Evaluation of New Molecules in Severe Infectious Diseases, 2nd Edition

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10808

Special Issue Editors


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Guest Editor
Laboratory of Chemistry of Biological Macromolecules, Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdańsk, Poland
Interests: peptides chemistry; antimicrobial peptides; enkephalinase inhibitors; lipopeptides; ESKAPE pathogens; Staphylococcus aureus; biofilm; toxicity; inflammatory bowel diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Dermatological Clinic- Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
Interests: antibiotic resistance; antimicrobial peptides; quorum sensing inhibitor; infected wounds; wound healing; biofilm; Staphylococcal infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hospital- and community-acquired Gram-positive and Gram-negative infections introduce substantial burdens in terms of morbidity, mortality, and healthcare costs. The emergence of bacterial resistance to conventional antibiotics has become a commonplace and heightened concern about the need for new drugs endowed with broader activity, which are useful in cases of infections unresponsive to common antimicrobial agents. Moreover, the introduction of new traditional antibiotics to counter these pathogens has frequently been closely followed by the emergence of resistant strains. For this reason, recent interest in the search for alternative therapeutics is growing, and identifying effective agents to treat multidrug-resistant infections with novel mechanisms of activity has become critical.

Prof. Dr. Elżbieta Kamysz
Prof. Dr. Oriana Simonetti
Guest Editors

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Keywords

  • antibiotic resistance
  • in vitro susceptibility
  • antimicrobial peptides
  • quorum sensing inhibitors
  • terpenoids

Published Papers (7 papers)

