Arno Muller

Danish Integrated Antimicrobial Resistance Monitoring and Research Program

This program has led to changes in the use of antimicrobial agents in Denmark and other countries.

Relationship between Spread of Methicillin-Resistant Staphylococcus aureus and Antimicrobial Use in a French University Hospital

The objective of our study was to determine whether antibiotic pressure in the units of a teaching hospital affects the acquisition of methicillin-resistant Staphylococcus aureus (MRSA), independently of the other collective risk factors previously shown to be involved (MRSA colonization pressure, type of hospitalization unit, and care workload). The average incidence of acquisition of MRSA during the 1-year study period was 0.31 cases per 1000 days of hospitalization, and the use of ineffective antimicrobials reached 504.54 daily defined doses (DDDs) per 1000 days of hospitalization. Univariate analysis showed that acquisition of MRSA was significantly correlated with the use of all antimicrobials, as well as correlated with the use of each class of antimicrobial and with colonization pressure. Multivariate analysis with a Poisson regression model showed that the use of antimicrobials was associated with the incidence of acquisition of MRSA, independently of the other variables studied, but it did not allow us to determine the hierarchy of the different antimicrobial classes with respect to the effect.

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 β-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.

European Surveillance of Antibiotic Consumption (ESAC) point prevalence survey 2008: paediatric antimicrobial prescribing in 32 hospitals of 21 European countries.

BACKGROUND Antimicrobials are the most common medicines prescribed to children, but very little is known about patterns of hospital paediatric antimicrobial prescribing. This study aimed at describing paediatric antimicrobial prescribing in European hospitals to identify targets for quality improvement. METHODS The European Surveillance of Antibiotic Consumption (ESAC) project (www.esac.ua.ac.be) collected data during 2 calendar weeks between May and June 2008 in 32 hospitals of 21 European countries with paediatric departments, using a standardized method. The ESAC point prevalence survey included all inpatient beds and identified all patients who were receiving systemic antimicrobials on the day of the survey or had received antimicrobial surgical prophylaxis on the previous day. RESULTS Of 1799 children, 583 (32%) received one or more antimicrobials (range 17%-100%). The indications were therapeutic in 71%, prophylactic in 26% and both indications in 3% of patients. The parenteral route was used in 82% of therapeutic indications and in 63% of prophylactic indications. Third-generation cephalosporins were the most prescribed antimicrobials for therapeutic indications (18%). A high proportion of treated children received antimicrobial combinations (37%). The most commonly treated diagnosis site was the respiratory tract for both therapeutic use (30%) and prophylaxis (25%). The duration of surgical prophylaxis was >1 day in 67%. CONCLUSIONS Targets identified for quality improvement of antimicrobial use in children included excessive use of antimicrobial combinations and a high proportion of parenteral antimicrobials, both of which require further investigation. Surgical prophylaxis for >1 day should also be curbed in order to achieve quality improvement.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient parenteral antibiotic treatment in Europe

OBJECTIVES To assess the proportion of parenteral treatment of the total outpatient antibiotic use in Europe, and to identify the antibiotic groups and individual antibiotics most commonly administered in this way. METHODS Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomic therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of antibacterials for systemic use (ATC J01), aggregated at the level of the active substance and expressed in DDD per 1000 inhabitants per day (DID; WHO version 2007), were extracted for 2006 by route of administration and by country. Parenteral use was expressed as a percentage of the total outpatient use in DID. RESULTS In 20 European countries, the total outpatient antibiotic use ranged from 27.91 DID in France to 9.58 DID in Russia. The proportion of outpatient parenteral antibiotic treatment ranged from 6.75% in Russia to 0.001% in Iceland. The three most commonly used antibiotic groups for parenteral treatment in Europe were the cephalosporins (J01D; 44.58%), the aminoglycosides (J01G; 25.27%) and the penicillins (J01C; 17.78%). Four antibiotics [gentamicin (J01GB03) 18.53%; ceftriaxone (J01DD04) 17.85%; cefazolin (J01DB04) 13.16%; and lincomycin (J01FF02) 5.47%] represented more than half of the use. CONCLUSIONS In all 20 European countries studied together, 2.04% of outpatient antibiotics were used for parenteral treatment. However, as for the total outpatient antibiotic use and the use of different antibiotic groups and antibiotics, there is a striking variation in the proportions of parenteral antibiotic use in Europe. More in-depth data on outpatient antibiotic use are needed to explain this variation.

Use of intranasal mupirocin to prevent methicillin-resistant Staphylococcus aureus infection in intensive care units

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) causes severe morbidity and mortality in intensive care units (ICUs) worldwide. The purpose of this study was to determine whether intranasal mupirocin prophylaxis is useful to prevent ICU-acquired infections with MRSA.Materials and methodsWe conducted a 4-year observational retrospective study in a 15-bed adult medical ICU. During the first 2-year period mupirocin ointment was included in the MRSA control programme; during the second, mupirocin was not used. The main endpoint was the number of endogenous ICU-acquired infections with MRSA.ResultsThe number of endogenous acquired infections was significantly higher during the second period than during the first (11 versus 1; P = 0.02), although there was no significant difference in the total number of patients infected with MRSA between the two periods. We also observed that nasal MRSA decolonisation was significantly higher in the mupirocin period than in mupirocin-free period (P = 0.002).ConclusionOur findings suggest that intranasal mupirocin can prevent endogenous acquired MRSA infection in an ICU. Further double-blind, randomised, placebo-controlled studies are needed to demonstrate its cost-effectiveness and its impact on resistance.

Relationship between Antibiotic Use and Incidence of MexXY-OprM Overproducers among Clinical Isolates of Pseudomonas aeruginosa

ABSTRACT In a university hospital, time-series analysis revealed a significant relationship between antibiotic (aminoglycoside, fluoroquinolone, and cefepime) use and incidence of MexXY-OprM-overproducing Pseudomonas aeruginosa. In vitro experiments confirm that such mutants were readily selected from both PAO1 and clinical strains when grown in the presence of these antibiotics.

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

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.

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 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.