Alleged Penicillin Allergies Lead to Higher Risk of MRSA and C difficile

Penicillins are among the most commonly reported medications to be listed as an allergy.¹ Many patients with a documented penicillin allergy, however, do not have a true immunoglobulin E (IgE)-mediated reaction or have outgrown a childhood allergy.² These allergy labels translate to important clinical implications, as ß-lactams are often the antibiotics of choice for many infections.³ In addition to compromising clinical outcomes, the use of alternative antibiotics in the setting of a documented allergy has been shown to increase length-of-stay, readmission rates, rates of drug toxicity, and associated health care costs.^4,5 Alternative agents are often broader spectrum than ß-lactams, subjecting patients to collateral damage and subsequent selection for resistant organisms and Clostridium difficile.

Using national data from electronic medical records within the United Kingdom, a retrospective study sought to associate the risks of acquiring methicillin-resistant Staphylococcus aureus (MRSA) or C difficile in patients who have documented penicillin allergies.⁶ Penicillin-allergic patients and non-allergic patients were matched based on age, sex, and study entry time. Patients were excluded if they had a history of MRSA or C difficile infection prior to enrollment. The primary outcome was the rate of index cases of MRSA and C difficile. Antibiotic consumption during the follow-up period was assessed as a secondary outcome.

A total of 64,141 patients with a declared penicillin allergy were included and compared to 237,258 patients without a documented allergy. Overall, there was a slight predominance in females with a median age of about 57 years. Cohort characteristics were well-balanced between the 2 study arms and suggested most patients had a favorable socioeconomic status and were relatively healthy, indicated by low Charlson Comorbidity Indices. Of the patients with a documented penicillin allergy, most reactions were thought to be secondary to a true allergy (74.5%) versus drug intolerance (14.5%) or adverse effect (11.1%). Many of these reactions were thought to be of moderate severity (86%) and of likely certainty (73.6%).

Patients were followed for a median of 6 years following enrollment into the study. During this period, there were increased rates of MRSA (0.689% vs 0.389%) and C difficile (0.689% vs 0.525%) in patients with a penicillin allergy compared to those without. Adjusted hazard ratios for patients with a penicillin allergy were 1.69 and 1.26 for acquiring MRSA and C difficile, respectively. Unsurprisingly, this population had a higher utilization of ß-lactam alternatives including macrolides, clindamycin, and fluoroquinolones. The authors concluded that patients with a listed penicillin allergy are at a significantly higher risk for MRSA and C difficile, which is in part mediated through the prescription of alternative antibiotics.

Findings from this study further add credence to the collateral damage of inappropriately labeled penicillin allergies. Although prior studies evaluating the impact of penicillin allergies have focused on patient-centered outcomes, this study further compounds onto these findings with public health and infection control implications. It is imperative, therefore, that antimicrobial stewardship programs continue to spearhead initiatives to elucidate penicillin allergies, appropriately de-label allergies, and provide ongoing education regarding the risks of alternative antibiotics.

References:

1. Zhou L, Dhopeshwarkar N, Blumenthal KG, et al. Drug allergies documented in electronic health records of a large healthcare system. Allergy. 2016;71:1305-13.
2. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients. J Allergy Clin Immunol. 2014;133(3):790-796.
3. Jeffres MN, Narayanan PP, Shuster JE, et al. Consequences of avoiding B-lactams in patients with B-lactam allergies. J Allergy Clin Immunol. 2016;137(4):1148-1153.
4. MacFadden DR, LaDelfa A, Leen J, et al. Impact of reported beta-lactam allergy on inpatient outcomes: a multicenter prospective cohort study. Clin Infect Dis. 2016;63:904-10.
5. Huang KG, Cluzet V, Hamilton K, et al. The impact of reported beta-lactam allergy in hospitalized patients with hematologic malignancy requiring antibiotics. Clin Infect Dis. 2018;67(1):27-33.
6. Blumenthal KG, Lu N, Zhang Y, et al. Risk of methicillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018;361:k2400.