Discussion

Antimicrobial stewardship plays a critical role in healthcare, aiming to improve antibiotic use and prevent resistance. Analyzing prescribing patterns is the initial step toward developing effective interventions. This study analyzed over 800,000 antibiotic prescriptions from more than 300 outpatient facilities between Q1 2021 and Q2 2023 to assess the trend and guideline concordance. Antibiotic use in the outpatient setting fluctuated, gradually increasing when comparing the same quarter each year. Upper respiratory tract infections such as sinusitis and otitis media were the most common reasons for prescribing antibiotics in outpatient settings. The COVID-19 pandemic’s influence on outpatient antibiotic prescribing patterns was likely substantial. In our study, the antibiotic prescribing rate was notably low in 2021, likely due to pandemic-related factors such as reduced in-person visits, increased telehealth services, and widespread public health measures such as social distancing and mask-wearing. These measures led to a decline in respiratory infections and other communicable diseases, reducing the need for antibiotics. However, as the pandemic progressed and healthcare systems adapted, the antibiotic use rate gradually increased, reaching higher levels by Q2 2023. This overall increase may reflect a return to prepandemic healthcare utilization patterns and a resurgence in infections as public health measures were relaxed.

One of the key strengths of this study is that it analyzes EHR data extracted from various outpatient facilities. Each facility’s EHR system may have unique data structures and coding practices, making the harmonization of data a complex and meticulous process. Our study integrated diverse data sources to analyze antibiotic prescribing trends across multiple facilities. This approach enhances the robustness of our findings and the reliability of the observed trends. For example, a pattern of antibiotic use similar to our observations was reported by Bizune et al., utilizing the IQVIA National Prescription Audit (NPA) Extended Insights data set, which encompasses nationwide antibiotic prescription transactions in retail pharmacies across the United States. ^{Reference Bizune, Gouin, Powell, Hersh, Hicks and Kabbani24} The overall increase in antibiotic use and the quarterly trends from 2021 to 2022 are comparable. As in their study, we observed a gradual increase in antibiotic use from the first quarter to the last quarter of 2021. From the last quarter of 2021 to the first quarter of 2022, there was a reduction, followed by a stable rate until the fourth quarter, which saw the sharpest increase since the first quarter of 2021. These consistent trends across different datasets highlight the reliability of our findings and the broader applicability of our study’s conclusions.

Our analysis captures important trends in antibiotic prescribing, emphasizing the need for continued surveillance and stewardship efforts. The increasing rate of antibiotic prescriptions, particularly among children, underscores the need for ongoing monitoring and intervention. The prescription rate for otitis media increased by 152% in the last quarter of 2022, and GAS increased by 165% in the first quarter of 2023 compared to their respective previous quarters. This trend coincides with the 2022–2023 viral respiratory disease season, during which COVID-19, influenza, and respiratory syncytial virus (RSV) infection rates were elevated. ^{Reference Luo, Liu and Zhou25} The increased incidence of otitis media and GAS infections could have been complications of these viral infections. ^{Reference Herrera, Huber and Chaussee26} The elevated viral respiratory infections and the corresponding surge in antibiotic prescriptions raise questions about the appropriateness of these treatments. Viral infections are often self-limiting and do not require antibiotic therapy; however, healthcare providers might prescribe antibiotics preemptively against secondary bacterial infections. ^{Reference Ciesla, Leader and Stoddard27} Also, if the diagnosis of bacterial and viral infections is uncertain, overprescribing could occur as a precautionary measure. This practice, although it is sometimes necessary, emphasizes the need for advanced diagnostic techniques to assist with clinical decision-making.

The discrepancies observed in antibiotic and duration concordance with guidelines indicate substantial room for improvement. Less than 60% of sinusitis-related prescriptions were antibiotic concordant. Nearly 10% of sinusitis-related prescriptions were azithromycin in adults and children, despite guidelines advising against its use for sinus infections. ^{Reference Chow, Benninger and Brook19,Reference Rosenfeld, Piccirillo and Chandrasekhar20} Longer than recommended duration contributed to low concordance rates in UTIs, GAS, and cellulitis. While sometimes prescriptions may have extended durations based on clinical improvement, we observed that prescriptions with an extended duration are prevalent. For example, over 80% of cellulitis-related prescriptions were for 7–14 days, compared to the recommended 5-day course. ^{Reference Stevens, Bisno and Chambers15}

Ciprofloxacin’s frequent use for UTIs and the tendency to prescribe it to older adults indicate another critical gap in practice. Ciprofloxacin was the fourth most used drug for UTIs, accounting for 12% of all UTI-related prescriptions in adults. Notably, more than half of ciprofloxacin prescriptions were provided to individuals aged 60 or older. The overuse of fluoroquinolones, such as ciprofloxacin, is known to increase the risk of severe and potentially irreversible long-term adverse side effects, such as tendon rupture and peripheral neuropathy, especially in older adults. ^{Reference Baggio and Ananda-Rajah28} There is also a greater risk of developing antimicrobial resistance with these broad-spectrum antibiotics. ^{Reference Kherroubi, Bacon and Rahman29} Future studies should investigate factors affecting the prescribing of fluoroquinolone and develop appropriate interventions to reduce its use.

