Special Issue "Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition"

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

Deadline for manuscript submissions: 15 July 2021.

Special Issue Editor

Prof. Dr. Yuji Morita
E-Mail Website
Guest Editor
Department of Infection Control Science, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, Japan
Interests: antimicrobial resistance; antimicrobial action; development of antimicrobial agents or adjuvant; microbial transporter; microbial molecular genetics
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

This is the 2nd edition of the Special Issue “Antimicrobial Resistance in Gram-negative Bacteria”. Gram-negative bacteria possess an intrinsic resistance to many antimicrobials because of the bacterium’s outer-membrane barrier, the presence of multidrug efflux transporters, endogenous antimicrobial inactivation, etc. Moreover, Gram-negative bacteria readily acquire resistance to antimicrobial agents via chromosomal mutations and lateral gene transfers. In order to overcome this problem, it is necessary to tackle the development of antibacterial agents, drug resistance inhibitors, antipathogenic factors, and vaccines. Thus, this Special Issue features interdisciplinary studies that build our understanding of the underlying antimicrobial resistance in Gram-negative bacteria. It also covers studies on the development of antibacterial agents and adjuvants against antimicrobial-resistant Gram-negative bacteria.

Prof. Dr. Yuji Morita
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 papers will be 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 1800 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

  • antimicrobial resistance
  • antimicrobial responce
  • development of antimicrobial agents or adjuvant

Published Papers (6 papers)

