Antibiotic Stewardship und Hygiene – 2 Seiten einer Medaille

Zusammenfassung

In der öffentlichen Wahrnehmung werden hohe Raten von multiresistenten Erregern in medizinischen Einrichtungen vor allem mit zwei Begriffen assoziiert: erstens „Krankenhaus“ und zweitens „Hygieneproblem“. Wahrscheinlich mindestens ebenso wichtig oder sogar wichtiger ist jedoch der Antibiotikaeinsatz im ambulanten und stationären Bereich. Antibiotika selektionieren multiresistente Erreger (MRE). Durch die Mikrobiomforschung werden wir diese Zusammenhänge in der Zukunft besser verstehen. Wahrscheinlich bieten sich dadurch auch neue Ansatzpunkte für die Prävention der Ausbreitung von multiresistenten Erregern. Die vorliegenden Daten unterstreichen die Notwendigkeit der engen Interaktion zwischen Krankenhaushygiene und einer rationalen Antiinfektiva-Verordnung (Antibiotic Stewardship).

Lange Zeit wurde versucht, die hohen Raten an multiresistenten Erregern (MRE) in medizinischen Einrichtungen durch immer strengere Hygienemaßnahmen zu bekämpfen. Aber mittlerweile ist klar: Mindestens ebenso wichtig ist der Antibiotikaeinsatz, denn Antibiotika selektionieren MRE. Dieser Beitrag erläutert die aktuelle Studienlage und unterstreicht: Nur durch Antibiotic Stewardship und Hygiene zusammen ist eine Reduktion der MRE zu erreichen.

Abstract

According to public awareness, high rates of multiresistant organisms in healthcare facilities are mainly associated with two terms: “Hospital” and “Infection control problem”. The use of antibiotics in ambulatory and hospital care is probable at least as important or even more important. Antibiotics lead to selection of multiresistant organisms. Microbiome research will lead to a better understanding of this relationship and may provide new measures for preventing the spread of multiresistant organisms. The available data underline the need of a close interaction between antibiotic stewardship and infection control.

Kernaussagen

• Im Krankenhaus sind Patienten häufiger gegenüber Antibiotika exponiert als gegenüber Patienten, die mit multiresistenten Erregern (MRE) kolonisiert sind.

• Die Anwendung von Antibiotika bei Patienten führt durch verschiedene Mechanismen zu einem signifikant erhöhten Risiko, dass die Patienten MRE erwerben bzw. diese bei ihnen nachzuweisen sind.

• Durch Antibiotika-Stewardship-Interventionen ist es möglich, die nosokomialen Erwerbsraten zu reduzieren.

• Der Zusammenhang zwischen Antibiotikaanwendung und Clostridium-difficile-Infektionen (CDI) ist eindeutig gegeben.

• Der Interventionseffekt von Antibiotic Stewardship (ABS) auf die nosokomialen CDI-Raten ist nachgewiesen.

• In den verschiedenen Interventionsstudien wurden unterschiedliche Stewardship-Methoden eingesetzt, sodass bisher noch unklar ist, welche ABS-Maßnahmen den größten Effekt haben.

• Es ist notwendig, auch im ambulanten Bereich die Anwendung von Antibiotika zu reduzieren.

• Das Konzept der Isolierung von Patienten mit MRE stammt aus einer Zeit, als die Präventionsmaßnahmen durch rationale Überlegungen begründet wurden.

• Die Evidenz für die Effektivität der Isolierungsmaßnahmen ist begrenzt und resultiert überwiegend aus Studien, bei denen verschiedene Präventionsmaßnahmen zugleich eingesetzt wurden.

• Die Mikrobiomforschung wird unser Wissen zur Entwicklung und Verbreitung von MRE in den kommenden Jahren mit Sicherheit deutlich erweitern.

