Use of 27 parenteral antimicrobial agents in north of France hospitals

Méthodes Nous avons collecté de 1995 à 2001 la consommation en doses définies journalières (DDJ) et les journées d'hospitalisation (JH) d'hôpitaux volontaires. La surveillance a porté sur : 23 antibiotiques (amikacine, aztréonam, céfépime, céfotaxime, cefpirome, ceftazidime, ceftriaxone, ciprofloxacine, fosfomycine, acide fusidique, lévofloxacine, imipéneme, isépamicine, ofloxacine, pefloxacine, pipéracilline (± tazobactam, quinupristine/dalfopristine, sulbactam, teicoplanine, ticarcillin ± acide clavulanique, vancomycine) et quatre antifungiques (amphotéricine B lipidiques, caspofungine, fluconazole). Les données sont exprimées en DDJ/1000 JH. Résultats Cinquante-huit hôpitaux ont participé en 2001. La consommation était plus élevée dans les hôpitaux de plus de > 400 lits de MCO (214,8 ± 116 DDJ/JH) que dans ceux entre 200 et 400 (134,2 ± 39 DDJ/JH) ou de moins de 200 (104,3 ± 74 DDJ/JH) p  = 0,0005. Des variations importantes étaient notées chez des hôpitaux de taille similaire. Quinze hôpitaux, représentant 1/3 des lits de MCO de la région ont fourni des données pendant sept ans. La consommation a augmenté de 23 % (119,9 à 147,2 DDJ/JH). L'essentiel de l'augmentation portait sur les fluoroquinolones (plus 72 %; 17,8 vs 30,6, p  = 0,0068), la ceftriaxone (plus 90 %; 14,4 vs 27,4; p < 0,0001) et le céfépime (plus 264 %; 3,4 vs. 12,2 %, p  = 0,028). La seule classe en diminution était les aminosides (moins 48 %; 27,7 vs. 14,5; p  = 0,003). Conclusion Cela confirme le niveau élevé de consommation antibiotique dans les hôpitaux français. Keywords Antimicrobial use Network Good use of antibiotics Mots clés Antibiotiques Réseau Bon usage des antibiotiques 1 Introduction Antibiotic (AB) use has been linked to the steady increase in drug resistant microorganisms throughout the world [1] . The use of AB in France is among the highest in Europe [2] . Hospital consumption is thought to represent approximately 10% of the overall human consumption but precise data are unavailable. The administrative region “Nord – Pas de Calais” includes 139 public and private hospitals serving 4 million inhabitants, i.e. approximately 7% of the French population. The ARECLIN group, a network of infectious diseases physicians, infection control physicians, and hospital pharmacist conducts nosocomial infection surveys, organizes infection control meetings, and trains infection control professionals. In 1997, the ARECLIN issued guidelines on the use of AB in hospitals. A monitoring of selected AB use was decided to define prescribing patterns and to allow comparisons between hospitals. This study presents the consumption figures from 1995 to 2001. 2 Materials and methods The consumption project began in 1998. Volunteer hospitals were recruited through their representative in the ARECLIN group. A standardized data collection sheet was filled in by all participating hospitals. Annual data were collected retrospectively from 1995 and prospectively from 1998 to 2001. Hospitals that merged during the study were treated as a single group for the entire study. Among the 139 hospitals, 50 were public, 32 non-profit, and 57 private. Data collected included the annual consumption of 23 intravenous AB: amikacin, aztreonam, cefepim, cefotaxime, cefpirome, ceftazidime, ceftriaxone, ciprofloxacin, fosfomycin, fusidic acid, imipenem, isepamicin, levofloxacin, ofloxacin, pefloxacin, piperacillin, quinupristin/dalfopristin, sulbactam, tazocillin, teicoplanin, ticarcillin, ticarcillin-clavulanic acid, vancomycin and four intravenous antifungals: amphotericin B lipid formulations, caspofungin and fluconazole. New drugs were added as they became available. Number of beds, hospitalization days (HD), and admissions were recorded annually. Consumption data were expressed using WHO defined daily doses (DDD). In this article, the 2005 version was used [3] . In hospitals including acute and long term care sections, we used only the acute care data. Each year, feedback, in the form of personalized charts and graphs, was sent to each participating center. They included an analysis of hospital consumption compared to the whole region and to similar sized hospitals. Data were collected on a Microsoft Excel spreadsheet and analyzed with Statview 4.57 (Abacus Concept, Berkeley, CA, USA). Antimicrobial use was expressed as a number of DDD per 1000 HD (DDD/HD). Linear regression was used to assess the change in AB use in the study period. The Kruskall–Wallis test was used to assess differences in AB use according to hospital size. 3 Results Among the 139 hospitals in the region, 62 (44.6%) participated at least 1 year and 15 sent complete data from 1995 to 2001. 