While improving antibiotic prescribing in outpatient settings is crucial for patient safety, several challenges exist. Many healthcare providers may lack awareness of antibiotic resistance issues surrounding outpatient care or have insufficient knowledge about appropriate antibiotic prescribing practices. ^{Reference O’Neill4,Reference Zetts, Garcia, Doctor, Gerber, Linder and Hyun30,Reference Nemr, Kishk, Elsaid, Louis, Fahmy and Khattab31} Diagnostic uncertainties and limited abilities to conduct a test create challenges to optimal antibiotic treatment. ^{Reference Beal, Assarzadegan and Rand32} Conducting a test to make a definitive diagnosis may not be feasible in some settings, especially if the providers have limited time to see patients. ^{Reference Beal, Assarzadegan and Rand32} The fear of undertreatment and the motivation to satisfy patient expectations may add pressure to overprescribe antibiotics. ^{Reference Cziner, Park, Hamdy, Rogers, Turner and Liu33,Reference Kohut, Keller and Linder34} Patients may expect or demand antibiotics when they visit providers, and it can be difficult for providers to manage these expectations under pressure to achieve better patient satisfaction. Studies have shown that reducing diagnostic uncertainty through point-of-care testing (POCT) could decrease unnecessary antibiotic use. ^{Reference Schuetz, Wirz and Sager35} Delayed prescribing, a practice in which a patient receiving an antibiotic prescription is instructed to fill it later if their symptoms do not improve, has been shown to reduce antibiotic use in outpatient settings. ^{Reference Spurling, Del Mar, Dooley, Clark and Askew36–Reference Mas-Dalmau, Villanueva López and Gorrotxategi Gorrotxategi38}

The study’s methodology, including the use of a three-tier approach to classifying diagnoses and the assessment of prescribing concordance with guidelines, provides a robust framework for assessing prescribing practices and opportunities to benchmark. However, the reliance on EHR data means that the accuracy of the diagnosis and prescribing information depends on the quality of the data entered. ^{Reference Ray, Tallman, Bearden, Elman and McGregor39} Unique clinical cases may warrant antibiotic treatments that deviate from guidelines. Some instances of guideline discordance, such as the use of metronidazole for UTIs, may reflect clinically appropriate decisions that were not discernible in our data. Furthermore, this study did not capture delayed antibiotic prescribing or whether prescriptions were filled. Other factors, such as dosage adjustment for renal function, consideration of drug allergies, and the appropriate testing procedure, were not assessed.

The sensitivity analyses provided valuable insights into the implications of analytical approaches, particularly for sinusitis. The substantial increase in drug concordance rates for sinusitis when encounters with multiple diagnoses from the same tier were excluded suggests that diagnostic coding complexities may have influenced our primary results. Additionally, the notable improvement in drug concordance for sinusitis after excluding prescriptions with durations exceeding 21 days indicates that unusually long durations may have contributed to the lower concordance observed in the primary analysis. These findings highlight the importance of refining analytic approaches to account for potential misclassification and outlier prescription patterns in sinusitis treatment. On the other hand, the minimal changes observed for UTI, cellulitis, GAS, and otitis media suggest that the initial estimates for these conditions were less sensitive to alternative analytic decisions.

To enhance the interpretability of the results, we focused on prescription-related outpatient visits to estimate the antibiotic prescribing rates. Including all visits, regardless of whether a prescription was issued, could introduce noise into the data, as fluctuations in visits that do not require treatment, such as wellness visits and follow-ups, could obscure actual prescribing trends. However, it should be noted that care-seeking patterns may indirectly affect our findings. During the COVID-19 pandemic, the number of outpatient visits with upper respiratory infections not requiring antibiotic prescriptions increased. ^{Reference Hersh, Stenehjem, Fino and Spivak14} If providers altered their prescribing thresholds in response to changes in patient volume or illness severity, this could influence observed trends. Our estimates reflect prescribing among visits that resulted in a prescribing and may not capture broader changes in care-seeking behavior or treatment thresholds. Additionally, our data does not account for over-the-counter medication use or treatment delays, which could affect the overall antibiotic prescribing landscape.

Clinical guidelines are not always updated frequently, and some recommendations may not fully reflect the most recent evidence. While we strictly adhered to published guidelines from authoritative bodies, some of these guidelines were developed several years ago and have not been revised to incorporate more recent findings on optimal antibiotic duration. For this reason, there may be instances where a prescription classified as concordant in our analysis would be considered excessive by more current best practices. The aggregate data reported in this study should not be extrapolated to make inferences about local practices. A number of local factors can influence antibiotic selection, including access to POCT or other diagnostic techniques, the prescriber’s training and specialty, local antimicrobial resistance patterns, and the characteristics of the local patient population. ASPs must review their facility-specific data and tailor interventions to address the facility-specific practices and challenges. ^{Reference Shrestha, Zahra and Cannady40} A more tailored approach is needed to ensure ASP initiatives are relevant and responsive. ^{Reference Shrestha, Zahra and Cannady40}

The findings of this study highlight the urgency of bolstering ASP efforts in outpatient settings. By analyzing antibiotic use trends and identifying areas for intervention, healthcare systems can implement more effective stewardship strategies. The increasing rate of antibiotic prescriptions, particularly among children, and the discrepancies in guidelines concordance emphasize the need for ongoing monitoring and interventions. Future research should focus on understanding the factors influencing prescribing behaviors and developing targeted interventions to promote appropriate antibiotic use. Strengthening ASPs and ensuring data-informed decision-making are critical steps toward mitigating antibiotic resistance and improving patient care.