Schlüsselwörter

Antibiotic Stewardship - Hygiene - multiresistente Erreger

Key words

antibiotic stewardship - infection control - multiresistant organisms

• Literatur

• 1 Hahn J, Gaida U, Hulverschmidt M. Hrsg. 125 Jahre Hygiene-Institute an Berliner Universitäten – Eine Festschrift. Berlin 2010.
• 2 Berger S. Bakterien in Krieg und Frieden – Eine Geschichte der medizinischen Bakteriologie in Deutschland 1890 – 1933. Göttingen: Wallstein; 2009
• 3 Kappstein I, Daschner FD. Potential inroads to reducing hospital-acquired staphylococcal infection and its cost. J Hosp Infect 1991; 19 (Suppl. B) 31-34
• 4 Witte B, Braulke C, Heuck D. et al. Analysis of nosocomial outbreaks with multiply and methicillin-resistant Staphylococcus aureus (MRSA) in Germany: implications for hospital hygiene. Infection 1994; 22 (Suppl. 02) S128-S134
• 5 Monnet D. Methicillin-resistant Staphylococcus aureus and its relationship to antimicrobial use: possible implications for control. Infect Control Hosp Epidemiol 1998; 19: 552-559
• 6 Tacconelli E, De Angelis G, Cataldo M. et al. Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J Antimicrob Chemother 2008; 61: 26-38
• 7 Huskins WC, Huckabee CM, OʼGrady NP. et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med 2011; 364: 1407-1418
• 8 Derde LP, Cooper BS, Goossens H. et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31-39
• 9 Lee AS, Cooper BS, Malhotra-Kumar S. et al. Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial. BMJ Open 2013; 3: e003126
• 10 Stewardson AJ, Sax H, Gayet-Ageron A. et al. Enhanced performance feedback and patient participation to improve hand hygiene compliance of health-care workers in the setting of established multimodal promotion: a single-centre, cluster randomised controlled trial. Lancet Infect Dis 2016; 16: 1345-1355
• 11 ESAC-Net. ECDC summary of the latest data on antibiotic consumption in the European Union, November 2015. Im Internet: http://ecdc.europa.eu/en/eaad/antibiotics-get-informed/antibiotics-resistance-consumption/Pages/data-reports.aspx Stand: 20.02.2017
• 12 Hamprecht A, Rohde AM, Behnke M. et al. Colonization with third-generation cephalosporin-resistant Enterobacteriaceae on hospital admission: prevalence and risk factors. J Antimicrob Chemother 2016; 71: 2957-2963
• 13 Pettigrew MM, Johnson JK, Harris AD. The human microbiota: novel targets for hospital-acquired infections and antibiotic resistance. Ann Epidemiol 2016; 26: 342-347
• 14 van der Waaij D, Berghuis JM, Lekkerkerk JE. Colonization resistance of the digestive tract of mice during systemic antibiotic treatment. J Hyg (Lond) 1972; 70: 605-610
• 15 Thijm HA, van der Waaij D. The effect of three frequently applied antibiotics on the colonization resistance of the digestive tract of mice. J Hyg (Lond) 1979; 82: 397-405
• 16 Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A 2011; 108 (Suppl. 01) 4554-4561
• 17 Hu Y, Yang X, Qin J. et al. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nat Commun 2013; 4: 2151
• 18 Zaborin A, Smith D, Garfield K. et al. Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness. MBio 2014; 5: e01361-14
• 19 Davey P, Brown E, Charani E. et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2013; (04) CD003543
• 20 Akpan MR, Ahmad R, Shebl NA. et al. A review of quality measures for assessing the impact of antimicrobial stewardship programs in hospitals. Antibiotics (Basel) 2016;
• 21 Lawes T, Lopez-Lozano JM, Nebot CA. et al. Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study. Lancet Inf Dis 2015; 15: 1438-1449
• 22 Saizy-Callaert S, Causse R, Furhman C. et al. Impact of a multidisciplinary approach to the control of antibiotic prescription in a general hospital. J Hosp Infect 2003; 53: 177-182
• 23 Martin C, Ofotokun I, Rapp R. et al. Results of an antimicrobial control program at a university hospital. Am J Health Syst Pharm 2005; 62: 732-738
• 24 Fowler S, Webber A, Cooper BS. et al. Successful use of feedback to improve antibiotic prescribing and reduce Clostridium difficile infection: a controlled interrupted time series. J Antimicrob Chemother 2007; 59: 990-995
