Analysing the trend over time of antibiotic consumption in the community

This tutorial describes and illustrates statistical methods to detect time trends possibly including abrupt changes (referred to as change-points) in the consumption of antibiotics in the community.For the period 1997-2017, data on consumption of antibacterials for systemic use (ATC group J01) in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. Trends over time and presence of common change-points were studied through a set of non-linear mixed models.After a thorough description of the set of models used to assess the time trend and presence of common change-points herein, the methodology was applied to the consumption of antibacterials for systemic use (ATC J01) in 25 EU/European Economic Area (EEA) countries. The best fit was obtained for a model including two change-points: one in the first quarter of 2004 and one in the last quarter of 2008.Allowing for the inclusion of common change-points improved model fit. Individual countries investigating changes in their antibiotic consumption pattern can use this tutorial to analyse their country data

Consumption of antibiotics in the community, European Union/European Economic Area, 1997-2017: data collection, management and analysis

This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997-2003 and 1997-2009.In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described.In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA.The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe

European Surveillance of Antimicrobial Consumption (ESAC) : quality appraisal of antibiotic use in Europe

Objectives: To assess quality of outpatient antibiotic use in Europe in 2009 based on the 12 European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators and to evaluate changes in quality between 2004 and 2009. Methods: Quality of outpatient antibiotic use in 2009 was compared between 32 countries by calculating the indicator values for 2009 for each of the 12 ESAC drug-specific quality indicators based on outpatient antibiotic use data expressed in defined daily doses per 1000 inhabitants per day (DID). For each of the indicators we grouped the 2009 indicator values into four quartiles. To evaluate changes in quality between 2004 and 2009, based on their respective indicator values, countries were also grouped according to the quartile distribution of the 2004 indicator values. Only countries able to deliver data for both years were included in this analysis. Results: In 2009 a difference in the quality of outpatient antibiotic use between Nordic and Southern European countries was observed. Quality of outpatient antibiotic use decreased between 2004 and 2009. In particular, there were increases in the quality indicators [J01F_DID], [J01M_DID], [J01CR_%] and [J01_B/N], i.e. the use of macrolides, lincosamides and streptogramins in DID, the use of quinolones in DID, the proportional use of combinations of penicillins, including b-lactamase inhibitors and the ratio of broad- to narrow-spectrum antibiotics. Conclusions: Quality of outpatient antibiotic use in DID decreased between 2004 and 2009. A continuous effort to improve outpatient antibiotic consumption seems to be essential to reduce outpatient antibiotic use in general and the use of broad-spectrum antibiotics in particular.peer-reviewe

Patterns of Antimicrobial Use in a Specialized Surgical Hospital in Southeast Nigeria: Need for a Standardized Protocol of Antimicrobial Use in the Tropics

Background: Antimicrobial resistance remains a growing global health menace. One of the key actions to curb this menace by the World Health Organization is antimicrobial stewardship (AMS). A prescription protocol is one of the cost‑effective AMS interventions in surgery. This study determines the patterns of antimicrobial usage in a hospital specialized in orthopedic and plastic surgeries care in Nigeria. Methods: A cross-sectional survey was carried out at National Orthopaedic Hospital Enugu, a tertiary hospital specialized in orthopedic and plastic surgeries in Southeast Nigeria in May 2019. All the inpatients were included in the study. A standardized tool for point prevalence survey was used to collect data. Data were analyzed using Epi Info version 7.2.4. Results: A total of 127 inpatients  participated in the survey with 387 antimicrobial encounters. The most common reasons for antimicrobial use were for the treatment of community-acquired infections (65.0%) and prophylaxis (29.4%). The decision for their use was made majorly on an empirical basis (92.4%). The reasons for antimicrobial prescriptions were documented in the majority (97.5%) of the cases and stop review dates in all (100%) of the prescriptions. Ceftriaxone (25.7%), tinidazole (21.9%), and metronidazole (14.6%) were the commonest antimicrobials prescribed among the patients. Conclusion: Orthopedic and plastic surgery practices require tailored prophylactic antibiotic regimens in the tropics due to peculiarities of both the specialties and the subregion. The claim that existing protocols in the temperate regions may apply in the tropics has been questioned due to the microbial profile on the tropics. Keywords: Antimicrobial protocol in surgery, antimicrobial resistance, antimicrobial stewardship, prophylactic antibiotic

Change-points in antibiotic consumption in the community, European Union/European Economic Area, 1997-2017

Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship.For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups.For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013.Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community

European Surveillance of Antimicrobial Consumption (ESAC) : outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe (1997–2009)

Background: Data on more than a decade of outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe were collected from 33 countries as part of the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). Methods: For the period 1997–2009, data on outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials aggregated at the level of the active substance were collected and expressed in defined daily doses (DDD; WHO, version 2011) per 1000 inhabitants per day (DID). Using the Anatomical Therapeutic Chemical (ATC) classification, trends in the use of tetracyclines (J01A), sulphonamides and trimethoprim (J01E) and other antibacterials (J01X) over time, seasonal variation and composition of use were analysed. Results: In 2009, the variations in outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials between countries, and also in the composition of use over time, were huge. For tetracyclines a significant and for sulphonamides and trimethoprim a non-significant decrease in use was observed between 1997 and 2009 in Europe. The seasonal variation in their use significantly decreased over time. For the other antibacterials, no significant changes in the volume of use or its seasonal variation were seen. Conclusions: As for all other major antibiotic subgroups, a striking variation in use and composition of use between countries in Europe was observed for outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials. In combination with the decreasing use, especially of recommended substances, this represents an opportunity not only to reduce antibiotic use but also to improve its quality.peer-reviewe

