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A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions...
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A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 45339

Special Issue Editor

Dr. Sara M. Soto

E-Mail Website
Guest Editor
Barcelona Institute for Global Health (ISGlobal), Universitat de Barcelona, 08036 Barcelona, Spain
Interests: drug discovery; metallodrugs; antimicrobial resistance; biofilm; gold complexes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Professor Dr. Jordi Vila has significantly contributed to the fields of antibiotic resistance and bacterial infectious diseases. His main fields of interest are research on the molecular basis of antimicrobial resistance as well as development of new drugs against MDR bacteria and molecular tools for rapid diagnosis of infectious disease. Prof. Vila has made important contributions in the field of antimicrobial resistance. He was the first to describe a broad-spectrum oxacillinase (OXA-37) in A. baumannii. In addition, Prof. Vila was also the first to describe those mutations in the parC gene associated with quinolone resistance. He conducted a study characterizing, for the first time, mutations in the parC gene that encodes subunit A of topoisomerase IV. This work is extensively cited in most reviews on quinolone resistance. Based on the results, he developed a DNA–DNA gyrase and quinolone interaction model and carried out a study to characterize 31 ciprofloxacin derivatives, finding a promising molecule that shows good “in vitro” activity against A. baumannii but also presented “in vivo” in an animal model of pneumonia by this microorganism. In recent years, he has been working with peptides with antibacterial activity as well as with peptides with virulence inhibitory activity. In 2007, he organized the “International Symposium on Acinetobacter” in Barcelona.

Professor Vila was born in Barcelona, Spain. He carried out his residency in Clinical Microbiology in the Hospital Clinic of Barcelona from 1981 to 1984. Moreover, he received his PhD in Biochemistry from the University of Barcelona in 1985. He was an associate researcher in the Department of Microbiology, School of Medicine, University of Virginia, Charlottesville, USA during 1986 and 1987. He was also a visiting professor in the Center for Genetic Adaptation and Antimicobial Resistance (Tufts University, Boston) in 1995 in the group of Dr.S.B. Levy, and at the Department of Cellular and Molecular Biology of the University of California, Berkeley during the year 2000 in the group of Dr. N. Cozzarrelli. Coming back from the United States in 1987, he became a consultant of the Department of Clinical Microbiology of the Hospital Clinic of Barcelona, Spain, and assistant professor at the University of Barcelona, associate professor in 1991, and full professor in 2008. Since 2010, he has been the Head of the Department of Clinical Microbiology at the Hospital Clinic of Barcelona, Spain. He has received several awards, the last one being “Award of the National Plan against Antibiotic Resistance (PRAN) 2018 for the Micro-combat card game, presented by the Barcelona Global Health Institute Foundation (ISGlobal) in the category of better communication and public awareness initiative on the antibiotic resistance”. He has published 469 articles in peer-reviewed journals (Citations: 28.626, index H: 84). He has supervised 25 PhD theses and patented two molecules. Professor Vila was the Program Director of the Congress of ESCMID from 2009 to 2014, member of the ICAAC scientific committee from 2007 to 2010, and President of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) from 2019 to 2021. Prof. Vila is the Head of the Department of Clinical Microbiology of the Hospital Clinic in Barcelona, Full Professor of the School of Medicine, University of Barcelona, and Research Professor in the Institute for Global Health (ISGlobal) of Barcelona, Spain. In this last institution, he is leading the initiative on “Antimicrobial Resistance”. Professor Vila serves as a member of Board of Reviewers for the Journal of Clinical Microbiology, Clinical Microbiology and Infection, and Antimicrobial Agents and Chemotherapy, among others.

Antibiotics is pleased to announce a Special Issue honoring Professor Jordi Vila for his outstanding contributions to the knowledge of antibiotic resistance in bacterial pathogens. This Special Issue is dedicated to all aspects of antibiotic resistance in, but not limited to, the following topics:

  1. Advances in antibiotic resistance of Gram-negative and Gram-positive bacteria;
  2. Novel antimicrobial agents against multidrug-resistant pathogens;
  3. Molecular epidemiology of antibiotic resistance;
  4. One Health vision on antimicrobial resistance.

We are pleased to invite you to submit a manuscript to this Special Issue; regular articles, communications, and reviews are all welcome.

