Since 2007, the American Heart Association, with input from the American Dental Association, has limited the target populations for antibiotic prophylaxis prior to dental procedures for the prevention of infective endocarditis to only those with cardiac conditions at highest risk.Reference Wilson, Gewitz and Lockhart1 This guidance reflected an acknowledgment of the lack of evidence on effectiveness of prophylaxis in preventing infective endocarditis, concerns about drug-associated adverse events, and development of bacterial resistance. The guideline recommends prophylaxis only prior to dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa in patients with valvular heart disease; patients with selected congenital heart conditions; and patients with previous, relapsed, or recurrent infective endocarditis.Reference Wilson, Gewitz and Lockhart1
Although overall antibiotic use in this setting has declined substantially since 2007, inappropriate use remains an ongoing problem.Reference Suda, Calip and Zhou2 Several analyses have shown that ∼5 of every 6 dental prophylactic prescriptions are inconsistent with guidelines.Reference Suda, Fitzpatrick and Gibson3,Reference Hubbard, Evans, Calip, Zhou, Rowan and Suda4 In this study, we estimated costs associated with this practice behavior from a healthcare payer perspective.
Methods
Based on 2018 census data, we modeled adults aged ≥18 years in the United States who had a dental visit with an antibiotic prescribed over a 1-year period. According to published data from large cohorts, ∼83.1% of these prescriptions are considered inappropriate.Reference Suda, Calip and Zhou2–Reference Hubbard, Evans, Calip, Zhou, Rowan and Suda4 We considered only amoxicillin, cephalexin, and clindamycin because they account for 94% of the prescribed drugs in the dental setting.Reference Suda, Calip and Zhou2–Reference Gross, Suda and Zhou5 We calculated the costs of drug-related adverse effects by estimating the likelihood of the most impactful adverse events related to dental antibiotic prophylaxis: Clostridioides difficile infection and anaphylaxis or severe hypersensitivity requiring an emergency department (ED) visit or hospitalization.Reference Gross, Suda and Zhou5–Reference Thornhill, Dayer, Prendergast, Baddour, Jones and Lockhart7 When possible, we used estimates derived from studies specific to antibiotics given for dental prophylaxis to reduce the likelihood of overestimating the probability of adverse effects. For C. difficile infection, we calculated the proportion of cases that would be treated outpatient versus inpatient.Reference Ofori, Ramai, Dhawan, Mustafa, Gasperino and Reddy8 We applied a highly conservative definition to calculate the risk of hypersensitivity or anaphylaxis to only include the most severe reactions requiring an ED visit or hospitalization.Reference Gross, Suda and Zhou5,Reference Thornhill, Dayer, Prendergast, Baddour, Jones and Lockhart7,Reference Liang, Chen and Macy9,Reference Macy and Contreras10 We also evaluated the potential risk of infective endocarditis if inappropriate antibiotic prescribing did not occur.Reference Duval, Alla and Hoen11,Reference Quan, Muller-Pebody and Fawcett12
We used the reported incidence of infective endocarditis among those without known predisposing cardiac conditions undergoing dental procedures,Reference Duval, Alla and Hoen11 and we extrapolated this value to a population-wide estimate based on the incidence of infective endocarditis according to predetermined diagnostic criteria.Reference Quan, Muller-Pebody and Fawcett12 The cost of adverse effects was determined by costs reported per the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project based on International Classification of Disease, Ninth Revision (ICD-9) codes, ICD-10 codes, and Clinical Classifications Software Refined (CCSR) codes, and drug treatment cost based on the Veterans’ Affairs Federal Supply Schedule pricing. We also estimated patient burden based on average prescription drug copay. Finally, we performed one-way sensitivity analyses to assess the robustness of our results to changes in model parameters. All costs are reported in 2022 USD. Probability and cost parameters are reported in Table 1.
Table 1. Clinical and Cost-Related Parameters and Values Used for Cost Estimation
Note. ADE, adverse drug event; AE, adverse event; AQRH, Agency for Healthcare Research and Quality; VA FSS, Department of Veterans’ Affairs Federal Supply Schedule; IE, infective endocarditis; ICD, International Classification of Diseases; CCSR, Clinical Classifications Software Refined.
a Units as specified per row.
b Health, United States, 2019. US National Center for Health Statistics website. https://www.ncbi.nlm.nih.gov/books/NBK569310/. Published 2021. Accessed July 11, 2022.
c Thompson W, Teoh L, Hubbard CC, et al. Patterns of dental antibiotic prescribing in 2017: Australia, England, United States, and British Columbia (Canada). Infect Control Hosp Epidemiol 2022;43:191–198.
d VA National Acquisition Center contract catalog search tool. Veterans’ Affairs website. https://www.vendorportal.ecms.va.gov/nac/Pharma/List. Accessed April 30, 2023.
e Prescription Prices, Coupons & Pharmacy Information. GoodRx website. https://www.goodrx.com/. Accessed May 3, 2023.
f Clinical Classifications Software Refined (CCSR) for ICD-10-CM diagnoses. Healthcare Cost and Utilization Project. Agency for Healthcare Research and Qualitywebsite. https://www.hcup-us.ahrq.gov/toolssoftware/ccsr/dxccsr.jsp#download. Published 2022. Accessed July 12, 2022.
