Antibiotikaverbrauch und Resistenzentwicklung in der Chirurgie

Zusammenfassung

Hintergrund: Antibiotikaresistenzen nehmen weltweit zu. Ziel: Longitudinale Analyse des Einflusses der Antibiotika-Anwendungsdichte auf die Resistenzentwicklung in der Chirurgie. Material/Methoden: Über 5 Jahre wurden die Erregerhäufigkeit und die Resistenzrate von Isolaten von Patienten der chirurgischen Normalstationen und der Intensivstation eines Universitätsklinikums untersucht. Die Resistenzraten wurden mit der Antibiotika-Anwendungsdichte korreliert, berechnet aus dem Antibiotikaverbrauch (in DDD) und der Anzahl der Patiententage. Ergebnisse: Auf beiden Stationen wurden am häufigsten Enterobacteriaceae und Enterokokken angezüchtet. Bei den Enterobacteriaceae überwogen E. coli, P. mirabilis, Klebsiella und Enterobacter. Bei den Enterokokken dominierte auf der Normalstation E. faecalis, auf der Intensivstation E. faecium. Als dritthäufigste Erregergruppe wurden auf der Normalstation Anaerobier und auf der Intensivstation Candida spp. isoliert. Von 2007–2011 kam es auf den Normalstationen zu einem Anstieg der Ciprofloxacin-Resistenz bei P. mirabilis (r = 0,87; p = 0,054) sowie der von Imipenem (r = 0,86; p = 0,06) und Piperacillin (r = 0,81; p = 0,09) bei P. aeruginosa. Auf der Intensivstation stieg die Resistenzrate von Imipenem bei P. aeruginosa (r = 0,88; p = 0,049) und die Ciprofloxacin-Resistenzrate (r = 0,65; p = 0,23). Bedingt durch den zunehmenden Verbrauch von Ciprofloxacin und Meropenem stieg die Antibiotika-Anwendungsdichte auf den Normalstationen (r = 0,94; p = 0,02). Auf der Intensivstation blieb der Gesamtverbrauch der Antibiotika in etwa gleich, obwohl der Verbrauch von Meropenem zunahm (r = 0,9; p = 0,035). Die Antibiotika-Anwendungsdichten waren auf der Intensivstation 3-mal so hoch wie auf der Normalstation. Auf der Normalstation korrelierte die Anwendungsdichte von Ciprofloxacin mit der Ciprofloxacin-Resistenzrate von P. mirabilis. Auf der Intensivstation wurde ein Zusammenhang zwischen dem Verbrauch von Ceftazidim und der Cefotaxim-Resistenzrate in der CES-Gruppe nachgewiesen. Bei P. aeruginosa korrelierten Piperacillin-Resistenzrate und -Verbrauch. Schlussfolgerungen: Der hohe Verbrauch von Fluorchinolonen und Carbapenemen geht mit einer Zunahme von Resistenzen einher. Die Qualität des Hygienemanagements und der mikrobiologischen Diagnostik beeinflusst die Resistenzraten. Der verstärkte Einsatz von Carbapenemen sollte auf beiden Stationen überdacht werden, um einer weiteren Verbreitung resistenter Erreger zu begegnen.

