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Article: Heteroresistance to Colistin in Clinical Isolates of

Sánchez-León, Irene / García-Martínez, Teresa / Diene, Seydina M / Pérez-Nadales, Elena / Martínez-Martínez, Luis / Rolain, Jean-Marc

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 7

Abstract: Heteroresistance to colistin can be defined as the presence of resistant subpopulations in an isolate that is susceptible to this antibiotic. Colistin resistance in Gram-negative bacteria is more frequently related to chromosomal mutations and insertions. ...

Abstract	Heteroresistance to colistin can be defined as the presence of resistant subpopulations in an isolate that is susceptible to this antibiotic. Colistin resistance in Gram-negative bacteria is more frequently related to chromosomal mutations and insertions. This work aimed to study heteroresistance in nine clinical isolates of
Language	English
Publishing date	2023-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12071111
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Article ; Online: Heteroresistance to colistin in wild-type

Sánchez-León, Irene / Pérez-Nadales, Elena / Marín-Sanz, Juan Antonio / García-Martínez, Teresa / Martínez-Martínez, Luis

Microbiology spectrum

2023 Volume 11, Issue 6, Page(s) e0223823

Abstract: Importance: Colistin is one of the last remaining therapeutic options for dealing with Enterobacteriaceae. Unfortunately, heteroresistance to colistin is also rapidly increasing. We described the prevalence of colistin heteroresistance in a variety of ... ...

Abstract	Importance: Colistin is one of the last remaining therapeutic options for dealing with Enterobacteriaceae. Unfortunately, heteroresistance to colistin is also rapidly increasing. We described the prevalence of colistin heteroresistance in a variety of wild-type strains of
MeSH term(s)	Humans ; Colistin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Klebsiella pneumoniae ; Bacterial Proteins/genetics ; Drug Resistance, Bacterial/genetics ; Klebsiella Infections/drug therapy ; Klebsiella Infections/epidemiology ; Microbial Sensitivity Tests
Chemical Substances	Colistin (Z67X93HJG1) ; Anti-Bacterial Agents ; Bacterial Proteins
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02238-23
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Article ; Online: Community-acquired bacteraemia by Klebsiella pneumoniae producing KPC-3 and resistant to ceftazidime/avibactam.

Machuca, Isabel / Guzmán-Puche, Julia / Pérez-Nadales, E / Gracia-Ahufinger, I / Mendez, A / Cano, A / Castón, J J / Domínguez, A / Torre-Cisneros, J / Martínez-Martínez, L

Journal of global antimicrobial resistance

2022 Volume 30, Page(s) 399–402

Abstract: Objectives: To describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI).: Methods: Identification of microorganisms was performed ... ...

Abstract	Objectives: To describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI). Methods: Identification of microorganisms was performed with MALDI Biotyper CA System (BrukerDaltonics, Madrid, Spain). Antimicrobial susceptibility testing was performed using Sensitre EURGNCOL panels (Thermo Fisher Scientific, Madrid, Spain) and gradient strips (Etest, bioMérieux, Madrid, Spain) in the case of CAZ-AVI, using EUCAST breakpoints for interpretation. Whole genome sequencing of blood culture and rectal swab isolates was performed using the Illumina NovaSeq 6000 sequencing system, with 2 × 150-bp paired-end reads (Illumina, Inc.). Results: Blood culture and rectal swab KPCKP isolates were resistant to carbapenems and to CAZ-AVI. The blood culture isolate showed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), but the rectal swab culture isolate was resistant to this antibiotic. Both isolates belonged to clonal lineage ST512, harboured a single copy of bla Conclusions: Resistance to ceftazidime-avibactam is an emerging nosocomial problem. This case shows that CAZ-AVI-resistant KPCKP strains may disseminate into the community and cause serious infections.
MeSH term(s)	Azabicyclo Compounds ; Bacteremia ; Ceftazidime/pharmacology ; Drug Combinations ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/genetics ; Microbial Sensitivity Tests ; Trimethoprim, Sulfamethoxazole Drug Combination
Chemical Substances	Azabicyclo Compounds ; Drug Combinations ; avibactam, ceftazidime drug combination ; avibactam (7352665165) ; Trimethoprim, Sulfamethoxazole Drug Combination (8064-90-2) ; Ceftazidime (9M416Z9QNR)
Language	English
Publishing date	2022-07-22
Publishing country	Netherlands
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2710046-7
ISSN	2213-7173 ; 2213-7173
ISSN (online)	2213-7173
ISSN	2213-7173
DOI	10.1016/j.jgar.2022.07.017
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Article ; Online: In vivo selection of KPC-94 and KPC-95 in Klebsiella pneumoniae isolates from patients treated with ceftazidime/avibactam.

Guzmán-Puche, J / Pérez-Nadales, E / Pérez-Vázquez, M / Causse, M / Gracia-Ahufinger, I / Mendez-Natera, A / Allalou-Ruiz, Y / Elías, C / Oteo-Iglesias, J / Torre-Cisneros, J / Martínez-Martínez, L

International journal of antimicrobial agents

2022 Volume 59, Issue 2, Page(s) 106524

Abstract: Ceftazidime/avibactam (CZA) is used to treat infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). Resistance to CZA is commonly related to point mutations in the ... ...

