The authors declare the following interests: TM and JS are employees of the commercial company, QS GmbH. There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.
The development of antimicrobial resistance is triggered by the use of antibiotic drugs. Therefore, the consumption of antibiotics in livestock is monitored, and different measures may be applied if the usage of antibiotic drugs seems inappropriate. Unfortunately, the surveillance of antibiotic consumption is not standardised, and surveillance systems differ. In Germany, the food quality assurance system QS Qualität und Sicherheit GmbH (QS) began the documentation of antibiotic drug usage in pigs in 2012 in a private economic based database, and for its members, documentation has been mandatory in all pig age groups since 2014. In this investigation, we calculated the distribution of the antibiotics use per pig age group and half-year, and the percentage of the active substances used from overall treatments within German pig holdings from 1 July, 2013 to 30 June, 2015. In fattening pigs, the median of the treatment frequency is 4.3 in 2013–2 and exhibits a decreasing trend in this time period up to 2.1 in 2015–1. In weaners the median ranged between 11.3 in 2014–2 and 5.8 in 2013–2. The median of sucklers varies between 21.6 and 25.0. In sucklers and weaners, a clear temporal trend is not seen to date. The share of the active substances differs between the age groups. In fattening pigs, mostly tetracyclines and penicillines were used, occurring in approximately 60% of the total treatments. In weaners, amoxicillin and colistin have the highest shares of the treatment frequency, at approximately 60%. The treatment frequencies of macrolides and penicillines have the highest share in sucklers.
The relationship between the development of resistance in bacteria and the use of antibiotics is well-known [
Another starting point to fight antimicrobial resistance is to reduce the use of antibiotics in veterinary medicine in general. Therefore monitoring the use of antibiotics is essential. For that purpose, different systems were established in the recent years for example in Austria [
In Germany as well systems for data collection and reduction of antibiotics are established for farm animals in the recent years. The amount of active substances from sales data and the frequency of use of antibiotics is monitored via different systems. Sales data is available by a regulatory act [
This paper focuses on the antibiotic monitoring system of the QS and takes the different age groups of pigs into consideration. The aim of the study is to describe the use of the various antibiotic substances in the entire German pork production and examine its temporal development.
Approximately 32,913 national Farm-IDs from pig farmers in Germany are connected to the QS system; as such, approximately 95% of the pigs slaughtered in Germany are related to the QS system. The collection of data regarding the use of antibiotics in fattening pigs began in 2012. Since 2014, the input of data has also been mandatory for farms holding weaners and sucklers [
As proposed by Jensen et al. [
The prescription of antibiotics for livestock in Germany is subject to various legal regulations. For example, only veterinarians are allowed to prescribe antibiotics after examination of affected animals [
Different plausibility checks were performed at the input process in the database, for example the "no antibiotic use" input is only possible if no ADF is entered in the database. Furthermore employees of QS give feedback to the responsible veterinarian about potentially implausible or missing values which should be corrected afterwards by the veterinarian.
All data was pseudonymised by QS by using codes instead of full names and addresses to ensure data privacy. After receiving the data set from QS the variables needed for calculation were checked once more and ADFs with "number of days treated" = 0, "number of animals treated" = 0, "amount of substance" = 0 or "population size" = 0 were excluded from the evaluation which effects about 3,000 ADFs.
A list of long acting products was made available from QS. For those products the number of days treated is extended by the veterinarian's individual definition. For reporting of results on active substances this correction factors were taken into account.
Antibiotic usage was calculated by means of the treatment frequency TF per half year, which relates the number of used daily doses to the farm size, i.e.
The definition of TF follows the concept of the (cumulative) incidence in epidemiology by relating events (here nUDD) to a (fixed) population size (here the farm size). As nUDD may be re-arranged
TF describes the number of days all animals within the stock are treated in average. This is the same as Timmermanns et al. [
This is in a slight contrast to other definitions, which follow the concept of an incidence density, where nUDD is divided by a farm-individual time-at-risk.
Pharmaceuticals or treatments containing two or more different active substances are entered into the calculation with a value of two, or more. The combination of sulfonamides with trimethoprim, ampicillin and cloxacillin, benzylpenicillin-benzathin and benzylpenicillin-procain, as well as benzylpenicillin-kalium and benzylpenicillin-procain are interpreted as one active substance.
