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1.
Microbiol Spectr ; : e0070424, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860818

RESUMO

The impact of chromosomally encoded wild-type or extended-spectrum (ESAC) AmpC ß-lactamases of Escherichia coli on susceptibility to ceftazidime, cefepime, and cefiderocol was evaluated in different genetic backgrounds, including wild-type, PBP3-modified, and porin-deficient E. coli strains. Recombinant E. coli strains possessing the different backgrounds and producing variable ESACs were evaluated. Although ESAC enzymes conferred resistance to ceftazidime and decreased susceptibility to cefepime as expected, we showed here that cefiderocol was also a substrate of ESAC enzymes. IMPORTANCE: We showed here that chromosomally encoded intrinsic extended-spectrum cephalosporinases of Escherichia coli may impact susceptibility not only to ceftazidime and cefepime but also to cefiderocol.

2.
Antimicrob Agents Chemother ; : e0157023, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727224

RESUMO

Xeruborbactam is a newly developed ß-lactamase inhibitor designed for metallo-ß-lactamases (MBLs). This study assessed the relative inhibitory properties of this novel inhibitor in comparison with another MBL inhibitor, namely taniborbactam (TAN), against a wide range of acquired MBL produced either in Escherichia coli or Pseudomonas aeruginosa. As observed with taniborbactam, the combination of xeruborbactam (XER) with ß-lactams, namely, ceftazidime, cefepime and meropenem, led to significantly decreased MIC values for a wide range of B1-type MBL-producing E. coli, including most recombinant strains producing NDM, VIM, IMP, GIM-1, and DIM-1 enzymes. Noteworthily, while TAN-based combinations significantly reduced MIC values of ß-lactams for MBL-producing P. aeruginosa recombinant strains, those with XER were much less effective. We showed that this latter feature was related to the MexAB-OprM efflux pump significantly impacting MIC values when testing XER-based combinations in P. aeruginosa. The relative inhibitory concentrations (IC50 values) were similar for XER and TAN against NDM and VIM enzymes. Noteworthily, XER was effective against NDM-9, NDM-30, VIM-83, and most of IMP enzymes, although those latter enzymes were considered resistant to TAN. However, no significant inhibition was observed with XER against IMP-10, SPM-1, and SIM-1 as well as the representative subclass B2 and B3 enzymes, PFM-1 and AIM-1. The determination of the constant inhibition (Ki) of XER revealed a much higher value against IMP-10 than against NDM-1, VIM-2, and IMP-1. Hence, IMP-10 that differs from IMP-1 by a single amino-acid substitution (Val67Phe) can, therefore, be considered resistant to XER.

3.
Int J Antimicrob Agents ; 64(2): 107206, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754526

RESUMO

BACKGROUND: Recently developed therapeutics against Gram-negative bacteria include the ß-lactam-ß-lactamase inhibitor combinations ceftazidime-avibactam (CZA), meropenem-vaborbactam (MEV), and imipenem-relebatam (IPR), and the siderophore cephalosporin cefiderocol (FDC). The aim of this study was to develop a test for rapid identification of susceptibility/resistance to CZA, MEV, IPR, and FDC for Enterobacterales in a single test for rapid clinical decision making. METHODS: The MultiRapid ATB NP test is based on the detection of glucose metabolism occurring after bacterial growth in the presence of defined concentrations of CZA, MEV, IPR, and FDC, followed by visual detection of colour change of the pH indicator red phenol (red to yellow) generated by the acidification of the medium upon bacterial growth. This test is performed in 96-well microplates. The MultiRapid ATB NP test was evaluated using 78 Enterobacterales isolates and compared to the reference method broth microdilution. RESULTS: The MultiRapid ATB NP test displayed 97.0% (confidence interval [CI] 92.6-98.8) sensitivity, 97.7% (CI 94.3-99.1) specificity, and 97.4% (CI 95.0-98.7) accuracy. The results were obtained after 3 h of incubation at 35 °C ± 2 °C, representing at least a 15-h gain-of-time compared with currently used antimicrobial susceptibility testing methods. CONCLUSION: The MultiRapid ATB NP test provided accurate results for the concomitant detection of susceptibility/resistance to CZA, MEV, IPR, and FDC in Enterobacterales, independent of the resistance mechanism. This test may be suitable for implementation in any microbiology routine laboratory.