Dr. Sara M. Soto
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (15 papers)

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Editorial

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2 pages, 185 KiB  
Editorial
Antibiotic Resistance in Bacterial Pathogens
by Sara M. Soto
Antibiotics 2023, 12(3), 451; https://doi.org/10.3390/antibiotics12030451 - 24 Feb 2023
Cited by 1 | Viewed by 1795
Abstract
The increasing number of infections caused by antibiotic-resistant bacterial pathogens over the last few decades has become a critical global health problem, the scale of which has led to it being named a “silent pandemic” [...] Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)

Research

Jump to: Editorial, Other

10 pages, 691 KiB  
Article
Comparison of Lateral Flow Immunochromatography and Phenotypic Assays to PCR for the Detection of Carbapenemase-Producing Gram-Negative Bacteria, a Multicenter Experience in Mexico
by Braulio Josue Mendez-Sotelo, Luis Esaú López-Jácome, Claudia A. Colín-Castro, Melissa Hernández-Durán, Maria Guadalupe Martínez-Zavaleta, Frida Rivera-Buendía, Consuelo Velázquez-Acosta, Ana Patricia Rodríguez-Zulueta, Maria del Rayo Morfín-Otero and Rafael Franco-Cendejas
Antibiotics 2023, 12(1), 96; https://doi.org/10.3390/antibiotics12010096 - 6 Jan 2023
Cited by 8 | Viewed by 3406
Abstract
The identification of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa is important for treating and controlling hospital infections. The recommended methods for their identification require a long waiting time, technical training, and expertise. Lateral flow immunoassays such as NG-Test CARBA 5® overcome these needs. [...] Read more.
The identification of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa is important for treating and controlling hospital infections. The recommended methods for their identification require a long waiting time, technical training, and expertise. Lateral flow immunoassays such as NG-Test CARBA 5® overcome these needs. We analyzed 84 clinical isolates of carbapenem-resistant Enterobacterales and P. aeruginosa from four different hospitals in a two-year period. Antimicrobial resistance patterns were confirmed with the broth dilution method. Evaluation of KPC, VIM, NDM, IMP, and OXA-48-like enzymes was performed and compared to NG-Test CARBA 5 and phenotypic assays. Enterobacterales represented 69% of isolates and P. aeruginosa represented 31%. Carbapenemase-producing strains were 51 (88%) of Enterobacterales and 23 (88.4%) of P. aeruginosa; 20 (34%) and 23 (88%) were Class B ß-lactamases, respectively. The NG-Test CARBA 5® assay for Enterobacterales showed high sensitivity (98%), specificity (100%), and PPV (100%); however, it did not for P. aeruginosa. The Kappa concordance coefficient was 0.92 for Enterobacterales and 0.52 for P. aeruginosa. NG-Test CARBA 5® is a fast and easy-to-use assay. In Enterobacterales, we found excellent agreement in our comparison with molecular tests. Despite the low agreement in P. aeruginosa, we suggest that this test could be used as a complementary tool. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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10 pages, 293 KiB  
Article
Differences in Drug-Susceptibility Patterns between Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera Clinical Isolates: Prospective 8.5-Year Analysis by Three Laboratories
by Mariana Fernandez-Pittol, Sara Batista-Arnau, Angely Román, Lorena San Nicolás, Laura Oliver, Olga González-Moreno, José Antonio Martínez, Rosanel Amaro-Rodríguez, Néstor Soler, Amadeu Gené, Araceli González-Cuevas, Griselda Tudó and Julian Gonzalez-Martin
Antibiotics 2023, 12(1), 64; https://doi.org/10.3390/antibiotics12010064 - 29 Dec 2022
Cited by 6 | Viewed by 2167
Abstract
Background: It has been suggested that Mycobacterium avium, Mycobacterium intracellulare, and M. chimaera have differential drug susceptibility patterns. We prospectively analyzed and compared the drug susceptibility patterns among these species over an 8.5-year period. Methods: A microdilution method (Slomyco [...] Read more.
