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Antibiotics
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Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches...
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Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 23162

Special Issue Editor

Prof. Dr. María Soledad Ramírez

E-Mail Website
Guest Editor
Department of Biological Science, California State University Fullerton, 800 N State College Blvd, Fullerton, CA 92831, USA
Interests: mechanisms of antibiotic resistance; bacterial pathogenesis; dissemination and evolution of pathogens; morbidity and mortality of bacterial infections; molecular mechanism of virulence; bacterial evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, the number of antibiotic-resistant bacteria prevalent in clinical settings has dramatically risen worldwide, increasing the number of deaths caused by resistant bacteria. The CDC’s 2019 Antibiotic Resistance Threats Report states that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths per year and result in annual healthcare costs exceeding $281 million (2017) in the United States. Different mechanisms of antibiotic resistance and the way these mechanisms can spread are causing an increase in antibiotic resistance. In some cases, no available antibiotics are left to deal with some of these bacterial infections.

This Special Issue seeks manuscript submissions that further our understanding of dissemination, evolution, the mechanism behind the antimicrobial resistance phenotype, and novel approaches to treating multidrug-resistant isolates.

Dr. María Soledad Ramírez
Guest Editor

Manuscript Submission Information

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.

Keywords

  • antibiotic resistance
  • beta-lactamases
  • mobile elements
  • horizontal gene transfer
  • novel therapies
  • extreme-drug resistance
  • pan-drug resistance
  • carbapenems
  • inhibitors
  • plasmids
  • clones

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Published Papers (6 papers)

