Antimicrobial Resistance: Current Status and Future Directions

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

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 8384

Special Issue Editors

Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: microbiology; antimicrobial resistance; antifungal drugs; antibiotics; multidrug-resistant infections
Special Issues, Collections and Topics in MDPI journals
Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: microbiology; antimicrobial resistance; antifungal drugs; antibiotics; multidrug-resistant infections

Special Issue Information

Dear Colleagues,

Resistance to antimicrobial drugs and the emergence of multi-resistant bacterial and fungal strains represent a problem of clinical relevance that poses serious threats to public health worldwide. Currently, available data have shown a significant increase in drug resistance rates by bacterial and fungal pathogens responsible for nosocomial and community infections worldwide. This leads to reduced effectiveness of conventional drugs and consequently an increase in mortality rates. The World Health Organization (WHO) has underlined that epidemiological surveillance is considered an essential factor for the control and management of the antimicrobial resistance problem. In addition, WHO has also highlighted the importance of researching new classes of antimicrobial drugs to implement currently available drugs.

This Special Issue covers all aspects contributing to the resolution of the antimicrobial resistance phenomenon, i.e., epidemiological surveillance and all aspects of the discovery of new therapeutic options for multidrug-resistant infections, which include nanomaterials, natural and synthetic compounds, repurposed drugs and existing drugs modified to treat multidrug-resistant infections. We invite researchers to contribute original research and review articles.

Dr. Veronica Folliero
Dr. Federica Dell’Annunziata
Guest Editors

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Keywords

  • antimicrobial resistance
  • bacteria
  • fungi
  • epidemiology
  • infection
  • antibiotics
  • antifungal drugs
  • surveillance
  • drug discovery

Published Papers (7 papers)