Abstract

Background: Antibiotic resistence is increasing worldwide. Aim: A longitudinal analysis of the influence of the density of antibiotic use on the development of resistance in surgical units was undertaken. Material and Methods: Over five years the incidence of pathogens and the resistance rates of isolates from patients of normal surgical units and those of a surgical ICU at a university hospital were examined. The resistence rates were correlated with the density of antibiotic use – calculated from the antibiotic consumption (in DDD) and the number of patient-days. Results: At both units, Enterobacteriaceae and Enterococci were mostly cultured. Among the Enterobacteriaceae, E. coli, Klebsiella spp., Proteus mirabilis and Enterobacter predominated. In the group of Enterococci, E. faecalis predominated at wards whereas at ICU E. faecium was the most frequent. Anaerobes ranked third at normal wards and Candida spp. at ICU. From 2007 to 2011, there was an increasing resistance against ciprofloxacin in P. mirabilis (r = 0.87; p = 0.054) and against imipenem (r = 0.86; p = 0.06) and piperacillin (r = 0.81; p = 0.09) in P. aeruginosa at normal wards. At ICU, the resistance rates of imipenem in P. aeruginosa rose (r = 0.88; p = 0.049). Resistance against ciprofloxacin in E. coli increased (r = 0.65; p = 0.23). Due to the increasing use of ciprofloxacin and meropenem at normal wards, the density of antibiotic usage rose 1.4 %/year (r = 0.94; p = 0.02). Despite the increase of meropenem use at ICU (r = 0.9; p = 0.035), the total antibiotic uptake rate remained almost constant. The antibiotic usage density was 3-fold higher at ICU than at normal wards. At normal wards, the ciprofloxacin usage correlated with the rate of resistance against ciprofloxacin in P. mirabilis P. m. At ICU, an association was detected between the uptake rate of ceftazidime and the rate of resistance against cefotaxime in the CES group. In P. aeruginosa, the use of piperacillin and the rate of resistance against piperacillin correlated. Conclusion: The high uptake rates of fluoroquinolones and carbapenems were accompanied by increases in resistances. The resistance rates are influenced by hygiene management and microbiological diagnostics. The extensive use of carbapenems should be reassessed on both units to counter further development of antibiotic resistance.

Schlüsselwörter

Antibiotika-Anwendungsdichte - Resistenzrate - Enterokokken - Enterobacteriaceae - Pseudomonas - MRSA

Key words

antibiotic consumption - resistance rate - Enterococcus species - Enterobacteriaceae - Pseudomonas - MRSA

