WHO's essential medicines and AWaRe: recommendations on first- and second-choice antibiotics for empiric treatment of clinical infections.

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 clinical infections targeting both the primary health care and hospital facility setting. A further 257 antibiotics not included on the EML have been allocated an AWaRe group for stewardship and monitoring purposes. This article describes the development of AWaRe, focussing on the clinical evidence base that guided the selection of Access, Watch, or Reserve antibiotics as first and second choices for each infection. The overarching objective was to offer a tool for optimizing the quality of global antibiotic prescribing and reduce inappropriate use by encouraging the use of Access antibiotics (or no antibiotics) where appropriate. This clinical evidence evaluation and subsequent EML recommendations are the basis for the AWaRe antibiotic book and related smartphone applications. By providing guidance on antibiotic prioritization, AWaRe aims to facilitate the revision of national lists of essential medicines, update national prescribing guidelines, and supervise antibiotic use. Adherence to AWaRe would extend the effectiveness of current antibiotics while helping countries expand access to these life-saving medicines for the benefit of current and future patients, health professionals, and the environment.

Antimicrobial Consumption in Latin American Countries: First Steps of a Long Road Ahead.

BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.

An Assessment of the Impact of Coronavirus Disease (COVID-19) Pandemic on National Antimicrobial Consumption in Jordan.

Coronavirus disease 2019 (COVID-19) has overlapping clinical characteristics with bacterial respiratory tract infection, leading to the prescription of potentially unnecessary antibiotics. This study aimed at measuring changes and patterns of national antimicrobial use for one year preceding and one year during the COVID-19 pandemic. Annual national antimicrobial consumption for 2019 and 2020 was obtained from the Jordan Food and Drug Administration (JFDA) following the WHO surveillance methods. The WHO Access, Watch, and Reserve (AWaRe) classification was used. Total antibiotic consumption in 2020 (26.8 DDD per 1000 inhabitants per day) decreased by 5.5% compared to 2019 (28.4 DDD per 1000 inhabitants per day). There was an increase in the use of several antibiotics during 2020 compared with 2019 (third generation cephalosporins (19%), carbapenems (52%), macrolides (57%), and lincosamides (106%)). In 2020, there was a marked reduction in amoxicillin use (-53%), while the use of azithromycin increased by 74%. National antimicrobial consumption of the Access group decreased by 18% from 2019 to 2020 (59.1% vs. 48.1% of total consumption). The use of the Watch group increased in 2020 by 26%. The study highlighted an increase in the use of certain antibiotics during the pandemic period that are known to be associated with increasing resistance. Efforts to enhance national antimicrobial stewardship are needed to ensure rational use of antimicrobials.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Research activities to improve the utilization of antibiotics in Africa.

There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

Variations in the sales and sales patterns of veterinary antimicrobial agents in 25 European countries.

OBJECTIVES: To describe sales and sales patterns of veterinary antimicrobial agents in 25 European Union (EU)/European Economic Area (EEA) countries for 2011. METHODS: Data on the sales of veterinary antimicrobial agents from 25 EU member states and EEA countries for 2011 were collected at package level (name, formulation, strength, pack size, number of packages sold) according to a standardized protocol and template and presented in a harmonized manner. These data were calculated to express amounts sold, in metric tonnes, of active ingredient of each package. A population correction unit (PCU) was applied as a proxy for the animal biomass potentially treated with antimicrobial agents. The indicator used to express sales was milligrams of active substance per PCU. RESULTS: Substantial variations in the sales patterns and in the magnitude of sales of veterinary antimicrobial agents, expressed as mg/PCU, between the countries were observed. The proportion of sales, in mg/PCU, of products applicable for treatment of groups or herds of animals (premixes, oral powders and oral solution) varied considerably between the countries. CONCLUSIONS: Some countries reported much lower sales of veterinary antimicrobial agents than others, when expressed as mg/PCU. Sales patterns varied between countries, particularly with respect to pharmaceutical forms. Further studies are needed to understand the factors that explain the observed differences.

Sales of veterinary antibacterial agents in nine European countries during 2005-09: trends and patterns.

OBJECTIVES: To identify trends and patterns of sales of veterinary antimicrobial agents in nine European countries during 2005-09 in order to document the situation. METHODS: Existing sales data, in tonnes of active ingredients, of veterinary antimicrobial agents by class were collected from nine European countries in a standardized manner for the years 2005-09 (one country for 2006-09). A population correction unit (PCU) is introduced as a proxy for the animal population potentially treated with antimicrobial agents. The sales data are expressed as mg of active substance/PCU. RESULTS: Data coverage was reported to be 98%-100% for the nine countries. Overall, sales of veterinary antimicrobials agents, in mg/PCU, declined during the reporting period in the nine countries. Substantial differences in the sales patterns and in the magnitude of sales of veterinary antimicrobial agents, expressed as mg/PCU, between the nine countries are observed. The major classes sold were penicillins, sulphonamides and tetracyclines. The sales accounted for by the various veterinary antimicrobial agents have changed substantially for most countries. An increase in the sales of third- and fourth-generation cephalosporins and fluoroquinolones were observed for the majority of the countries. CONCLUSIONS: Through re-analysis of existing data by application of a harmonized approach, an overall picture of the trends in the sales of veterinary antimicrobial agents in the nine countries was obtained. Notable differences in trends in sales between the countries were observed. Further studies, preferably including data by animal species, are needed to understand the factors that explain these observations.

Indications for antimicrobial prescribing in European nursing homes: results from a point prevalence survey.