Abstract	Ceftazidime/avibactam (CZA) is used to treat infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). Resistance to CZA is commonly related to point mutations in the bla
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Azabicyclo Compounds/pharmacology ; Azabicyclo Compounds/therapeutic use ; Bacterial Proteins/genetics ; Ceftazidime/pharmacology ; Ceftazidime/therapeutic use ; Drug Combinations ; Drug Resistance, Bacterial ; Humans ; Klebsiella Infections/drug therapy ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/drug effects ; Klebsiella pneumoniae/genetics ; Microbial Sensitivity Tests ; beta-Lactamases/genetics
Chemical Substances	Anti-Bacterial Agents ; Azabicyclo Compounds ; Bacterial Proteins ; Drug Combinations ; avibactam (7352665165) ; Ceftazidime (9M416Z9QNR) ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2022-01-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2022.106524
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Zs.A 3368: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Quantification and Isolation of Spontaneous Colony Growth Variants.

Díaz, Cristina López / Gómez-Gil, Lucía / Pérez-Nadales, Elena / Velasco, Gesabel Navarro / Di Pietro, Antonio

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2391, Page(s) 55–62

Abstract: The appearance of colony growth sectors on solid medium plates has been described in many fungi. Although the molecular bases of this phenomenon remain largely unknown, possible relationships with genetic or epigenetic changes have been reported. Here we ...

Abstract	The appearance of colony growth sectors on solid medium plates has been described in many fungi. Although the molecular bases of this phenomenon remain largely unknown, possible relationships with genetic or epigenetic changes have been reported. Here we present a method to quantify the frequency of colony growth sectors in Fusarium oxysporum, which can be used to compare different fungal strains and to infer their genetic instability.
MeSH term(s)	Culture Media ; Fusarium/genetics
Chemical Substances	Culture Media
Language	English
Publishing date	2021-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1795-3_5
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Article ; Online: Reply to "CMV merits further evolutionary and biological view".

Gutiérrez-Gutiérrez, Belén / Pérez-Nadales, Elena / Rodríguez-Baño, Jesús / Torre-Cisneros, Julián

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2020 Volume 20, Issue 5, Page(s) 1467–1468

MeSH term(s)	Bacterial Proteins ; Cytomegalovirus ; Cytomegalovirus Infections ; Humans ; Lymphopenia ; Transplant Recipients ; beta-Lactamases
Chemical Substances	Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
Language	English
Publishing date	2020-04-12
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.15867
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Article: The transmembrane protein Sho1 cooperates with the mucin Msb2 to regulate invasive growth and plant infection in Fusarium oxysporum

Perez‐Nadales, Elena / Di Pietro, Antonio

Molecular plant pathology. 2015 Aug., v. 16, no. 6

2015

Abstract: In the vascular wilt pathogen Fusarium oxysporum, the mitogen‐activated protein kinase (MAPK) Fmk1 is essential for plant infection. The mucin‐like membrane protein Msb2 regulates a subset of Fmk1‐dependent functions. Here, we examined the role of the ... ...

Abstract	In the vascular wilt pathogen Fusarium oxysporum, the mitogen‐activated protein kinase (MAPK) Fmk1 is essential for plant infection. The mucin‐like membrane protein Msb2 regulates a subset of Fmk1‐dependent functions. Here, we examined the role of the tetraspan transmembrane protein Sho1 as an additional regulator of the Fmk1 pathway and determined its genetic interaction with Msb2. Targeted Δsho1 mutants were generated in wild‐type and Δmsb2 backgrounds to test possible interactions between the two genes. The mutants were examined for hyphal growth under different stress conditions, phosphorylation of the MAPK Fmk1 and an array of Fmk1‐dependent virulence functions. Similar to Msb2, Sho1 was required for the activation of Fmk1 phosphorylation, as well as Fmk1‐dependent gene expression and invasive growth functions, including extracellular pectinolytic activity, cellophane penetration, plant tissue colonization and virulence on tomato plants. Δsho1 mutants were hypersensitive to the cell wall‐perturbing compound Calcofluor White, and this phenotype was exacerbated in the Δmsb2 Δsho1 double mutant. These results highlight that Sho1 and Msb2 have partially overlapping functions upstream of the Fmk1 MAPK cascade, to promote invasive growth and plant infection, as well as cell wall integrity, in F. oxysporum.
Keywords	Fusarium oxysporum ; cell walls ; cellophane ; gene expression ; genes ; hyphae ; membrane proteins ; mitogen-activated protein kinase ; mucins ; mutants ; pathogens ; phenotype ; phosphorylation ; plant tissues ; tomatoes ; vascular wilt ; virulence
Language	English
Dates of publication	2015-08
Size	p. 593-603.
Publishing place	Blackwell Science in collaboration with the British Society of Plant Pathology
Document type	Article
ZDB-ID	2020755-4
ISSN	1364-3703 ; 1464-6722
ISSN (online)	1364-3703
ISSN	1464-6722
DOI	10.1111/mpp.12217
Database	NAL-Catalogue (AGRICOLA)

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Article: In vivo selection of KPC-94 and KPC-95 in Klebsiella pneumoniae isolates from patients treated with ceftazidime/avibactam

Guzmán-Puche, J. / Pérez-Nadales, E. / Pérez-Vázquez, M. / Causse, M. / Gracia-Ahufinger, I. / Mendez-Natera, A. / Allalou-Ruiz, Y. / Elías, C. / Oteo-Iglesias, J. / Torre-Cisneros, J. / Martínez-Martínez, L.