• 25 Altunsoy A, Aypak C, Azap A. et al. The impact of a nationwide antibiotic restriction program on antibiotic usage and resistance against nosocomial pathogens in Turkey. Int J Med Sci 2011; 8: 339-344
• 26 Niwa T, Shinoda Y, Suzuki A. et al. Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital. Int J Clin Pract 2012; 66: 999-1008
• 27 Dancer SJ, Kirkpatrick P, Corcoran DS. et al. Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum β-lactamase-producing coliforms and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 2013; 41: 137-142
• 28 Aldeyab MA, Scott MG, Kearney MP. et al. Impact of an enhanced antibiotic stewardship on reducing methicillin-resistant Staphylococcus aureus in primary and secondary healthcare settings. Epidemiol Infect 2014; 142: 494-500
• 29 Richardson LP, Wiseman SW, Malani PN. et al. Effectiveness of a vancomycin restriction policy in changing the prescribing patterns of house staff. Microb Drug Resist 2000; 6: 327-330
• 30 Carling P, Fung T, Killion A. et al. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003; 24: 699-706
• 31 Ozorowski T, Kawalec M, Zaleska M. et al. The effect of an antibiotic policy on the control of vancomycin-resistant enterococci outbreak and on the resistance patterns of bacteria isolated from the blood of patients in a hematology unit. Pol Arch Med Wewn 2009; 119: 712-718
• 32 Bantar C, Sartori B, Vesco E. et al. A hospitalwide intervention program to optimize the quality of antibiotic use: impact on prescribing practice, antibiotic consumption, cost savings, and bacterial resistance. Clin Infect Dis 2003; 37: 180-186
• 33 Brahmi N, Blel Y, Kouraichi N. et al. Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit. J Infect Chemother 2006; 12: 190-194
• 34 Ntagiopoulos PG, Paramythiotou E, Antoniadou A. et al. Impact of an antibiotic restriction policy on the antibiotic resistance patterns of Gram-negative microorganisms in an Intensive Care Unit in Greece. Int J Antimicrob Agents 2007; 30: 360-365
• 35 Meyer E, Lapatschek M, Bechtold A. et al. Impact of restriction of third generation cephalosporins on the burden of third generation cephalosporin resistant K. pneumoniae and E. coli in an ICU. Intensive Care Med 2009; 35: 862-870
• 36 Sarraf-Yazdi S, Sharpe M, Bennett KM. et al. A 9-Year retrospective review of antibiotic cycling in a surgical intensive care unit. J Surg Res 2012; 176: e73-e78
• 37 Knudsen JD, Andersen SE. Bispebjerg Intervention Group. A multidisciplinary intervention to reduce infections of ESBL- and AmpC-producing, gram-negative bacteria at a University Hospital. PLoS One 2014; 9: e86457
• 38 Khan R, Chessbrough J. Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital. J Hosp Infect 2003; 54: 104-108
• 39 Valiquette L, Cossette B, Garant MP. et al. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007; 45 (Suppl. 02) S112-S121
• 40 Talpaert MJ, Gopal Rao G, Cooper BS. et al. Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection. J Antimicrob Chemother 2011; 66: 2168-2174
• 41 Cook PP, Rizzo S, Gooch M. et al. Sustained reduction in antimicrobial use and decrease in methicillin-resistant Staphylococcus aureus and Clostridium difficile infections following implementation of an electronic medical record at a tertiary-care teaching hospital. J Antimicrob Chemother 2011; 66: 205-209
• 42 Aldeyab MA, Kearney MP, Scott MG. et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother 2012; 67: 2988-2996
• 43 Nowak MA, Nelson RE, Breidenbach JL. et al. Clinical and economic outcomes of a prospective antimicrobial stewardship program. Am J Health Syst Pharm 2012; 69: 1500-1508
• 44 Malani AN, Richards PG, Kapila S. et al. Clinical and economic outcomes from a community hospitalʼs antimicrobial stewardship program. Am J Infect Control 2013; 41: 145-148
• 45 Wenisch JM, Equiluz-Bruck S, Fudel M. et al. Decreasing Clostridium difficile infections by an antimicrobial stewardship program that reduces moxifloxacin use. Antimicrob Agents Chemother 2014; 58: 5079-5083
• 46 Ostrowsky B, Ruiz R, Brown S. et al. Lessons learned from implementing Clostridium difficile-focused antibiotic stewardship interventions. Infect Control Hosp Epidemiol 2014; 35 (Suppl. 03) S86-S95
