scholarly journals The Effect of Posaconazole, Itraconazole and Voriconazole in the Culture Medium on Aspergillus fumigatus Triazole Resistance

2020 ◽  
Vol 8 (2) ◽  
pp. 285 ◽  
Author(s):  
Martyna Mroczyńska ◽  
Ewelina Kurzyk ◽  
Magdalena Śliwka-Kaszyńska ◽  
Urszula Nawrot ◽  
Marta Adamik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aspergillus Fumigatus ◽  
Culture Medium ◽  
Acquired Resistance ◽  
Azole Resistance ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Selection Of

Triazoles are the only compounds used as antibiotics in both medicine and agriculture. The presence of triazoles in the environment can contribute to the acquisition of azole resistance among isolates of Aspergillus fumigatus. The objective of this study was to investigate the effect of A. fumigatus exposure to triazoles on susceptibility to these compounds. Seventeen triazole-resistant and 21 triazole-sensitive A. fumigatus isolates were examined. The isolates were transferred 20 times on the Sabouraud medium supplemented with posaconazole, itraconazole or voriconazole, followed by five times on the medium not supplemented. The minimum inhibitory concentrations of antimycotics were examined according to the EUCAST broth microdilution method after the 20th transfer and also the 25th transfer. In addition, the expression levels of genes mdr1, mdr2, mdr3, atrF, cyp51A and cyp51B were determined. Cultivation of A. fumigatus on media supplemented with posaconazole, itraconazole and voriconazole resulted in the acquisition of resistance to the tested triazoles of all examined isolates. After recultivation on Sabouraud without azoles, most of the isolates lost their acquired resistance. The long-term use of triazole compounds in agriculture may result in the occurrence of triazole resistant A. fumigatus isolates in the environment, not only by induction or selection of mutations in the cyp51A gene, but also by contribution to changes in the gene expression.

scholarly journals In Vitro Evaluation of the activity of Ceftazidime-avibactam and Aztreonam-Avibactam against 76 Stenotrophomonas maltophilia isolates from a teaching hospital in Chongqing

2020 ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018. Methods: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates of which were available for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM) and aztreonam-avibactam (ATM-AVI) were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more effective in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” with CAZ or ATM alone to “Susceptible” or “Intermediate” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 2-fold lower than the MIC of CAZ or ATM alone. Results: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 μg/mL, respectively. In combined therapy, AVI was effective at restoring the susceptibility of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs.56.58%, P<0.001), MIC50 (2μg/mL vs. 8μg/mL, P<0.05), and MIC distribution (P<0.001) when compared to CAZ. According to our definition, CAZ-AVI was more effective in vitro than CAZ alone for 84.21% of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79%vs. 10.53%, P<0.001), MIC50 (2μg/mL vs. 64μg/mL, P<0.001), and MIC distribution (P<0.001) when compared to ATM. According to our definition, ATM-AVI was also more effective in vitro than ATM alone for 97.37% of the isolates. Conclusions: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

scholarly journals Multicenter Study of Anidulafungin and Micafungin MIC Distributions and Epidemiological Cutoff Values for Eight Candida Species and the CLSI M27-A3 Broth Microdilution Method

2013 ◽  
Vol 58 (2) ◽  
pp. 916-922 ◽  
Author(s):  
M. A. Pfaller ◽  
A. Espinel-Ingroff ◽  
B. Bustamante ◽  
E. Canton ◽  
D. J. Diekema ◽  
...  
Keyword(s):  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method ◽  
Species Specific

ABSTRACTSince epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available forCandidaspp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210Candida albicans, 3,102C. glabrata, 3,976C. parapsilosis, 2,042C. tropicalis, 617C. krusei, 258C. lusitaniae, 234C. guilliermondii, and 131C. dubliniensisisolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml forC. albicans, 0.12 and 0.03 μg/ml forC. glabrata, 8 and 4 μg/ml forC. parapsilosis, 0.12 and 0.06 μg/ml forC. tropicalis, 0.25 and 0.25 μg/ml forC. krusei, 1 and 0.5 μg/ml forC. lusitaniae, 8 and 2 μg/ml forC. guilliermondii, and 0.12 and 0.12 μg/ml forC. dubliniensis. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (nofksmutations) and 51 isolates withfksmutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of thefksmutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due tofksmutations.

scholarly journals Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for Aspergillus spp. for the CLSI M38-A2 Broth Microdilution Method