Results
In our base case, we estimate that among 253,815,197 US adults aged ≥18 years, 167,010,400 (65.8%) have a dental visit each year. Among them, 7,965,084 (4.8%) receive prophylactic antibiotics.Reference Suda, Fitzpatrick and Gibson3 Among those receiving prophylactic antibiotics, 6,617,132 (83.1%) are inappropriately prescribed antibiotic prophylaxis. This practice incurs ∼$10.8 million in excess healthcare costs per year, or $1,620 per 1,000 dental visits. This includes antibiotic use amounting to $2.69 million per year, and adverse effect costs of $5.82 million, $1.99 million, and $380,849 for amoxicillin, clindamycin, and cephalexin, respectively. Inappropriate prophylaxis leads to an excess 768 inpatient C. difficile cases annually and up to 103 cases of severe hypersensitivity or anaphylaxis requiring hospitalization, amounting to $7.30 million and $874,584, respectively. If no inappropriate antibiotic use occurs, we estimate an excess of ∼3 cases of infective endocarditis, or $131,149 per year. The antibiotic prescriptions further amount to $20,500,703 in patient out-of-pocket expenses per year.
One-way sensitivity analyses indicated that the percentage of dental visits in which an antibiotic was prescribed had the largest impact on the total excess costs associated with inappropriate antibiotic prescribing, followed by the percentage of inappropriate antibiotic prophylaxis prescribed (Fig. 1). The next-largest impacts were the drug costs for each antibiotic followed by the distribution of drugs used for prophylaxis, though these parameters had minimal (<5%) impacts on the overall costs. For key clinical outcomes (CDI, anaphylaxis, and endocarditis cases), the most sensitive parameter was also the percentage of dental visits in which an antibiotic was prescribed, followed by percentage of inappropriate antibiotics prescribed and percentage of individuals aged >18 years with a dental visit (Supplementary Fig. 1 online). For CDI and anaphylaxis, this was followed by the distribution of antibiotics prescribed. For endocarditis, this was followed by the risk of endocarditis among those with no predisposing cardiac conditions, with and without prophylaxis (Supplementary Fig. 1 online).
Figure 1. One-Way Sensitivity Analysis for Overall Budget Impact
Discussion
The burden of inappropriate use of antibiotics in dentistry for prevention of infective endocarditis prophylaxis in the United States has been well described. At least 75% of such prescriptions are not consistent with published guidelines. The potential impacts of this reality, however, are unclear. These might include clinically meaningful adverse events from the antibiotic taken, the development of and spread of antibiotic resistance, and/or the costs associated with each. The direct medical costs associated with the above have not been reported in dentistry. Inappropriate antibiotic prescriptions for dental prophylaxis cost the US healthcare system and patients >$31 million per year, the former due primarily to adverse effects associated with even just a single dose of antibiotics; drug costs alone make up ∼25% of the total healthcare system burden.
Although indications for prophylaxis have been substantially narrowed, prevention of infective endocarditis remains the goal for the high-risk groups for whom it is still recommended. Therefore, we also considered the potential costs under the assumption that had inappropriate antibiotics not been prescribed, some cases of endocarditis may have occurred. We estimated that at most, there may be an excess of up to three cases, incurring a trivial direct cost burden in aggregate, nationally.
The study had several limitations. The datasets used to assess inappropriate antibiotic prescribing (specifically) did not include the uninsured, and they reflected nonprobability samples of dataReference Suda, Calip and Zhou2 or select populations (eg, Veterans’ Affairs).Reference Suda, Fitzpatrick and Gibson3 However, each data set referenced is national in scope and links dental claims with medical and prescription claims of patients enrolled in both medical and dental health plans, with similarly concluded high rates of inappropriate dental prophylaxis. In addition, our estimates of endocarditis risk after a dental procedure were extrapolated from studies in France and England. Thus, the calculated incidence of endocarditis used in our model may not represent the true incidence in the United States. Lastly, our estimates do not contain costs associated with antibiotics not included in our analysis; indirect costs associated with adverse effects; pharmacist time spent filling the drug and counseling a patient; patient time lost to pick up a prescription; or the impact of unnecessary antibiotic use promoting community antibiotic resistance, which is very difficult to robustly assess.
Overall, while the estimated costs associated with inappropriate antibiotic use in dentistry may not be significant, dentists account for 6%–10% of all antibiotic prescriptions in the United States,Reference Suda, Fitzpatrick and Gibson3 resulting in a nontrivial burden of preventable adverse effects.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ice.2023.126
Acknowledgments
The authors thank Hollie Y. Wong and Elizabeth Ling for their contributions to the literature search and the parameters for this project.
Financial support
No financial support was provided relevant to this article.
Competing interests
All authors report no conflicts of interest relevant to this article.
