S76
17th ECCMID / 25th ICC, Oral presentations
O359 Is the ratio of associated Escherichia coli resistance comparable over Europe?
O360 Multidrug-resistance among invasive Klebsiella pneumoniae in Europe in 2005, the first full year of EARSS reporting
N. van de Sande-Bruinsma, G. Kahlmeter, M. de Kraker, E. Tiemersma, J. Monen, H. Grundmann and EARSS participants
J. Monen, N. van de Sande-Bruinsma, E. Tiemersma, M. de Kraker, H. Grundmann and EARSS participants
Introduction: The EARSS database discloses increasing levels of antimicrobial resistance in Escherichia coli in most parts of Europe. We investigated the levels of associated resistance in the E. coli database. Methods: Invasive E. coli susceptibility results to aminopenicillin (AMP), 3rd-gen cephalosporins (3CP), fluoroquinolones (FQ) and aminoglycosides (AG) from 2005 were extracted for 7 countries representing different geographic areas and levels of antimicrobial resistance: the Czech Republic (CZ), Germany (DE), Ireland (IE), Finland (FI), France (FR), Slovenia (SI) and Spain (ES). Associated resistance was defined as “resistance to one drug in the presence of resistance of another drug”. The levels of associated resistance were determined. For each drug the levels of resistance was determined for isolates susceptible and resistant to the other drugs. Table. Minimum (min) and maximum (max) % resistance reported per antimicrobial group, and level of associated resistance within these groups of resistant isolates Resistant to:
Aminopenicillins (AMP)
3rd gen cephalosporins (3CP)
Fluoroquinolones (FQ)
Aminoglycosides (AG)
Min/max resistance (country)
Associated resistance versus (resistance in susceptible group)a AMP 3CP FQ AG
Min
36% (FI)
–
Max
68% (IE)
–
Min
1% (FR)
Max
8% (ES)
Min
9% (FI)
Max
28% (ES)
Min
3% (FI)
Max
10% (ES)
99% (49%) 100% (59%) 86% (31%) 86% (52%) 97% (34%) 93% (58%)
7% (0%)a 5% (0%) – – 22% (1%) 19% (3%) 66% (1%) 27% (5%)
21% (2%) 24% (2%) 69% (10%) 70% (25%) – – 91% (6%) 82% (22%)
Objectives: We explore the resistance to important antibiotic groups of invasive Klebsiella pneumoniae isolates reported to the European Antimicrobial Resistance Surveillance System (EARSS) by participating laboratories. Methods: Participating laboratories carry out routine antimicrobial susceptibility testing (AST) for invasive K. pneumoniae isolates. The EARSS protocol includes aminoglycosides, fluoroquinolones and thirdgeneration cephalosporins, but results on carbapenems are also accepted. EARSS accepts the interpretations as defined by the guidelines used by the participating laboratories. Data are collected at the national level and forwarded to EARSS at the National Institute for Public Health and the Environment (RIVM) in Bilthoven, The Netherlands. Results: In the year 2005, 23 countries reported AST results for 4,929 K. pneumoniae isolates. Of these, 4,597 isolates were tested for all classes in the protocol. Six countries reported proportion of less than 1% for the combined resistance against aminoglycosides, fluoroquinolones and third-generation cephalosporins, 7 reported between 1% and 5%, one country between 5% and 10%, 7 between 10% and 25% and 2 more than 25% (see figure). The resistance to carbapenems was <1% in all countries but one, the exception being Greece that reported 25% combined resistance to all 4 groups.
7% (0%) 11% (1%) 42% (4%) 35% (8%) 26% (0%) 29% (2%) – –
a
Interpretation: “In Finland 36% of E. coli were resistant to AMP; in these resistance to 3CP was 7% as compared to 0% in the 64% not resistant to AMP.”
Results: Overall, most if not all resistance to a drug was in the presence of resistance to one or more of the other drugs. More than half of the isolates resistant to 3CP were resistant to FQ. Whereas only 3−10% of all isolates were resistant to AG, similarly almost all isolates resistant to AG were also resistant to FQ (82−91%) as compared to the much lower rates in those sensitive to AG (6−22%). Large differences were observed between countries in antimicrobial resistance rates, whereas the levels of associated resistance among the group of resistant isolates did not vary to the same extent (Table). Conclusions: (i) The level of associated resistance for the isolates resistant to the different antimicrobial groups under EARSS study seemed comparable between countries, irrespective of their differences in overall resistance proportions. (ii) The group of isolates resistant to one group of antibiotics was more likely to be resistant to other antimicrobial groups (under EARSS surveillance) compared to their susceptible counterparts. The observation that most resistance is associated with other types of resistance and that the level of associated resistance seems comparable between countries would suggest that the overall reduction of the antibiotic use is probably more important in the society as a whole than targeted reduction of single drugs. Our analysis suggest that efforts should be focused on these ‘multi’ resistant strains.