4.
Diagn Microbiol Infect Dis ; 109(4): 116356, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38763036

RESUMO

Plasmid-encoded DHA-type AmpCs have been extensively reported in Enterobacterales. The expression of the genes encoding these plasmid-mediated enzymes are inducible and these enzymes are capable of conferring resistance to a wide spectrum of beta-lactams including penicillins and broad-spectrum cephalosporins. The identification of infections caused by AmpC-producing bacteria is a necessity, both for infection control/epidemiology purposes and to inform treatment choices. A common testing method for AmpC production in the clinical laboratory setting is to supplement Mueller-Hinton agar plates used for antibiotic disk diffusion with cloxacillin, a potent inhibitor of AmpC enzymes. Here we describe a novel DHA variant, produced by a clinical Escherichia coli isolate, which is resistant to cloxacillin inhibition.


Assuntos
Antibacterianos , Proteínas de Bactérias , Cloxacilina , Escherichia coli , Testes de Sensibilidade Microbiana , beta-Lactamases , Cloxacilina/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/tratamento farmacológico
5.
Antimicrob Agents Chemother ; 68(4): e0145923, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38441061

RESUMO

Beta-lactamase-mediated degradation of beta-lactams is the most common mechanism of beta-lactam resistance in Gram-negative bacteria. Beta-lactamase-encoding genes can be transferred between closely related bacteria, but spontaneous inter-phylum transfers (between distantly related bacteria) have never been reported. Here, we describe an extended-spectrum beta-lactamase (ESBL)-encoding gene (blaMUN-1) shared between the Pseudomonadota and Bacteroidota phyla. An Escherichia coli strain was isolated from a patient in Münster (Germany). Its genome was sequenced. The ESBL-encoding gene (named blaMUN-1) was cloned, and the corresponding enzyme was characterized. The distribution of the gene among bacteria was investigated using the RefSeq Genomes database. The frequency and relative abundance of its closest homolog in the global microbial gene catalog (GMGC) were analyzed. The E. coli strain exhibited two distinct morphotypes. Each morphotype possessed two chromosomal copies of the blaMUN-1 gene, with one morphotype having two additional copies located on a phage-plasmid p0111. Each copy was located within a 7.6-kb genomic island associated with mobility. blaMUN-1 encoded for an extended-spectrum Ambler subclass A2 beta-lactamase with 43.0% amino acid identity to TLA-1. blaMUN-1 was found in species among the Bacteroidales order and in Sutterella wadsworthensis (Pseudomonadota). Its closest homolog in GMGC was detected frequently in human fecal samples. This is, to our knowledge, the first reported instance of inter-phylum transfer of an ESBL-encoding gene, between the Bacteroidota and Pseudomonadota phyla. Although the gene was frequently detected in the human gut, inter-phylum transfer was rare, indicating that inter-phylum barriers are effective in impeding the spread of ESBL-encoding genes, but not entirely impenetrable.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , beta-Lactamases/genética , beta-Lactamases/metabolismo , Infecções por Escherichia coli/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
6.
Artigo em Inglês | MEDLINE | ID: mdl-38319508

