Evaluation of New Molecules in Severe Infectious Diseases

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 December 2021) | Viewed by 24381

Special Issue Editors


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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
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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

Special Issue Information

Dear Colleagues,

Hospital- and community-acquired Gram-positive and Gram-negative infections pose a substantial burden in terms of morbidity, mortality, and healthcare costs. The emergence of bacterial resistance to conventional antibiotics has become 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 it is becoming critical to identify effective agents to treat multidrug-resistant infections with novel mechanisms of activity.

Prof. Dr. Oriana Simonetti
Prof. Dr. Elżbieta Kamysz

Guest Editors

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Keywords

  • Antibiotic resistance
  • In vitro susceptibility
  • Antimicrobial peptides
  • Quorum sensing inhibitors
  • Terpenoids

Published Papers (9 papers)

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Research

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8 pages, 369 KiB  
Article
Ceftazidime–Avibactam for the Treatment of Multidrug-Resistant Pathogens: A Retrospective, Single Center Study
by Maria Di Pietrantonio, Lucia Brescini, Jennifer Candi, Morroni Gianluca, Francesco Pallotta, Sara Mazzanti, Paolo Mantini, Bianca Candelaresi, Silvia Olivieri, Francesco Ginevri, Giulia Cesaretti, Sefora Castelletti, Emanuele Cocci, Rosaria G. Polo, Elisabetta Cerutti, Oriana Simonetti, Oscar Cirioni, Marcello Tavio, Andrea Giacometti and Francesco Barchiesi
Antibiotics 2022, 11(3), 321; https://doi.org/10.3390/antibiotics11030321 - 28 Feb 2022
Cited by 7 | Viewed by 2722
Abstract
Background: Ceftazidime/avibactam is a new cephalosporin/beta-lactamase inhibitor combination approved in 2015 by the FDA for the treatment of complicated intra-abdominal and urinary tract infection, hospital-acquired pneumoniae and Gram-negative infections with limited treatment options. Methods: In this retrospective study, we evaluate the efficacy of [...] Read more.
Background: Ceftazidime/avibactam is a new cephalosporin/beta-lactamase inhibitor combination approved in 2015 by the FDA for the treatment of complicated intra-abdominal and urinary tract infection, hospital-acquired pneumoniae and Gram-negative infections with limited treatment options. Methods: In this retrospective study, we evaluate the efficacy of ceftazidime/avibactam treatment in 81 patients with Gram-negative infection treated in our center from January 2018 to December 2019. The outcome evaluated was 30-days survival or relapse of infection after the first positive blood culture. Results: the majority of patients were 56 male (69%), with median age of 67. Charlson’s Comorbidity Index was >3 in 58 patients. In total, 46% of the patients were admitted into the medical unit, 41% in the ICU, and 14% in the surgical ward. Of the patients, 78% had nosocomial infections, and 22% had healthcare-related infections. The clinical failure rate was 35%: 13 patients died within 30 days from the onset of infection. The outcome was influenced by the clinical condition of the patients: solid organ transplantation (p = 0.003) emerged as an independent predictor of mortality; non-survival patients most frequently had pneumonia (p = 0.009) or mechanical ventilation (p = 0.049). Conclusion: Ceftazidime–avibactam showed high efficacy in infections caused by MDR Gram-negative pathogens with limited therapeutic options. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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12 pages, 1032 KiB  
Article
Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model
by Oriana Simonetti, Oscar Cirioni, Gaia Goteri, Guendalina Lucarini, Elżbieta Kamysz, Wojciech Kamysz, Fiorenza Orlando, Giulio Rizzetto, Elisa Molinelli, Gianluca Morroni, Roberto Ghiselli, Mauro Provinciali, Andrea Giacometti and Annamaria Offidani
Antibiotics 2021, 10(10), 1210; https://doi.org/10.3390/antibiotics10101210 - 05 Oct 2021
Cited by 12 | Viewed by 2524
Abstract
Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male [...] Read more.
Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male BALB/c mice was made and inoculated with Staphylococcus aureus. Two control groups were formed (uninfected and not treated, C0; infected and not treated, C1) and six contaminated groups were treated, respectively, with: teicoplanin, LL-37, given topically and /or systemically. Histological examination of VEGF expression and micro-vessel density, and bacterial cultures of wound tissues, were performed. Results: Histological examination of wounds in the group treated with topical and intraperitoneal LL-37 showed increased re-epithelialization, formation of the granulation tissue, collagen organization, and angiogenesis. Conclusions: Based on the mode of action, LL-37 has a potential future role in the management of infected wounds. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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8 pages, 1300 KiB  
Article
Antibiotic-Related Adverse Drug Reactions in Patients Treated on the Dermatology Ward of Medical University of Gdańsk
by Ewa Maria Sokolewicz, Martyna Rogowska, Miłosz Lewandowski, Monika Puchowska, Dorota Piechota and Wioletta Barańska-Rybak
Antibiotics 2021, 10(10), 1144; https://doi.org/10.3390/antibiotics10101144 - 22 Sep 2021
Cited by 1 | Viewed by 3018
Abstract
Adverse drug reactions (ADRs) are unexpected reactions to a medication administered in a correct way at a standard dose. Drug-induced skin reactions account for 60–70% of all ADRs. The aim of the study is to determine the prevalence of antibiotic-related dermatological ADR in [...] Read more.
Adverse drug reactions (ADRs) are unexpected reactions to a medication administered in a correct way at a standard dose. Drug-induced skin reactions account for 60–70% of all ADRs. The aim of the study is to determine the prevalence of antibiotic-related dermatological ADR in patients treated in the department of Dermatology, Venerology and Allergology of the University Clinical Center in Gdańsk, Poland, in the years 2004–2021. A retrospective analysis of patients’ medical files was conducted in order to identify cases of ADR connected with the use of antibiotics, yielding 84 cases. The most common group of antibiotics were β-lactam, causing ADR in 47 patients. β-lactam antibiotics in our study included amoxicillin, alone and combined with clavulanic acid, and cephalosporins, affecting 22, 18 and 7 patients, respectively. In conclusion, β-lactam antibiotics showed the highest prevalence among antibiotic-induced skin reactions. They accounted for 15% of cases of all dermatological drug reactions and 55% of those caused by antibiotics. Especially amoxicillin, prescribed as a single drug or in combination with clavulanic acid, was commonly the culprit. Due to its wide use in the hospital and outpatient clinic, these adverse reactions have to be kept in mind by both hospital staff and general practitioners. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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10 pages, 401 KiB  
Article
Use of Dalbavancin in Skin, Bone and Joint Infections: A Real-Life Experience in an Italian Center
by Lucia Brescini, Filippo Della Martera, Gianluca Morroni, Sara Mazzanti, Maria Di Pietrantonio, Paolo Mantini, Bianca Candelaresi, Francesco Pallotta, Silvia Olivieri, Valentina Iencinella, Sefora Castelletti, Emanuele Cocci, Rosaria G. Polo, Salvatore Veccia, Oscar Cirioni, Marcello Tavio and Andrea Giacometti
Antibiotics 2021, 10(9), 1129; https://doi.org/10.3390/antibiotics10091129 - 19 Sep 2021
Cited by 10 | Viewed by 2241
Abstract
Dalbavancin is a lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The aim of the study was to evaluate the efficacy and safety in all patients who received at least one administration of dalbavancin. Methods: We carried [...] Read more.
Dalbavancin is a lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The aim of the study was to evaluate the efficacy and safety in all patients who received at least one administration of dalbavancin. Methods: We carried out a retrospective study of the use of dalbavancin in 55 patients at the Azienda Ospedaliera Ospedali Riuniti Umberto I (Ancona, Italy) from February 2017 to May 2020 and compared “on label” and “off label” use of dalbavancin in ABSSSI and non-ABSSSI. Results: A total of 55 patients were included in the study. The median age was 61 years; 51% had ABSSSI; 24% had prosthetic joint infections, and 14% had osteomyelitis. A total of 53% received a single 1500 mg infusion of dalbavancin, and 18% received a second dose 14 days later; 24% of patients received further doses at 14-day intervals. In 91% of cases, patients achieved clinical objectives with dalbavancin: 96% of patients with ABSSSI and 69% of those with prosthetic joint infections. Conclusions: Dalbavancin was shown to have an excellent tolerability profile and to be a highly successful therapeutic approach even in those cases treated “off-label”. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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7 pages, 628 KiB  
