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JAC Antimicrob Resist
JAC Antimicrob Resist
jacamr
JAC-Antimicrobial Resistance
2632-1823
Oxford University Press UK

10.1093/jacamr/dlae137
dlae137
Correspondence
AcademicSubjects/MED00740
AcademicSubjects/SCI01150
QMAC-dRAST for direct testing of antibiotic susceptibility in positive blood-culture broth: a comparison with the BD Phoenix® system and the disc diffusion method
https://orcid.org/0000-0003-3989-733X
Ponderand L Laboratoire de Bactériologie-Hygiène Hospitalière, Centre Hospitalier Universitaire Grenoble Alpes, F-38000, Grenoble, France
University of Grenoble Alpes, CEA, CNRS, IBS, Team Bacterial Pathogenesis and Cellular Responses, 38000 Grenoble, France

Brunet C Laboratoire de Bactériologie-Hygiène Hospitalière, Centre Hospitalier Universitaire Grenoble Alpes, F-38000, Grenoble, France

Lanoe F Laboratoire de Bactériologie-Hygiène Hospitalière, Centre Hospitalier Universitaire Grenoble Alpes, F-38000, Grenoble, France

Sanchez-Garcia K Laboratoire de Bactériologie-Hygiène Hospitalière, Centre Hospitalier Universitaire Grenoble Alpes, F-38000, Grenoble, France

Caspar Y Laboratoire de Bactériologie-Hygiène Hospitalière, Centre Hospitalier Universitaire Grenoble Alpes, F-38000, Grenoble, France
University of Grenoble Alpes, CEA, CNRS, IBS, Team Bacterial Pathogenesis and Cellular Responses, 38000 Grenoble, France

Corresponding author. E-mail: lponderand@chu-grenoble.fr
10 2024
16 9 2024
16 9 2024
6 5 dlae137© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

QuantaMatrix
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pmcWe read with great interest the work of Gallois et al. presenting the performance of the QMAC-dRAST system, which provides direct antibiotic susceptibility testing (AST) results in 6 h from positive blood cultures (PBCs). They presented AST data for 124 monomicrobial PCBs containing unique isolates of Enterobacterales from 13 different species. We also tested the QMAC-dRAST system on 80 PBCs, among which 45 contained a single isolate of Gram-negative (GN) bacteria and 35 a single isolate of Gram-positive (GP) bacteria, and would like to share our results to provide additional data from our own evaluation.

Sepsis related to bloodstream infection is one of the major causes of death from infection.1 Early and effective antibacterial therapy is associated with an increase in patient survival.2,3 Rapid bacterial identification and direct AST from PBCs, obtained in a few hours, could accelerate the switch for effective antimicrobial treatment when empirical treatment is inappropriate, and reduce mortality. It may also allow faster de-escalation to improve antibiotic stewardship of bloodstream infections. Rapid species identification and AST are now possible using several techniques directly from PBCs. Two panels for direct AST are available for GP and GN bacteria on the QMAC-dRAST system, which provides final AST data in approximately 6 h for 16 antibiotics plus an ESBL screening test in the GN panel, and 18 antibiotics plus a cefoxitin screening test and clindamycin resistance test in the GP panel.

We evaluated the performances of the QMAC-dRAST system (GN E19, GP E19, software v1.5.0.012) on 80 PCBs: 35 clinical and 45 artificial blood cultures (BCs) sampled in August 2022. Artificial BCs were spiked with a single isolate: 22 third-generation cephalosporin- and carbapenem-susceptible strains and 23 expressing various resistant mechanisms including 11 ESBL-producing Enterobacterales carrying the blaCTX-M gene (2 Escherichia coli, 4 Enterobacter cloacae, 3 Klebsiella species, 1 Morganella morganii and 1 Serratia marcescens), 2 E. cloacae overexpressing AmpC cephalosporinase (AmpC), 5 strains carrying GES-5, NDM, VIM or DIM-1 carbapenemases (3 Pseudomonas aeruginosa, 1 E. cloacae and 1 Klebsiella pneumoniae), 3 MRSA strains and 2 VRE strains (Table S1, available as Supplementary data at JAC-AMR Online). An average of 10 cfu were inoculated into the BC bottle previously filled with 7–10 mL of healthy volunteer’s blood, as described in a previously published protocol.4 BCs were incubated in a BD BACTECTM FX instrument (Becton Dickinson). AST results obtained with the QMAC-dRAST system were compared with standard AST techniques used in the laboratory: disc diffusion (DD), performed directly from PBCs in accordance with the guidelines of the ‘Comité de l’Antibiogramme de la Société Française de Microbiologie’ or broth microdilution (BMD) with the BD Phoenix® system (PMIC-96 and NMIC-417) from isolated colonies after subcultures.5 AST results were interpreted according to the 2019 CA-SFM/EUCAST breakpoints. We followed the definitions of EA (essential agreement), CA (categorical agreement), VME (very major error), ME (major error) or mE (minor error) previously described.6 However, the ‘I’ category was regarded as a susceptible category, which will result in major and very major discrepancies only.

