This retrospective observational study examined the prescribed antibiotic pack sizes and their conformity with the treatment recommendations for the five most common infections treated with antibiotics in Swiss primary care. The study found that in 10 out of 23 of the investigated substance / indication combinations, none of the observed prescriptions aligns with the recommendations in the respective guidelines and that across all substances, 31.6% of all prescriptions were potentially non-conform with any of the guideline recommendations.

To the best of our knowledge, the present study is the first to compare prescribed pack sizes of antibiotics for the most frequent infections for which antibiotics are recommended in a real-world setting based on healthcare claims data. Analysing patterns of prescribed antibiotics in general, we found a high degree of single pack prescriptions, especially for those antibiotics most commonly prescribed in Swiss primary care, e.g. amoxicillin/clavulanic acid. However, unexpectedly, there was a non-negligible level of partial pack prescriptions. In up to 3.6% partial packs were prescribed. This even though there was no legal basis for partial distribution in Switzerland in 2022 and blister packaging or unit dose systems are primarily an option for nursing homes [26]. One might assume that prescribing or dispensing partial packs may be an attempt to circumvent the dilemma of lack of appropriate pack sizes. We are unaware of any national evidence on the behaviour and intentions of physicians on prescribing partial packs of antibiotics. Consequently, this hypothesis should be investigated in further studies. On the other hand, we found a substantial degree of prescribing multiple packs, especially for fosfomycin or doxycycline. The underlying clinical reasons might be diverse, such as prolonged and chronic treatment or the prescription for the travel first aid kit.

We found that for 10 out of 23 of the investigated substance / indication combinations not a single antibiotic prescription was appropriate because no appropriate prepacked pack size is available. The absence of appropriate pack sizes affected both first-line and second-line recommendations. This is of great importance as second-line antibiotics are still frequently prescribed [21, 27]. For instance, in the case of urinary tract infections, which have recently been the most common single indication for the use of antibiotics [21], there are no suitable products available for either of the substances nitrofurantoin and trimethoprim/sulfamethoxazole. Both substances are frequently used [21, 27]. Due to the absence of suitable pack sizes, all patients receive an excessive number of tablets. While leftover nitrofurantoin pills may be used for an additional complete second treatment, the remaining trimethoprim/sulfamethoxazole pills are only enough for two-thirds of a full treatment. However, in both scenarios, there is a risk of inappropriate self-treatment afterwards that in turn may foster AMR development [28]. The same applies to the use of amoxicillin/clavulanic acid in patients with CAP or amoxicillin in patients with SP. Amoxicillin/clavulanic acid is the most commonly used substance for CAP and amoxicillin for SP [21] and for both indications not a single appropriate product is available.

Our results are in line with previous studies, although we found a lower degree of potential non-conform prescriptions [16, 17, 29]. These differences can be explained by the methodologies used. Firstly, in our explorative analysis, we considered all prescriptions with a total dosage in line with any of the treatment recommendations as appropriate, resulting in overall conservative estimates for non-conformity. Secondly, our study relies on real world prescribing data instead of theoretical models and thirdly, different reference guidelines were used. On the other hand, there may be clinical reasons to deviate from treatment recommendations and prescriptions outside the recommendations may be clinically appropriate.

Füri et al. [16] for example, matched available pack sizes with 70 different Swiss guidelines for five common infections in a modelling study. Guidelines were obtained from both national organizations and individual hospitals. They came to the result that for only 47% of guidelines adequate packs were available. A number which is lower than the 57% (13/23 substance indication combinations) of available conform pack sizes in our study and also lower than the weighted mean of potentially conform prescriptions (68.4%) in our explorative analysis. A feasibility study by the Swiss Federal Office of Public Health [18] came to similar results: In the two small, distinct geographic cohorts analysed, adequate pack sizes were available in 65% (n = 1,911 prescriptions) and 49% (n = 94) of antibiotic dispensations.

Determining the precise number of overprescribed tablets is crucial in understanding the magnitude of the impact of inappropriate pack sizes. However, obtaining this information from routine data is notoriously challenging, as it necessitates knowledge of the prescribed packs, the indication, and ultimately, the doctor’s recommendations to the patient. Theoretically, surplus tablets could be disposed of at pharmacies, reducing their environmental impact and preventing inappropriate use by patients later.

In our exploratory analysis, we estimated the excess tablets for each substance and in sum for all substances. The figures for fosfomycin and nitrofurantoin are likely very close to the true value in the analyzed population of GP, as these substances are almost exclusively used in Switzerland for the analyzed indication. We calculated over 780,000 overprescribed tablets for nitrofurantoin, the most frequently used substance in UTI [21]. As we only analyzed data from GP, it is likely that the number of overprescribed tablets in the entire outpatient setting is much higher, considering that many UTI are also treated in other outpatient settings such as gynecology, emergency departments, walk-in practices and pharmacies.