RESUMO

PURPOSE: Carbapenemase-producing Enterobacterales are a growing threat, and very few therapeutic options remain active against those multidrug resistant bacteria. Aztreonam is the molecule of choice against metallo-beta-lactamases (MBL) producers since it is not hydrolyzed by those enzymes, but the co-production of acquired plasmidic cephalosporinases or extended-spectrum ß-lactamases leading to aztreonam resistance may reduce the efficacy of this molecule. Hence, the development of the aztreonam-avibactam (AZA) combination provides an interesting therapeutic alternative since avibactam inhibits the activity of both cephalosporinases and extended-spectrum ß-lactamases. However, structural modifications of penicillin binding protein PBP3, the target of aztreonam, may lead to reduced susceptibility to aztreonam-avibactam. METHODS: Here the impact of various plasmid-encoded AmpC-type ß-lactamases (ACC-1, ACT-7, ACT-17, CMY-2, CMY-42, DHA-1, FOX-1, and FOX-5) on susceptibility to aztreonam-avibactam was evaluated using isogenic E. coli MG1655 strains harboring insertions in PBP3 (YRIN and YRIK). The inhibitory activity of various ß-lactamase inhibitors (clavulanic acid, tazobactam, avibactam, relebactam, and vaborbactam) were also compared against these enzymes. RESULTS: Hence, we showed that reduced susceptibility to AZA was due to the combined effect of both AmpC production and amino acid insertions in PBP3. The highest resistance level was achieved in strains possessing the insertions in PBP3 in association with the production of ACT-7, ACC-1, or CMY-42. CONCLUSION: Although none of the recombinant strains tested displayed clinical resistance to aztreonam-avibactam, our data emphasize that the occurrence of such profile might be of clinical relevance for MBL-producing strains.

9.
Antimicrob Agents Chemother ; 68(4): e0154823, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38415988

RESUMO

The impact of penicillin-binding protein 3 (PBP3) modifications that may be identified in Escherichia coli was evaluated with respect to susceptibility to ß-lactam/ß-lactamase inhibitor combinations including ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and to cefiderocol. A large series of E. coli recombinant strains producing broad-spectrum ß-lactamases was evaluated. While imipenem-relebactam showed a similar activity regardless of the PBP3 background, susceptibility to other molecules tested was affected at various levels. This was particularly the case for ceftazidime-avibactam, aztreonam-avibactam, and cefepime-taniborbactam.


Assuntos
Aztreonam , Ácidos Borínicos , Ácidos Borônicos , Ácidos Carboxílicos , Cefiderocol , Ceftazidima , Aztreonam/farmacologia , Meropeném/farmacologia , Cefepima/farmacologia , Proteínas de Ligação às Penicilinas , Escherichia coli , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/química , Combinação de Medicamentos , Imipenem/farmacologia , Imipenem/química , Testes de Sensibilidade Microbiana
10.
Eur J Clin Microbiol Infect Dis ; 43(3): 551-557, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38233610

RESUMO

OBJECTIVES: The occurrence of metallo-beta-lactamase-producing Pseudomonas aeruginosa (MBL-PA) isolates is increasing globally, including in Switzerland. The aim of this study was to characterise, phenotypically and genotypically, the MBL-PA isolates submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) reference laboratory over a 12-month period from July 2022 to July 2023. METHODS: Thirty-nine non-duplicate MBL-PA Isolates were submitted to NARA over the study period from across Switzerland. Susceptibility was determined by broth microdilution according to EUCAST methodology. Whole-genome sequencing was performed on 34 isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. MBL genes, blaNDM-1, blaIMP-1, and blaVIM-2, were cloned into vector pUCP24 and transformed into P. aeruginosa PA14. RESULTS: The most prevalent MBL types identified in this study were VIM (21/39; 53.8%) followed by NDM (11/39; 28.2%), IMP (6/39; 15.4%), and a single isolate produced both VIM and NDM enzymes. WGS identified 13 different STs types among the 39 isolates. They all exhibited resistance to cephalosporins, carbapenems, and the beta-lactam-beta-lactamase inhibitor combinations, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam, and 8 isolates were cefiderocol (FDC) resistant. Recombinant P. aeruginosa strains producing blaNDM-1, blaIMP-1, and blaVIM-2 exhibited FDC MICs of 16, 8, and 1 mg/L, respectively. CONCLUSIONS: This study showed that the MBL-PA in Switzerland could be attributed to the wide dissemination of high-risk clones that accounted for most isolates in this study. Although FDC resistance was only found in 8 isolates, MBL carriage was shown to be a major contributor to this phenotype.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Suíça/epidemiologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia
11.
Emerg Infect Dis ; 30(2): 255-261, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38270160

