The 2022 to 2023 Amoxicillin Shortage and Acute Otitis Media Treatment

We retrospectively analyzed encounters for children < 18 years old diagnosed with AOM between May 15^th, 2022 and April 14^th, 2023 at an urban freestanding children’s hospital system and affiliate community health center. Our exclusion criteria were a previous episode of AOM within 30 days, concomitant respiratory infections that might alter treatment (sinusitis, pharyngitis, pneumonia, and conjunctivitis), and an amoxicillin or penicillin allergy (International Classification of Diseases – 10^th Revision codes in Appendix 1).

We described patient demographic characteristics by pre and postshortage period. We used a sharp regression discontinuity design to assess whether prescribing changed immediately after the FDA’s declaration (October 28th, 2022).⁶  This approach used logistic regressions to evaluate the causal impact of the shortage on the odds of being prescribed amoxicillin, amoxicillin-clavulanate, cefdinir, other antibiotics, or no antibiotic. Analysis details and sensitivity checks are described in Appendices 2 and 3. Of note, racial and ethnic categories were included as covariates to evaluate differential impacts of the amoxicillin shortage resulting from known inequities in access to prescription medications. The study was exempted by the Boston Children’s Hospital Institutional Review Board.

We identified 3076 encounters for AOM, with 1677 (54.5%) occurring after the amoxicillin shortage (Table 1). The median patient age was 3.1 years (interquartile range [IQR] 1.6–5.4), and most patients were male (n = 1695, 55.1%), Hispanic (n = 1252, 40.7%), and evaluated in the emergency department (n = 1900, 61.8%). The most prescribed antibiotics were amoxicillin (n = 1662, 54.0%), amoxicillin-clavulanate (n = 671, 21.8%), and cefdinir (n = 263, 8.6%).

The odds of being prescribed amoxicillin decreased by 91% after the FDA shortage declaration (odds ratio 0.09 [95% confidence interval 0.07–0.12]) (Fig 1A). In contrast, the odds of being prescribed amoxicillin-clavulanate or cefdinir increased sevenfold and ninefold (7.90 [5.59–11.31] and 9.25 [5.27–17.17]), respectively (Fig 1, B and C). Management without antibiotics (0.82 [0.55–1.23]) and prescriptions for other antibiotics (1.73 [0.96–3.19]) did not significantly change (Fig 1, D and E). By the end of the study period, antibiotic prescribing approached preshortage levels. Trends in AOM management were similar across sociodemographic characteristics (Appendix 4)

The 2022 to 2023 amoxicillin shortage had significant and immediate impacts on antibiotic choice for AOM. As amoxicillin prescribing declined, the use of alternative agents like amoxicillin-clavulanate and cefdinir sharply increased. Rates of watchful waiting remained unchanged and lower than anticipated, which may suggest a propensity to treat higher acuity patients in the emergency department.

Antimicrobial and other drug shortages have become increasingly common consequences of limited investment in low-profit, generic medications and regulatory challenges, among other factors.^7,8  Our study illustrates one direct and previously underexplored impact: how dramatically clinical practice responds to market disruptions. Although amoxicillin-clavulanate and cefdinir have comparable efficacy to amoxicillin for AOM, they are less cost-effective, carry worse side effect profiles, and exhibit broader spectrum activity, raising concerns for economic impacts and downstream antimicrobial resistance.⁹  Antibiotic shortages may also contribute to medication errors, adverse events, and treatment delays.¹⁰ 

Study limitations include the retrospective, single-center design; local constraints may have varied by drug supplier, region, or rurality. The lack of differences across sociodemographic characteristics likely reflects the small catchment area and uniform pharmacy availability. That said, our rigorous quasi-experimental methods and sensitivity checks improve the validity of our findings. Another limitation is that we did not examine prescribing trends for other respiratory infections but anticipate that similar shifts occurred.

Drug shortages have an immediate, sweeping effect on prescribing patterns and should be monitored and intervened upon by regulatory agencies, policymakers, and health systems alike. The FDA should consider increasing oversight of essential medications, requiring disclosure of supply issues, and incentivizing antibiotic production to mitigate their low profitability.⁴ 

The authors would like to express their gratitude for support from the Digital Innovation Network for House Officers (DINHO) of the Boston Combined Residency Program.

AOM

acute otitis media

FDA

US Food and Drug Administration