from antibiotics
Limited by:

  • All patients admitted
  • No standardized antibiotic regimen
  • Exclusions not well described
  • Variability in recruitment rates
  • High rate of recurrent diverticulitis included (40 %)
Methodologically sound RCT with large sample size and standard antibiotic regimens
Limited by:

  • 87 % admission rate unlike our practice
  • Reasons for readmission not described
  • Small sub-group of patients with Hinchey 1b disease (abscess)


Take Home Points

  1. Antibiotic overuse is a growing concern – emergency departments must be leaders in antibiotic stewardship
  2. The role of antibiotics is questionable in:
    • Catheter-associated asymptomatic bacteriuria
    • Uncomplicated dental pain with no signs of cellulitis
    • Acute uncomplicated first episode diverticulitis


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