Aztreonam/avibactam (ATM/AVI) has been recently approved drug for clinical use in the European Union. The aim of this study was to develop and evaluate a novel selective medium for the isolation of ATM/AVI-resistant strains (Super ATM/AVI selective medium) to help to control their spread. Minimum inhibitory concentrations of ATM/AVI were determined using the broth microdilution method for 77 Gram-negative isolates, including 62 Enterobacterales and 15 Pseudomonas aeruginosa. The Super ATM/AVI selective medium was elaborated using optimal final concentrations of ATM at 5 mg/L and AVI at 4 mg/L, being supplemented with amphotericin B and vancomycin to prevent growth of yeasts and Gram-positive bacteria and with ZnSO4 to optimize the expression of metallo-β-lactamase producers. Super ATM/AVI showed high sensitivity (94.6%) and specificity (100%) at a detection limit of 103 CFU/mL.
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References
1.
ARC (Antimicrobial Resistance Collaborators). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 2022; 399(10325):629–655; doi: 10.1016/s0140-6736(21)02724-0
2.
NelsonRE, HatfieldKM, WolfordH, et al.National estimates of healthcare costs associated with multidrug-resistant bacterial infections among hospitalized patients in the United States. Clin Infect Dis, 2021; 72(Suppl 1):S17–S26; doi: 10.1093/cid/ciaa1581
3.
ZhenX, Stålsby LundborgC, SunX, et al.Economic burden of antibiotic resistance in China: A national level estimate for inpatients. Antimicrob Resist Infect Control, 2021; 10(1):5; doi: 10.1186/s13756-020-00872-w
4.
ECDC and WHO (European Centre for Disease Prevention and Control and World Health Organization). Antimicrobial Resistance Surveillance in Europe 2023–2021 Data. European Centre for Disease Prevention and Control and World Health Organization: Stockholm; 2023.
5.
WHO and ECDC. WHO Regional Office for Europe/European Centre for Disease Prevention and Control. Antimicrobial Resistance Surveillance in Europe 2022–2020 Data. WHO Regional Office for Europe: Copenhagen; 2022.
6.
Le TerrierC, FreireS, NordmannP, PoirelL. Multidrug-resistant Gram-negative clinical isolates with reduced susceptibility/resistance to cefiderocol: Which are the best present and future therapeutic alternatives? Eur J Clin Microbiol Infect Dis, 2024; 43(2):339–354; doi: 10.1007/s10096-023-04732-4
7.
Blanco-MartínT, Alonso-GarcíaI, González-PintoL, et al.GEMARA/SEIMC-CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT). Activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double β-lactamases under high and low permeability conditions. Int J Antimicrob Agents, 2024; 63(5):107150; doi: 10.1016/j.ijantimicag.2024.107150
8.
WongD, van DuinD. Novel β-Lactamase inhibitors: Unlocking their potential in therapy. Drugs, 2017; 77(6):615–628; doi: 10.1007/s40265-017-0725-1
9.
ZhangS, LiaoX, DingT, AhnJ. Role of β-Lactamase inhibitors as potentiators in antimicrobial chemotherapy targeting gram-negative bacteria. Antibiotics, 2024; 13(3):260.
10.
CornelyOA, CisnerosJM, Torre-CisnerosJ, et al.COMBACTE-CARE consortium/REJUVENATE Study Group. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: Results from the REJUVENATE study. J Antimicrob Chemother, 2020; 75(3):618–627; doi: 10.1093/jac/dkz497
11.
TsolakiV, MantzarlisK, MpakalisA, et al.Ceftazidime-Avibactam to treat life-threatening infections by carbapenem-resistant pathogens in critically Ill mechanically ventilated patients. Antimicrob Agents Chemother, 2020; 64(3); doi: 10.1128/aac.02320-19
12.
CarmeliY, CisnerosJM, PaulM, et al.A efficacy and safety of aztreonam-avibactam for the treatment of serious infections due to gram-negative bacteria, including Metallo-β-Lactamase-producing pathogens: Phase 3 REVISIT study. Lancet Infet Dis, 2023:ofad500.2476. 2328–o8957.
13.
SaderHS, MendesRE, PfallerMA, et al.Antimicrobial activities of -Avibactam and comparator agents against contemporary clinical enterobacteriaceae isolates. Antimicrob Agents Chemother, 2018; 62(1); doi: 10.1128/aac.01856-17
14.
KarlowskyJA, KazmierczakKM, de JongeBLM, et al.In Vitro Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015. Antimicrob Agents Chemother, 2017; 61(9); doi: 10.1128/aac.00472-17
15.
HuangYS, ChenPY, ChouPC, WangJT. In Vitro activities and inoculum effects of cefiderocol and aztreonam-avibactam against Metallo-β-Lactamase-producing enterobacteriaceae. Microbiol Spectr, 2023; 11(3):e0056923; doi: 10.1128/spectrum.00569-23
16.
SaderHS, MendesRE, KimbroughJH, et al.Activity of aztreonam/avibactam and recently approved β-Lactamase inhibitor combinations against enterobacterales and pseudomonas aeruginosa from intensive care unit and non-intensive care unit patients. Antibiotics (Basel), 2024; 13(6); doi: 10.3390/antibiotics13060564
17.
JacobsLMC, ConsolP, ChenY. Drug discovery in the field of β-Lactams: An academic perspective. Antibiotics (Basel), 2024; 13(1); doi: 10.3390/antibiotics13010059
18.