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12 pages, 1377 KiB  
Article
Bacterial Species Involved in Venous Leg Ulcer Infections and Their Sensitivity to Antibiotherapy—An Alarm Signal Regarding the Seriousness of Chronic Venous Insufficiency C6 Stage and Its Need for Prompt Treatment
by Sergiu-Ciprian Matei, Cristina Stefania Dumitru, Ayman Mohamed Fakhry, Nenad Ilijevski, Slobodan Pešić, Jovan Petrović, Zorin Petrişor Crăiniceanu, Marius-Sorin Murariu and Sorin Olariu
Microorganisms 2024, 12(3), 472; https://doi.org/10.3390/microorganisms12030472 - 26 Feb 2024
Viewed by 601
Abstract
Background: Venous leg ulcers (VLUs) are a common chronic wound condition susceptible to infection by various bacterial species. Understanding bacterial presence and antibiotic sensitivity is crucial for effective treatment. Methodsː Medical records of 60 patients diagnosed with the C6 chronic venous insufficiency stage [...] Read more.
Background: Venous leg ulcers (VLUs) are a common chronic wound condition susceptible to infection by various bacterial species. Understanding bacterial presence and antibiotic sensitivity is crucial for effective treatment. Methodsː Medical records of 60 patients diagnosed with the C6 chronic venous insufficiency stage were analyzed retrospectively. The patients were divided into an active recurrent VLU group (33 cases) and a first-onset active VLU group (27 cases). Bacterial identification, antibiotic sensitivity, and laboratory markers were assessed. Resultsː Pseudomonas aeruginosa was the most prevalent bacterial species in both the study (72.72%) and control (37.03%) groups, along with other common bacteria such as Proteus mirabilis, Enterococcus sp., Staphylococcus aureus, Acinetobacter baumannii, Klebsiella spp., and Escherichia coli. Furthermore, uncommon bacteria, including Providencia rettgeri, Group B Streptococcus, and Salmonella Paratyphi B, and a fungal infection with Candida albicans, were identified only in the study group, while Morganella morganii was found exclusively in the control group. Pseudomonas aeruginosa showed significant sensitivity to several antibiotics, particularly Amikacin and Meropenem. Nonspecific laboratory markers, such as CRP, fibrinogen, ESR, WBC, CK, neutrophils, and lymphocytes, revealed statistically significant differences between groups, indicating their potential as biomarkers for monitoring recurrent VLUs. Conclusionsː These results highlight the need for comprehensive diagnostic approaches to effectively manage VLU infections and improve patient outcomes. Further research is warranted to explore factors influencing the presence of uncommon bacteria and to develop targeted interventions for VLU management. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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15 pages, 4317 KiB  
Article
The Staphylococcus aureus ArlS Kinase Inhibitor Tilmicosin Has Potent Anti-Biofilm Activity in Both Static and Flow Conditions
by Zihui Wang, Haoran Wang, Jinna Bai, Shen Cai, Di Qu, Youhua Xie and Yang Wu
Microorganisms 2024, 12(2), 256; https://doi.org/10.3390/microorganisms12020256 - 25 Jan 2024
Viewed by 724
Abstract
Staphylococcus aureus can form biofilms on biotic surfaces or implanted materials, leading to biofilm-associated diseases in humans and animals that are refractory to conventional antibiotic treatment. Recent studies indicate that the unique ArlRS regulatory system in S. aureus is a promising target for [...] Read more.
Staphylococcus aureus can form biofilms on biotic surfaces or implanted materials, leading to biofilm-associated diseases in humans and animals that are refractory to conventional antibiotic treatment. Recent studies indicate that the unique ArlRS regulatory system in S. aureus is a promising target for screening inhibitors that may eradicate formed biofilms, retard virulence and break antimicrobial resistance. In this study, by screening in the library of FDA-approved drugs, tilmicosin was found to inhibit ArlS histidine kinase activity (IC50 = 1.09 μM). By constructing a promoter-fluorescence reporter system, we found that tilmicosin at a concentration of 0.75 μM or 1.5 μM displayed strong inhibition on the expression of the ArlRS regulon genes spx and mgrA in the S. aureus USA300 strain. Microplate assay and confocal laser scanning microscopy showed that tilmicosin at a sub-minimal inhibitory concentration (MIC) had a potent inhibitory effect on biofilms formed by multiple S. aureus strains and a strong biofilm-forming strain of S. epidermidis. In addition, tilmicosin at three-fold of MIC disrupted USA300 mature biofilms and had a strong bactericidal effect on embedded bacteria. Furthermore, in a BioFlux flow biofilm assay, tilmicosin showed potent anti-biofilm activity and synergized with oxacillin against USA300. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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19 pages, 7467 KiB  
Article
Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired Staphylococcus aureus Infections
by Veronica Folliero, Federica Dell’Annunziata, Biagio Santella, Emanuela Roscetto, Carla Zannella, Nicoletta Capuano, Alessandro Perrella, Anna De Filippis, Giovanni Boccia, Maria Rosaria Catania, Massimiliano Galdiero and Gianluigi Franci
Microorganisms 2023, 11(9), 2242; https://doi.org/10.3390/microorganisms11092242 - 06 Sep 2023
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Abstract
The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference [...] Read more.
The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against Staphylococcus aureus (S. aureus), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical S. aureus isolates with different antibiotic resistance profiles. Mean MIC90 values of 6.2 μg/mL were reported for all tested S. aureus strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC90 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC50) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of S. aureus infections. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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11 pages, 772 KiB  
Article
Antimicrobial Resistance in Pseudomonas aeruginosa before and during the COVID-19 Pandemic
by Enrica Serretiello, Roberta Manente, Federica Dell’Annunziata, Veronica Folliero, Domenico Iervolino, Vincenzo Casolaro, Alessandro Perrella, Emanuela Santoro, Massimiliano Galdiero, Mario Capunzo, Gianluigi Franci and Giovanni Boccia
Microorganisms 2023, 11(8), 1918; https://doi.org/10.3390/microorganisms11081918 - 28 Jul 2023
Cited by 1 | Viewed by 1127
Abstract
Pseudomonas aeruginosa (PA) is a major Gram-negative opportunistic pathogen causing several serious acute and chronic infections in the nosocomial and community settings. PA eradication has become increasingly difficult due to its remarkable ability to evade antibiotics. Therefore, epidemiological studies are needed to limit [...] Read more.