International journal of antimicrobial agents. 2022 Feb., v. 59, no. 2

2022

Abstract	Ceftazidime/avibactam (CZA) is used to treat infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). Resistance to CZA is commonly related to point mutations in the blaKPC gene. Here we describe the in vivo emergence of CZA resistance in clinical isolates of KPC-Kp from four patients treated with this combination therapy. Four pre-therapy and five post-therapy KPC-Kp isolates were examined. Antibiogram (microdilution and gradient strips) and whole-genome sequencing were performed. The role of KPC mutations was validated by cloning blaKPC genes into competent Escherichia coli. All KPC-Kp isolates recovered before treatment with CZA were susceptible to CZA and produced KPC-3. Five KPC-Kp isolates recovered after treatment were resistant to this combination. Three post-therapy isolates from two patients produced KPC-31 (D179Y mutation). Additionally, we identified the novel substitution LN169–170H (KPC-94) in one isolate, and the combination of two independently described mutations, D179Y and A172T (KPC-95), in another isolate. All KPC-Kp isolates belonged to sequence type 512 (ST512). All CZA-resistant isolates with blaKPC variants had restoration of carbapenem susceptibility. In conclusion, resistance to CZA was related to blaKPC mutations, including the new KPC-94 and KPC-95 alleles, which do not cause carbapenem resistance.
Keywords	Escherichia coli ; Klebsiella pneumoniae ; carbapenems ; ceftazidime ; therapeutics
Language	English
Dates of publication	2022-02
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2022.106524
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Article ; Online: Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing

Pérez-Nadales, Elena / Cano, Ángela / Recio, Manuel / Artacho, María José / Guzmán-Puche, Julia / Doblas, Antonio / Vidal, Elisa / Natera, Clara / Martínez-Martínez, Luis / Torre-Cisneros, Julian / Castón, Juan José

BMJ open

2022 Volume 12, Issue 4, Page(s) e058124

Abstract: Introduction: Infections caused by carbapenemase-producing : Methods and analysis: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal ... ...

Abstract	Introduction: Infections caused by carbapenemase-producing Methods and analysis: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention. Ethics and dissemination: Ethical approval was obtained from Reina Sofía University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences. Trial registration number: NCT04760665.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins ; Carbapenem-Resistant Enterobacteriaceae ; Fecal Microbiota Transplantation/methods ; Humans ; Klebsiella Infections/drug therapy ; Klebsiella pneumoniae ; beta-Lactamases
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
Language	English
Publishing date	2022-04-06
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-058124
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Article ; Online: Association between Timing of Colonization and Risk of Developing Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infection in Hospitalized Patients.

Cano, Ángela / Gutiérrez-Gutiérrez, Belén / Machuca, Isabel / Torre-Giménez, Julián / Gracia-Ahufinger, Irene / Natera, Alejandra M / Pérez-Nadales, Elena / Castón, Juan Jose / Rodríguez-Baño, Jesús / Martínez-Martínez, Luis / Torre-Cisneros, Julián

Microbiology spectrum

2022 Volume 10, Issue 2, Page(s) e0197021

Abstract: Colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) is associated with the risk of developing KPC-Kp infection. The impact of the time elapsed since a patient becomes colonized on this risk is not well known. An observational, prospective, ... ...

Abstract	Colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) is associated with the risk of developing KPC-Kp infection. The impact of the time elapsed since a patient becomes colonized on this risk is not well known. An observational, prospective, longitudinal cohort study of colonized patients undergoing active rectal culture screening to rule out KPC-Kp colonization (July 2012 to November 2017). Patients with a positive culture at inclusion (colonized at start of follow-up) and those with a negative culture at inclusion who became colonized within 90 days (colonized during follow-up) were included in the analysis. CART analysis was used to dichotomize variables according to their association with infection. Kaplan-Meier infection-free survival curves and the log-rank test were used for group comparisons. Logistic regression was used to identify variables associated with KPC-Kp infection. Among 1310 patients included, 166 were colonized at the end of follow-up. Forty-seven out of 118 patients colonized at start of follow-up developed infection (39.8%) versus 31 out of 48 patients colonized during follow-up (64.6%;
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins ; Humans ; Klebsiella Infections/drug therapy ; Klebsiella Infections/epidemiology ; Klebsiella Infections/prevention & control ; Klebsiella pneumoniae ; Longitudinal Studies ; Prospective Studies ; beta-Lactamases
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01970-21
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