SadekM, JuhasM, PoirelL, NordmannP. Genetic features leading to reduced susceptibility to aztreonam-avibactam among Metallo-β-Lactamase-Producing escherichia coli isolates. Antimicrob Agents Chemother, 2020; 64(12); doi: 10.1128/aac.01659-20
19.
TellapragadaC, RazaviM, PerisPS, et al.Resistance to aztreonam-avibactam among clinical isolates of E. coli is primarily mediated by altered penicillin binding protein 3 and impermeability. Int J Antimicrob Agents, 2024; 64(3):107256; doi: 10.1016/j.ijantimicag.2024.107256
20.
WangHY, YooG, KimJ, et al.Development of a rapid reverse blot hybridization assay for detection of clinically relevant antibiotic resistance genes in blood cultures testing positive for gram-negative bacteria. Front Microbiol, 2017; 8:185; doi: 10.3389/fmicb.2017.00185
21.
ViguierC, BouvierM, SadekM, et al.Rapid Aztreonam/Avibactam NP test for detection of aztreonam/avibactam susceptibility/resistance in Enterobacterales. J Clin Microbiol, 2023; 61(10):e0058823; doi: 10.1128/jcm.00588-23
22.
EUCAST. Breakpoint tables for interpretation of MICs and zone diameters. Version 14.0. The European Committee on Antimicrobial Susceptibility Testing. 2024. Available from: http://www.eucast.org
23.
NordmannP, GirlichD, PoirelL. Detection of carbapenemase producers in Enterobacteriaceae by use of a novel screening medium. J Clin Microbiol, 2012; 50(8):2761–2766; doi: 10.1128/jcm.06477-11
24.
SadekM, PoirelL, TinguelyC, NordmannP. A selective culture medium for screening ceftazidime-avibactam resistance in Enterobacterales and Pseudomonas aeruginosa. J Clin Microbiol, 2020; 58(9); doi: 10.1128/jcm.00965-20
25.
NordmannP, SadekM, Ortiz de la RosaJM, et al.Selective culture medium for screening of fosfomycin resistance in Enterobacterales. J Clin Microbiol, 2022; 60(1):e0206321; doi: 10.1128/jcm.02063-21
26.
NordmannP, FournierC, PoirelL. A selective culture medium for screening carbapenem resistance in Pseudomonas spp. Microb Drug Resist, 2021; 27(10):1355–1359; doi: 10.1089/mdr.2020.0461
27.
IbrahimA, BouvierM, SadekM, et al.A selective culture medium for screening cefiderocol resistance in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. J Clin Microbiol, 2023; 61(7):e0188322; doi: 10.1128/jcm.01883-22
28.
HumphriesRM, AmblerJ, MitchellSL, et al.CLSI Methods Development and Standardization Working Group of the Subcommittee on Antimicrobial Susceptibility Testing. CLSI methods development and standardization working group best practices for evaluation of antimicrobial susceptibility tests. J Clin Microbiol, 2018; 56(4); doi: 10.1128/jcm.01934-17
29.
WuS, MaK, FengY, ZongZ. Resistance to aztreonam-avibactam due to a mutation of SHV-12 in Enterobacter. Ann Clin Microbiol Antimicrob, 2023; 22(1):49; doi: 10.1186/s12941-023-00605-y
30.
MushtaqS, VickersA, WoodfordN, LivermoreDM. Activity of aztreonam/avibactam and ceftazidime/avibactam against Enterobacterales with carbapenemase-independent carbapenem resistance. Int J Antimicrob Agents, 2024; 63(3):107081; doi: 10.1016/j.ijantimicag.2023.107081
31.
Le TerrierC, NordmannP, SadekM, PoirelL. In vitro activity of cefepime/zidebactam and cefepime/taniborbactam against aztreonam/avibactam-resistant NDM-like-producing Escherichia coli clinical isolates. J Antimicrob Chemother, 2023; 78(5):1191–1194; doi: 10.1093/jac/dkad061
32.
HelsensN, SadekM, Le TerrierC, et al.Reduced susceptibility to aztreonam-avibactam conferred by acquired AmpC-type β-lactamases in PBP3-modified Escherichia coli. Eur J Clin Microbiol Infect Dis, 2024; doi: 10.1007/s10096-024-04769-z
33.
WuS, ZongZ. Aztreonam-avibactam: An option against carbapenem-resistant Enterobacterales with emerging resistance. Precis Clin Med, 2022; 5(4):pbac029; doi: 10.1093/pcmedi/pbac029
34.
MaK, ZongZ. Resistance to aztreonam-avibactam due to CTX-M-15 in the presence of penicillin-binding protein 3 with extra amino acids in Escherichia coli. Front Microbiol, 2022; 13:1047109; doi: 10.3389/fmicb.2022.1047109
35.
NordmannP, YaoY, FalgenhauerL, et al.Recent emergence of Aztreonam-Avibactam resistance in NDM and OXA-48 Carbapenemase-Producing Escherichia coli in Germany. Antimicrob Agents Chemother, 2021; 65(11):e0109021; doi: 10.1128/aac.01090-21
36.
LinkeviciusM, BonninRA, AlmE, et al.Rapid cross-border emergence of NDM-5-producing Escherichia in the European Union/European economic area, 2021 to June 2022. Eurosurveillance, 2023; 28(19):1–6.