The treatment frequency is calculated for every age group per national Farm-ID and half year as its whole as well as for every active substance separately. To illustrate the distribution of treatment frequencies, an empirical density function was approximated (restricted to treatment frequencies smaller than or equal to 100) by means of a negative binomial model.
The percentage of the treatment frequency of an active substance per total treatment is calculated using a unilateral alpha trimmed data set (1%) for a more robust statistical inference [
All ADF information and basic farm data were linked by national Farm-ID and evaluated with SAS®, version 9.3 TS level 1M2 (SAS Institute Inc., Cary, NC, United States).
In total, 924,771 ADFs (100%) were made available from QS during the study period. The number of participating holdings in each age group increased steadily until 2014–2 (
age groups | half-year | number of holdings | number of ADF′s | average number of ADF′s per age group | number of holdings with no recorded treatment | % of holdings with no recorded treatment |
---|---|---|---|---|---|---|
2013–2 | 374 | 3,867 | 10.3 | 40 | 1.5 | |
2014–1 | 4,815 | 40,795 | 8.5 | 388 | 8.1 | |
2014–2 | 6,727 | 71,803 | 10.7 | 443 | 6.6 | |
2015–1 | 6,812 | 77,793 | 11.4 | 319 | 4.7 | |
2013–2 | 522 | 3,395 | 6.5 | 51 | 9.8 | |
2014–1 | 6,048 | 57,805 | 9.6 | 750 | 12.4 | |
2014–2 | 8,577 | 98,132 | 11.4 | 1,159 | 13.5 | |
2015–1 | 8,293 | 84,914 | 10.2 | 759 | 9.2 | |
2013–2 | 9,588 | 70,926 | 7.4 | 791 | 8.3 | |
2014–1 | 16,960 | 116,798 | 6.9 | 2,958 | 17.4 | |
2014–2 | 20,374 | 140,619 | 6.9 | 3,645 | 17.9 | |
2015–1 | 19,324 | 125,078 | 6.5 | 2,770 | 14.3 |
The distribution of the relative treatment frequency in all three age groups is shown for 2015–1 as an example in
Statistical measures of the treatment frequency distribution for the observation period are shown in
treatment frequency | ||||||||
---|---|---|---|---|---|---|---|---|
age group | half year | number of holdings | minimum | 5%-percentile | median | upper quartile | 95%-percentile | maximum |
374 | 0 | 0 | 21.6 | 60.8 | 170.7 | 664.3 | ||
4,815 | 0 | 0 | 18.3 | 45.3 | 122.7 | 1,249.0 | ||
6,727 | 0 | 0 | 25.0 | 57.2 | 133.0 | 3,394.0 | ||
6,812 | 0 | 0.2 | 23.0 | 55.7 | 150.8 | 1,322.0 | ||
522 | 0 | 0 | 5.8 | 14.3 | 55.7 | 196.6 | ||
6,048 | 0 | 0 | 9.7 | 26.2 | 74.6 | 3,076.0 | ||
8,577 | 0 | 0 | 11.3 | 29.7 | 76.9 | 6,118.0 | ||
8,293 | 0 | 0 | 9.4 | 22.1 | 56.8 | 29,550.0 | ||
9,588 | 0 | 0 | 4.3 | 11.6 | 30.4 | 7,700.0 | ||
16,960 | 0 | 0 | 3.4 | 10.6 | 29.4 | 27,801.0 | ||
20,374 | 0 | 0 | 3.0 | 9.6 | 26.1 | 490.0 | ||
19,324 | 0 | 0 | 2.1 | 6.7 | 19.0 | 425.0 |
We found a decrease in the median from 2013–2 (4.3) to 2015–1 (2.1) in fattening pigs. In weaners, we found an increase of the median up to 11.3 in 2014–2, and then a decline in 2015–1 to 9.4. The median of the sucklers showed an alternating trend, with a higher median in 2015–1 compared to 2013–2 and 2014–1. Similar trends were found in the 75% and 95% quartile of all age groups.