2013 ◽  
Vol 57 (8) ◽  
pp. 3823-3828 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
G. M. Gonzalez ◽  
C. Lass-Flörl ◽  
E. Martin-Mazuelos ◽  
...  
Keyword(s):  
Species Complex ◽  
Acquired Resistance ◽  
Resistance Mechanism ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTEpidemiological cutoff values (ECVs) were established for the new triazole isavuconazole andAspergillusspecies wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) that were defined with 855Aspergillus fumigatus, 444A. flavus, 106A. nidulans, 207A. niger, 384A. terreus, and 75A. versicolorspecies complex isolates; 22AspergillussectionUstiisolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico, and the United States were aggregated to statistically define ECVs. ECVs were 1 μg/ml for theA. fumigatusspecies complex, 1 μg/ml for theA. flavusspecies complex, 0.25 μg/ml for theA. nidulansspecies complex, 4 μg/ml for theA. nigerspecies complex, 1 μg/ml for theA. terreusspecies complex, and 1 μg/ml for theA. versicolorspecies complex; due to the small number of isolates, an ECV was not proposed forAspergillussectionUsti. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to isavuconazole due tocyp51A(anA. fumigatusspecies complex resistance mechanism among the triazoles) or other mutations.

scholarly journals Wild-Type MIC Distributions and Epidemiological Cutoff Values for Amphotericin B and Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)

2011 ◽  
Vol 55 (11) ◽  
pp. 5150-5154 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
M. Ghannoum ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTAlthough clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available forAspergillusspp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for sixAspergillusspp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those forA. fumigatus(3,988/833),A. flavus(793/194),A. nidulans(184/69),A. niger(673/140),A. terreus(545/266), andA. versicolor(135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: forA. fumigatus, 2, 2, and 4; forA. flavus, 2, 4, and 4; forA. nidulans, 4, 4, and 4; forA. niger, 2, 2, and 2; forA. terreus, 4, 4, and 8; and forA. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.

scholarly journals Antifungal resistance modulation of Aspergillus fumigatus isolates from brooder pneumonia affected birds by Eucalyptus globulus extracts

2020 ◽  
pp. 145-155
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Eucalyptus Globulus ◽  
Ethanol Extract ◽  
Diffusion Method ◽  
Broth Microdilution ◽  
Diffusion Test ◽  
Base Pairs ◽  
Microdilution Method ◽  
Broth Microdilution Method

Brooder pneumonia is a common respiratory problem during brooding period of poultry. It is most frequently caused by Aspergillus fumigatus. Use of azole drugs for treatment and prophylaxis results in resistance. The aim of this study was to determine whether the phytochemicals of Eucalyptus globulus are modulating resistance in Aspergillus fumigatus. Lung samples n = 50 of dead broiler chicks were collected from different farms of Lahore. Out of 50 lung samples 28 % (14) were considered positive for Aspergillus fumigatus after observing their macroscopic, microscopic characteristics and by performing PCR by amplifying ITS1-ITS4 gene (597 base pairs) and RodA gene (313 base pairs). Kirby-Bauer disc diffusion test was performed 14 isolates (100 %) were resistant towards both Fluconazole and Ketoconazole whereas 11 (78.57 %) were resistant towards Itraconazole. Eucalyptus globulus leaves were collected, and these were identified. Three solvent extracts were prepared. Maximum yield was of ethanolic extract. Antifungal activity was evaluated by agar well diffusion method. Highest antifungal activity was shown by Eucalyptus globulus Ethanol followed by chloroform and hexane extract showed no activity against any isolate then minimum inhibitory concentration of plant extracts that previously showed antifungal activity against isolates were evaluated by broth microdilution method. Modulation effect was checked by combining antifungal drug one by one with subinhibitory concentration of plant extract evaluated previously by broth microdilution method. 5 isolates were subjected into this experiment which are all sensitive towards Eucalyptus globulus ethanol and chloroform extracts tested previously in agar well diffusion test and MIC values were also evaluated. It was concluded that when Itraconazole was combined with E. globulus Ethanol extract then resistance was modified. Data of modulation was analyzed by One-way ANOVA and it reported P value of <0.05. It was synergistic inhibitory effect when Itraconazole was combined with Eucalyptus globulus Ethanol extract.

scholarly journals Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018. Methods We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. Results For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 μg/mL vs. 8 μg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 μg/mL vs. 64 μg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. Conclusions AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

scholarly journals A Novel Combination of CYP51A Mutations Confers Pan-Azole Resistance in Aspergillus fumigatus

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Daiana Macedo ◽  
Tomás Brito Devoto ◽  
Santiago Pola ◽  
Jorge L. Finquelievich ◽  
María L. Cuestas ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Gene Replacement ◽  
Azole Resistance ◽  
New Mutation ◽  
Content Type ◽  
The Third ◽  
Resistant Phenotype ◽  
Intensive Use ◽  
Selection Of