3.1 2001 survey In 2001, 58 hospitals participated in the study. They included 65% of those with more than 100 acute care beds. The total number of DDD of the 23 surveyed IV antibacterials reached 538,622 DDD. Antifungal use was 30,724 DDD. Corresponding DDD/HD were 123 for antibacterials and 5.16 for antifungals. Table 1 shows the 2001 consumption of surveyed IV drugs among 58 hospitals expressed as ddd/HD. AB consumption was higher in hospitals with > 400 acute care beds (214.8 ± 116 DDD/HD) than in 200–400 beds hospitals (134.2 ± 39 DDD/HD) or < 200 beds hospitals (104.3 ± 74 DDD/HD), and the differences were highly significant P  = 0.0005. 3.2 Seven-year survey Among the 15 hospitals for which complete data were available, three were hospitals with over 400 acute care beds, including the only university hospital of the region, five had 200–400 beds, and seven less than 200 beds. These 15 hospitals grouped 5000 acute care beds (one-third of the acute care beds in the region). Antibacterial use increased 23% from 119.9 to 147.2 DDD per 1000 HD. Table 2 shows the evolution of AB consumption in the 15 hospitals participating in the 7-year survey. Wide variations were observed with a significant reduction in the use of amikacin, pefloxacin, fusidic acid and the following beta-lactams: imipenem, piperacillin, ticarcillin/clavulanic acid, sulbactam, aztreonam, and cefpirome. A significant increase was noted for ofloxacin, ciprofloxacin, vancomycin, and, among beta-lactams, ceftriaxone, cefepime, piperacillin/tazobactam, and ticarcillin. Analysis by AB class showed an increase of fluoroquinolones (plus 72%; 17.8 vs. 30.6, P  = 0.0068), cephalosporins (plus 63%, 34.2 vs. 55.6, P  = 0.0003), glycopeptides ( P  = 0.0069), and a decrease of aminoglycosides (minus 48%; 27.7 vs. 14.5; P  = 0.003). 4 Discussion The main objective of the study was to provide epidemiological data to better understand the AB use pattern in our hospitals. We found a wide variation in AB use among 58 hospitals of the same region. These variations were apparent between hospitals of different sizes but also among similar sized hospitals. As expected, the level of use we observed was high. In 2001, it reached 123 DDD/HD for 23 IV AB compared to a similar sized area, Denmark, which recently published a 2001 hospital consumption of all AB of 448 DDD/HD [4] . We can only draw direct comparisons for a few classes. Cephalosporins use in Denmark (combining oral and IV drugs) was 55.9 compared to 48.5 in our study (combining only ceftriaxone, cefotaxime, ceftazidime, cefepime, and cefpirome). Glycopeptides use in our study was 16.2 DDD/HD compared to 3.1 in Denmark. Carbapenems use was 4.6 in our study compared to 3.9 in Denmark. Monobactams 0.17 vs. 0.1 and fusidic acid 0.37 vs. 0.19 also showed a higher consumption. Drug consumption data from 14 hospitals in the USA, was published in 1999. The daily doses used in this study differed from the ones proposed by the WHO [5] . When adjusting their data to the 2005 WHO DDD, mean consumption of ceftriaxone was 29.4 compared to our 22.3, vancomycin 9.3 compared to our 8.7, and ceftazidime 6.2 to 4.2. Part of this consumption can be explained by the higher prevalence of resistant microorganisms, particularly methicillin resistant Staphylococcus aureus which is highly prevalent in French hospitals [6] . However, French data from 49 southwestern France hospitals [7] does not support this hypothesis. Glycopeptides is the only class which can be directly compared and we observed a much higher consumption (16.2 vs. 5.3) than in the above mentioned study. This might reflect differences in participating hospitals, or regional variations in prescribing choices. Almost all the increase in consumption from 1995 to 2001 is due to an increasing use of ceftriaxone and fluoroquinolones. The only recently marketed fluoroquinolone, levofloxacin, represented only a small part of the consumption (1 DDD/HD in 2001). Among the drugs with the highest increase, ceftriaxone and ofloxacin were in their last year before the arrival of generic drugs. This might have resulted in a higher marketing pressure. However, in the late 90s, French therapeutic guidelines for severe pneumonia or meningitis highlighted the risk of penicillin non-susceptible organisms [8,9] and promoted the use of more broad-spectrum agents, probably resulting in an increase of other drug prescription for empirical therapy. Data on the use of aminoglycosides is incomplete as it only concerns amikacin and isepamicin. The decrease seems however to be quite significant. It can be explained by the issuing of national and regional guidelines emphasizing the use of short term (3–5 days), once daily, aminoglycoside dosing except for bacterial