Klebsiella pneumoniae. Combined resistance to aminoglycosides, fluoroquinolones and third-generation cephalosporins. Conclusion: Our data suggest that multidrug resistance among K. pneumoniae is high in many European countries, but that carbapenems can still be used in most of them. The data from Greece predominantly reflect the situation among ICU patients (for which more bloodculture results were available). It must be kept in mind that most guidelines (including CLSI) use breakpoints which are not designed to detect metallo-b-lactamases and that therefore the dissemination of this important resistance trait cannot be deduced from the EARSS data at present. O361 The prevalence and genetic relatedness of KPC-possessing Klebsiella pneumoniae isolates from a United States hospital R. Tibbetts, W.M. Dunne (St. Louis, US) Background: Carbapenem resistance due to KPC-possessing Klebsiella pneumoniae is a major healthcare concern. KPC-1 was first identified in South Carolina in 2001 and since then KPC-1 and the KPC-2 and KPC-3 derivations have been identified throughout the USA, Southeast
Resistance in clinical isolates Asia, and Europe. Following the identification of the first imipenemresistant, KPC-positive Klebsiella pneumoniae isolate in our institution, we initiated a prospective study from August 2006 to November 2006 of 108 consecutive isolates of this organism to determine the prevalence and genetic relatedness of KPC-positive strains. Methods: KPC-specific polymerase chain reaction was performed on total DNA and plasmid DNA from 108 consecutive Klebsiella pneumoniae isolates. Repetitive sequence PCR was performed on all KPC-positive isolates to determine genetic relatedness Results: Of the 108 isolates collected over the four-month period, 13 (12.0%) were shown to harbour the KPC ORF by PCR. Six of the 13 isolates were identified from three patients, while each of the remaining seven came from individual patients. Eight of the eleven isolates were resistant to imipenem by disk diffusion testing while three of the isolates were fully susceptible. Plasmids containing the KPC gene were isolated and verified by PCR from the 8 imipenem-resistant isolates. In contrast, we were unable to isolate any plasmids from the 3 imipenem-sensitive strains; however, they were positive for the KPC ORF using PCR on total genomic DNA. Two distinct clusters of Klebsiella pneumoniae were seen following repetitive sequence PCR. The first cluster of 7 isolates was 86.0% identical suggesting a clonal expansion while the other 5 isolates were unrelated. As expected, multiple isolates from single patients were between 94.8% and 97.4% identical. Conclusions: The prevalence of KPC-possessing Klebsiella pneumoniae in our institution has risen to 9.2% in 4 months thereby compromising empiric treatment options for patients infected with Klebsiella pneumoniae. Both a clonal expansion and horizontal plasmid transfer appear to be involved in KPC dissemination. In addition, these data suggest that the KPC ORF may reside in the chromosome and is not expressed until the proper inducing agent is present or that the KPC ORF may reside on a transposable element that is not expressed until transferred into a plasmid. O362 Pseudomonas aeruginosa resistance rates in association with level of hospital care: data from the EARSS E.W. Tiemersma, N. van de Sande, G. Kahlmeter, M. de Kraker, J. Monen, H. Grundmann and EARSS participants Objective: Pseudomonas aeruginosa (PAE) is known to cause problems mainly in severely immunocompressed patients. This frequently involves multiresistance phenotypes. PAE resistance rates can reach levels of over 10%. Since July 2005, EARSS has been collecting antimicrobial susceptibility testing (AST) data from invasive PAE isolates. Here, we report for the first time the data for 2006 and relate these to hospital characteristics. We investigated the potential importance of levels of hospital care. Methods: Participating laboratories carry out routine AST for invasive PAE isolates. Data are collected at national level and are forwarded to the EARSS database. AST data and information on hospital characteristics were available for 2,316 isolates from 262 hospitals in 20 countries. AST data included aminopenicillins, ceftazidim, fluoroquinolones, aminoglycosides and carbapenems. Multiple drug resistance was defined as resistance to all 5 drug classes. A logistic model was used to test the association between resistance and hospital characteristics (two-sided p-value <0.05). Hospital characteristics included were type (university/ teaching, general/secondary and other), presence of (neonatal) intensive care units (ICUs), and transplants, burns and heamatology units, number of beds, and number of ICU beds. Results: A significant proportion of isolates was resistant against piperacillin (± tazobactam) (14.5%), ceftazidim (13.6%), fluoroquinolones (25.0%), aminoglycosides (19.7%) and/or carbapenems (16.7%). Multiple drug resistance occurred in 4.7% of all isolates, although proportions varied between countries. All multiple drug resistant isolates originated from hospitals with ICUs, although not all isolates originated from patients being treated at ICUs. Resistance rates in hospitals were associated with the number of intensive-care beds and presence of a neonatal ICU (p < 0.0001) only. None of the other hospital characteristics influenced the resistance rates.