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Research

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12 pages, 1253 KiB  
Article
Synthesis, Antimicrobial and Mutagenic Activity of a New Class of d-Xylopyranosides
by Karol Sikora, Piotr Szweda, Karolina Słoczyńska, Justyna Samaszko-Fiertek, Janusz Madaj, Beata Liberek, Elżbieta Pękala and Barbara Dmochowska
Antibiotics 2023, 12(5), 888; https://doi.org/10.3390/antibiotics12050888 - 10 May 2023
Cited by 1 | Viewed by 1173
Abstract
Eight N-[2-(2′,3′,4′-tri-O-acetyl-α/β-d-xylopyranosyloxy)ethyl]ammonium bromides, a new class of d-xylopyranosides containing a quaternary ammonium aglycone, were obtained. Their complete structure was confirmed using NMR spectroscopy (1H, 13C, COSY and HSQC) and high-resolution mass spectrometry (HRMS). An [...] Read more.
Eight N-[2-(2′,3′,4′-tri-O-acetyl-α/β-d-xylopyranosyloxy)ethyl]ammonium bromides, a new class of d-xylopyranosides containing a quaternary ammonium aglycone, were obtained. Their complete structure was confirmed using NMR spectroscopy (1H, 13C, COSY and HSQC) and high-resolution mass spectrometry (HRMS). An antimicrobial activity against fungi (Candida albicans, Candida glabrata) and bacteria (Staphylococcus aureus, Escherichia coli) and a mutagenic Ames test with Salmonella typhimurium TA 98 strain were performed for the obtained compounds. The greatest activity against the tested microorganisms was shown by glycosides with the longest (octyl) hydrocarbon chain in ammonium salt. None of the tested compounds exhibited mutagenic activity in the Ames test. Full article
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9 pages, 444 KiB  
Article
Secondary Infections in Critically Ill Patients with COVID-19: A Retrospective Study
by Luca Caiazzo, Chiara Temperoni, Benedetta Canovari, Oriana Simonetti, Roberto Montalti and Francesco Barchiesi
Antibiotics 2022, 11(11), 1598; https://doi.org/10.3390/antibiotics11111598 - 11 Nov 2022
Cited by 3 | Viewed by 1200
Abstract
Patients with severe COVID-19, especially those followed in the ICU, are at risk for developing bacterial and fungal superinfections. In this study, we aimed to describe the burden of hospital-acquired superinfections in a cohort of consecutive, severe COVID-19 patients hospitalized between February and [...] Read more.
Patients with severe COVID-19, especially those followed in the ICU, are at risk for developing bacterial and fungal superinfections. In this study, we aimed to describe the burden of hospital-acquired superinfections in a cohort of consecutive, severe COVID-19 patients hospitalized between February and May 2021 in the intensive care unit (ICU) department of San Salvatore Hospital in Pesaro, Italy. Among 89 patients considered, 68 (76.4%) acquired a secondary infection during their ICU stay. A total of 46 cases of ventilator-associated pneumonia (VAP), 31 bloodstream infections (BSIs) and 15 catheter-associated urinary tract infections (CAUTIs) were diagnosed. Overall mortality during ICU stay was 48%. A multivariate analysis showed that factors independently associated with mortality were male gender (OR: 4.875, CI: 1.227–19.366, p = 0.024), higher BMI (OR: 4.938, CI:1.356–17.980, p = 0.015) and the presence of VAP (OR: 6.518, CI: 2.178–19.510, p = 0.001). Gram-negative bacteria accounted for most of the isolates (68.8%), followed by Gram-positive bacteria (25.8%) and fungi (5.3%). Over half of the infections (58%) were caused by MDR opportunistic pathogens. Factors that were independently associated with an increased risk of infections caused by an MDR pathogen were higher BMI (OR: 4.378, CI: 1.467–13.064, p = 0.0008) and a higher Charlson Comorbidity Index (OR: 3.451, 95% CI: 1.113–10.700, p = 0.032). Secondary infections represent a common and life-threatening complication in critically ill patients with COVID-19. Efforts to minimize the likelihood of acquiring such infections, often caused by difficult-to-treat MDR organisms—especially in some subgroups of patients with specific risk factors—must be pursued. Full article
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28 pages, 4289 KiB  
Article
Understanding the Role of Self-Assembly and Interaction with Biological Membranes of Short Cationic Lipopeptides in the Effective Design of New Antibiotics
by Oktawian Stachurski, Damian Neubauer, Aleksandra Walewska, Emilia Iłowska, Marta Bauer, Sylwia Bartoszewska, Karol Sikora, Aleksandra Hać, Dariusz Wyrzykowski, Adam Prahl, Wojciech Kamysz and Emilia Sikorska
Antibiotics 2022, 11(11), 1491; https://doi.org/10.3390/antibiotics11111491 - 27 Oct 2022
Cited by 3 | Viewed by 1743
Abstract
This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C12-C18 fatty acids attached to the N-terminal part of the peptides. The findings were discussed in the context of the relationship among biological activity, self-assembly, stability, [...] Read more.
This study investigates short cationic antimicrobial lipopeptides composed of 2–4 amino acid residues and C12-C18 fatty acids attached to the N-terminal part of the peptides. The findings were discussed in the context of the relationship among biological activity, self-assembly, stability, and membrane interactions. All the lipopeptides showed the ability to self-assemble in PBS solution. In most cases, the critical aggregation concentration (CAC) much surpassed the minimal inhibitory concentration (MIC) values, suggesting that monomers are the main active form of lipopeptides. The introduction of β-alanine into the peptide sequence resulted in a compound with a high propensity to fibrillate, which increased the peptide stability and activity against S. epidermidis and C. albicans and reduced the cytotoxicity against human keratinocytes. The results of our study indicated that the target of action of lipopeptides is the bacterial membrane. Interestingly, the type of peptide counterion may affect the degree of penetration of the lipid bilayer. In addition, the binding of the lipopeptide to the membrane of Gram-negative bacteria may lead to the release of calcium ions necessary for stabilization of the lipopolysaccharide layer. Full article
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Review