Background: It has been suggested that Mycobacterium avium, Mycobacterium intracellulare, and M. chimaera have differential drug susceptibility patterns. We prospectively analyzed and compared the drug susceptibility patterns among these species over an 8.5-year period. Methods: A microdilution method (Slomyco®) was performed for drug susceptibility testing of 402 M. avium, 273 M. intracellulare, and 139 M. chimaera clinical isolates. Results: M. avium showed significantly higher resistance to moxifloxacin, ciprofloxacin, rifampicin, ethambutol, streptomycin, linezolid, cotrimoxazole, and clarithromycin. M. avium also showed higher minimum inhibitory concentrations (MIC) than M. intracellulare and M. chimaera against all drugs except ethionamide, to which M. intracellulare and M. chimaera showed greater resistance. Conclusions: Our series demonstrated differential drug resistance patterns among the most frequent M. avium complex species. M. avium was more resistant than M. intracellulare and M. chimaera versus eight antibiotics and showed greater MIC values to most of the antibiotics studied. These data suggest that knowledge of the local distribution and susceptibility profiles of these pathogens is essential for adequate clinical management. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
16 pages, 1129 KiB  
Article
Gold(III) Complexes Activity against Multidrug-Resistant Bacteria of Veterinary Significance
by Carlos Ratia, Sara Sueiro, Raquel G. Soengas, María José Iglesias, Fernando López-Ortiz and Sara María Soto
Antibiotics 2022, 11(12), 1728; https://doi.org/10.3390/antibiotics11121728 - 1 Dec 2022
Cited by 14 | Viewed by 1978
Abstract
The emergence and spread of multidrug-resistant bacteria are a global concern. The lack of new antibiotics in the pipeline points to the need for developing new strategies. In this sense, gold(III) complexes (G3Cs) could be a promising alternative due to their recently described [...] Read more.
The emergence and spread of multidrug-resistant bacteria are a global concern. The lack of new antibiotics in the pipeline points to the need for developing new strategies. In this sense, gold(III) complexes (G3Cs) could be a promising alternative due to their recently described antibacterial activity. The aim of this study was to evaluate the antimicrobial activity of G3Cs alone and in combination with colistin against pathogenic bacteria from veterinary sources. Minimal inhibitory concentration (MIC) values were determined by broth microdilution and compared with clinically relevant antibiotics. Antibiofilm activity was determined by crystal violet staining. Combinations of selected G3Cs with colistin and cytotoxicity in commercial human cell lines were evaluated. Four and seven G3Cs showed antibacterial effect against Gram-negative and Gram-positive strains, respectively, with this activity being higher among Gram-positive strains. The G3Cs showed antibiofilm activity against Gram-negative species at concentrations similar or one to four folds higher than the corresponding MICs. Combination of G3Cs with colistin showed a potential synergistic antibacterial effect reducing concentrations and toxicity of both agents. The antimicrobial and antibiofilm activity, the synergistic effect when combined with colistin and the in vitro toxicity suggest that G3Cs would provide a new therapeutic alternative against multidrug-resistant bacteria from veterinary origin. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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16 pages, 1490 KiB  
Article
Antimicrobial Resistance Profile of Common Foodborne Pathogens Recovered from Livestock and Poultry in Bangladesh
by Kazi Rafiq, Md Rafiqul Islam, Nure Alam Siddiky, Mohammed Abdus Samad, Sharmin Chowdhury, K. M. Mozaffor Hossain, Farzana Islam Rume, Md Khaled Hossain, ATM Mahbub-E-Elahi, Md Zulfekar Ali, Moizur Rahman, Mohammad Rohul Amin, Md Masuduzzaman, Sultan Ahmed, Nazmi Ara Rumi and Muhammad Tofazzal Hossain
Antibiotics 2022, 11(11), 1551; https://doi.org/10.3390/antibiotics11111551 - 4 Nov 2022
Cited by 19 | Viewed by 4912
Abstract
Multidrug-resistant (MDR) foodborne pathogens have created a great challenge to the supply and consumption of safe & healthy animal-source foods. The study was conducted to identify the common foodborne pathogens from animal-source foods & by-products with their antimicrobial drug susceptibility and resistance gene [...] Read more.