Article
High Prevalence of Antibiotic Resistance among Opportunistic Pathogens Isolated from Patients with COVID-19 under Mechanical Ventilation: Results of a Single-Center Study
by Chiara Temperoni, Luca Caiazzo and Francesco Barchiesi
Antibiotics 2021, 10(9), 1080; https://doi.org/10.3390/antibiotics10091080 - 06 Sep 2021
Cited by 17 | Viewed by 2602
Abstract
The effect of the COVID-19 pandemic on antibiotic resistance diffusion in healthcare settings has not been fully investigated. In this study we evaluated the prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation. An observational, retrospective, analysis [...] Read more.
The effect of the COVID-19 pandemic on antibiotic resistance diffusion in healthcare settings has not been fully investigated. In this study we evaluated the prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation. An observational, retrospective, analysis was performed on confirmed cases of COVID-19 patients who were admitted to the ICU department of San Salvatore Hospital in Pesaro, Italy, from 1 February 2021 to 31 May 2021. We considered all consecutive patients aged ≥ 18, under mechanical ventilation for longer than 24 h. Eighty-nine patients, 66 (74.1%) men and 23 (25.9%) women, with a median age of 67.1 years, were recruited. Sixty-eight patients (76.4%) had at least one infection, and 11 patients (12.3%) were colonized, while in the remaining 10 patients (11.2%) neither colonization nor infection occurred. In total, 173 microorganisms were isolated. There were 73 isolates (42.2%) causing bacterial or fungal infections while the remaining 100 isolates (57.8%) were colonizers. Among Gram-negative bacteria, E. coli, A. baumannii and K. pneumoniae were the most common species. Among Gram-positive bacteria, S. aureus and E. faecalis were the most common species. Overall, there were 58/105 (55.2%) and 22/59 (37.2%) MDR isolates among Gram-negative and Gram-positive bacteria, respectively. The prevalence of an MDR microorganism was significantly higher in those patients who had been exposed to empiric antibiotic treatment before ICU admission. In conclusion, we found a high prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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8 pages, 369 KiB  
Article
Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy
by Gianluca Morroni, Simona Fioriti, Federica Salari, Andrea Brenciani, Lucia Brescini, Marina Mingoia, Eleonora Giovanetti, Antonella Pocognoli, Andrea Giacometti, Elisa Molinelli, Annamaria Offidani, Oriana Simonetti and Oscar Cirioni
Antibiotics 2021, 10(8), 1026; https://doi.org/10.3390/antibiotics10081026 - 23 Aug 2021
Cited by 2 | Viewed by 1897
Abstract
Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically [...] Read more.
Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically characterized by pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing, and further investigated by PCR and whole genome sequencing to detect penicillin-binding protein (PBP) mutations as well as antibiotic resistance and virulence genes. Results: Fourteen isolates out of two hundred and thirty-nine (5.8%) were non-susceptible to ceftaroline (MIC > 1 mg/L), with differences between the EUCAST and CLSI interpretations. The characterized isolates belonged to seven different pulsotypes and three different clones (ST228/CC5-t041-SCCmecI, ST22/CC22-t18014-SCCmecIV, and ST22/CC22-t022-SCCmecIV), confirming a clonal diffusion of ceftaroline non-susceptible strains. Mutations in PBPs involved PBP2a for ST228-t041-SCCmecI strains and all the other PBPs for ST22-t18014-SCCmecIV and ST22-t022-SCCmecIV clones. All isolates harbored antibiotic resistance and virulence genes with a clonal distribution. Conclusion: Our study demonstrated that ceftaroline non-susceptibile isolates belonged not only to ST228 strains (the most widespread clone in Italy) but also to ST22, confirming the increasing role of these clones in hospital infections. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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Review