PURPOSE: In light of the emerging problem with multiresistant microorganisms in nursing homes (NHs), the European Surveillance of Antimicrobial Consumption NH subproject was set up to measure and describe antimicrobial use across Europe. The aim of this paper was to investigate the indications for antimicrobial use and hence identify targets for quality improvement. METHODS: Data were obtained from a point prevalence survey conducted in 323 NHs across 21 European countries. A resident questionnaire had to be completed for each resident receiving an antimicrobial, collecting data such as compound name and indication for antimicrobial prescribing. Four main indications for antimicrobial use were recorded: nasal decolonisation of methicillin-resistant Staphylococcus aureus (MRSA) carriage with mupirocin, prophylactic, empirical, and microbiologically documented treatments. The latter three treatment types were further subdivided according to the targeted infections. RESULTS: In total, 1966 residents were treated with 2046 antimicrobials. Empirical treatments were most common (54.4% of all antimicrobial therapies; prevalence: 3.39 per 100 eligible residents), followed by prophylactic (28.8%; prevalence: 1.87%) and microbiologically documented (16.1%; prevalence: 1.01%) regimes. MRSA decolonisation with nasal mupirocin (0.7%; prevalence: 0.02%) was uncommon. Antimicrobials were most frequently prescribed for the prevention or treatment of urinary (49.5%; prevalence: 3.23%) and respiratory (31.8%; prevalence: 1.81%) tract infections. A very high proportion of uroprophylaxis was reported (25.6% of all prescribed antimicrobials; prevalence: 1.67%). CONCLUSIONS: The indications for antimicrobial prescribing varied markedly between countries. We identified uroprophylaxis as a possible target for quality improvement.

Antimicrobial prescribing in hospitalized adults stratified by age: data from the ESAC point-prevalence surveys.

BACKGROUND: Geriatric infectious diseases are a major health care issue. Infections in the elderly occur more frequently than in younger adults, are often associated with higher morbidity and mortality, and may present atypically. Elderly patients are also often taking multiple medications, which increases the likelihood of drug-drug interactions. Dosing decisions should take into consideration the reduced lean body mass and declining renal function in this age group. OBJECTIVE: Antimicrobial prescribing in three age groups (65-74, 75-84 and ≥85 years) was compared with a reference age group (18-64 years), with the aim of identifying quality of care indicators specific to the elderly. METHODOLOGY: The ESAC (European Surveillance of Antimicrobial Consumption) final phase performed two hospital point-prevalence surveys in 2008 and 2009, respectively, using the defined daily dose (DDD) and Anatomical Therapeutic Chemical (ATC) classification system. The prescribed daily dose (PDD) was compared with the DDD. Differences in prescribing were assessed using multivariate logistic regression analyses. RESULTS: The majority of patients (19,549 [64% of 30,836]) were from Northern Europe and 13,830 (48%) belonged to the reference group. The largest proportion of patients was admitted through the hospital's medical specialty (55% of patients) [range: 49% in the reference group to 72% in the ≥85 years age group]. Penicillins were the most frequently used antimicrobials in all age groups (range: 32% in the reference group to 41% in the ≥85 years age group). Multivariate analyses showed three significant variations between the 65-74 years age group and the reference group (quinolones: odds ratio [OR] 1.17 [95% CI 1.05, 1.29]; tetracyclines: OR 1.58 [95% CI 1.26, 1.98]; aminoglycosides: OR 0.81 [95% CI 0.70, 0.93]). The number of significant variations increased to seven and eight in the 75-84 and ≥85 years age groups, respectively. A lower likelihood for PDD > DDD was observed in the 65-74 years age group for three parenteral antimicrobials (amoxicillin/clavulanic acid, gentamicin and vancomycin). This was reiterated in the older age groups (75-84 and ≥85 years), where piperacillin/tazobactam, meropenem and oral ciprofloxacin also showed a lower likelihood for PDD > DDD. CONCLUSIONS: Despite the methodology not being dedicated to elderly patients, the study identified elevated use of antimicrobial agents that are associated with serious adverse effects or a narrow therapeutic index as a target for quality of care improvement in elderly patients.

European Surveillance of Antimicrobial Consumption (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), penicillinase-resistant penicillins (PRP) and combinations with ß-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.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient cephalosporin use in Europe (1997-2009).

BACKGROUND: Data on 13 years of outpatient cephalosporin 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), and analysed in detail. METHODS: For the period 1997-2009, data on outpatient use of systemic cephalosporins 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 cephalosporin use in 33 European countries, we distinguished between first-generation (J01DB), second-generation (J01DC), third-generation (J01DD) and fourth-generation (J01DE) cephalosporins. RESULTS: Total outpatient cephalosporin use in 2009 varied from 8.7 DID in Greece to 0.03 DID in Denmark. In general, use was higher in Southern and Eastern European countries than in Northern European countries. Total outpatient cephalosporin use increased over time by 0.364 (SD 0.473) DID between 1997 and 2009. Cephalosporin use increased for half of the countries. Low-consuming Northern European countries and the UK further decreased their use. Second-generation cephalosporins increased by >20% in seven countries (mainly cefuroxime), coinciding with a decrease in first-generation cephalosporins. Substantial parenteral use of third-generation substances (mainly ceftriaxone) was observed in France, Italy and the Russian Federation. CONCLUSIONS: Since 1997, the use of the older (narrow-spectrum) cephalosporins decreased in favour of the newer (i.e. broad-spectrum) cephalosporins in most countries. Extreme variations between European countries in cephalosporin use over time suggest that they are to a large extent inappropriately used.

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.

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 first-generation 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.

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.

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-, intermediate- and 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 long-acting 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.

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 ß-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.