Determinants of outpatient antibiotic consumption in Europe: bacterial resistance and drug prescribers

This paper investigates socioeconomic determinants of outpatient antibiotic consumption in Europe. Comparable data on antibiotic use measured in the defined daily doses per 1000 inhabitants (DID) are currently provided by the ESAC project. Results from applied econometric estimations for panel data reveal a link between antibiotic use and the per capita income, the demographic structure of the population, the level of education and cultural aspects. Supply-side factors, such as the density of providers and their remuneration methods, are also considered. We provide the first estimate of the impact of bacterial resistance on consumption when the e?ect of other determinants is simultaneously taken into account.Antibiotic use, Cross-country variations, Bacterial resistance, Supply-induced demand

Socioeconomic determinants of outpatient antibiotic use in Europe

Objectives: Outpatient antibiotic consumption widely varies across Europe. The investigation of the causes of such variation may help to identify interventions that would improve the efficient use of antibiotics. The aim of this study was to assess the impact of socioeconomic determinants and the role played by information about bacterial resistance. Methods: Comparable data on systemically administered antibiotics and socioeconomic determinants in 17 European countries were available between 2000 and 2005. We estimated an ad hoc econometric model by means of a hybrid log-log functional form and random effects generalised least squares regressions. Lagged values and the instrumental variable method were applied to address endogeneity of bacterial resistance and infections. Bacterial resistance was measured by the rate of penicillin non-susceptible Streptococcus pneumoniae isolates (PNSP) and methicillin-resistant Staphylococcus aureus (MRSA). Results: The population income, demographic structure, density of general practitioners and their remuneration method appeared to be significant determinants of antibiotic consumption. Although countries with higher levels of bacterial resistance exhibited significantly higher levels of per capita antibiotic use, ceteris paribus, the responsiveness of antibiotic use to changes in bacterial resistance was relatively low (0.09-0.18). Conclusions: The study confirms that socioeconomic factors should be taken into account while explaining differences in outpatient antibiotic use across countries. The impact of supply-side factors and incentives attached to payment schemes for physicians need to be considered in government interventions to reduce inequalities and improve effectiveness in antibiotic utilisatio

The Belgian policy of funding antimicrobial stewardship in hospitals and trends of selected quality indicators for antimicrobial use, 1999-2010: a longitudinal study

Objectives: In order to improve antimicrobial (AM) use, a policy of providing technical and financial support to AM management teams (AMTs) was rolled out in all Belgian hospitals between 2002 and 2008. We aimed to analyse the association of this policy with AM use for the two indications accounting for the largest number of patients receiving AM: prophylaxis for major lower limb orthopaedic surgery and pneumonia. Design, setting, participants: We used patient-level data routinely collected in all Belgian acute care hospitals between 1999 and 2010. We modelled trends for selected quality indicators (QIs) using the year of AMT implementation in each hospital as the main 'change point', with fine-tuned case-mix adjustment. Of all admissions for lower limb orthopaedic surgery, and pneumonia between 1999 and 2010, 90% (325 094) and 95% (327 635), respectively, were found eligible for analyses. Outcomes: The surgery QI was defined as: cefazolin, dose in the expected range, and no use of other AM. For pneumonia, QIs were: ratio of oral/parenteral defined daily doses (DDD, O/P QI), and mean number of DDD minus penicillin, per 100 days of hospitalisation (DDD QI). Results: Between 1999 and 2010, the surgery QI improved from 59% to 71%, the O/P QI from 0.72 to 0.97, and the DDD QI from 96 to 64. Heterogeneity between hospitals was high. Overall, no association was found with the year of implementation of the AMT. Conclusions: Improvements have been observed but could not be related at the national level to the policy under study. However, these results cannot be extrapolated to other QIs for AM use in hospitals. Our findings do not question the need for AMT, nor the need for continuation of AMT funding. Several recommendations can be made in order to make the best of Belgium's unique political and financial commitments in that field

European surveillance of antimicrobial consumption (ESAC)