The estimates of the other substances analyzed may be confounded as they can be used for different indications than those investigated. Especially the substances amoxicillin/clavulanic acid and doxycycline, the two most common substances prescribed in the Swiss outpatient setting, have multiple further indications to use. Nevertheless, these figures provide insight into a problem whose scale cannot yet well be captured by routine data and should be further investigated.

The results of this study are in line with previous studies highlighting the fact, that for many indications appropriate pack sizes are lacking. The inadequate pack sizes undermine the numerous antibiotic stewardship interventions aimed at improving the quality of prescribing in outpatient medicine. Countries like the Netherlands [30] or the UK [11] offer the option of dispensing partial packs or a specific number of tablets. In other countries, exact tablet dispensing has recently been evaluated by research teams. For example, in a French cluster randomized trial [31] there was evidence that per unit dispense of antibiotics could not only reduce the number of tablets to reimburse and deposed to the environment but could also improve the treatment adherence of patients. Individual dispensing of antibiotics was also viewed positively by both patients and healthcare providers in a Swiss feasibility study [18]. For example, it was highlighted that patients were more knowledgeable about their treatment and the importance of the correct dosage.

These dispensing options are likely to be more promising in the long term than continuously adjusting pack sizes, especially considering changing guideline recommendations. For example, in 2024, the SSI changed the guideline for the treatment of urinary tract infections with nitrofurantoin from 2 × 100 mg per day to 3 × 100 mg per day, resulting in a lower level of waste but still equivalent to an overprescription of 5/20 tablets in the smallest available pack size. On the other hand, using pack sizes that adhere to guideline recommendations would be an immediate intervention to improve the quality of prescribing.

The short- and long-term costs of exact pill distribution are regularly discussed in health politics, attempting to determine the additional expense of the dispensing practice or pharmacy, (e.g. due to printing out missing package leaflets), compared to savings from leftovers [18, 31, 32], but exact cost-efficiency analysis are lacking to date. But even if higher short-term costs were demonstrated it is important to consider that, similar to other global pressures such as the climate crisis, the true costs of antibiotic resistance are enormous and can hardly be quantified [30, 33,34,35].

An up-to-date and comprehensive analysis of the discrepancies between pack sizes and patient needs, as carried out in our study, is particularly important in times of rising healthcare costs, medication shortage and increasing demands on sustainability, and ultimately builds an empirical foundation for political decisions. In fact, since March 2023 the partial dispensing of four antibiotics (amoxicillin, amoxicillin/clavulanic acid, cefuroxime and levofloxacin) is for the first time legally possible due to the situation of medication shortage in Switzerland and could pave the way for further part-quantity levies [32].

This study analyses prescriptions of Swiss primary care. The analysis is based on a large dataset and the methodology used to extrapolate medication prescriptions to the whole population is well established and has been used before [24, 36]. In addition, age and gender distribution of antibiotic recipients in this study were similar to other analyses of antibiotic prescriptions in Swiss primary care [20]. Accordingly, we assume a high degree of external validity. Compared to theoretical modelling approaches [16], the use of real-life data has the advantage that one can observe what was prescribed, rather than what could have been prescribed.

The main limitation of the study is that health insurance data lack information about the specific indication of the prescribed medication, as the data base lacks diagnoses. Accordingly, we were unaware of the specific indication for each antibiotic prescription. In substance/ indication combinations with a potential appropriate pack size, the true proportion of appropriate pack sizes prescribed for the specific indication might be lower than the numbers reported in this study. For substances with further indications outside the analysed ones, e.g. amoxicillin/clavulanic acid or doxycycline, the true proportion of appropriate packs sizes prescribed may be even higher. We have to acknowledge that treatment recommendations may differ to a certain degree and physicians may use regional guidance or international guidelines instead of the national guidelines provided by the Swiss Society of Infectious Diseases. This may also result in a higher degree of appropriate pack sizes. Similarly, it is possible that pregnant women - for whom there are special guidelines which are not considered in the current study - may be treated by general practitioners, potentially causing a slight bias. However, we assume minimal variation, as many pregnant women in Switzerland are treated by their gynaecologist, and thus do not appear in our sample.

A further limitation of the present study, which is based on reimbursement data, is the inability to differentiate between the antibiotics purchased by patients and those actually consumed. Therefore, the actual amount of waste could vary, potentially exceeding the amount estimated in this analysis, as there are indications that a relevant proportion of patients do not adhere to the prescribed treatment duration [37].