Multidrug-resistant (MDR) foodborne pathogens have created a great challenge to the supply and consumption of safe & healthy animal-source foods. The study was conducted to identify the common foodborne pathogens from animal-source foods & by-products with their antimicrobial drug susceptibility and resistance gene profile. The common foodborne pathogens Escherichia coli (E. coli), Salmonella, Streptococcus, Staphylococcus, and Campylobacter species were identified in livestock and poultry food products. The prevalence of foodborne pathogens was found higher in poultry food & by-product compared with livestock (p < 0.05). The antimicrobial drug susceptibility results revealed decreased susceptibility to penicillin, ampicillin, amoxicillin, levofloxacin, ciprofloxacin, tetracycline, neomycin, streptomycin, and sulfamethoxazole-trimethoprim whilst gentamicin was found comparatively more sensitive. Regardless of sources, the overall MDR pattern of E. coli, Salmonella, Staphylococcus, and Streptococcus were found to be 88.33%, 75%, 95%, and 100%, respectively. The genotypic resistance showed a prevalence of blaTEM, blaSHV, blaCMY, tetA, tetB, sul1, aadA1, aac(3)-IV, and ereA resistance genes. The phenotype and genotype resistance patterns of isolated pathogens from livestock and poultry had harmony and good concordance, and sul1 & tetA resistance genes had a higher prevalence. Good agricultural practices along with proper biosecurity may reduce the rampant use of antimicrobial drugs. In addition, proper handling, processing, storage, and transportation of foods may decline the spread of MDR foodborne pathogens in the food chain. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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12 pages, 987 KiB  
Article
Suboptimal Concentrations of Ceftazidime/Avibactam (CAZ-AVI) May Select for CAZ-AVI Resistance in Extensively Drug-Resistant Pseudomonas aeruginosa: In Vivo and In Vitro Evidence
by Inmaculada Lopez-Montesinos, María Milagro Montero, Sandra Domene-Ochoa, Carla López-Causapé, Daniel Echeverria, Luisa Sorlí, Nuria Campillo, Sonia Luque, Eduardo Padilla, Nuria Prim, Santiago Grau, Antonio Oliver and Juan P. Horcajada
Antibiotics 2022, 11(11), 1456; https://doi.org/10.3390/antibiotics11111456 - 22 Oct 2022
Cited by 5 | Viewed by 3157
Abstract
This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically [...] Read more.
This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically ill with ventilator-associated pneumonia caused by XDR P. aeruginosa ST175 with CAZ-AVI MIC of 6 mg/L and was treated with CAZ-AVI in continuous infusion at doses adjusted for renal function. Plasma concentrations of CAZ-AVI were analyzed on days 3, 7, and 10. In the HIFM, the efficacy of different steady-state concentrations (Css) of CAZ-AVI (12, 18, 30 and 48 mg/L) was evaluated. In both models, a correlation was observed between the decreasing plasma levels of CAZ-AVI and the emergence of resistance. In the HIFM, a Css of 30 and 48 mg/L (corresponding to 5× and 8× MIC) had a bactericidal effect without selecting resistant mutants, whereas a Css of 12 and 18 mg/L (corresponding to 2× and 3× MIC) failed to prevent the emergence of resistance. CAZ/AVI resistance development was caused by the selection of a single ampC mutation in both patient and HFIM. Until further data are available, strategies to achieve plasma CAZ-AVI levels at least 4× MIC could be of interest, particularly in severe and high-inoculum infections caused by XDR P. aeruginosa with high CAZ-AVI MICs. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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18 pages, 341 KiB  
Article
In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium
by Saoussen Oueslati, Pierre Bogaerts, Laurent Dortet, Sandrine Bernabeu, Hend Ben Lakhal, Christopher Longshaw, Youri Glupczynski and Thierry Naas
Antibiotics 2022, 11(10), 1352; https://doi.org/10.3390/antibiotics11101352 - 4 Oct 2022
Cited by 23 | Viewed by 3190
Abstract
Infections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro [...] Read more.
