Linköping University Medical Dissertations No. 1019 SURVEILLANCE OF ANTIBIOTIC CONSUMPTION AND ANTIBIOTIC RESISTANCE IN SWEDISH INTENSIVE CARE UNITS MARCUS ERLANDSSON Linköping 2007 1 Linköping University Medical Dissertations No. 1019 SURVEILLANCE OF ANTIBIOTIC CONSUMPTION AND ANTIBIOTIC RESISTANCE IN SWEDISH INTENSIVE CARE UNITS MARCUS ERLANDSSON Department of Clinical and Experimental Medicine, Division of Infectious Diseases, Faculty of Health Sciences, Linköping University, Sweden Linköping 2007 Surveillance of Antibiotic Consumption and Antibiotic Resistance in Swedish Intensive Care Units © Marcus Erlandsson 2007 All previously published papers, figures and tables are reprinted with permission from the publishers. Date of disputation: 2007-10-26 Institution: IKE ISBN: 978-91-85895-77-9 ISSN: 0345-0082 Art direction: Niklas Ramviken, ENO form Printed by LiU-Tryck, Linköping, Sweden, 2007 ABSTRACT INTRODUCTION: Nosocomial infec- in the ICU, and to investigate the emer- tions remain a major cause of mortal- gence of resistance and transmission of ity and morbidity. The problem is most Pseudomonas aeruginosa in the ICU apparent in intensive care units (ICUs). using cluster analysis based on antibio- Most ICU patients are compromised and grams and genotype data obtained by vulnerable as a result of disease or se- AFLP. vere trauma. One in ten people admitted to hospital is given an antibiotic for in- MATERIAL AND METHODS: In pa- fection. The risk of acquiring a nosoco- per 1-3, antibiotic consumption data mial infection in a European ICU is ap- together with bacterial antibiotic resist- proximately 20%. It is vitally important ance data and specific ICU-demographic that ways are found to prevent transmis- data were collected from an increasing sion between patients and personnel, and number of ICUs over the years 1997- that local hygiene routines and antibiotic 2001. Data from ICUs covering up to policies are developed. This thesis is a six million out of Sweden’s nine million holistic work focused particularly on an- inhabitants were included. In paper 4, timicrobial antibiotic resistance, antibi- the indications for antibiotic prescribing otic consumption and to some extent on were studied during two weeks in 2000. hygiene in Swedish ICUs. Paper 5 investigated Pseudomonas aeru- ginosa isolates in order to detect cross- AIMS: The general aim of this thesis was transmission with genotype obtained by to investigate bacterial resistance and AFLP, and antibiogram-based cluster antibiotic consumption in Swedish ICUs analysis was also performed in order to and to try to correlate ICU demographic see if this could be a quicker and easier data with antibiotic consumption and an- substitute for AFLP. tibiotic resistance. Additional aims were to investigate on which clinical indica- tions antibacterial drugs are prescribed 6 RESULTS: This thesis has produced CONCLUSION: For the period studied, three important findings. Firstly, antibi- multidrug resistance in Swedish ICUs otic consumption in participating ICUs was not a major problem. Signs of cross- was relatively high during the study pe- transmission with non-multiresistant riod, and every patient received on aver- bacteria were observed, indicating a age more than one antimicrobial drug per hygiene problem and identifying sim- day (I-IV). Secondly, levels of antimi- ple improvements that could be made in crobial drug resistance seen in S. aureus, patient care guidelines and barrier pre- E. coli and Klebsiella spp remained low cautions. A need for better follow up of when data were pooled from all ICUs prescribed antibiotics was evident. With throughout the study period, despite further surveillance studies and moni- relatively high antibiotic consumption toring of antibiotics and bacterial resist- (I-V). Thirdly, the prevalence of antibi- ance patterns in the local setting as well otic resistance in CoNS and E. faecium, as on a national and international level, cefotaxime resistance in Enterobacter, some of the strategic goals in the pre- and ciprofloxacin and imipenem resist- vention and control of the emergence of ance in P. aeruginosa was high enough antimicrobial-resistant microbes may be to cause concern. achievable. 7 TABLE OF CONTENTS ABSTRACT .................................................................................................. 6 TABLE OF CONTENTS ................................................................................ 8 LIST OF PUBLICATIONS ............................................................................ 10 ABBREVIATIONS ....................................................................................... 12 INTRODUCTION ......................................................................................... 14 Nosocomial ICU infections .......................................................................... 15 ICU pathogens .......................................................................................... 16 Antimicrobial drugs .................................................................................... 18 Susceptibility breakpoints ........................................................................... 21 ATC, DDD and DDD ............................................................................. 21 1000 Antimicrobial drug resistance mechanisms, development and spread ............. 21 Surveillance of microbial antibiotic resistance, antibiotic consumption and nosocomial infections ........................................ 24 Hospital hygiene and factors affecting nosocomial infection rates ................. 24 AIMS .......................................................................................................... 26 MATERIALS AND METHODS .................................................................... 28 Patients and settings ................................................................................ 28 Susceptibility testing and bacterial isolates .................................................. 30 Antibiotic consumption .............................................................................. 30 Laboratory and physiological parameters ..................................................... 31 Questionnaire on ICU characteristics and Infection control ............................ 31 Genotyping of Pseudomonas aeruginosa ..................................................... 31 Detection of Metallo-β-lactamases in Pseudomonas aeruginosa ................... 31 Antibiogram-based cluster analysis of Pseudomonas aeruginosa ................... 32 Statistical methods ..................................................................................... 32 RESULTS ................................................................................................... 34 ICU characteristics and infection control ...................................................... 35 Antibiotic consumption and prescriptions ..................................................... 37 Bacterial species and antibiotic resistance ................................................... 39 8 DISCUSSION ............................................................................................ 44 Main findings ............................................................................................. 45 Settings .................................................................................................... 45 Antibiotic consumption .............................................................................. 46 Testing for bacterial antibiotic resistance and breakpoints ............................. 52 Bacterial isolates, antibacterial drug resistance and the emergence of resistance ..................................................................... 54 Genotyping methods ................................................................................. 57 Validation of antibiogram-based cluster analysis ........................................... 58 Adherence to hospital hygiene procedures, hygiene factors and infection control measures .......................................................................... 58 Validation of the ICU-STRAMA database .................................................... 60 How to continue the battle against multiresistant microbes in Swedish ICUs .......................................................................... 61 CONCLUSION ........................................................................................... 64 ACKNOWLEDGEMENTS ........................................................................... 00 REFERENCES ............................................................................................ 70 9 LIST OF PUBLICATIONS 10
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