Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study
Authors: de la Court Jara R. , Woudt Sjoukje H. S. , Schoffelen Annelot F. , Heijmans Jarom , de Jonge Nick A. , van der Bruggen Tjomme , Bomers Marije K. , Lambregts Merel M. C. , Schade Rogier P. , Sigaloff Kim C. E. ,   ISIS-AR study group, Stuart J. W. T. Cohen , Melles D. C. , van Dijk K. , Alzubaidy A. , Werdmuller B. F. M. , Blaauw G. J. , Diederen B. M. W. , Alblas H. J. , der Kuil W. Altorf-van , Bierman S. M. , de Greeff S. C. , Groenendijk S. R. , Hertroys R. , Kuijper E. J. , Monen J. C. , Notermans D. W. , van den Reek W. J. , Smilde A. E. , Wielders C. C. H. , Zoetigheid R. E. , van den Bijllaardt W. , Kraan E. M. , Mattsson E. E. , da Silva J. M. , de Jong E. , Maraha B. , van Asselt G. J. , Demeulemeester A. , Wintermans B. B. , van Trijp M. , Ott A. , Sinnige J. , Melles D. C. , Silvis W. , Bakker L. J. , Dorigo-Zetsma J. W. , Waar K. , Bernards A. T. , Hall M. A. Leversteijn-van , Schaftenaar E. , Nabuurs-Franssen M. H. , Wertheim H. , Diederen B. M. W. , Bode L. , van Rijn M. , Dinant S. , Pontesilli O. , de Man P. , Wong M. , Muller A. E. , Renders N. H. , Bentvelsen R. G. , Buiting A. G. M. , Vlek A. L. M. , Stam A. J. , Troelstra A. , Overdevest I. T. M. A. , van Meer M. P. A. , dos Santos C. Oliveira , Wolfhagen M. J. H. M. 
Published: November 2022

Abstract
Objectives
Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third-generation cephalosporins (3GC) is increasing. In order to explore the value of using surveillance cultures to guide empirical treatment e.g. choosing between carbapenem versus ceftazidime- we aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-resistant GNB (3GC-R GNB) bacteraemia that was preceded by 3GC-R GNB colonization.

Methods
Using 11 years of data (2008–2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of 3GC-R GNB in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Colonization was defined as availability of any GNB surveillance isolate in the year before, independent of the causative micro-organism (time-paired isolates).

Results
We included 3887 patients, representing 4142 episodes of bacteraemia. GNB were identified in 715/4142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In 139 of these 221 patients a time-paired surveillance culture was available. In 76.2% (106/139) of patients these surveillance cultures already showed 3GC-R GNB isolates in the year prior to the culture date of the 3GC-R GNB positive blood isolate.

Conclusions
This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of the use of surveillance-cultures to guide empirical therapy to restrict the empirical use of carbapenems in this population.