S77 Conclusions: An important proportion of PAE isolates was found resistant to multiple drugs. The proportion of multiple drug resistance was associated with the number of ICU beds and presence of a neonatal ICU. Hospital types (university, general, other) were not associated to PAE resistance, which might reflect differences in definition of hospital type. O363 Resistance in Pseudomonas aeruginosa and Acinetobacter spp. from blood in the UK and Ireland, 2001−2005 R. Reynolds, R. Hope on behalf of BSAC Working Party on Bacteraemia Resistance Surveillance Objective: The BSAC Bacteraemia Resistance Surveillance Programme monitors resistance to established and developmental antibiotics among the pathogens of bacteraemia in the UK and Ireland. Methods: Between 2001 and 2005, 29 laboratories sent 1,014 P. aeruginosa and 200 Acinetobacter spp. for central MIC testing by BSAC methods. Ceftazidime, ciprofloxacin, gentamicin, imipenem and piperacillin-tazobactam (CAZ, CIP, GEN, IPM and TZP) were tested throughout. Tetracycline, minocycline and tigecycline (TET, MIN and TGC) were tested from 2002, ceftobiprole (BPR) from 2004, and doripenem (DOR) from 2005. Results were compared with LabBase2, a voluntary system taking routine results for blood isolates from nearly 400 centres in England, Wales and (from 2002) N. Ireland. Results: Non-susceptibility in P. aeruginosa was 3% for CAZ, 7% for GEN, IPM and TZP and 19% for CIP; 8/1,014 (1%) were non-susceptible to all 5 agents, and 8% non-susceptible to 2 classes of agents. LabBase2 results differed for CAZ and CIP (both 6% nonsusceptible). For CIP, a lower breakpoint (set in 2005, and used for all BSAC isolates, but not in LabBase) explained the difference. Factors independently associated with increased risk of non-susceptibility to 1 of these agents in P. aeruginosa were intensive care, young age, >48 hours prior hospitalisation, and infections arising from skin/soft tissue and lines. Among Acinetobacter, resistance was concentrated in A. baumannii: 2/110 (2%) of A. baumannii were non-susceptible to all 5 agents, and 36% to 2 classes of agents. Overall, 5% of Acinetobacter were nonsusceptible to GEN and IPM, and 17%, 27% and 63% to TZP, CIP and CAZ respectively. Numbers were too small to assess trend, predictors or agreement with LabBase2. MIN and TGC largely overcame TET resistance in Acinetobacter, with maximum MICs of 8 and 4 mg/L respectively. DOR MICs were closely related to IPM, on average 2.8 dilutions lower for P. aeruginosa and 0.5 dilutions higher for Acinetobacter. BPR MICs were on average 1.2 dilutions higher than CAZ for P. aeruginosa and 2 dilutions lower for Acinetobacter. Drug Pseudomonas aeruginosa Acinetobacter spp. N MIC MIC90 %NS (MIC) N MIC MIC90 mode mode
%NS (MIC)
CAZ CIP GEN IPM TZP TET MIN TGC BPR DOR
63% (>2) 27% (>0.5) 5% (>4) 2% (>4) 17% (>16) n/a n/a n/a n/a n/a
1,014 1 4 3% (>8) 1,014 0.25 4 19% (>0.5) 1,014 1 4 7% (>4) 1,014 1 4 7% (>16) 1,014 4 16 7% (>16) Not tested – inherently resistant Not tested – inherently resistant Not tested – inherently resistant 442 2 8 n/a 226 0.06 0.5 n/a
200 200 200 200 200 156 156 156 81 35
4 0.12 0.12 0.06 0.5 2 0.06 0.25 0.5 0.06
16 64 16 0.25 512 256 2 2 32 0.5
MICs in mg/L. NS = non-susceptible (MICs in the range defined in brackets).
Conclusion: Most bloodstream P. aeruginosa in the UK and Ireland remain susceptible to relevant antibiotics. Carbapenem-resistant Acinetobacter, although widely referred to the HPA specialist laboratory from other infection sites, are rare in bacteraemia. TGC may be useful for Acinetobacter infections and BPR for P. aeruginosa; DOR has good activity against both species.