European Surveillance of Antimicrobial Consumption (ESAC) : outpatient antibiotic use in Europe (1997–2009)

Objectives: To describe total outpatient systemic antibiotic use in Europe from 1997 to 2009 and to analyse statistically trends of total use and composition of use over time. Methods: For the period 1997–2009, data on outpatient use of systemic antibiotics aggregated at the level of the active substance were collected and expressed in defined daily doses (WHO, version 2011) and packages per 1000 inhabitants per day (DID and PID, respectively). Outpatient antibiotic (ATC J01) use in DID in the 33 European countries able to deliver valid data was analysed using longitudinal and compositional data analyses. Results: Total outpatient antibiotic use in 2009 varied by a factor of 3.8 between the countries with the highest (38.6 DID in Greece) and lowest (10.2 DID in Romania) use. For Europe, a significant increase was found in total outpatient antibiotic use, as well as a significant seasonal variation, which decreased over time from 1997 to 2009. Relative use of penicillins and quinolones significantly increased over time with respect to sulphonamides and trimethoprim, and relative use of quinolones increased with respect to macrolide/lincosamide/streptogramin as well. More detailed analyses of these major antibiotic subgroups will be described in separate papers. Conclusions: Outpatient antibiotic use in Europe measured as DID has increased since 1997, whereas seasonal variation has decreased over time. European Surveillance of Antimicrobial Consumption (ESAC) data on outpatient antibiotic use in Europe enable countries to audit their antibiotic use. Complemented by longitudinal and compositional data analyses, these data provide a tool for assessing public health strategies aimed at reducing antibiotic resistance and optimizing antibiotic prescribing.peer-reviewe

European Surveillance of Antimicrobial Consumptionesac (ESAC) : outpatient penicillin use in Europe (1997-2009)

Background: Data on 13 years (1997–2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. Methods: For the period 1997–2009, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinaseresistant penicillins (PRP) and combinations with b-lactamase inhibitors (COP). Results: Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). Conclusions: Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997–2009.peer-reviewe

European Surveillance of Antimicrobial Consumption (ESAC) : outpatient quinolone use in Europe (1997–2009)

Background: Data on more than a decade of outpatient quinolone use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). Methods: For the period 1997–2009, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011), and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Using a classification based on pharmacokinetic and in vitro potency profiles, quinolone use was analysed with regard to trends over time, seasonal variation and composition. Results: Total outpatient quinolone use in 2009 varied by a factor of 7.5 between the country with the highest (Italy, 3.61 DID) and the country with the lowest (the UK, 0.48 DID) quinolone use. The second-generation quinolones accounted for .50% of quinolone use (mainly ciprofloxacin), except for Croatia, where first-generation quinolones (mainly norfloxacin) were mostly used. A significant increase in outpatient quinolone use was found for Europe, as well as a large seasonal variation, which increased significantly over time from 1997 to 2009. Relative use of third-generation quinolones significantly increased over time with respect to the use of second-generation quinolones, while the relative use of both significantly increased with respect to the firstgeneration quinolones. Levofloxacin and moxifloxacin (respiratory quinolones) represented .10% of quinolone outpatient use in 17 countries, with extreme seasonal variation in all countries. Conclusions: There was a substantial increase and change in the pattern of quinolone use between 1997 and 2009, a period during which quinolones that are effective for the treatment of respiratory tract infections were introduced. These quinolones are not the first-line antibiotics for this indication and their use should generally be limited, and quinolones should ideally show no substantial seasonal variation in terms of their use.peer-reviewe

European Surveillance of Antimicrobial Consumption (ESAC): outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe (1997–2009)

Background: Data on more than a decade of outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe were collected from 33 countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), using the WHO Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. Methods: For the period 1997–2009, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2011) per 1000 inhabitants per day (DID). Using a classification based on mean plasma elimination half-life, macrolide use was analysed for trends over time, seasonal variation and composition. Results: Total outpatient MLS use in 2009 varied by a factor of 18 between the countries with highest (11.5 DID in Greece) and lowest (0.6 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediateand long-acting macrolides were the most commonly used agents in 2, 25 and 5 countries, respectively (mainly erythromycin, clarithromycin and azithromycin, respectively). In Sweden, mainly lincosamides (clindamycin) were used. Lincosamide use was observed in all countries, while substantial use of a streptogramin was only seen in France (pristinamycin). For Europe, a significant increase in outpatient MLS use was found, as well as a significant seasonal variation, which increased over time from 1997 to 2009. Relative use of longacting macrolides and lincosamides significantly increased over time with respect to intermediate-acting macrolides, and relative use of the latter increased with respect to short-acting macrolides. Conclusions: The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this subgroup of antibiotics is still prescribed inappropriately in many countries.peer-reviewe