Infections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro activity of cefiderocol and comparators against multidrug-resistant (MDR) bacteria including meropenem-resistant (MR) or pandrug-resistant (PR) GN clinical isolates from France and Belgium. The minimum inhibitory concentrations (MICs) of CFDC were determined by broth microdilution, using iron-depleted cation-adjusted Mueller–Hinton broth, and were compared to those of 10 last-line antibiotics. The MICs were interpreted according to EUCAST and CLSI breakpoints, and in the absence of species-specific breakpoints, non-species-related pharmacokinetic/pharmacodynamic breakpoints were used. Among the 476 isolates tested, 322 were carbapenemase producers (CP), 58 non-CP-CRs, 52 intrinsically CR, 41 expanded-spectrum cephalosporin resistant and 5 were multi-susceptible. Susceptibility to CFDC was high using EUCAST breakpoints 81%, 99% and 84%, and was even higher using CLSI breakpoints to 93%, 100% and 88% for Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii, respectively. Susceptibility to cefiderocol using non-species-related breakpoints for Stenotrophomonas maltophilia, Achromobacter xylosoxydans and Burkholderia cepacia, was 100%, 100% and 92.3%, respectively. The susceptibility rates were lower with the NDM producers, with values of 48% and 30% using EUCAST breakpoints and 81% and 50% using CLSI breakpoints for Enterobacterales and Acinetobacter spp, respectively. CFDC demonstrated high in vitro susceptibility rates against a wide range of MDR GN pathogens, including MR and PR isolates. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
15 pages, 1087 KiB  
Article
Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany
by Kyriaki Xanthopoulou, Can Imirzalioglu, Sarah V. Walker, Michael Behnke, Ariane G. Dinkelacker, Simone Eisenbeis, Petra Gastmeier, Hanna Gölz, Nadja Käding, Winfried V. Kern, Axel Kola, Evelyn Kramme, Kai Lucassen, Alexander Mischnik, Silke Peter, Anna M. Rohde, Jan Rupp, Evelina Tacconelli, David Tobys, Maria J. G. T. Vehreschild, Julia Wille, Harald Seifert, Paul G. Higgins and on behalf of the DZIF R-Net Study Groupadd Show full author list remove Hide full author list
Antibiotics 2022, 11(10), 1286; https://doi.org/10.3390/antibiotics11101286 - 21 Sep 2022
Cited by 5 | Viewed by 2522
Abstract
To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016–2019). Also collected were 3GCR/CR and susceptible [...] Read more.
To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016–2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016–2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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15 pages, 19850 KiB  
Article
Resistance to Fluoroquinolones in Pseudomonas aeruginosa from Human, Animal, Food and Environmental Origin: The Role of CrpP and Mobilizable ICEs
by María López, Beatriz Rojo-Bezares, Gabriela Chichón and Yolanda Sáenz
Antibiotics 2022, 11(9), 1271; https://doi.org/10.3390/antibiotics11091271 - 19 Sep 2022
Cited by 5 | Viewed by 3174
Abstract
Fluoroquinolone resistance and the associated genetic mechanisms were assessed by antimicrobial susceptibility and whole genome sequencing in 56 Pseudomonas aeruginosa strains from human, animal, food and environmental origins. P. aeruginosa PAO1, PA7 and PA14 reference strains were also included in the study. Twenty-two [...] Read more.