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20 pages, 1151 KiB  
Review
Antimicrobial Potential of the Genera Geobacillus and Parageobacillus, as Well as Endolysins Biosynthesized by Their Bacteriophages
by Joanna Zebrowska, Małgorzata Witkowska, Anna Struck, Patrycja E. Laszuk, Edyta Raczuk, Małgorzata Ponikowska, Piotr M. Skowron and Agnieszka Zylicz-Stachula
Antibiotics 2022, 11(2), 242; https://doi.org/10.3390/antibiotics11020242 - 12 Feb 2022
Cited by 9 | Viewed by 2893
Abstract
In the recent decades, antibiotic resistance has emerged and spread rapidly among clinically relevant pathogens. The natural ability of bacteria to transmit resistance determinants through horizontal gene transfer poses constant challenges to drug development. Natural molecules produced by soil microorganisms continue to be [...] Read more.
In the recent decades, antibiotic resistance has emerged and spread rapidly among clinically relevant pathogens. The natural ability of bacteria to transmit resistance determinants through horizontal gene transfer poses constant challenges to drug development. Natural molecules produced by soil microorganisms continue to be a key source of new antimicrobial agents. In this context, bacteria from the Geobacillus and Parageobacillus genera deserve special attention. Although there is commercial and industrial interest in these microorganisms, the full range of antibacterial compounds biosynthesized by the Geobacillus and Parageobacillus species remains largely unexplored. The aim of this review is to present the strong antimicrobial potential of these bacteria and endolysins produced by their bacteriophages. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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21 pages, 393 KiB  
Review
New Perspectives on Old and New Therapies of Staphylococcal Skin Infections: The Role of Biofilm Targeting in Wound Healing
by Oriana Simonetti, Giulio Rizzetto, Giulia Radi, Elisa Molinelli, Oscar Cirioni, Andrea Giacometti and Annamaria Offidani
Antibiotics 2021, 10(11), 1377; https://doi.org/10.3390/antibiotics10111377 - 10 Nov 2021
Cited by 13 | Viewed by 2561
Abstract
Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant [...] Read more.
Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant Staphylococcus aureus (MRSA) and become a therapeutic challenge. The aim of this narrative review is to collect the latest evidence on old and new anti-staphylococcal therapies, assessing their anti-biofilm properties and their effect on skin wound healing. We considered antibiotics, quorum sensing inhibitors, antimicrobial peptides, topical dressings, and antimicrobial photo-dynamic therapy. According to our review of the literature, targeting of biofilm is an important therapeutic choice in acute and chronic infected skin wounds both to overcome antibiotic resistance and to achieve better wound healing. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
15 pages, 972 KiB  
Review
Nanomaterials as a Successor of Antibiotics in Antibiotic-Resistant, Biofilm Infected Wounds?
by Marcela Nowak and Wioletta Barańska-Rybak
Antibiotics 2021, 10(8), 941; https://doi.org/10.3390/antibiotics10080941 - 04 Aug 2021
Cited by 10 | Viewed by 2682
Abstract
Chronic wounds are a growing problem for both society and patients. They generate huge costs for treatment and reduce the quality of life of patients. The greatest challenge when treating a chronic wound is prolonged infection, which is commonly caused by biofilm. Biofilm [...] Read more.
Chronic wounds are a growing problem for both society and patients. They generate huge costs for treatment and reduce the quality of life of patients. The greatest challenge when treating a chronic wound is prolonged infection, which is commonly caused by biofilm. Biofilm makes bacteria resistant to individuals’ immune systems and conventional treatment. As a result, new treatment options, including nanomaterials, are being tested and implemented. Nanomaterials are particles with at least one dimension between 1 and 100 nM. Lipids, liposomes, cellulose, silica and metal can be carriers of nanomaterials. This review’s aim is to describe in detail the mode of action of those molecules that have been proven to have antimicrobial effects on biofilm and therefore help to eradicate bacteria from chronic wounds. Nanoparticles seem to be a promising treatment option for infection management, which is essential for the final stage of wound healing, which is complete wound closure. Full article
(This article belongs to the Special Issue Evaluation of New Molecules in Severe Infectious Diseases)
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