• Literatur

• 1 Wener KM, Schechner V, Gold HS et al. Treatment with fluoroquinolones or with beta-lactam-beta-lactamase inhibitor combinations is a risk factor for isolation of extended-spectrum-beta-lactamase-producing Klebsiella species in hospitalized patients. Antimicrob Agents Chemother 2010; 54: 2010-2016
• 2 Hagel S, Stallmach A, Keller P et al. [Multiresistant Organisms]. Zentralbl Chir 2013; Jul 3 [Epub ahead of print]
• 3 Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen. Modul ITS-KISS, Referenzdaten, Berechnungszeitraum Januar 2006 bis Dezember 2010 (22.04.2013). Im Internet: http://www.nrz-hygiene.de Stand: 18.05.2013
• 4 Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339: 520-532
• 5 Klein E, Smith DL, Laxminarayan R. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999–2005. Emerg Infect Dis 2007; 13: 1840-1846
• 6 European Centre for Disease Prevention and Control. Antimicrobiol resistance interactive database (EARS net). Im Internet: http://www.ecdc.europa.eu/en/activities/surveillance/ears-net/about_ears-net/pages/about_network.aspx Stand: 05.01.2013
• 7 European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2009. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Im Internet: http://www.ecdc.europa.eu Stand: 05.01.2013
• 8 Vandenesch F, Naimi T, Enright MC et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 2003; 9: 978-984
• 9 Fridkin SK, Hageman J, McDougal LK et al. Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997–2001. Clin Infect Dis 2003; 36: 429-439
• 10 Protonotariou E, Dimitroulia E, Pournaras S et al. Trends in antimicrobial resistance of clinical isolates of Enterococcus faecalis and Enterococcus faecium in Greece between 2002 and 2007. J Hosp Infect 2010; 75: 225-227
• 11 Streit JM, Jones RN, Sader HS et al. Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents 2004; 24: 111-118
• 12 Wisplinghoff H, Bischoff T, Tallent SM et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39: 309-317
• 13 Canton R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol 2006; 9: 466-475
• 14 Decre D, Burghoffer B, Gautier V et al. Outbreak of multi-resistant Klebsiella oxytoca involving strains with extended-spectrum beta-lactamases and strains with extended-spectrum activity of the chromosomal beta-lactamase. J Antimicrob Chemother 2004; 54: 881-888
• 15 Schwaber MJ, Navon-Venezia S, Schwartz D et al. High levels of antimicrobial coresistance among extended-spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2005; 49: 2137-2139
• 16 Talbot GH, Bradley J, Edwards jr. JE et al. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 2006; 42: 657-668
• 17 National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32: 470-485
• 18 Weber A, Schneider C, Grill E et al. [Interventions by clinical pharmacists on surgical wards – impact on antibiotic therapy]. Zentralbl Chir 2011; 136: 66-73
• 19 Austin DJ, Kristinsson KG, Anderson RM. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci U S A 1999; 96: 1152-1156
• 20 Fridkin SK, Steward CD, Edwards JR et al. Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals. Clin Infect Dis 1999; 29: 245-252
• 21 CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Informational Supplement. CLSI document M100-S. Wyne, PA: Clinical and Laborytory Standards Institute; 2007.  – 2011
• 22 CLSI. Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data; Approved Guideline-Third Edition. CLSI document M39-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2009
• 23 Meyer E, Jonas D, Schwab F et al. [SARI: surveillance of antibiotic use and bacterial resistance in German intensive care units. Correlation between antibiotic use and the emergence of resistance]. Bundesgesundheitsbl 2004; 47: 345-351
• 24 Robert Koch-Institut. ARS (08.01.2013). Im Internet: https://ars.rki.de Stand: 16.01.2013
• 25 Meyer E, Gastmeier P. [Surveillance of antibiotic use and resistance]. Anasthesiol Intensivmed Notfallmed Schmerzther 2007; 42: 116-120
• 26 Meyer E, Schroeren-Boersch B, Schwab F et al. Quality assurance in intensive care medicine. SARI-surveillance on antibiotic use and bacterial resistance in intensive care units. Anaesthesist 2004; 53: 427-433
• 27 Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut (RKI). Hygienemaßnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stäbchen. Bundesgesundheitsbl 2012; 55: 1311-1354
• 28 Jacoby TS, Kuchenbecker RS, dos Santos RP et al. Impact of hospital-wide infection rate, invasive procedures use and antimicrobial consumption on bacterial resistance inside an intensive care unit. J Hosp Infect 2010; 75: 23-27
• 29 Weiss G, Tammer I, Wolff S. [Antibiotic resistance: development in surgical intensive care]. Zentralbl Chir 2011; 136: 143-151
• 30 Pieracci FM, Barie PS. Intra-abdominal infections. Curr Opin Crit Care 2007; 13: 440-449