Treatment frequencies and related statistical measures were stratified into twelve antibiotic drug classes. Due to the age group and indication, the distributional patterns differed substantially. Drug classes which were used in many holdings, like penicillines, had a relatively similar distribution of treatment frequency compared to the overall treatment frequency. The 2014–1 median of penicillines was 3.5 in sucklers, 0.6 in weaners and 0.1 in fattening pigs (not shown in detail). In drug classes which were used in fewer holdings, the median was zero. In polypeptides, for example, the upper quartile in sucklers and fattening pigs was zero as well; there are only figures above zero in the 95% quartile. Because all drug classes (except penicillines) were used in less than 50% of the holdings, the percentage of the treatment frequency for all drug classes and active substances per total treatments was analysed in depth. The three age groups were considered separately (Tables
Drug class |
2013–2 | 2014–1 | 2014–2 | 2015–1 |
---|---|---|---|---|
Apramycin | 1.09 | 0.87 | 0.58 | 0.61 |
Dihydrostreptomycin | 7.92 | 6.05 | 5.39 | 6.43 |
Gentamicin | 0.45 | 1.20 | 1.25 | 1.29 |
Kanamycin | 0 | 0.00 | 0- | 0 |
Neomycin | 0.39 | 0.57 | 0.28 | 0.09 |
Paromomycin | 0 | 0 | 0 | 0.00 |
Spectinomycin | 0.21 | 0.76 | 0.59 | 0.51 |
Cefquinom | 0.28 | 1.03 | 0.87 | 0.90 |
Ceftiofur | 3.54 | 13.31 | 14.44 | 15.62 |
Florfenicol | 0.02 | 0.33 | 0.33 | 0.38 |
Danofloxacin | 0.10 | 0.52 | 0.53 | 0.60 |
Difloxacin | 0 | 0 | 0.00 | 0 |
Enrofloxacin | 1.77 | 5.73 | 5.73 | 5.96 |
Marbofloxacin | 0.19 | 0.47 | 0.40 | 0.51 |
Lincomycin | 0.14 | 0.66 | 0.45 | 0.34 |
Erythromycin | 0- | 0.00 | 0.01 | 0.00 |
Tildipirosin | 0.30 | 0.86 | 0.72 | 0.82 |
Tilmicosin | 0- | 0.07 | 0.08 | 0.04 |
Tulathromycin | 8.44 | 13.81 | 16.19 | 25.98 |
Tylosin | 1.21 | 1.18 | 0.62 | 0.45 |
Tylvalosin | 0 | 0- | 0.00 | 0- |
Amoxicillin | 35.17 | 31.16 | 35.17 | 26.55 |
Ampicillin | 0 | 0.01 | 0.00 | 0.00 |
Benzylpenicilin | 8.78 | 8.25 | 7.48 | 7.72 |
Cloxacillin | 0 | 0 | 0.00 | 0 |
Phenoxymethylpenicilin | 0 | 0.00 | 0.01 | 0.00 |
Tiamulin | 0.03 | 0.10 | 0.15 | 0.08 |
Colistin | 12.53 | 5.78 | 3.64 | 2.15 |
Sulfadiazin and Trimethoprim | 0.54 | 0.10 | 0.02 | 0.04 |
Sulfadimethoxin and Trimethoprim | 0 | 0.12 | 0.04 | 0.01 |
Sulfadimidin and Trimethoprim | 0.03 | 0.12 | 0.14 | 0.10 |
Sulfadoxin and Trimethoprim | 0.07 | 0.15 | 0.12 | 0.15 |
Sulfamethoxazol and Trimethoprim | 3.23 | 0.71 | 0.21 | 0.06 |
Sulfadimidin | 0 | 0.00 | 0 | 0.00 |
Sulfadoxin | 0 | 0.00 | 0.00 | 0 |
Sulfamethoxpyridazin | 0 | 0 | 0 | 0.00 |
Chlortetracyclin | 1.37 | 1.55 | 1.45 | 0.68 |
Doxycyclin | 8.84 | 1.48 | 0.71 | 0.30 |
Oxytetracyclin | 1.06 | 2.08 | 1.86 | 1.49 |
Tetracyclin | 2.30 | 0.98 | 0.53 | 0.13 |
* Cephalosporines of the 1st and 2nd generation as well as Cefoperazon, valnemulin, sulfaclozin, sulfadimethoxin, sulfaquinoxalin and sulfathiazol were not used in sucklers in this study.