AST results were obtained for 71/80 (89%) BCs. Among the nine invalid AST results, four did not show bacterial growth (two P. aeruginosa, one Stenotrophomonas maltophilia and one Enterococcus faecium strains), two species were not included in the panel tested (one Achromobacter spp. strain and one Chryseobacterium spp. strain) and three BCs were polymicrobial. Species and resistance profiles are summarized in Table S1. Overall, with the QMAC-dRAST GN panel relative to BD Phoenix® results, EA and CA for Enterobacterales were 92.5% and 93.4%, respectively, with 13.5% VME, 2.5% ME and 0% mE. For non-fermenting GN bacteria (NFGNB), 80.8% EA and 86.9% CA with 9.1% VME, 19.6% ME and 0% mE were obtained. CA of QMAC-dRAST was 95.5% and 99.0% in comparison with the DD method for Enterobacterales and NFGNB, respectively (Table S2). For Staphylococcus species, EA and CA of QMAC-dRAST were 96.2% and 92.9%, respectively, in comparison with BD Phoenix® results with 6.4% VME, 7.6% ME and 0% mE. For Enterococcus species, EA and CA were 82.6% and 87.2% with 9.1% VME, 14.1% ME and 0% mE (Table S2). As previously described for GN bacteria, EA and CA exceeded 90%, relative to BD Phoenix® results except for piperacillin, ceftazidime, imipenem, meropenem, amikacin and co-trimoxazole for NFGNB, and piperacillin/tazobactam, ceftazidime, cefepime and co-trimoxazole for Enterobacterales. For GP bacteria, EA and CA exceeded 90% except for ampicillin, levofloxacin and erythromycin for Enterococcus species. For Staphylococcus species, CA of vancomycin was 76.2%. For Enterococcus species, EA of vancomycin and teicoplanin was 72.7% and CA of daptomycin was 81.8% (Table 1). Results for the ESBL detection test was obtained for the 15 strains not producing AmpC cephalosporinase. Five were ESBL positive and 10 were ESBL-negative with no discrepant results, leading to 100% sensitivity and specificity for the assay in our study. The cefoxitin screening test, performed on the 10 Staphylococcus aureus (3 MRSA and 7 MSSA) also showed 100% sensitivity and specificity.

Table 1. Performance of QMAC-dRAST and the DD method relative to BMD (BD Phoenix®) for GN and GP bacteria