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Research

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Open AccessArticle
Multimodal Interventions to Prevent and Control Carbapenem-Resistant Enterobacteriaceae and Extended-Spectrum β-Lactamase Producer-Associated Infections at a Tertiary Care Hospital in Egypt
Antibiotics 2021, 10(5), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050509 - 30 Apr 2021
Viewed by 231
Abstract
The current rise of multidrug-resistant (MDR) Gram-negative Enterobacteriaceae including the extended-spectrum β-lactamase (ESBL)-producing organisms and carbapenem-resistant Enterobacteriaceae (CRE) has been increasingly reported worldwide, posing new challenges to health care facilities. Accordingly, we evaluated the impact of multimodal infection control interventions at one of [...] Read more.
The current rise of multidrug-resistant (MDR) Gram-negative Enterobacteriaceae including the extended-spectrum β-lactamase (ESBL)-producing organisms and carbapenem-resistant Enterobacteriaceae (CRE) has been increasingly reported worldwide, posing new challenges to health care facilities. Accordingly, we evaluated the impact of multimodal infection control interventions at one of the major tertiary healthcare settings in Egypt for the aim of combating infections by the respective pathogens. During the 6-month pre-intervention period, the incidence rate of CRE and ESBL-producing clinical cultures were 1.3 and 0.8/1000 patient days, respectively. During the post-intervention period, the incidence of CRE and ESBL producers continued to decrease, reaching 0.5 and 0.28/1000 patient days, respectively. The susceptibility rate to carbapenems among ESBL producers ranged from 91.4% (ertapenem) to 98.3% (imipenem), amikacin (93%), gentamicin (56.9%), and tobramycin (46.6%). CRE showed the highest resistance pattern toward all of the tested β-lactams and aminoglycosides, ranging from 87.3% to 94.5%. Both CRE and ESBL producers showed a high susceptibility rate (greater than 85.5%) to colistin and tigecycline. In conclusion, our findings revealed the effectiveness of implementing multidisciplinary approaches in controlling and treating infections elicited by CRE and ESBL producers. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)
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Open AccessArticle
Molecular Detection of Antibiotic Resistance Genes in Shiga Toxin-Producing E. coli Isolated from Different Sources
Antibiotics 2021, 10(4), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040344 - 24 Mar 2021
Viewed by 457
Abstract
Shiga toxin-producing Escherichia coli (STEC) is an enteric pathogen associated with human gastroenteritis outbreaks. Extensive use of antibiotics in agriculture selects resistant bacteria that may enter the food chain and potentially causes foodborne illnesses in humans that are less likely to respond to [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) is an enteric pathogen associated with human gastroenteritis outbreaks. Extensive use of antibiotics in agriculture selects resistant bacteria that may enter the food chain and potentially causes foodborne illnesses in humans that are less likely to respond to treatment with conventional antibiotics. Due to the importance of antibiotic resistance, this study aimed to investigate the combination of phenotypic and genotypic antibiotic resistance in STEC isolates belonging to serogroups O26, O45, O103, O104, O111, O121, O145, and O157 using disc diffusion and polymerase chain reaction (PCR), respectively. All strains were phenotypically resistant to at least one antibiotic, with 100% resistance to erythromycin, followed by gentamicin (98%), streptomycin (82%), kanamycin (76%), and ampicillin (72%). The distribution of antibiotic resistance genes (ARGs) in the STEC strains was ampC (47%), aadA1 (70%), ere(A) (88%), blaSHV (19%), blaCMY (27%), aac(3)-I (90%), and tet(A) (35%), respectively. The results suggest that most of the strains were multidrug-resistant (MDR) and the most often observed resistant pattern was of aadA1, ere(A), and aac(3)-I genes. These findings indicate the significance of monitoring the prevalence of MDR in both animals and humans around the globe. Hence, with a better understanding of antibiotic genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)
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Open AccessCommunication
Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak
Antibiotics 2020, 9(12), 862; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120862 - 03 Dec 2020
Cited by 1 | Viewed by 673
Abstract
Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and [...] Read more.
Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and genomic characteristics of an MDR hvKp isolate, MAR14-456, representative of a nosocomial outbreak in Moscow, Russia, that was recovered from a postoperative wound in a patient who later developed multiple abscesses, fatal sepsis, and septic shock. Broth microdilution testing revealed decreased susceptibility of MAR14-456 to carbapenems (MICs 0.5–2 mg/L) and a high-level resistance to most β-lactams, β-lactam-β-lactamase-inhibitor combinations, and non-β-lactam antibiotics, except ceftazidime-avibactam, amikacin, tigecycline, and colistin. Whole-genome sequencing using Illumina MiSeq and ONT MinION systems allowed to identify and completely assemble two conjugative resistance plasmids, a typical ‘European’ epidemic IncL/M plasmid that carries the gene of OXA-48 carbapenemase, and an IncFIIK plasmid that carries the gene of CTX-M-15 ESBL and other resistance genes. MLST profile, capsular, lipopolysaccharide, virulence genes encoded on chromosome and IncHI1B/FIB plasmid, and the presence of apparently functional type I-E* CRISPR-Cas system were all characteristic of hvKp ST23, serotype K1-O1v2. Phylogenetic analysis showed the closest relatedness of MAR14-456 to ST23 isolates from China. This report highlights the threat of multiple resistance acquisition by hvKp strain and its spread as a nosocomial pathogen. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)
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Open AccessArticle
Increased Azithromycin Susceptibility of Multidrug-Resistant Gram-Negative Bacteria on RPMI-1640 Agar Assessed by Disk Diffusion Testing
Antibiotics 2020, 9(5), 218; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9050218 - 29 Apr 2020
Cited by 4 | Viewed by 1284
Abstract
Increasing antibiotic resistances and a lack of new antibiotics render the treatment of Gram-negative bacterial infections increasingly difficult. Therefore, additional approaches are being investigated. Macrolides are not routinely used against Gram-negative bacteria due to lack of evidence of in vitro effectiveness. However, it [...] Read more.
Increasing antibiotic resistances and a lack of new antibiotics render the treatment of Gram-negative bacterial infections increasingly difficult. Therefore, additional approaches are being investigated. Macrolides are not routinely used against Gram-negative bacteria due to lack of evidence of in vitro effectiveness. However, it has been shown that Pseudomonas spp. are susceptible to macrolides in liquid RPMI-1640 and clinical data suggest improvement in patients’ outcomes. So far, these findings have been hardly applicable to the clinical setting due to lack of routine low-complexity antimicrobial susceptibility testing (AST) for macrolides. We therefore optimized and compared broth microdilution and disk diffusion AST. Multidrug-resistant Gram-negative bacteria (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa) were tested for azithromycin susceptibility by disk diffusion and broth microdilution in Mueller–Hinton and RPMI-1640 media. Azithromycin susceptibility of Enterobacteriaceae and a subgroup of P. aeruginosa increased significantly on RPMI-1640 agar compared to Mueller–Hinton agar. Further, a significant correlation (Kendall, τ, p) of zone diameters and minimal inhibitory concentrations (MICs) was found on RPMI-1640 agar for E. coli (−0.4279, 0.0051), E. cloacae (−0.3783, 0.0237) and P. aeruginosa (−0.6477, <0.0001). Performing routine disk diffusion AST on RPMI-1640 agar may lead to the identification of additional therapeutic possibilities for multidrug-resistant bacterial infections in the routine clinical diagnostic setting. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)
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Review