• 47 Sarma JB, Marshall B, Cleeve V. et al. Effects of fluoroquinolone restriction (from 2007 to 2012) on Clostridium difficile infections: interrupted time-series analysis. J Hosp Infect 2015; 91: 74-80
• 48 DiDiodato G, McArthur L. Evaluating the effectiveness of an antimicrobial stewardship program on reducing the incidence rate of healthcare-associated Clostridium difficile infection: a non-randomized, stepped wedge, single-site, observational study. PLoS One 2016; 11: e0157671
• 49 Tacconelli E, De Angelis G, Cataldo MA. et al. Antibiotic usage and risk of colonization and infection with antibiotic-resistant bacteria: a hospital population-based study. Antimicrob Agents Chemother 2009; 53: 4264-4269
• 50 Pasricha J, Koessler T, Harbarth S. et al. Carriage of extended-spectrum beta-lactamase-producing enterobacteriacae among internal medicine patients in Switzerland. Antimicrob Resist Infect Control 2013; 2: 20
• 51 Kluytmans-van den Bergh M, Rossen J, Friedrich A. et al. The prevention paradox of ESBL-E: Species-specific risk and burden of transmission. ECCMID Amsterdam, 11.04.2016.
• 52 Hetem DJ, Derde LP, Empel J. et al. Molecular epidemiology of MRSA in 13 ICUs from eight European countries. J Antimicrob Chemother 2015; 71: 45-52
• 53 Bell BG, Schellevis F, Stobberingh E. et al. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 2014; 14: 13
• 54 Costelloe C, Metcalfe C, Lovering A. et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010; 340: c2096
• 55 Friedmann R, Raveh D, Zartzer E. et al. Prospective evaluation of colonization with extended-spectrum beta-lactamase (ESBL)-producing enterobacteriaceae among patients at hospital admission and of subsequent colonization with ESBL-producing enterobacteriaceae among patients during hospitalization. Infect Control Hosp Epidemiol 2009; 30: 534-542
• 56 De Angelis G, Restuccia G, Venturiello S. et al. Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised patients: a prospective multicenter study. BMC Infect Dis 2012; 12: 74
• 57 Gorska A, Marasca G, Beryl P. et al. Selection of antibiotic resistant bacteria is a predictable severe adverse drug event of the most used antibiotics in hospitalized patients. Kopenhagen, 25.04.2015.
• 58 Razazi K, Derde LP, Verachten M. et al. Clinical impact and risk factors for colonization with extended-spectrum β-lactamase-producing bacteria in the intensive care unit. Intensive Care Med 2012; 38: 1769-1778
• 59 Tschudin-Sutter S, Frei R, Dangel M. et al. Rate of transmission of extended-spectrum Beta-lactamase-producing enterobacteriaceae without contact isolation. Clin Infect Dis 2012; 55: 1505-1511
• 60 Kola A, Holst M, Chaberny IF. et al. Surveillance of extended-spectrum beta-lactamase-producing bacteria and routine use of contact isolation: experience from a three-year period. J Hosp Infect 2007; 66: 46-51
• 61 Tschudin-Sutter S, Frei R, Schwahn F. et al. Prospective validation of cessation of contact precautions for extended-spectrum β-lactamase-producing Escherichia coli. Emerg Infect Dis 2016; 22: 1094-1097
• 62 Mutters N, Brooke R, Frank U. et al. Low risk of apparent transmission of vancomycin-resistant Enterococci from bacteraemic patients to hospitalized contacts. Am J Infect Control 2013; 41: 778-781
• 63 Hamel M, Zoutman D, OʼCallaghan C. Exposure to hospital roommates as a risk factor for health care-associated infection. Am J Infect Control 2010; 38: 173-181
• 64 Chaberny IF, Ziesing S, Mattner F. et al. The burden of MRSA in four German university hospitals. Int J Hyg Environ Health 2005; 208: 447-453
• 65 Moore C, Dhaliwal J, Tong A. et al. Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) acquisition in roommate contacts of patients colonized or infected with MRSA in an acute-care hospital. Infect Control Hosp Epidemiol 2008; 29: 600-606
• 66 Williams VR, Callery S, Vearncombe M. et al. Acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in contacts of patients newly identified as colonized or infected with MRSA in the immediate postexposure and postdischarge periods. Am J Infect Control 2017; 45: 295-297
• 67 Holmes AH, Moore LS, Sundsfjord A. et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387: 176-187