Antibiotic		BMD (n)	QMAC-dRAST (%)	DD (%)	
N	S	I	R	EA	CA	VME	ME	mE	CA	VME	ME	mE	
Enterobacterales	
 Ampicillin	27	2	0	25	96.3	96.3	4.0	0	0	100	0	0	0	
 Amoxicillin/clavulanate	27	7	0	20	96.3	96.3	5.0	0	0	96.3	5.0	0	0	
 Piperacillin	—	—	—	—	—	—	—	—	—	—	—	—	—	
 Piperacillin/tazobactam	27	17	0	10	81.5	81.5	50.0	0	0	92.6	0,0	11.8	0	
 Cefotaxime	27	13	0	14	96.3	100	0	0	3.7	100	0	0	0	
 Ceftazidime	27	14	2	11	85.2	85.2	18.2	21.0	3.7	96.3	0	7.1	0	
 Cefepime	27	13	2	12	77.8	77.8	50.0	0	3.7	88.9	25.0	0	0	
 Imipenem	26	24	1	1	92.3	96.2	100	0	0	96.2	0	4.2	0	
 Meropenem	21	21	0	0	95.2	100	—	0	0	100	—	0	0	
 Gentamicin	26	17	0	9	100	100	0	0	0	100	0	0	0	
 Amikacin	27	26	0	1	100	100	0	0	0	88.9	0	11.5	0	
 Co-trimoxazole	27	17	0	10	88.9	88.9	10.0	11.8	0	88.9	10.0	11.8	0	
 Ciprofloxacin	26	13	3	10	96.2	96.2	0	7.7	0	100	0	0	0	
 Levofloxacin	18	14	1	3	100	100	0	0	0	94.4	33.3	0	0	
NFGNB	
 Ampicillin	—	—	—	—	—	—	—	—	—	—	—	—	—	
 Amoxicillin/clavulanate	—	—	—	—	—	—	—	—	—	—	—	—	—	
 Piperacillin	10	5	1	4	80.0	90.0	0	20.0	0	100	0	0	0	
 Piperacillin/tazobactam	11	5	1	5	100	100	0	0	0	100	0	0	0	
 Cefotaxime	—	—	—	—	—	—	—	—	—	—	—	—	—	
 Ceftazidime	11	5	1	5	81.8	90.9	0	20.0	0	100	0	0	0	
 Cefepime	11	5	1	5	90.9	100	0	0	0	100	0	0	0	
 Imipenem	11	5	4	2	54.5	72.7	50.0	40.0	0	90.9	50.0	0	0	
 Meropenem	11	8	0	3	54.5	63.6	0	50.0	0	100	0	0	0	
 Gentamicin	5	5	0	0	100	100	—	0	0	100	—	0	0	
 Amikacin	11	8	0	3	72.7	72.7	66.7	12.5	0	100	0	0	0	
 Co-trimoxazole	6	5	1	0	83.3	83.3	—	20.0	0	100	—	0	0	
 Ciprofloxacin	6	0	3	3	100	100	0	—	0	100	0	—	0	
 Levofloxacin	6	0	3	3	100	100	0	—	0	100	0	0	0	
Staphylococcus spp.	
 Penicillin G	10	1	0	9	90.0	90.0	0	100	0					
 Ampicillin	—	—	—	—	—	—	—	—	—					
 Oxacillin	21	8	0	13	100	95.2	0	12.5	0					
 Gentamicin	21	12	0	9	95.2	95.2	11.1	0	0					
 Gentamicin HL	—	—	—	—	—	—	—	—	—					
 Levofloxacin	21	9	0	12	100	100	0	0	0					
 Fusidic acid	20	12	0	8	95.0	95.0	12.5	0	0					
 Erythromycin	21	8	0	13	90.5	85.7	15.4	12.5	0					
 Clindamycin	20	13	1	6	100	100	0	0	0					
 Daptomycin	21	21	0	0	95.2	95.2	—	0	0					
 Linezolid	21	21	0	0	95.2	95.2	—	0	0					
 Tetracycline	21	15	2	4	100	95.2	25.0	0	0					
 Teicoplanin	21	17	0	4	90.5	90.5	0	11.8	0					
 Vancomycin	21	21	0	0	100	76.2	—	23.8	0					
Enterococcus spp.	
 Penicillin G	—	—	—	—	—	—	—	—	—					
 Ampicillin	11	8	0	3	81.8	81.8	0	25.0	0					
 Oxacillin	—	—	—	—	—	—	—	—	—					
 Gentamicin	—	—	—	—	—	—	—	—	—					
 Gentamicin HL	11	10	0	1	100	100	0	0	0					
 Levofloxacin	10	6	0	4	60.0	60.0	0	66.7	0					
 Fusidic acid	—	—	—	—	—	—	—	—	—					
 Erythromycin	11	0	0	11	81.8	81.8	18.2	0	0					
 Clindamycin	—	—	—	—	—	—	—	—	—					
 Daptomycin	11	11	0	0	90.9	81.8	0	18.2	0					
 Linezolid	10	10	0	0	100	100	0	0	0					
 Tetracycline	—	—	—	—	—	—	—	—	—					
 Teicoplanin	11	10	0	1	72.7	100	0	0	0					
 Vancomycin	11	9	0	2	72.7	90.9	0	11.1	0					
S, susceptible; I, intermediate; R, resistant; HL, high level.

Our study was small and did not evaluate a representative collection of strains as we spiked PBCs with various resistant strains. This prevents us from drawing any conclusions about the ability of the QMAC-dRAST system to fulfil the criteria of ISO 20776-2:2021. However, results of similar studies could be aggregated to have a better overview of the performance of the system.7 The CA and EA were lower than those obtained in previous studies whether the QMAC-dRAST system was compared with BMD or DD reference method.6,8,9 These results may be explained by the small number of strains tested or by the heterogeneity of the resistance mechanisms included in our study.

To conclude, the QMAC-dRAST system showed interesting performance that could allow its use for rapid AST for Enterobacterales or Staphylococcus. However, results for some antibiotics or some bacterial genera require more caution. Additional studies on large cohorts of strains are necessary to validate its performance.

Supplementary Material

dlae137_Supplementary_Data

Funding

This study was funded by internal funding. The cartridges and the automaton were provided by QuantaMatrix, which did not participate in the study design, data interpretation or the writing of the manuscript.

Transparency declarations

Y. Caspar declares study grants from QIAGEN, Becton Dickinson and BAIO-Dx to Grenoble University Hospital and Congress, travel and meeting support from Becton Dickinson France SAS, MENARINI FRANCE and MSD France, all outside the submitted work. All other authors: none to declare.

Supplementary data

Tables S1 and S2 are available as Supplementary data at JAC-AMR Online.
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