Drug class |
2013–2 | 2014–1 | 2014–2 | 2015–1 |
---|---|---|---|---|
Apramycin | 0.34 | 0.21 | 0.24 | 0.28 |
Dihydrostreptomycin | 0.35 | 0.30 | 0.21 | 0.10 |
Gentamicin | 0.10 | 0.11 | 0.08 | 0.10 |
Kanamycin | 0 | 0.00 | 0.00 | 0 |
Neomycin | 0.87 | 1.51 | 1.54 | 1.55 |
Spectinomycin | 0.87 | 0.87 | 0.81 | 0.78 |
Cefoperazon | 0 | 0- | 0 | 0.00 |
Cefquinom | 0.47 | 0.18 | 0.13 | 0.15 |
Ceftiofur | 0.24 | 0.54 | 0.46 | 0.42 |
0.28 | 0.28 | 0.26 | 0.41 | |
Florfenicol | 0.28 | 0.28 | 0.26 | 0.41 |
Danofloxacin | 0.02 | 0.18 | 0.23 | 0.12 |
Enrofloxacin | 1.20 | 1.22 | 1.08 | 1.17 |
Marbofloxacin | 0.25 | 0.25 | 0.22 | 0.21 |
Lincomycin | 1.15 | 1.22 | 1.31 | 1.29 |
Erythromycin | 0 | 0.00 | 0.00 | 0.01 |
Tildipirosin | 0.06 | 0.21 | 0.19 | 0.20 |
Tilmicosin | 0.31 | 1.24 | 1.22 | 1.23 |
Tulathromycin | 1.63 | 1.54 | 1.49 | 2.21 |
Tylosin | 7.23 | 6.58 | 5.37 | 4.42 |
Tylvalosin | 0.03 | 0.12 | 0.13 | 0.05 |
Amoxicillin | 32.28 | 28.93 | 31.58 | 31.38 |
Ampicillin | 0.06 | 0.15 | 0.14 | 0.12 |
Benzylpenicilin | 0.71 | 0.67 | 0.49 | 0.28 |
Cloxacillin | 0 | 0 | 0.00 | 0.00 |
Tiamulin | 0.19 | 1.16 | 1.07 | 1.30 |
Colistin | 25.56 | 30.16 | 29.50 | 30.80 |
Sulfadiazin and Trimethoprim | 0.67 | 0.10 | 0.08 | 0.08 |
Sulfadimethoxin and Trimethoprim | 0 | 0.18 | 0.10 | 0.13 |
Sulfadimidin and Trimethoprim | 0.01 | 0.05 | 0.03 | 0.03 |
Sulfadoxin and Trimethoprim | 0.05 | 0.08 | 0.07 | 0.09 |
Sulfamethoxazol and Trimethoprim | 3.61 | 4.02 | 3.78 | 3.24 |
Sulfadimidin | 0.12 | 0.04 | 0.04 | 0.07 |
Sulfamethoxpyridazin | 0 | 0 | 0.00 | 0.00 |
Sulfathiazol | 0 | 0 | 0 | 0.00 |
Chlortetracyclin | 5.61 | 3.30 | 3.43 | 3.01 |
Doxycyclin | 12.87 | 9.23 | 9.94 | 10.29 |
Oxytetracyclin | 0.13 | 0.35 | 0.28 | 0.27 |
Tetracyclin | 2.72 | 4.99 | 4.49 | 4.21 |
*Cephalosporines of the 1st and 2nd generation as well as Paromomycin, phenoxymethylpen, difloxacin, valnemulin, sulfaclozin, sulfadimethoxin, sulfadoxin and sulfaquinoxalin were not used in weaners in this study.