endocarditis. Larger hospitals (measured by number of acute care beds) use more IV AB than smaller ones. They probably dealt with more severely ill and/or more immunocompromised patients with more frequent and/or more severe infections. Among similarly sized hospitals, consumption also varied, probably reflecting different case mix and/or physician training. Our study has limitations. First, we only studied a limited number of IV antimicrobial agents. However, these parenteral agents are mostly broad-spectrum and are available only in hospitals; thus, we offer an accurate view of their consumption. Second, we only offer hospital wide data not broken by department or patient case mix. This limits our ability to interpret variations in AB use as patient severity and admission diagnosis might differ. Third, only a small sample of hospitals displayed complete data. However, these hospitals represent a high proportion of the largest hospitals in the region and we believe their data to be representative of prescription habits in our region. Overall, this study documents the high level of broad-spectrum AB use in French hospitals. Feedback to individual institution could help target hospital specific intervention strategies to control AB use. Acknowledgments Members of ARECLIN network: Berneron, C tamise, Calais - Bertrande, pol vauban, Valenciennes- Biet et Frimat; CH Lens - Bocket, C. Paré, Béthune - Bonenfant; CH Armentières - Boury et Begon; St Philibert Lomme- Boutemy, C lille sud, Lesquin - Cailleux, pol st pol - Camus; HL Ayre/Lys - Carton; CH Boulogne - Chambrey; CH Montreuil - Chavatte; CHM Bercq - Claes; Pol Coudekerque Branche - Compagnon, C parc, Croix- Cuingnet; CH Le Quesnoy - Cuvelier, C Bon Secours, Arras - Debrumetz; CH Le Cateau - Debenest, Pol BoisBernard - Degrendel, C chir Calais - Delemer; Pol du Bois, Lille - Delette; CH Roubaix - Delobel et Odou; CH Dunkerke - Deneve, CH Hazebrouck - Depretere; CH St Omer - Deseine; CH Avesne - Desmarets; pol Auchel - Disset; Pol Grd Synthe - Dubois, St Vincent lille- Dupont; Pol Hénin Beaumont - Frys, croise laroche, Marcq - Gamot; CH Wattrelos - Gauthier; CH Felleries - Ghienne; CH St Pol - Gosselin; CH Cambrai - Gosselin; COL Lille - Gruson et Forestier; CH Arras - Guyot, C st anne, Lambres - Halliez et Deram; CH Douai - Hannoir, C st omer - Huguet, C cote d'opale boulogne - Jacquemin; CH Fourmies - Jombart; I Calot Bercq - Joron et Zawadski; CH Calais - Lebec et Floret; CH Béthune - Letard; CH St Amand - Loncle; CH Bapaume - Loreille; St Antoine Lille - Luyckx; CH Denain - Marcincal; CH Bailleul - Marel; CH Hesdin - Parlabene et De Zorzi; CH Maubeuge - Planckeel, C vilette, Dunkercke - Plateeuro; CH Seclin - Rouanet, C Bruay - Roussel; CH Tourcoing - Seguin, C St Marie, Cambrai - Schlemmer; Pol Artois Bethune - Slawinski; CH Somain - Thiery; C. Valenciennes - Triplet; Pol riaumont Liévin - Urbina; CH Valenciennes - Vertray; EPSM Henin Beaumont - Yilmaz et d'Haveloose; CHU de Lille. References [1] S.L. Bronzwaer O. Cars U. Buchholz S. Molstad W. Goettsch I.K. Veldhuijzen A European study on the relationship between antimicrobial use and antimicrobial resistance Emerg. Infect. Dis. 8 2002 278 282 [2] H. Goossens M. Ferech S.R. Vander M. Elseviers for the ESAC Project Group Outpatient antibiotic use in Europe and association with resistance: a cross-national database study Lancet 365 2005 579 587 [3] Collaborating WHO. Centre for Drug Statistics Methodology (2006), Oslo, http://www.whocc.no/atcddd/indexdatabase/. Cited 10 March 2006. [4] B. Muller-Pebody M. Muscat B. Pelle B.M. Klein C.T. Brandt D.L. Monnet Increase and change in pattern of hospital antimicrobial use, Denmark 1997–2001 J Antimicrob Chemother 54 2004 1122 1126 [5] P.C. Carling T. Fung J.S. Coldiron Parenteral antibiotic use in acute-care hospitals: a standardized analysis of fourteen institutions Clin. Infect. Dis. 29 1999 1189 1196 [6] M.T. Albertini C. Benoit L. Berardi Y. Berrouane A. Boisivon P. Cahen Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) and Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBLE) in Northern France: a five-year multicentre incidence study J. Hosp. Infect. 52 2002 107 113 [7] A.M. Rogues B. Placet-Thomazeau P. Parneix I. Vincent M.C. Ploy N. Marty Use of antibiotics in hospitals in south-western France J. Hosp. Infect. 58 2004 187 192 [8] Société de Pathologie Infectieuse de Langue Française 9e Conférence de Consensus en Thérapeutique Anti-Infectieuse. Les méningites purulentes communautaires Med. Mal. Infect. 26 1996 952 973 [9] Société de Pathologie Infectieuse de Langue Française Prise en charge des Infections respiratoires basses. Révision de la 4ème conférence de consensus de la SPILF Med. Mal. Infect. 30 2000 566 580