Pseudomonas aeruginosa (PA) is a major Gram-negative opportunistic pathogen causing several serious acute and chronic infections in the nosocomial and community settings. PA eradication has become increasingly difficult due to its remarkable ability to evade antibiotics. Therefore, epidemiological studies are needed to limit the infection and aim for the correct treatment. The present retrospective study focused on PA presence among samples collected at the San Giovanni di Dio and Ruggi D’Aragona University Hospital in Salerno, Italy; its resistance profile and relative variations over the eight years were analyzed. Bacterial identification and antibiotic susceptibility tests were performed by VITEK® 2. In the 2015–2019 and 2020–2022 timeframes, respectively, 1739 and 1307 isolates of PA were obtained from respiratory samples, wound swabs, urine cultures, cultural swabs, blood, liquor, catheter cultures, vaginal swabs, and others. During 2015–2019, PA strains exhibited low resistance against amikacin (17.2%), gentamicin (25.2%), and cefepime (28.3%); moderate resistance against ceftazidime (34.4%), imipenem (34.6%), and piperacillin/tazobactam (37.7%); and high resistance against ciprofloxacin (42.4%) and levofloxacin (50.6%). Conversely, during the 2020–2022 era, PA showed 11.7, 21.1, 26.9, 32.6, 33.1, 38.7, and 39.8% resistance to amikacin, tobramycin, cefepime, imipenem, ceftazidime, ciprofloxacin, and piperacillin/tazobactam, respectively. An overall resistance-decreasing trend was observed for imipenem and gentamicin during 2015–2019. Instead, a significant increase in resistance was recorded for cefepime, ceftazidime, and imipenem in the second set of years investigated. Monitoring sentinel germs represents a key factor in optimizing empirical therapy to minimize the spread of antimicrobial resistance. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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20 pages, 5133 KiB  
Article
Effect of Essential Oils of Apiaceae, Lamiaceae, Lauraceae, Myrtaceae, and Rutaceae Family Plants on Growth, Biofilm Formation, and Quorum Sensing in Chromobacterium violaceum, Pseudomonas aeruginosa, and Enterococcus faecalis
by Patrizia D’Aquila, Giada Sena, Michele Crudo, Giuseppe Passarino and Dina Bellizzi
Microorganisms 2023, 11(5), 1150; https://doi.org/10.3390/microorganisms11051150 - 28 Apr 2023
Cited by 2 | Viewed by 1175
Abstract
The biological role played by essential oils extracted from aromatic plants is progressively being recognized. This study evaluated the potential antibacterial activity of ten essential oils against Chromobacterium violaceum, Pseudomonas aeruginosa, and Enterococcus faecalis by measuring their minimum inhibitory concentration. We [...] Read more.
The biological role played by essential oils extracted from aromatic plants is progressively being recognized. This study evaluated the potential antibacterial activity of ten essential oils against Chromobacterium violaceum, Pseudomonas aeruginosa, and Enterococcus faecalis by measuring their minimum inhibitory concentration. We found that essential oils exert different antimicrobial effects, with Origanum vulgare and Foeniculum vulgare demonstrating the most significant inhibitory effect on bacterial growth for C. violaceum and E. faecalis. The growth of P. aeruginosa was not affected by any essential oil concentration we used. Sub-inhibitory concentrations of essential oils reduced in C. violaceum and E. faecalis biofilm formation, violacein amount, and gelatinase activity, all of which are biomarkers of the Quorum Sensing process. These concentrations significantly affect the global methylation profiles of cytosines and adenines, thus leading to the hypothesis that the oils also exert their effects through epigenetic changes. Considering the results obtained, it is possible that essential oils can find a broad spectrum of applications in counteracting microbial contamination and preserving sterility of surfaces and foods, as well as inhibiting microbial growth of pathogens, alone or in combination with traditional antibiotics. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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10 pages, 2834 KiB  
Article
Characterization of Linezolid-Analogue L3-Resistance Mutation in Staphylococcus aureus
by Anna Zanfardino, Michela Di Napoli, Federica Migliore, Bruno Hay Mele, Annunziata Soriente, Margherita De Rosa, Eugenio Notomista and Mario Varcamonti
Microorganisms 2023, 11(3), 700; https://doi.org/10.3390/microorganisms11030700 - 08 Mar 2023
Viewed by 1018
Abstract
In a previous study, a linezolid analogue, called 10f, was synthesized. The 10f molecule has an antimicrobial activity comparable to that of the parental compound. In this study, we isolated a Staphylococcus aureus (S. aureus) strain resistant to 10f. After sequencing [...] Read more.
In a previous study, a linezolid analogue, called 10f, was synthesized. The 10f molecule has an antimicrobial activity comparable to that of the parental compound. In this study, we isolated a Staphylococcus aureus (S. aureus) strain resistant to 10f. After sequencing the 23S rRNA and the ribosomal proteins L3 (rplC) and L4 (rplD) genes, we found that the resistant phenotype was associated with a single mutation G359U in rplC bearing to the missense mutation G120V in the L3 protein. The identified mutation is far from the peptidyl transferase center, the oxazolidinone antibiotics binding site, thus suggesting that we identified a new and interesting example of a long-range effect in the ribosome structure. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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9 pages, 268 KiB  
Case Report
Detection of mcr-1-1 Positive Enteropathogenic Escherichia coli Isolates Associated with Post-Weaning Diarrhoea in an Organic Piglet-Producing Farm in Austria
by René Renzhammer, Lukas Schwarz, Adriana Cabal Rosel, Werner Ruppitsch, Andreas Fuchs, Erwin Simetzberger, Andrea Ladinig and Igor Loncaric
Microorganisms 2024, 12(2), 244; https://doi.org/10.3390/microorganisms12020244 - 24 Jan 2024
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Abstract
Postweaning diarrhoea (PWD) is a frequent multifactorial disease occurring in swine stocks worldwide. Since pathogenic Escherichia (E.) coli play a pivotal role in the pathogenesis of PWD and porcine E. coli are often resistant to different antibiotics, colistin is frequently applied [...] Read more.
Postweaning diarrhoea (PWD) is a frequent multifactorial disease occurring in swine stocks worldwide. Since pathogenic Escherichia (E.) coli play a pivotal role in the pathogenesis of PWD and porcine E. coli are often resistant to different antibiotics, colistin is frequently applied to treat piglets with PWD. However, the application of colistin to livestock has been associated with the emergence of colistin resistance. This case report describes the detection of the colistin resistance gene mcr-1-1 in two E. coli isolated from piglets with PWD in an Austrian organic piglet-producing farm, which was managed by two farmers working as nurses in a hospital. Both mcr-1-positive E. coli were further analysed by Illumina short-read-sequencing, including assemblies and gene prediction. Both isolates belonged to the same clonal type and were positive for eaeH and espX5, which are both virulence genes associated with enteropathogenic E. coli (EPEC). Due to the detection of mcr-1-positive EPEC and based on the results of the antimicrobial resistance testing, the veterinarian decided to apply gentamicin for treatment instead of colistin, leading to improved clinical signs. In addition, after replacing faba beans with whey, PWD was solely observed in 2/10 weaned batches in the consecutive months. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Current Status and Future Directions)
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