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10 pages, 1350 KiB  
Article
A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant Acinetobacter baumannii (CRAB) Isolates
by Fernando Pasteran, Jose Cedano, Michelle Baez, Ezequiel Albornoz, Melina Rapoport, Jose Osteria, Sabrina Montaña, Casin Le, Grace Ra, Robert A. Bonomo, Marcelo E. Tolmasky, Mark Adams, Alejandra Corso and Maria Soledad Ramirez
Antibiotics 2021, 10(5), 577; https://doi.org/10.3390/antibiotics10050577 - 13 May 2021
Cited by 11 | Viewed by 4271
Abstract
An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter [...] Read more.
An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter clinical isolates; both sulbactam/avibactam and sulbactam/relebactam restored sulbactam activity. A decrease ≥2 dilutions in sulbactam MICs was observed in 89% of the isolates when tested in combination with avibactam. Sulbactam/relebactam was able to restore sulbactam susceptibility in 40% of the isolates. In addition, the susceptibility testing using twenty-three A. baumannii AB5075 knockout strains revealed potential sulbactam and/or sulbactam/avibactam target genes. We observed that diazabicyclooctanes (DBOs) β-lactamase inhibitors combined with sulbactam restore sulbactam susceptibility against carbapenem-resistant Acinetobacter clinical isolates. However, relebactam was not as effective as avibactam when combined with sulbactam. Exploring novel combinations may offer new options to treat Acinetobacter spp. infections, especially for widespread oxacillinases and metallo-β-lactamases (MBLs) producers. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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13 pages, 1248 KiB  
Article
Molecular Epidemiology of Extensively Drug-Resistant mcr Encoded Colistin-Resistant Bacterial Strains Co-Expressing Multifarious β-Lactamases
by Hasan Ejaz, Sonia Younas, Muhammad Usman Qamar, Kashaf Junaid, Abualgasim Elgaili Abdalla, Khalid Omer Abdalla Abosalif, Ayman Ali Mohammed Alameen, Mohammed Yagoub Mohammed Elamir, Naveed Ahmad, Sanaa Samir Mohamed Hamam, Eman Hosney Mohammed Salem and Syed Nasir Abbas Bukhari
Antibiotics 2021, 10(4), 467; https://doi.org/10.3390/antibiotics10040467 - 20 Apr 2021
Cited by 28 | Viewed by 4164
Abstract
Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory [...] Read more.
Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory concentration (MIC) breakpoint ≥4 µg/mL. Resistant isolates were examined for mcr variants, extended-spectrum β-lactamase, AmpC, and carbapenemase genes using polymerase chain reaction (PCR). The MIC breakpoints for mcr-positive strains were determined using broth microdilution and E-test strips. Overall, 19/718 (2.6%) gram-negative rods (GNRs) harboring mcr were identified, particularly in pus (p = 0.01) and tracheal secretions (p = 0.03). Molecular epidemiology data confirmed 18/19 (95%) mcr-1 and 1/19 (5%) mcr-2 genes. Integron detection revealed 15/17 (88%) Int-1 and 2/17 (12%) Int-2. Common co-expressing drug-resistant β-lactamase genes included 8/16 (50%) blaCTM-1, 3/16 (19%) blaCTM-15, 3/3 (100%) blaCMY-2, 2/8 (25%) blaNDM-1, and 2/8 (25%) blaNDM-5. The MIC50 and MIC90 values (µg/mL) were as follows: Escherichia coli, 12 and 24; Klebsiella pneumoniae, 12 and 32; Acinetobacter baumannii, 8 and 12; and Pseudomonas aeruginosa, 32 and 64, respectively. Treatment of XDR strains has become challenging owing to the co-expression of mcr-1, mcr-2, multifarious β-lactamase genes, and integrons. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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9 pages, 1315 KiB  
Article
Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions
by Craig M. Reeves, Jesus Magallon, Kenneth Rocha, Tung Tran, Kimberly Phan, Peter Vu, Yang Yi, Crista L. Oakley-Havens, José Cedano, Verónica Jimenez, Maria S. Ramirez and Marcelo E. Tolmasky
Antibiotics 2021, 10(1), 29; https://doi.org/10.3390/antibiotics10010029 - 31 Dec 2020
Cited by 11 | Viewed by 3474
Abstract
Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies [...] Read more.
Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies that combine the antibiotic and an inhibitor of the inactivation reaction could be an alternative to treat infections caused by resistant bacteria. We previously observed that metal ions such as Zn2+ or Cu2+ in complex with ionophores interfere with the AAC(6′)-Ib-mediated inactivation of aminoglycosides and reduced resistance to susceptibility levels. Ag1+ recently attracted attention as a potentiator of aminoglycosides′ action by mechanisms still in discussion. We found that silver acetate is also a robust inhibitor of the enzymatic acetylation mediated by AAC(6′)-Ib in vitro. This action seems to be independent of other mechanisms, like increased production of reactive oxygen species and enhanced membrane permeability, proposed to explain the potentiation of the antibiotic effect by silver ions. The addition of this compound to aac(6′)-Ib harboring Acinetobacter baumannii and Escherichia coli cultures resulted in a dramatic reduction of the resistance levels. Time-kill assays showed that the combination of silver acetate and amikacin was bactericidal and exhibited low cytotoxicity to HEK293 cells. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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9 pages, 786 KiB  
Communication
An Acinetobacter non-baumannii Population Study: Antimicrobial Resistance Genes (ARGs)
by Adam Baraka, German M. Traglia, Sabrina Montaña, Marcelo E. Tolmasky and Maria Soledad Ramirez
Antibiotics 2021, 10(1), 16; https://doi.org/10.3390/antibiotics10010016 - 26 Dec 2020
Cited by 16 | Viewed by 3541
Abstract
Acinetobacter non-baumannii species are becoming common etiologic agents of nosocomial infections. Furthermore, clinical isolates belonging to this group of bacteria are usually resistant to one or more antibiotics. The current information about antibiotic resistance genes in the different A. non-baumannii species [...] Read more.