• 31 Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., Infektiologie Freiburg. GERMAP 2010. Antibiotika-Resistenz und -Verbrauch. Bericht über den Antibiotikaverbrauch und die Verbreitung von Antibiotika-resistenzen in der Human- und Veterinärmedizin in Deutschland. Rheinbach: Antiinfectives Intelligence Gesellschaft für klinisch-mikrobiologische Forschung und Kommunikation mbH; 2011
• 32 Swenson BR, Metzger R, Hedrick TL et al. Choosing antibiotics for intra-abdominal infections: what do we mean by “high risk”?. Surg Infect (Larchmt) 2009; 10: 29-39
• 33 Bernhardt H, Wellmer A, Zimmermann K et al. [Growth of Candida albicans in normal and altered faecal flora in the model of continuous flow culture]. Mycoses 1995; 38: 265-270
• 34 Charles PE, Dalle F, Aube H et al. Candida spp. colonization significance in critically ill medical patients: a prospective study. Intensive Care Med 2005; 31: 393-400
• 35 Nett J, Andes D. Candida albicans biofilm development, modeling a host-pathogen interaction. Curr Opin Microbiol 2006; 9: 340-345
• 36 Leon C, Ruiz-Santana S, Saavedra P et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med 2009; 37: 1624-1633
• 37 Ibanez-Nolla J, Nolla-Salas M, Leon MA et al. Early diagnosis of candidiasis in non-neutropenic critically ill patients. J Infect 2004; 48: 181-192
• 38 Carmeli Y, Troillet N, Eliopoulos GM et al. Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999; 43: 1379-1382
• 39 Livermore DM. Current epidemiology and growing resistance of gram-negative pathogens. Korean J Intern Med 2012; 27: 128-142
• 40 Kaase M. Nachweis von Carbapenemasen im Jahr 2010 – Bericht des NRZ für gramnegative Krankenhauserreger. Epidemiologisches Bulletin 2011; 32: 301-307
• 41 Arndt S, Lauf H, Weiss G et al. [Spectrum of microbial colonisation and resistance of a surgical ICU in a systematic comparison of the 10-year time period 1996–2005 using routine microbiological testing]. Zentralbl Chir 2011; 136: 152-158
• 42 Kern WV, de With K. [Rational antibiotic prescribing. Challenges and successes]. Bundesgesundheitsbl 2012; 55: 1418-1426
• 43 Meyer E, Schwab F, Schroeren-Boersch B et al. Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008. Crit Care 2010; 14: R113
• 44 Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen (SARI). Daten zum Verbrauch der chirurgischen Intensivstationen. Im Internet: http://www.antibiotika-sari.de Stand: 28.09.2013
• 45 Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., Infektiologie Freiburg Hrsg. GERMAP 2008. Antibiotika-Resistenz und -Verbrauch. Bericht über den Antibiotikaverbrauch und die Verbreitung von Antibiotikaresistenzen in der Human- und Veterinärmedizin in Deutschland. Rheinbach: Antiinfectives Intelligence Gesellschaft für klinisch-mikrobiologische Forschung und Kommunikation mbH; 2008
• 46 Courcol RJ, Pinkas M, Martin GR. A seven year survey of antibiotic susceptibility and its relationship with usage. J Antimicrob Chemother 1989; 23: 441-451
• 47 MacDougall C, Powell JP, Johnson CK et al. Hospital and community fluoroquinolone use and resistance in Staphylococcus aureus and Escherichia coli in 17 US hospitals. Clin Infect Dis 2005; 41: 435-440
• 48 Lai CC, Wang CY, Chu CC et al. Correlation between antibiotic consumption and resistance of Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. J Antimicrob Chemother 2011; 66: 1374-1382
• 49 Cohen AE, Lautenbach E, Morales KH et al. Fluoroquinolone-resistant Escherichia coli in the long-term care setting. Am J Med 2006; 119: 958-963
• 50 Vellinga A, Murphy AW, Hanahoe B et al. A multilevel analysis of trimethoprim and ciprofloxacin prescribing and resistance of uropathogenic Escherichia coli in general practice. J Antimicrob Chemother 2010; 65: 1514-1520
• 51 Arason VA, Sigurdsson JA, Erlendsdottir H et al. The role of antimicrobial use in the epidemiology of resistant pneumococci: A 10-year follow up. Microb Drug Resist 2006; 12: 169-176
• 52 Nissinen A, Leinonen M, Huovinen P et al. Antimicrobial resistance of Streptococcus pneumoniae in Finland, 1987–1990. Clin Infect Dis 1995; 20: 1275-1280
• 53 Theuretzbacher U. Beta-Lactamasen und Beta-Lactamase-Inhibitoren. CTJ 1998; 4: 136-142
• 54 Choi SH, Lee JE, Park SJ et al. Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC beta-lactamase: Implications for antibiotic use. Antimicrob Agents Chemother 2008; 52: 995-1000
• 55 Gatermann S. Erkennung von bakteriellen Resistenzmechanismen in der täglichen Diagnostik. Mikrobiologe 2007; 17: 181-195
• 56 Strateva T, Yordanov D. Pseudomonas aeruginosa – a phenomenon of bacterial resistance. J Med Microbiol 2009; 58: 1133-1148
• 57 Shlaes DM, Gerding DN, John jr. JF et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Clin Infect Dis 1997; 25: 584-599