Surveillance of Gram-negative bacteria: impact of variation in current European laboratory reporting practice on apparent multidrug resistance prevalence in paediatric bloodstream isolates
Surveillance of Gram-negative bacteria: impact of variation in current European laboratory reporting practice on apparent multidrug resistance prevalence in paediatric bloodstream isolates
J. A. Bielicki 0 1 2 3
D. A. Cromwell 0 1 2 3
A. Johnson 0 1 2 3
T. Planche 0 1 2 3
M. Sharland 0 1 2 3
for the ARPEC project 0 1 2 3
0 Department of Healthcare-Associated Infections and Antimicrobial Resistance, Centre for Infectious Disease Surveillance and Control, Public Health England , London , UK
1 Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine , London , UK
2 Paediatric Infectious Diseases Research Group (PIDRG), Institute for Infection and Immunity, St George's, University of London , Jenner Wing, Cranmer Terrace, London SW17 0RE , UK
3 Institute for Infection and Immunity, St George's, University of London , London , UK
This study evaluates whether estimated multidrug resistance (MDR) levels are dependent on the design of the surveillance system when using routine microbiological data. We used antimicrobial resistance data from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project. The MDR status of bloodstream isolates of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was defined using European Centre for Disease Prevention and Control (ECDC)-endorsed standardised algorithms (non-susceptible to at least one agent in three or more antibiotic classes). Assessment of MDR status was based on specified combinations of antibiotic classes reportable as part of routine surveillance activities. The agreement between MDR status and resistance to specific pathogen-antibiotic class combinations (PACCs) was assessed. Based on all available antibiotic susceptibility testing, the proportion of MDR isolates was 31% for E. coli, 30% for K. pneumoniae and 28% for P. aeruginosa isolates. These proportions fell to 9, 14 and 25%, respectively, when based only on classes collected by current ECDC surveillance methods. Resistance percentages for specific PACCs were lower compared with MDR percentages, except for P. aeruginosa. Accordingly, MDR detection based on these had low sensitivity for E. coli (2-41%) and K. pneumoniae (21-85%). Estimates of MDR percentages for Gram-negative bacteria are strongly influenced by the antibiotic classes reported. When a complete set of results requested by the algorithm is not available, inclusion of classes frequently tested as part of routine clinical care greatly improves the detection of MDR. Resistance to individual PACCs should not be considered reflective of MDR percentages in Enterobacteriaceae.
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for the ARPEC project
Bacteria resistant to multiple antibiotics have been identified as a
major challenge for patient management and public health [1, 2].
Multidrug-resistant Gram-negative bacteria (MDR-GNB) are
considered to be particularly worrying because the therapeutic
options are limited [3, 4]. Furthermore, certain MDR-GNB, such
as those producing extended-spectrum beta-lactamases or
carbapenemases encoded on plasmids, are of concern due to their
potential for interspecies plasmid transfer [5, 6].
Large-scale national and international surveillance is an
important tool in monitoring MDR-GNB resistance trends
[7]. At present, most surveillance relies on collecting results
from traditional antibiotic susceptibility testing (AST) to track
resistance epidemiology, including multidrug resistance
(MDR) [8–10]. It is, therefore, important that the
comparability of isolates identified as MDR by surveillance databases is
established. Standardised algorithms for reporting isolates as
MDR were proposed in 2012 by a group of international
experts, but these rely on a large number of antibiotics being
included in AST (Table 1) [11]. The selection of antibiotic
classes for routine testing continues to be highly variable
[16–19]. This potentially presents a major challenge for
estimating and comparing MDR-GNB prevalence from routine
data, given that individual laboratories may not test all
antibiotic classes required.
The monitoring of specific pathogen–antibiotic class
combinations (PACCs) can be an alternative surveillance strategy
to make best use of the available routine data [7, 12–14].
Some PACCs have been suggested as being useful for
MDR-GNB assessment based on the recognition of an
association in resistance between different antibiotic classes [15].
Using data on neonatal and paediatric GNB isolates
obtained from the Antibiotic Resistance and Prescribing in European
Children (ARPEC) project, this study evaluates the degree to
which estimated levels of MDR are dependent on surveillance
system design when routine microbiological data are used.
Materials and methods
The study used data from the ARPEC project, which was
cofunded by the European Commission DG Sanco through the
Executive Agency for Health and Consumers [20, 21].
ARPEC collected anonymised data on antimicrobial
resistance between Jan (...truncated)