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Open AccessReview
Carbapenem Therapeutic Drug Monitoring in Critically Ill Adult Patients and Clinical Outcomes: A Systematic Review with Meta-Analysis
Antibiotics 2021, 10(2), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020177 - 10 Feb 2021
Cited by 1 | Viewed by 942
Abstract
Drug monitoring is one strategy of antibiotic stewardship to face antimicrobial resistance. This strategy could have a determinant role in critically ill patients treated with carbapenems to overcome pharmacokinetic variability, reduce the risk of subtherapeutic dosage or toxicity, and reduce the risks inherent [...] Read more.
Drug monitoring is one strategy of antibiotic stewardship to face antimicrobial resistance. This strategy could have a determinant role in critically ill patients treated with carbapenems to overcome pharmacokinetic variability, reduce the risk of subtherapeutic dosage or toxicity, and reduce the risks inherent to treatment. However, the effectiveness of therapeutic drug monitoring (TDM) is unknown. This paper aims to identify TDM effectiveness in critically ill patients treated with carbapenems. English and ClinicalTrials.gov databases were searched to identify relevant studies evaluating carbapenem TDM. Randomized controlled trials (RCTs) and comparative cohort studies were selected for inclusion if they compared carbapenem TDM to standard care in adult critically ill or sepsis/septic shock patients. The primary outcome was mortality. Secondary outcomes included morbidity, clinical cure, microbiological eradication, antimicrobial resistance, drug-related side effects, and achievement of target plasma concentrations. Overall, performing carbapenem TDM was not associated with a decrease in mortality. However, it could be evidence for a relationship with clinical cure as well as target attainment. Some studies found favorable outcomes related to clinical and microbiological responses, such as lower procalcitonin levels at the end of the monitored therapy compared to standard care. For the primary and secondary outcomes analyzed, strong evidence was not identified, which could be due to the size, risk of bias, and design of selected studies. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)
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Open AccessReview
Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting
Antibiotics 2020, 9(4), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040196 - 20 Apr 2020
Cited by 12 | Viewed by 2127
Abstract
The increasing prevalence of antibiotic resistance is a threat to human health, particularly within vulnerable populations in the hospital and acute care settings. This leads to increasing healthcare costs, morbidity, and mortality. Bacteria rapidly evolve novel mechanisms of resistance and methods of antimicrobial [...] Read more.
The increasing prevalence of antibiotic resistance is a threat to human health, particularly within vulnerable populations in the hospital and acute care settings. This leads to increasing healthcare costs, morbidity, and mortality. Bacteria rapidly evolve novel mechanisms of resistance and methods of antimicrobial evasion. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii have all been identified as pathogens with particularly high rates of resistance to antibiotics, resulting in a reducing pool of available treatments for these organisms. Effectively combating this issue requires both preventative and reactive measures. Reducing the spread of resistant pathogens, as well as reducing the rate of evolution of resistance is complex. Such a task requires a more judicious use of antibiotics through a better understanding of infection epidemiology, resistance patterns, and guidelines for treatment. These goals can best be achieved through the implementation of antimicrobial stewardship programs and the development and introduction of new drugs capable of eradicating multi-drug resistant Gram-negative pathogens (MDR GNB). The purpose of this article is to review current trends in MDR Gram-negative bacterial infections in the hospitalized setting, as well as current guidelines for management. Finally, new and emerging antimicrobials, as well as future considerations for combating antibiotic resistance on a global scale are discussed. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Carbapenem Therapeutic drug monitoring as a strategy to decrease antimicrobial resistance: an overview
Authors: Sharon Lechtig-Wasserman; Liebisch Hans; Nicolás Díaz-Pinilla; Jhosep Blanco; Yuli-Viviana Fuentes-Barrero; Rosa-Helena Bustos
Affiliation: Evidence-Based Therapeutics Group, Clinical Pharmacology, Universidad de La Sabana, 140013 Chía, Colombia

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