Acinetobacter non-baumannii species are becoming common etiologic agents of nosocomial infections. Furthermore, clinical isolates belonging to this group of bacteria are usually resistant to one or more antibiotics. The current information about antibiotic resistance genes in the different A. non-baumannii species has not yet been studied as a whole. Therefore, we did a comparative study of the resistomes of A. non-baumannii pathogens based on information available in published articles and genome sequences. We searched the available literature and sequences deposited in GenBank to identify the resistance gene content of A. calcoaceticus, A. lwoffii, A. junii, A. soli, A. ursingii, A. bereziniae, A. nosocomialis, A. portensis, A. guerrae, A. baylyi, A. calcoaceticus, A. disperses, A. johnsonii, A. junii, A. lwoffii, A. nosocomialis, A. oleivorans, A. oryzae, A. pittii, A. radioresistens, and A. venetianus. The most common genes were those coding for different β-lactamases, including the carbapenemase genes blaNDM-1 and blaOXA-58. A. pittii was the species with the most β-lactamase resistance genes reported. Other genes that were commonly found include those encoding some aminoglycoside modifying enzymes, the most common being aph(6)-Id, ant(3″)-IIa, and aph(3″)-Ib, and efflux pumps. All or part of the genes coding for the AdeABC, AdeFGH, and AdeIJK efflux pumps were the most commonly found. This article incorporates all the current information about A. non-baumannii resistance genes. The comparison of the different resistomes shows that there are similarities in the genes present, but there are also significant differences that could impact the efficiency of treatments depending on the etiologic agent. This article is a comprehensive resource about A. non-baumannii resistomes. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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10 pages, 788 KiB  
Article
Prevalence of OXA-Type β-Lactamase Genes among Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates in Thailand
by Krit Thirapanmethee, Thayapa Srisiri-a-nun, Jantana Houngsaitong, Preecha Montakantikul, Piyatip Khuntayaporn and Mullika Traidej Chomnawang
Antibiotics 2020, 9(12), 864; https://doi.org/10.3390/antibiotics9120864 - 3 Dec 2020
Cited by 25 | Viewed by 4682
Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical health concern for the treatment of infectious diseases. The aim of this study was to investigate the molecular epidemiology of CRAB emphasizing the presence of oxacillinase (OXA)-type β-lactamase-encoding genes, one of the most important carbapenem resistance [...] Read more.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical health concern for the treatment of infectious diseases. The aim of this study was to investigate the molecular epidemiology of CRAB emphasizing the presence of oxacillinase (OXA)-type β-lactamase-encoding genes, one of the most important carbapenem resistance mechanisms. In this study, a total of 183 non-repetitive CRAB isolates collected from 11 tertiary care hospitals across Thailand were investigated. As a result, the blaoxa-51-like gene, an intrinsic enzyme marker, was detected in all clinical isolates. The blaoxa-23-like gene was presented in the majority of isolates (68.31%). In contrast, the prevalence rates of blaoxa-40/24-like and blaoxa-58-like gene occurrences in CRAB isolates were only 4.92% and 1.09%, respectively. All isolates were resistant to carbapenems, with 100% resistance to imipenem, followed by meropenem (98.91%) and doripenem (94.54%). Most isolates showed high resistance rates to ciprofloxacin (97.81%), ceftazidime (96.72%), gentamicin (91.26%), and amikacin (80.87%). Interestingly, colistin was found to be a potential drug of choice due to the high susceptibility of the tested isolates to this antimicrobial (87.98%). Most CRAB isolates in Thailand were of ST2 lineage, but some belonged to ST25, ST98, ST129, ST164, ST215, ST338, and ST745. Further studies to monitor the spread of carbapenem-resistant OXA-type β-lactamase genes from A. baumannii in hospital settings are warranted. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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6 pages, 229 KiB  
Case Report
Community-Acquired, Extended-Spectrum β-Lactamase-Producing and Extensively Drug-Resistant Escherichia coli in a 28-Year-Old Pyelonephritis Patient Lacking Risk Factors
by Connor W. Evins, Caroline M. Sutton, Sarah T. Withers, Jennifer T. Grier, Christine M. G. Schammel and Steven E. Fiester
Antibiotics 2021, 10(5), 533; https://doi.org/10.3390/antibiotics10050533 - 5 May 2021
Cited by 3 | Viewed by 2169
Abstract
While Escherichia coli is a common cause of urinary tract infections and pyelonephritis, there are few documented cases of extended-spectrum β-lactamase (ESBL)-producing and extensively drug-resistant (XDR) isolates from the community resulting in infection requiring hospitalization, especially in individuals lacking risk factors. In the [...] Read more.
While Escherichia coli is a common cause of urinary tract infections and pyelonephritis, there are few documented cases of extended-spectrum β-lactamase (ESBL)-producing and extensively drug-resistant (XDR) isolates from the community resulting in infection requiring hospitalization, especially in individuals lacking risk factors. In the United States, exposure to ESBL-producing E. coli is typically nosocomial, whereas patients from developing countries often encounter ESBL-producing E. coli in the community through the consumption of contaminated food or water. Considering the rarity at which XDR E. coli isolates are encountered, there is also a scarcity of literature describing the successful treatment of ESBL-producing XDR E. coli. Here we present a case of an otherwise healthy 28-year-old female delicatessen worker infected with ESBL-producing and XDR E. coli without recent travel, antibiotic use, or healthcare contact, who required admission to the intensive care unit (ICU) with pyelonephritis and septic shock. Treatment with intravenous meropenem through a peripherally inserted central catheter (PICC) line at home was curative and follow up thereafter unremarkable. Given the patient’s lack of obvious exposure to and risk factors for an ESBL-producing XDR E. coli infection and the specific lack of risk factors for severe pyelonephritis requiring hospitalization, this case represents a unique addition to the literature and is of value to clinicians by describing successful treatment. Full article
(This article belongs to the Special Issue Dissemination, Evolution, Molecular Mechanism of Antibiotic Resistance and Novel Approaches to Combat Multidrug Resistant Isolates)
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