All 27 EU member states and another seven countries participate in the European Surveillance of Antimicrobial Consumption (ESAC) project. ESAC carried out three hospital point-prevalence surveys on antimicrobial use. Point-prevalence surveys linked antimicrobial use to indication and also assessed dosing using a standardized methodology for data collection and online data submission with feedback capability using a dedicated web-based tool. The objectives of the ESAC hospital point-prevalence surveys were to first determine the feasibility of a pan-European survey and identify targets for quality improvement. Hospitals were voluntarily selected by the lead national or hospital representatives for each country. The WHO Anatomical Therapeutic Chemical Classification of drugs was used for classification of antimicrobials. The three surveys were carried out during a maximum of 2 weeks in the second quarter of 2006, 2008 and 2009. Each department had to be surveyed in 1 day. All systemic antibacterials (J01), rifampicin (J04AB), oral vancomycin (A07AA) and oral/rectal metronidazole (P01AB) were the antimicrobials surveyed, including the prescribed regimen. The number of participating hospitals increased from 20 to 172 from 2006 to 2009. The patient demographics and indications for treatment were similar throughout the three point-prevalence surveys. 'Reason in notes' and 'surgical prophylaxis >24 hours' were also similar. Guideline compliance (51%) was only introduced in the 2009 point-prevalence survey, replacing 'sample for culture and sensitivity' (50%) of patients. The use of combination therapy, although exhibiting a wide range within each category, was related to hospital type, with teaching and tertiary hospitals having a significantly higher use of combination therapy (teaching : non-teaching hospitals [p < 0.0001]; and primary : tertiary hospitals [p < 0.0001]). Point-prevalence surveys are useful when time and resources do not allow for continuous surveillance. Repeated point-prevalence surveys within the same institution(s) can be used to monitor trends and effectiveness of antimicrobial-stewardship initiatives. Targets should be set as quality indicators for the individual hospital(s) and effectiveness of any intervention monitored through repeated point-prevalence surveys. Spin-off initiatives, such as the Antibiotic Resistance and Prescribing in European Children, and the European Centre for Disease Prevention and Control point-prevalence survey on healthcare-associated infections and antimicrobial use, will utilize adapted versions of WebPPS, the point-prevalence survey software developed by ESAC. WebPPS will also be made available for non-commercial use to third parties. Interest has been shown from three continents outside Europe, namely North America, Australia and Africa.peer-reviewe

In vivo and In vitro Interactions between Pseudomonas aeruginosa and Staphylococcus spp.

The significance of polymicrobial infections is increasingly being recognized especially in a biofilm context wherein multiple bacterial species—including both potential pathogens and members of the commensal flora—communicate, cooperate, and compete with each other. Two important bacterial pathogens that have developed a complex network of evasion, counter-inhibition, and subjugation in their battle for space and nutrients are Pseudomonas aeruginosa and Staphylococcus aureus. Their strain- and environment-specific interactions, for instance in the cystic fibrosis lung or in wound infections, show severe competition that is generally linked to worse patient outcomes. For instance, the extracellular factors secreted by P. aeruginosa have been shown to subjugate S. aureus to persist as small colony variants (SCVs). On the other hand, data also exist where S. aureus inhibits biofilm formation by P. aeruginosa but also protects the pathogen by inhibiting its phagocytosis. Interestingly, such interspecies interactions differ between the planktonic and biofilm phenotype, with the extracellular matrix components of the latter likely being a key, and largely underexplored, influence. This review attempts to understand the complex relationship between P. aeruginosa and Staphylococcus spp., focusing on S. aureus, that not only is interesting from the bacterial evolution point of view, but also has important consequences for our understanding of the disease pathogenesis for better patient management

Convergence of virulence and antimicrobial resistance in increasingly prevalent Escherichia coli ST131 papGII+ sublineages

Escherichia coli lineage ST131 is an important cause of urinary tract and bloodstream infections worldwide and is highly resistant to antimicrobials. Specific ST131 lineages carrying invasiveness-associated papGII pathogenicity islands (PAIs) were previously described, but it is unknown how invasiveness relates to the acquisition of antimicrobial resistance (AMR). In this study, we analysed 1638 ST131 genomes and found that papGII+ isolates carry significantly more AMR genes than papGII-negative isolates, suggesting a convergence of virulence and AMR. The prevalence of papGII+ isolates among human clinical ST131 isolates increased dramatically since 2005, accounting for half of the recent E. coli bloodstream isolates. Emerging papGII+ lineages within clade C2 were characterized by a chromosomally integrated blaCTX-M-15 and the loss and replacement of F2:A1:B- plasmids. Convergence of virulence and AMR is worrying, and further dissemination of papGII+ ST131 lineages may lead to a rise in severe and difficult-to-treat extraintestinal infections