ABSTRACT The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates, and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide. The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment. Strain susceptibilities were assessed, and CYP51A gene sequences were analyzed. Two of the studied Aspergillus fumigatus strains harbored the TR34-L98H allele. These strains showed high MIC values for all tested triazoles (>16.00 μg/ml, 1.00 μg/ml, 1.00 μg/ml, and 2.00 μg/ml for itraconazole, isavuconazole, posaconazole, and voriconazole, respectively). The third strain had a novel amino acid change (R65K) combined with the TR34-L98H mutations. This new mutation combination induces a pan-azole MIC augment compared with TR34-L98H mutants (>16 μg/ml, 4.00 μg/ml, 4.00 μg/ml, and 8.00 μg/ml for itraconazole, isavuconazole, posaconazole, and voriconazole, respectively). The strain harboring the TR34-R65K-L98H allele showed no inhibition halo when voriconazole susceptibility was evaluated by disk diffusion. The effect of these mutations in the azole-resistant phenotype was confirmed by gene replacement experiments. Transformants harboring the TR34-L98H and TR34-R65K-L98H alleles mimicked the azole-resistant phenotype of the clinical isolates, while the incorporation of the TR34-R65K and R65K alleles did not significantly increase azole MIC values. This is the first report of the TR34-L98H allele in Argentina. Moreover, a novel CYP51A allele (TR34-R65K-L98H) that induces a pan-azole MIC augment is described.

scholarly journals Wild-Type MIC Distributions and Epidemiological Cutoff Values for Caspofungin and Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)

2011 ◽  
Vol 55 (6) ◽  
pp. 2855-2859 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Fothergill ◽  
J. Fuller ◽  
E. Johnson ◽  
T. Pelaez ◽  
...  
Keyword(s):  
Antifungal Susceptibility ◽  
Acquired Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTClinical breakpoints have not been established for mold testing. Epidemiologic cutoff values (ECVs) are available for sixAspergillusspp. and the triazoles, but not for caspofungin. Wild-type (WT) minimal effective concentration (MEC) distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for sixAspergillusspp. and caspofungin. The number of available isolates was as follows: 1,691A. fumigatus, 432A. flavus, 192A. nidulans, 440A. niger, 385A. terreus, and 75A. versicolorisolates. CLSI broth microdilution MEC data gathered in five independent laboratories in Canada, Europe, and the United States were aggregated for the analyses. ECVs expressed in μg/ml that captured 95% and 99% of the modeled wild-type population were forA. fumigatus0.5 and 1,A. flavus0.25 and 0.5,A. nidulans0.5 and 0.5,A. niger0.25 and 0.25,A. terreus0.25 and 0.5, andA. versicolor0.25 and 0.5. Although caspofungin ECVs are not designed to predict the outcome of therapy, they may aid in the detection of strains with reduced antifungal susceptibility to this agent and acquired resistance mechanisms.

Antifungal Activity of Coumarins

2008 ◽  
Vol 63 (1-2) ◽  
pp. 21-28 ◽  
Author(s):  
Cristina Montagner ◽  
Simone M. de Souza ◽  
Cláudia Groposo ◽  
Franco Delle Monache ◽  
Elza F. A. Smânia ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Fusarium Solani ◽  
Alkyl Group ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Antifungal Potential ◽  
Mic Value

The antifungal activity of 40 coumarins was tested against the fungal strains: Candida albicans (ATCC 14053), Aspergillus fumigatus (ATCC 16913) and Fusarium solani (ATCC 36031), using the broth microdilution method. Osthenol showed the most effective antifungal activity among all the compounds tested, with a MIC value of 125 μg/ml for Fusarium solani and 250 μg/ml for Candida albicans and Aspergillus fumigatus. The antifungal potential of this prenylated coumarin can be related to the presence of an alkyl group at C-8 position.

scholarly journals In Vitro Evaluation of The Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam Against 76 Stenotrophomonas Maltophilia Isolates From A Teaching Hospital in Chongqing

2020 ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018.Methods: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates of which were available for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM) and aztreonam-avibactam (ATM-AVI) were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more effective in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” with CAZ or ATM alone to “Susceptible” or “Intermediate” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 2-fold lower than the MIC of CAZ or ATM alone.Results: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 μg/mL, respectively. In combined therapy, AVI was effective at restoring the susceptibility of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs.56.58%, P<0.001), MIC50 (2μg/mL vs. 8μg/mL, P<0.05), and MIC distribution (P<0.001) when compared to CAZ. According to our definition, CAZ-AVI was more effective in vitro than CAZ alone for 84.21% of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79%vs. 10.53%, P<0.001), MIC50 (2μg/mL vs. 64μg/mL, P<0.001), and MIC distribution (P<0.001) when compared to ATM. According to our definition, ATM-AVI was also more effective in vitro than ATM alone for 97.37% of the isolates.Conclusions: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

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