Fluoroquinolone resistance and the associated genetic mechanisms were assessed by antimicrobial susceptibility and whole genome sequencing in 56 Pseudomonas aeruginosa strains from human, animal, food and environmental origins. P. aeruginosa PAO1, PA7 and PA14 reference strains were also included in the study. Twenty-two strains (37%) were resistant to, at least, one fluoroquinolone agent. Correlation between the number of changes in GyrA and ParC proteins and the level of fluoroquinolone resistance was observed. Mutations or absence of genes, such as mexZ, mvaT and nalD encoding efflux pumps regulators, were also found in resistant strains. The crpP gene was detected in 43 strains (72.9%; 17 of them non-clinical strains), and coded seven different CrpP variants, including a novel one (CrpP-7). The crpP gene was located in 23 different chromosomal mobile integrative and conjugative elements (ICEs), inserted in two tRNAs integration sites. A great variety of structures was detected in the crpP-ICEs elements, e.g., the fimbriae related cup clusters, the mercury resistance mer operon, the pyocin S5 or S8 bacteriocin encoding genes, and mobilization genes. The location of crpP-like genes in mobilizable ICEs and linked to heavy metal resistance and virulence factors is of significant concern in P. aeruginosa. This work provides a genetic explanation of the fluoroquinolone resistance and crpP-associated pathogenesis of P. aeruginosa from a One-Health approach. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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16 pages, 1758 KiB  
Article
Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis
by Soraya Herrera-Espejo, Ester Del Barrio-Tofiño, Tania Cebrero-Cangueiro, Carla López-Causapé, Rocío Álvarez-Marín, José Miguel Cisneros, Jerónimo Pachón, Antonio Oliver and María Eugenia Pachón-Ibáñez
Antibiotics 2022, 11(9), 1212; https://doi.org/10.3390/antibiotics11091212 - 7 Sep 2022
Cited by 8 | Viewed by 3036
Abstract
In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 [...] Read more.
In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64–256 for imipenem and 16–128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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10 pages, 612 KiB  
Article
Activity of Antibiotics and Potential Antibiofilm Agents against Biofilm-Producing Mycobacterium avium-intracellulare Complex Causing Chronic Pulmonary Infections
by Elena Portell-Buj, Cecibel González-Criollo, Alexandre López-Gavín, Mariana Fernández-Pittol, Maria Antònia Busquets, Joan Estelrich, Montserrat Garrigó, Marc Rubio, Griselda Tudó and Julian Gonzalez-Martin
Antibiotics 2022, 11(5), 589; https://doi.org/10.3390/antibiotics11050589 - 27 Apr 2022
Cited by 6 | Viewed by 2246
Abstract
Nontuberculous mycobacteria (NTM) cause lung infections in patients with underlying pulmonary diseases (PD). The Mycobacteriumavium-intracellulare complex (MAC) is the most frequently involved NTM. The MAC-PD treatment is based on the administration of several antibiotics for long periods of time. Nonetheless, [...] Read more.
Nontuberculous mycobacteria (NTM) cause lung infections in patients with underlying pulmonary diseases (PD). The Mycobacteriumavium-intracellulare complex (MAC) is the most frequently involved NTM. The MAC-PD treatment is based on the administration of several antibiotics for long periods of time. Nonetheless, treatment outcomes remain very poor. Among the factors involved is the ability of MAC isolates to form biofilm. The aim of the study was to assess the in vitro activity of different antibiotics and potential antibiofilm agents (PAAs) against MAC biofilm. Four antibiotics and six PAAs, alone and/or in combination, were tested against planktonic forms of 11 MAC clinical isolates. Biofilm was produced after 4 weeks of incubation and analyzed with the crystal violet assay. The antibiotics and PAAs were tested by measuring the absorbance (minimum biofilm inhibition concentrations, MBICs) and by performing subcultures (minimum biofilm eradication concentrations, MBECs). The clarithromycin/amikacin and clarithromycin/ethambutol combinations were synergistic, decreasing the MBECs values compared to the individual antibiotics. The amikacin/moxifloxacin combination showed indifference. The MBIC values decreased significantly when PAAs were added to the antibiotic combinations. These results suggest that antibiotic combinations should be further studied to establish their antibiofilm activity. Moreover, PAAs could act against the biofilm matrix, facilitating the activity of antibiotics. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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6 pages, 430 KiB  
Communication
Implementation of a New Protocol for Direct Identification from Urine in the Routine Microbiological Diagnosis
by Yuliya Zboromyrska, Verónica Rico, Cristina Pitart, Mariana José Fernández-Pittol, Álex Soriano and Jordi Bosch
Antibiotics 2022, 11(5), 582; https://doi.org/10.3390/antibiotics11050582 - 26 Apr 2022
Cited by 4 | Viewed by 2109
Abstract
Background: The direct identification of uropathogens from urine samples, in combination with the rapid detection of resistance, would allow early adjustment of empirical antimicrobial treatment. Methods: Two hundred and ninety-eight urine samples processed between 1 June and 31 December 2020, selected with flow [...] Read more.