RESUMO

We developed a novel culture-based test, the Rapid CAZ/AVI NP test, for rapid identification of ceftazidime/avibactam susceptibility/resistance in Enterobacterales. This test is based on glucose metabolization upon bacterial growth in the presence of a defined concentration of ceftazidime/avibactam (128/53 µg/mL). Bacterial growth is visually detectable by a red to yellow color change of red phenol, a pH indicator. A total of 101 well characterized enterobacterial isolates were used to evaluate the test performance. This test showed positive percent agreement of 100% and negative percent agreement of 98.5% with overall percent agreement of 99%, by comparison with the MIC gradient strip test (Etest) taken as the reference standard method. The Rapid CAZ/AVI NP test had only 1.5% major errors and 0% extremely major errors. This test is rapid (result within 2 hours 45 minutes), reliable, affordable, easily interpretable, and easy to implement in clinical microbiology laboratories without requiring any specific equipment.


Assuntos
Compostos Azabicíclicos , Ceftazidima , Gammaproteobacteria , Ceftazidima/farmacologia , Enterobacteriaceae , Laboratórios
12.
Antimicrob Agents Chemother ; 68(2): e0099123, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38047644

RESUMO

Taniborbactam (TAN) is a novel broad-spectrum ß-lactamase inhibitor with significant activity against subclass B1 metallo-ß-lactamases (MBLs). Here, we showed that TAN exhibited an overall excellent activity against B1 MBLs including most NDM- and VIM-like as well as SPM-1, GIM-1, and DIM-1 enzymes, but not against SIM-1. Noteworthy, VIM-1-like enzymes (particularly VIM-83) were less inhibited by TAN than VIM-2-like. Like NDM-9, NDM-30 (also differing from NDM-1 by a single amino acid substitution) was resistant to TAN.


Assuntos
Ácidos Borínicos , beta-Lactamases , beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , Ácidos Borínicos/farmacologia , Ácidos Carboxílicos/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
13.
Diagn Microbiol Infect Dis ; 108(2): 116153, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086168

RESUMO

The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.g., Gram-negatives. A pharmacometric model was built from tigecycline concentrations (100-600 mg daily doses) against clinical Klebsiella pneumoniae isolates (MIC 0.125-0.5 mg/L). Regrowth occurred at clinically used doses and stasis was only achieved with 100 mg q8h for the strain with the lowest studied MIC of 0.125 mg/L. Stasis at 24 h was related to fAUC/MIC of 38.5. Our study indicates that even intensified dosing regimens might prevent bloodstream infections only for MIC values ≤0.125 mg/L for tigecycline. This indicates an overly optimistic breakpoint of 1 mg/L for Enterobacterales, which are deemed to respond to the tigecycline high dose regimen (EUCAST Guidance Document on Tigecycline Dosing 2022).


Assuntos
Antibacterianos , Bacteriemia , Humanos , Tigeciclina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Klebsiella pneumoniae , Minociclina/farmacologia , Minociclina/uso terapêutico , Bacteriemia/tratamento farmacológico , Testes de Sensibilidade Microbiana , beta-Lactamases
14.
Microbiol Spectr ; 12(1): e0331823, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38063387

RESUMO

IMPORTANCE: Mechanistic understanding of pharmacodynamic interactions is key for the development of rational antibiotic combination therapies to increase efficacy and suppress the development of resistances. Potent tools to provide those insights into pharmacodynamic drug interactions are semi-mechanistic modeling and simulation techniques. This study uses those techniques to provide a detailed understanding with regard to the direction and strength of the synergy of ceftazidime-avibactam and ceftazidime-fosfomycin in a clinical Escherichia coli isolate expressing extended spectrum beta-lactamase (CTX-M-15 and TEM-4) and carbapenemase (OXA-244) genes. Enhanced killing effects in combination were identified as a driver of the synergy and were translated from static time-kill experiments into the dynamic hollow fiber infection model. These findings in combination with a suppression of the emergence of resistance in combination emphasize a potential clinical benefit with regard to increased efficacy or to allow for dose reductions with maintained effect sizes to avoid toxicity.