Drug class |
2013–2 | 2014–1 | 2014–2 | 2015–1 |
---|---|---|---|---|
Apramycin | 0.01 | 0.03 | 0.01 | 0.02 |
Dihydrostreptomycin | 0.12 | 0.08 | 0.04 | 0.02 |
Gentamicin | 0.01 | 0.03 | 0.04 | 0.03 |
Kanamycin | 0 | 0.00 | 0.00 | 0.00 |
Neomycin | 0.82 | 1.10 | 0.98 | 1.00 |
Spectinomycin | 0.92 | 1.12 | 1.58 | 1.41 |
Cefoperazon | 0 | 0 | 0 | 0.00 |
Cefquinom | 0.17 | 0.18 | 0.16 | 0.21 |
Ceftiofur | 0.12 | 0.10 | 0.05 | 0.08 |
Florfenicol | 0.47 | 0.47 | 0.54 | 0.65 |
Danofloxacin | 0.16 | 0.16 | 0.16 | 0.21 |
Enrofloxacin | 1.15 | 1.23 | 1.24 | 1.54 |
Marbofloxacin | 0.43 | 0.51 | 0.55 | 0.55 |
Lincomycin | 3.90 | 4.29 | 5.08 | 5.30 |
Erythromycin | 0.00 | 0.01 | 0.01 | 0.01 |
Tildipirosin | 0.22 | 0.21 | 0.19 | 0.20 |
Tilmicosin | 0.45 | 0.54 | 0.47 | 0.46 |
Tulathromycin | 0.22 | 0.28 | 0.23 | 0.49 |
Tylosin | 15.59 | 14.40 | 13.34 | 13.43 |
Tylvalosin | 0.05 | 0.09 | 0.06 | 0.03 |
Amoxicillin | 25.46 | 26.32 | 26.44 | 27.08 |
Ampicillin | 0.12 | 0.05 | 0.07 | 0.06 |
Benzylpenicilin | 0.81 | 0.79 | 0.75 | 0.43 |
Cloxacillin | 0 | 0 | 0 | 0.00 |
Tiamulin | 3.12 | 3.38 | 3.95 | 4.68 |
Valnemulin | 0 | 0.00 | 0.00 | 0 |
Colistin | 7.29 | 8.54 | 7.83 | 7.63 |
Sulfadiazin und Trimethoprim | 0.02 | 0.06 | 0.05 | 0.04 |
Sulfadimethoxin und Trimethoprim | 0.34 | 0.20 | 0.21 | 0.21 |
Sulfadimidin und Trimethoprim | 0.05 | 0.06 | 0.06 | 0.04 |
Sulfadoxin und Trimethoprim | 0.07 | 0.04 | 0.04 | 0.06 |
Sulfamethoxazol und Trimethoprim | 7.47 | 6.32 | 5.34 | 3.65 |
Sulfaclozin | 0.01 | 0 | 0 | 0 |
Sulfadimethoxin | 0.00 | 0 | 0 | 0 |
Sulfadimidin | 0.29 | 0.20 | 0.22 | 0.25 |
Sulfamethoxpyridazin | 0.00 | 0.00 | 0.00 | 0.00 |
Sulfaquinoxalin | 0- | 0.00 | 0.00 | 0.00 |
Sulfathiazol | 0 | 0.00 | 0 | 0 |
Chlortetracyclin | 5.08 | 4.59 | 4.62 | 4.08 |
Doxycyclin | 15.62 | 16.95 | 18.84 | 20.37 |
Oxytetracyclin | 0.22 | 0.22 | 0.20 | 0.30 |
Tetracyclin | 9.21 | 7.46 | 6.65 | 5.50 |
* Cephalosporines of the 1st and 2nd generation as well as Paromomycin, phenoxymethylpen, difloxacin and sulfadoxin were not used in fattening pigs in this study.
We found that penicillines, especially amoxicillin, were an antibiotic class often used in all of the considered age groups in pigs. In fattening pigs, the treatment frequency of tetracyclines had a higher percentage per total treatments, but this drug class became less important with decreasing pig age. Polypeptides also had high shares of the total treatments in all age groups, with an obviously decreasing percentage, especially in sucklers and fattening pigs. Cephalosporins, especially ceftiofur, were relatively often used in sucklers, with an increasing percentage. Aminoglycosides and enrofloxacin (fluoroquinolones) had relatively high shares per overall treatment in sucklers, whereas lincomycin only played a role in fattening pigs. Potentiated sulfonamides had a small share of the total treatments in all age groups, and over the course of the half-years, the percentage decreased.