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31 pages, 1816 KiB  
Review
New Strategies to Kill Metabolically-Dormant Cells Directly Bypassing the Need for Active Cellular Processes
by Karolina Stojowska-Swędrzyńska, Dorota Kuczyńska-Wiśnik and Ewa Laskowska
Antibiotics 2023, 12(6), 1044; https://doi.org/10.3390/antibiotics12061044 - 12 Jun 2023
Cited by 6 | Viewed by 2084
Abstract
Antibiotic therapy failure is often caused by the presence of persister cells, which are metabolically-dormant bacteria capable of surviving exposure to antimicrobials. Under favorable conditions, persisters can resume growth leading to recurrent infections. Moreover, several studies have indicated that persisters may promote the [...] Read more.
Antibiotic therapy failure is often caused by the presence of persister cells, which are metabolically-dormant bacteria capable of surviving exposure to antimicrobials. Under favorable conditions, persisters can resume growth leading to recurrent infections. Moreover, several studies have indicated that persisters may promote the evolution of antimicrobial resistance and facilitate the selection of specific resistant mutants; therefore, in light of the increasing numbers of multidrug-resistant infections worldwide, developing efficient strategies against dormant cells is of paramount importance. In this review, we present and discuss the efficacy of various agents whose antimicrobial activity is independent of the metabolic status of the bacteria as they target cell envelope structures. Since the biofilm-environment is favorable for the formation of dormant subpopulations, anti-persister strategies should also include agents that destroy the biofilm matrix or inhibit biofilm development. This article reviews examples of selected cell wall hydrolases, polysaccharide depolymerases and antimicrobial peptides. Their combination with standard antibiotics seems to be the most promising approach in combating persistent infections. Full article
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Other

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7 pages, 217 KiB  
Brief Report
The Effect of Dalbavancin in Moderate to Severe Hidradenitis Suppurativa
by Elisa Molinelli, Claudia Sapigni, Giovanni Marco D’Agostino, Valerio Brisigotti, Giulio Rizzetto, Ivan Bobyr, Oscar Cirioni, Andrea Giacometti, Lucia Brescini, Sara Mazzanti, Annamaria Offidani and Oriana Simonetti
Antibiotics 2022, 11(11), 1573; https://doi.org/10.3390/antibiotics11111573 - 8 Nov 2022
Cited by 8 | Viewed by 1277
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and fistulas, localized to the areas of the folds where apocrine glands are present: the armpits, groin, inframammary region, and genital or perineal region. The management is still challenging, [...] Read more.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and fistulas, localized to the areas of the folds where apocrine glands are present: the armpits, groin, inframammary region, and genital or perineal region. The management is still challenging, and it includes mainly systemic antibiotics, immunosuppressors, and biologic agents. Antibiotics are frequently used in the management of HS for their anti-inflammatory, immunomodulatory, and antimicrobial properties, but no data have been reported regarding the use of dalbavancin in HS. The aim of our practice was to evaluate efficacy, flare, and disease-free survival after dalbavancin therapy in a selected population with HS. We report the experience of the Ancona Dermatology Clinic in treating HS flare-ups with dalbavancin and its rationale for use. Our observation shows that the use of dalbavancin is an effective and well-tolerated treatment for the management of Hurley stage II-III HS; currently, dalbavancin should be considered as a supportive therapy for selected patients. Full article
10 pages, 282 KiB  
Perspective
MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives
by Giulio Rizzetto, Elisa Molinelli, Giulia Radi, Oscar Cirioni, Lucia Brescini, Andrea Giacometti, Annamaria Offidani and Oriana Simonetti
Antibiotics 2022, 11(11), 1504; https://doi.org/10.3390/antibiotics11111504 - 28 Oct 2022
Cited by 1 | Viewed by 1236
Abstract
Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization [...] Read more.
Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective. Full article
11 pages, 517 KiB  
Perspective
Role of Daptomycin in Cutaneous Wound Healing: A Narrative Review
by Giulio Rizzetto, Elisa Molinelli, Giulia Radi, Federico Diotallevi, Oscar Cirioni, Lucia Brescini, Andrea Giacometti, Annamaria Offidani and Oriana Simonetti
Antibiotics 2022, 11(7), 944; https://doi.org/10.3390/antibiotics11070944 - 14 Jul 2022
Cited by 5 | Viewed by 1548
Abstract
Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin [...] Read more.
Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin in the skin wound healing process, proposing our point of view on the possible association with other molecules that could improve the skin healing process. Daptomycin may improve wound healing in MRSA-infected burns, surgical wounds, and diabetic feet, but further studies in humans with histological examination are needed. In the future, the combination of daptomycin with other molecules with synergistic action, such as vitamin E and derivates, IB-367, RNA III-inhibiting peptide (RIP), and palladium nanoflowers, may help to improve wound healing and overcome forms of antibiotic resistance. Full article
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