Assuntos
Compostos Azabicíclicos , Ceftazidima , Fosfomicina , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Fosfomicina/farmacologia , Escherichia coli/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/genética , Testes de Sensibilidade Microbiana , Combinação de Medicamentos
15.
Eur J Clin Microbiol Infect Dis ; 43(2): 339-354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38095831

RESUMO

PURPOSE: To evaluate the different present and future therapeutic ß-lactam/ß-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. METHODS: MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being ≥1 mg/L. If unavailable, the respective ß-lactam breakpoints according to EUCAST were used for BL/BLI combinations. RESULTS: For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs. CONCLUSIONS: Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.


Assuntos
Compostos Azabicíclicos , Aztreonam , Ácidos Borínicos , Ácidos Borônicos , Ácidos Carboxílicos , Cefiderocol , Ciclo-Octanos , Lactamas , Piperidinas , Humanos , Meropeném/farmacologia , Cefepima , Aztreonam/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Imipenem/farmacologia , Inibidores de beta-Lactamases/farmacologia , Testes de Sensibilidade Microbiana , beta-Lactamases
16.
Microorganisms ; 11(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38138025

RESUMO

Heavy metals such as zinc (Zn) and copper (Cu) may be associated with antibiotic resistance dissemination. Our aim was to investigate whether sub-lethal dosage of Zn and Cu may enhance plasmid transfer and subsequently resistance genes dissemination. Plasmid conjugation frequencies (PCF) were performed with Escherichia coli strains bearing IncL-blaOXA-48, IncA/C-blaCMY-2, IncI1-blaCTX-M-1, IncF-blaCTX-M-1, and IncX3-blaNDM-5 as donors. Mating-out assays were performed with sub-dosages of zinc oxide (ZnO) and Cu sulfate (CuSO4). Quantification of the SOS response-associated gene expression levels and of the production of reactive oxygen species were determined. Increased PCF was observed for IncL, IncA/C, and IncX3 when treated with ZnO. PCF was only increased for IncL when treated with CuSO4. The ROS production presented an overall positive correlation with PCF after treatment with ZnO for IncL, IncA/C, and IncX3. For CuSO4 treatment, the same was observed only for IncL. No increase was observed for expression of SOS response-associated genes under CuSO4 treatment, and under ZnO treatment, we observed an increase in SOS response-associated genes only for IncX3. Our data showed that sub-dosages of ZnO and CuSO4 could significantly enhance PCF in E. coli, with a more marked effect observed with IncL, IncA/C, and IncX3 scaffolds. Our study suggested that use of certain heavy metals is not the panacea for avoiding use of antibiotics in order to prevent the dissemination of antibiotic resistance.

17.
Eur J Clin Microbiol Infect Dis ; 42(12): 1511-1518, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37910268

RESUMO

PURPOSE: Due to its ability to disseminate worldwide and its multiple resistance trait, Acinetobacter baumannii is becoming a threat for public health worldwide. Cefiderocol (FDC) is a promising broad-spectrum cephalosporin recently approved for treating Gram-negative infection. The aim of this study was to develop a rapid test, namely the rapid FDC Acinetobacter baumannii NP test, for the detection of FDC susceptibility/resistance in A. baumannii since the current FDC susceptibility tests are rather time-consuming (at least 24 h). MATERIALS AND METHODS: The rapid test is based on the reduction of resazurin to resorufin product by bacterial viable cells, thus detecting bacterial growth in the presence of FDC (38.4 mg/L). A color change from blue (resazurin) to violet or pink (resorufin) represents visual detection of bacterial growth. 95 randomly selected A. baumannii isolates were used to evaluate the performance of the rapid FDC Acinetobacter baumannii NP test. RESULTS: The test showed 95.5% (95% CI 78.2-99.2%) and 100.0% (95% CI 95.0-100.0%) of sensitivity and specificity, respectively. All the results were obtained within 4 h30-4 h45 incubation time at 35 °C ± 2 °C, saving virtually one day when compared with currently-used antimicrobial susceptibility tests. The test showed only a single very major error, an isolate with a MIC of 8 mg/L. CONCLUSIONS: The rapid FDC Acinetobacter baumannii NP test can be a valuable method which is easier and faster to interpret when compared with the gold standard broth microdilution method. The test showed remarkable performances; hence, it may be suitable for implementation in clinical microbiology routine laboratories.