Background: The direct identification of uropathogens from urine samples, in combination with the rapid detection of resistance, would allow early adjustment of empirical antimicrobial treatment. Methods: Two hundred and ninety-eight urine samples processed between 1 June and 31 December 2020, selected with flow cytometry, with direct identification by MALDI-TOF mass spectrometry, and rapid detection of extended-spectrum beta-lactamase (ESBL) and carbapenemases-producing strains by lateral flow were analyzed. Results: The positive predictive value of the direct identification of the 86 samples that met the flow cytometry criterion (>5000 bacteria/µL) was 96.4%. Reliable direct identification was obtained in 14 of the 27 (51.8%) urinary source bacteraemias. There was 100% agreement between the lateral flow and antibiogram in the detection of ESBL and carbapenemases. Conclusion: the protocol for the direct identification and rapid detection of ESBL and carbapenemases-producing strains from urine samples is a reliable and useful tool. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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14 pages, 1767 KiB  
Article
A New Variant of the aadE-sat4-aphA-3 Gene Cluster Found in a Conjugative Plasmid from a MDR Campylobacter jejuni Isolate
by Pedro Guirado, Elisenda Miró, Yaidelis Iglesias-Torrens, Ferran Navarro, Susana Campoy, Tyler Scott Alioto, Jessica Gómez-Garrido, Cristina Madrid and Carlos Balsalobre
Antibiotics 2022, 11(4), 466; https://doi.org/10.3390/antibiotics11040466 - 30 Mar 2022
Cited by 8 | Viewed by 2860
Abstract
Campylobacter jejuni is a foodborne pathogen causing bacterial gastroenteritis, with the highest incidence reported in Europe. The prevalence of antibiotic resistance in C. jejuni, as well as in many other bacterial pathogens, has increased over the last few years. In this report, [...] Read more.
Campylobacter jejuni is a foodborne pathogen causing bacterial gastroenteritis, with the highest incidence reported in Europe. The prevalence of antibiotic resistance in C. jejuni, as well as in many other bacterial pathogens, has increased over the last few years. In this report, we describe the presence of a plasmid in a multi-drug-resistant C. jejuni strain isolated from a gastroenteritis patient. Mating experiments demonstrated the transference of this genetic element (pCjH01) among C. jejuni by plasmid conjugation. The pCjH01 plasmid was sequenced and assembled, revealing high similarity (97% identity) with pTet, a described tetracycline resistance encoding plasmid. pCjH01 (47.7 kb) is a mosaic plasmid composed of a pTet backbone that has acquired two discrete DNA regions. Remarkably, one of the acquired sequences carried an undescribed variant of the aadE-sat4-aphA-3 gene cluster, providing resistance to at least kanamycin and gentamycin. Aside from the antibiotic resistance genes, the cluster also carries genes coding for putative regulators, such as a sigma factor of the RNA polymerase and an antisigma factor. Homology searches suggest that Campylobacter exchanges genetic material with distant G-positive bacterial genera. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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8 pages, 1045 KiB  
Article
Incidence of Vancomycin-Resistant Staphylococcus aureus Strains among Patients with Urinary Tract Infections
by Samy Selim, Osama Ahmed Faried, Mohammed S. Almuhayawi, Fayez M. Saleh, Mohamed Sharaf, Nihal El Nahhas and Mona Warrad
Antibiotics 2022, 11(3), 408; https://doi.org/10.3390/antibiotics11030408 - 18 Mar 2022
Cited by 21 | Viewed by 4172
Abstract
There has been a substantial rise in the number of vancomycin-resistant Staphylococcus aureus (VRSA) strains during the last several years. The proportion of vancomycin-resistant strains among isolated S. aureus has risen steadily in recent years, with the first spike occurring in critical care [...] Read more.