In the present investigation, we analysed the entire data set of the QS antibiotic monitoring system for pigs for the time period 1 July, 2013 to 31 June, 2015. The treatment frequencies were calculated and the percentages of active substances used per age group and time period were described.
There are two types of antibiotic consumption studies. On the one hand, there are full (nation-wide) surveys, such as Bos et al. [
The evaluation period was two years and was aligned to half-year analyses due to the mandatory documentation duties derived from the German Pharmaceuticals Act. Others studies, such as Bos et al. [
In general, the underlying information of antibiotic consumption differs between the studies, which originate in different calculation and reporting methods. In the QS system, the data of the mandatory ADFs are recorded and used to calculate nUDD per age group.
For calculation, the number of animals treated and days treated is used directly from the forms (see
An additional benefit of our investigation is that the use of antibiotics can be associated with an age group treated and the calculation method is not affected by varying dosages of antibiotics.
96.45% of the ADFs contained complete information regarding the variables needed to calculate the treatment frequency, a percentage stated as high quality for routine data. If one looked at robust statistical measures, like quartiles and alpha trimming for the percentile drug class, the data quality is sufficient for the analyses and interpretation suggested.
In addition to the aforementioned differences, there are more aspects that need to be kept in mind when comparing different studies, as well as participating farms. The stratification rules concerning production system and farm type are important, but differ among the different studies. In the present study, sucklers, weaners and fattening pigs are monitored separately; sows and boars are not taken into consideration. In different surveys, the various animal species and age groups were investigated in different combinations. For example, Sjölund et al. [
Also, the farm types of the participating farms are important. The consumption of antibiotics differs between specialised and non-specialised farms [
In spite of all these differences, it is interesting to notice that the distribution of the different antibiotic active substances and drug classes per treatment is similar in various studies. In this study, beta lactams, tetracyclines and polypeptides show high shares of the total treatments in all age groups.
Sjölund et al. [
In a Belgian study, the UDD treatment incidence per 1,000 pigs at risk per day for different active substances was calculated and divided into oral and injectable. Proportionally, amoxicillin (30.0%) and colistin (30.7%) had the highest share in oral treatments. We found similar shares in treatment with these two active substances. Tulathromycin, macrolide, and Ceftifur LA, a cephalosporin, had the highest percentages of injectable treatments [
Merle et al. [
Apart from the "highest priority critically important antimicrobials," Trauffler et al. [
In summary, it is remarkable that penicillines and tetracyclines show a high share of the total treatments in several studies, despite various study approaches and calculation methods. Other drug classes were only used in small shares, such as cephalosporins, fluoroquinolones or pleuromutilins.
The descriptive analysis shows a decreasing trend in the quartiles of the treatment frequencies in fattening pigs. This trend may result from the rising public interest and the change in legislation in 2014, which was followed by a rethinking by veterinarians and farmers. The treatment strategy may have changed to more single treatments or to more vaccinations. It is also possible that animal health has improved through better animal hygiene and animal welfare, leading to a reduced need for antibiotic treatment. The recent launch of this surveillance system for sucklers and weaners in 2014 could be the reason a clear trend in these age groups has yet to be seen.
As the monitoring system for sucklers and weaners is in its initial phase, the data should be interpreted with a certain caution and no detailed statistical inference should be made at this point. The trends indicate a certain stability of the data, but its sustainability is uncertain. A continuation of the system is needed to get more reliable values, especially in sucklers and weaners. Further investigation can be done in the upcoming years.
In this study, holdings with no treatment in one or more half-years are found in all three age groups. Approximately 15% of the fattening pig holdings, and approximately 10% and 5% of the weaner and suckler holdings, respectively, do not get any antibiotics. Sjölund et al. [
The calculation of the treatment frequency and of the percentage per active substance are appropriate methods to look at consumption and drug profile changes over time, but comparability with international studies is restricted. A reduction trend in total antibiotic usage can be seen in fattening pigs. In weaners and sucklers, clear trends cannot be observed to date, since the surveillance system, especially in sucklers and weaners, is still in the initial phase.