Assuntos
Acinetobacter baumannii , Antibacterianos , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Cefalosporinas/farmacologia , Testes de Sensibilidade Microbiana , Cefiderocol
18.
J Antimicrob Chemother ; 78(12): 2950-2960, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37923369

RESUMO

BACKGROUND: Enterobacter hormaechei producing the carbapenemase OXA-48 was identified repeatedly in infections in companion animals hospitalized at a Swiss veterinary clinic where OXA-48-producing Klebsiella pneumoniae was previously reported. OBJECTIVES: To determine the genetic relatedness of animal and human E. hormaechei strains collected in Switzerland during 2017-22 and their mobile genetic elements. METHODS: Hybrid assemblies for phylogenetic and comparative analysis of animal (n = 9) and human (n = 25) isolates were obtained by sequencing with Illumina, PacBio and Oxford Nanopore Technologies. Antimicrobial susceptibility was tested by broth microdilution. RESULTS: The animal strains were identified as E. hormaechei subsp. xiangfangensis ST114 (n = 6) and ST418 (n = 2), and E. hormaechei subsp. hoffmannii ST78 (n = 1). Human E. hormaechei belonged to subspecies steigerwaltii (n = 10), xiangfangensis (n = 13), hoffmannii (n = 1) and hormaechei (n = 1), with a heterogeneous ST distribution differing from the animal strains, except for two ST114. Core-gene SNP analysis confirmed the clonality of the animal ST114 and ST418 isolates (0 to 10 SNPs), and close relatedness of animal and human ST114 strains (80-120 SNPs). The strains harboured the blaOXA-48 gene on ca. 63 kb IncL-type plasmids (n = 27); on ca. 72 kb IncL plasmids co-harbouring blaCTX-M-14 (n = 2); and on ca. 150-180 kb IncFIB (n = 4) or hybrid IncFIB/IncL (n = 1) plasmids. The blaOXA-48-harbouring plasmids and the blaDHA-1-carrying ISCR1 element in one animal ST114 and both ST418 clones were likely acquired from previously spreading K. pneumoniae strains. CONCLUSIONS: Common ecological niches favour the spread of plasmid-borne carbapenemases among Enterobacterales and the emergence of MDR E. hormaechei clones.


Assuntos
Infecções por Klebsiella , Animais de Estimação , Animais , Humanos , Filogenia , Suíça , Proteínas de Bactérias/genética , beta-Lactamases/genética , Klebsiella pneumoniae/genética , Plasmídeos/genética , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
19.
J Clin Microbiol ; 61(10): e0058823, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37791761

RESUMO

Aztreonam-avibactam (AZA), a newly developed ß-lactam/ß-lactamase inhibitor combination, is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.


Assuntos
Antibacterianos , Aztreonam , Humanos , Aztreonam/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases , Compostos Azabicíclicos/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Testes de Sensibilidade Microbiana , Combinação de Medicamentos , Ceftazidima/farmacologia
20.
Diagn Microbiol Infect Dis ; 107(3): 116043, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37657230

RESUMO

The Resist Acineto from Coris Bioconcept is a novel immunochromatographic test for detection of the major acquired carbapenemases (OXA-23, OXA-40, OXA-58, and NDM) identified in Acinetobacter spp. This rapid and easy-to-perform test showed an excellent specificity and sensitivity, with positive and negatives predictive values of 100% in both cases.


Assuntos
Acinetobacter , Enterobacteriaceae , Humanos , Técnicas Bacteriológicas/métodos , Sensibilidade e Especificidade , beta-Lactamases/análise , Proteínas de Bactérias/análise , Testes Imunológicos , Testes de Sensibilidade Microbiana
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