There has been a substantial rise in the number of vancomycin-resistant Staphylococcus aureus (VRSA) strains during the last several years. The proportion of vancomycin-resistant strains among isolated S. aureus has risen steadily in recent years, with the first spike occurring in critical care units and thereafter in general hospital wards. S. aureus isolates from urinary tract infection patients were studied for their prevalence and antibiotic resistance. From 292 urine samples, 103 bacterial strains (35.3%) were identified as S. aureus. Various antibiotics were used to test the isolates’ antibacterial resistance profiles. Antibiotic resistance to erythromycin was found in most bacterial isolates, whereas tobramycin antibiotic sensitivity was found in most of them. Vancomycin resistance was found in 23 of all S. aureus isolates in this study. Analysis for β-lactamase found that 71% of S. aureus isolates were positive in all isolates. There was a single plasmid with a molecular weight of 39.306 Kbp in five selected VRSA isolates that was subjected to plasmid analysis. There was evidence of vancomycin resistance among the S. aureus isolates collected from UTI patients in this investigation. This vancomycin resistance pretenses a challenge in the treatment of S. aureus infections and the need to precisely recognize persons who require last-resort medication such as tobramycin. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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6 pages, 251 KiB  
Case Report
Nosocomial Pneumonia Caused in an Immunocompetent Patient by the Emergent Monophasic ST34 Variant of Salmonella enterica Serovar Typhimurium: Treatment-Associated Selection of Fluoroquinolone and Piperacillin/Tazobactam Resistance
by Xenia Vázquez, Lorena Forcelledo, Salvador Balboa-Palomino, Javier Fernández and María Rosario Rodicio
Antibiotics 2022, 11(3), 303; https://doi.org/10.3390/antibiotics11030303 - 24 Feb 2022
Cited by 3 | Viewed by 2726
Abstract
The present report describes an uncommon case of nosocomial pneumonia caused by Salmonellaenterica in an immunocompetent patient. The patient was admitted to ICU of a tertiary hospital due to low level of consciousness, aphasia and seizure episodes. Four days after hospitalization, he [...] Read more.
The present report describes an uncommon case of nosocomial pneumonia caused by Salmonellaenterica in an immunocompetent patient. The patient was admitted to ICU of a tertiary hospital due to low level of consciousness, aphasia and seizure episodes. Four days after hospitalization, he developed nosocomial pneumonia, which evolved into septic shock. Gram-negative bacilli were recovered from blood, tracheal aspirate and fecal samples of the patient. The isolates, which were identified as Salmonella enterica, proved to be resistant to ciprofloxacin, amoxicillin/clavulanic acid and piperacillin/tazobactam. Four months before, the same bacterial species was recovered from feces and blood cultures of the patient, admitted to the nephrology ward of the same hospital with diagnosis of gastroenteritis and acute renal failure. However, at that time, the isolates were susceptible to the above-mentioned antibiotics. Genome sequencing revealed that all isolates were closely related and belonged to the emergent ST34 monophasic variant of S. enterica serovar Typhimurium. Since the patient has received therapy with fluoroquinolones and amoxicillin/clavulanic acid, these results support treatment-associated selection of the acquired resistances. In conclusion, this case represents a paradigm of selective pressure leading to in vivo development of resistance to highly relevant antibiotics, including the piperacillin/tazobactam combination used for empirical management of severe infections at ICU. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)
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