Resistance Matters: Current Issues and Future Strategies to Combat Multidrug-Resistant Bugs

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 6923

Special Issue Editors


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Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Open University, IRCCS, 00166 Rome, Italy
Interests: bacterial pathogens; host-pathogen interactions; Acinetobacter baumannii; microRNAs; antibiotic-resistance

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Guest Editor
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Interests: bacterial pathogens; host-pathogen interactions; Shigella flexneri; Escherichia coli; Acinetobacter baumannii; microRNAs; organoids
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Research Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
Interests: bacterial pathogens; host-pathogen interactions; Shigella flexneri; Escherichia coli; Acinetobacter baumannii; microRNAs; genotyping
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Department of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran 37541-374, Iran
Interests: infectious diseases; molecular biology; cellular and molecular immunology and bioinformatics
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Special Issue Information

Dear Colleagues,

The rise in the number of bacterial isolates that show antibiotic resistance (AR) to several, if not all, antibiotics represents the most frightening challenge of the 21st century. Currently, AR bugs cause infections associated with high morbidity and mortality, especially in healthcare settings. The main cause of this AR phenomenon is the overuse and misuse of antibiotics, involving both prescribers and users; therefore, strict measures of prevention and control should be taken. Regarding the present situation, the World Health Organization states that “the success of modern medicine in treating infections, including during major surgery and cancer chemotherapy, would be at increased risk”. The huge adaptability of AR bacteria allows them to evolve new resistance mechanisms, undermining the efforts of finding novel molecules. Together with combined therapies, phages, efflux pump and beta-lactamase/carbapenamase inhibitors, anti-quorum sensing, anti-biofilm, anti-adhesion, anti-virulence, anti-plasmid and plasmid curing are recent approaches to fighting against AR pathogens, which are currently being researched. These strategies take into account bacterial behavior, selectively acting on those virulence determinants required for the establishment of the infections. Therefore, this Special Issue will focus on the various aspects of overcoming bacterial AR, including classical and innovative strategies to eradicate pathogens. This Special Issue also covers basic studies on potential and promising bacterial targets for the development of new molecules.

Prof. Dr. Cecilia Ambrosi
Dr. Daniela Scribano
Dr. Meysam Sarshar
Dr. Payam Behzadi
Guest Editors

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Keywords

  • antibiotic resistance
  • anti-microbial stewardship
  • hospital acquired infections
  • anti-quorum sensing
  • anti-biofilm
  • anti-adhesion
  • anti-virulence
  • anti-plasmid
  • plasmid curing
  • antibiotic alternatives

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Published Papers (3 papers)

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Research

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10 pages, 810 KiB  
Article
Antibiotic Resistance Rates for Helicobacter pylori in Rural Arizona: A Molecular-Based Study
by Fernando P. Monroy, Heidi E. Brown, Claudia M. Acevedo-Solis, Andres Rodriguez-Galaviz, Rishi Dholakia, Laura Pauli and Robin B. Harris
Microorganisms 2023, 11(9), 2290; https://doi.org/10.3390/microorganisms11092290 - 12 Sep 2023
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Abstract
Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the [...] Read more.
Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n = 67) were sequenced for clarithromycin- and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples which amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C being the most common mutation at 90%. While the prevalence of metronidazole-resistance-associated mutations was higher at 93.9%, the mutations were more variable, with D95N being the most common followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed. Full article
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11 pages, 275 KiB  
Article
Antimicrobial Resistance Pattern, Pathogenicity and Molecular Properties of Hypervirulent Klebsiella pneumonia (hvKp) among Hospital-Acquired Infections in the Intensive Care Unit (ICU)
by Mohanned Talal Alharbi, Mohammed S. Almuhayawi, Mohammed K. Nagshabandi, Muyassar K. Tarabulsi, Mohammed H. Alruhaili, Hattan S. Gattan, Soad K. Al Jaouni, Samy Selim, Awadh Alanazi, Yasir Alruwaili, Shaimaa Mohamed Zaied and Osama Ahmed Faried
Microorganisms 2023, 11(3), 661; https://doi.org/10.3390/microorganisms11030661 - 6 Mar 2023
Cited by 7 | Viewed by 2514
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired [...] Read more.
Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-β-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, <0.001, <0.001, 0.037 and <0.001, respectively). However, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections. Full article

Review

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18 pages, 360 KiB  
Review
Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms
by Joana Alves, Betânia Abreu, Pedro Palma, Emine Alp, Tarsila Vieceli and Jordi Rello
Microorganisms 2023, 11(5), 1127; https://doi.org/10.3390/microorganisms11051127 - 26 Apr 2023
Cited by 3 | Viewed by 2192
Abstract
The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing [...] Read more.
The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority. Full article
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