Use of antibiotics in the early COVID-19 pandemic in Poland, the Netherlands and Spain, from erraticism to (more) logic

This is an observational study on the use of antibiotics in COVID-19 patients in three different European hospitals in the early days after the onset of the COVID-19 pandemic in 2020. The observed differences are the result of prescribing practices, patient mix and disease burden, epidemiology of the disease and (changes in) hospital admission practices. The observed differences are the result of prescribing practices, patient mix, disease burden, epidemiology of the disease, hospital admission practices, as well as other known and unknown factors. We compared antibiotic use through the lens of different indicators in the very early days of the COVID-19 pandemic and about 9 months later. Our study demonstrates that in all three centres, the second period showed an improved, but modest, and more rational and logical picture. According to the EU guidelines for the prudent use of antimicrobials in humans [19], the rational use of antibiotics constitutes an important component of antimicrobial prudent use and appropriate stewardship strategy.

We saw in UHC (PL) an increase of the proportion of COVID-19 patients with at least one antibiotic course between the two periods of observation. Although this may be partly the result of a change in patient mix (i.e., more elderly patients, higher death rates), it is still an observation that gives concern. In contrast, both in UMCU (NL) and VHUH (ES), we saw a decrease in antibiotic use comparing the two periods, most dramatically in the VHUH (ES). Adherence to national prescribing guidelines, albeit the erratic situation of the pandemic, has been probably more pronounced in UMCU (NL) and VHUH (ES), compared to UHC (PL).

Our study showed that only minority of hospitalised patients in all three hospitals had the positive results of their bacterial tests. Although there may be apparent differences in the percentages of patients with a positive bacterial test (between first and second waves, between centres), this should be interpreted cautiously as they are based on limited numbers. Moreover, without more detailed information about the patients in question (e.g. respiratory status, comorbidity, oxygen level upon admission, ICU admission yes/no, reason for giving antibiotics), there is actually no conclusive explanation for these observations. Obviously, it is possible that at the time of the first wave, when there was still much uncertainty about the causative agent, bacterial origin was also considered with the empirical start of antibiotics for the treatment of possible pneumonia. Or in ICU patients, selective intestinal decontamination can also be started to prevent additional infections. Differences between countries might also be due to differences in national guidelines regarding empirical use of antibiotics when infection is suspected, or in ICU, but there may also have been differences in treatment recommendations for COVID-19 patients at the time depending on the COVID-19 pandemic situation.

The first guideline issued by the World Health Organization issues “The living guideline on the Therapeutics and COVID-19” [20] was published in September 2020. It recommended the use of antibiotics only in specific cases including confirmed bacterial infection. The unprecedented situation during the early stages of the COVID-19 pandemic with many uncertainties regarding effective treatment compelled healthcare professionals to use antibiotics more frequently in treatment of hospitalised patients. According to one research performed in four hospitals in the Netherlands, empiric antibiotic treatment during the early phase of hospitalised patients was frequent [21]. However, the empirical use of antibiotics constitutes a risk factor for the development of antibiotic resistance [22].

We assessed classes of antibiotics used in three European hospitals during two different periods of the initial stage of the COVID-19 pandemic. The most frequently utilised class of antibiotics in all three hospitals was third-generation cephalosporins, with a majority of patients receiving ceftriaxone. This broad-spectrum antibiotic belongs to the WHO “WATCH” group, which are recommended for patients with more severe clinical presentations [23]. Several studies around the world confirm the wide use of ceftriaxone during the COVID-19 pandemic. For example, a Spanish study examining antibiotic use during the COVID-19 pandemic concluded that the usage of ceftriaxone increased by 204% in March 2020 compared to February 2020 [24].

In all three hospitals, the majority of hospitalised patients were female. Some studies have confirmed that COVID-19 appears to affect women less than men [25, 26]. Nevertheless, there were variations in the age distribution of hospitalised patients across the three European hospitals. In the Netherlands and Spain, the majority of patients in both periods were over 65 years old (49 and 59 patients, respectively). In contrast, in the Polish hospital, there were only 34 patients in the same age group in both periods. Additionally, we observed a decrease in the number of patients over 65 years of age hospitalised in the Netherlands and Spain in the second period. The situation in Poland was the opposite, which might be related to the epidemiological picks of the COVID-19 recorded by the ECDC (Figs. 1, 2 and 3). To our knowledge, our study was the first to compare data from three prominent hospitals across distinct European countries—Poland, the Netherlands and Spain. It is important to acknowledge that one of the study’s limitations is the relatively small sample size of patients.

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