Special Issue "Emerging Treatment Options for Multidrug-Resistant Bacterial and Fungal Infections"

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

Deadline for manuscript submissions: 31 March 2023 | Viewed by 6845

Special Issue Editors

Biomedical and Biotechnological Sciences Department, University of Catania, Catania, Italy
Interests: infectious diseases; bacterial infections; vector-borne diseases
Special Issues, Collections and Topics in MDPI journals
Biomedical and Biotechnological Sciences Department, Section of Microbiology – University of Catania, Catania, Italy
Interests: bacterial genomic; bacterial transcriptomic; antimicrobial resistance; phage therapy
Biomedical and Biotechnological Sciences Department, Section of Microbiology – University of Catania, Catania, Italy
Interests: antimicrobial resistance; MRD bacteria; infectious diseases
Laboratory of Microbiology and Virology, Ospedale San Raffaele Dibit, Milan, Italy
Interests: Gram-negative bacteria; MDR bacteria; Klebsiella pneumonia; Pseudomonas aeruginosa

Special Issue Information

Dear Colleagues,

Infections by multidrug-resistance (MDR) pathogens are related to increased morbidity, mortality, in-hospital length of stay, and healthcare costs. The emergence of pathogenic microorganisms which cannot be effectively treated with existing drugs has been prioritized by the World Health Organization as one of the top ten global public health threats facing humanity. It has been reported that, without interventions, by the year 2050, 10 million people will die annually as a consequence of MDR infections, unless a global and effective response is achieved to tackle the problem. MDR Gram-negative Enterobacterales, MRSA, and VRE represent cumbersome to treat infections especially in a hospital setting as well as for more vulnerable patients such as those in ICU, where MDR bacteria and fungi could deteriorate the precarious patient clinical conditions. Furthermore, in these delicate settings, emerging MDR Candida spp. strains represent a rising dramatic phenomenon. The growing spread of MDR pathogens needs to be tackled by further research and new approaches in microbiological techniques that will enable the fast identification of resistance patterns; clinical management which assures the best diagnostic pathways avoiding useless antimicrobial therapies and performing the correct source control, and pharmacological options that could target pathogen-specific resistance mechanism avoiding drugs superfluous exposition and adverse events.

This Special Issue aims to collect original articles, literature reviews, and case reports/case series about emerging treatment options against MDR bacteria and fungi, with particular interest in new antibiotics and drug combination.

Dr. Andrea Marino
Dr. Stefano Stracquadanio
Dr. Stefania Stefani
Dr. Floriana Gona
Guest Editors

Manuscript Submission Information

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Keywords

  • MDR bacteria
  • antibiotic resistance
  • new antimicrobial
  • MDR fungi
  • antifungal therapies
  • alternative strategies

Published Papers (5 papers)

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Research

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Article
Comparison between EUCAST Broth Microdilution and MIC Strip Test in Defining Isavuconazole In Vitro Susceptibility against Candida and Rare Yeast Clinical Isolates
Antibiotics 2023, 12(2), 251; https://doi.org/10.3390/antibiotics12020251 - 26 Jan 2023
Viewed by 520
Abstract
Isavuconazole is a new broad-spectrum triazole, with significant in vitro activity against yeasts. Isavuconazole in vitro susceptibility can be evaluated through broth microdilution as a reference method. Considering difficulties in equipping such methods in a laboratory routine, a commercial MIC Strip test has [...] Read more.
Isavuconazole is a new broad-spectrum triazole, with significant in vitro activity against yeasts. Isavuconazole in vitro susceptibility can be evaluated through broth microdilution as a reference method. Considering difficulties in equipping such methods in a laboratory routine, a commercial MIC Strip test has been designed. This study aims to implement data about isavuconazole in vitro activity and compare EUCAST broth microdilution and MIC Strip test in defining yeast isavuconazole susceptibility. The study involved 629 isolates from positive blood cultures (January 2017–December 2021). The identified species were C. albicans (283), C. glabrata (53), C. krusei (23), C. tropicalis (68), C. parapsilosis complex (151), C. guilliermondii (12), C. famata (6), S. cerevisiae (12), C. neoformans (5), S. capitata (12), and Rhodotorula species (4). All the isolates were tested with EUCAST microdilution and MIC Strip methods. The total essential agreement between these two methods was 99.3%. As a result, we can consider that both methods are useful in testing isavuconazole susceptibility. Proposed cut-off values (P-ECOFF) were calculated using ECOFFinder software. Further studies could lead to either definitive E-COFF or clinical breakpoints, which represent the most important categorization tool of the laboratory data, allowing a better insertion of an antimicrobial drug in clinical practice. Full article
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Review

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Review
Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review
Antibiotics 2023, 12(3), 608; https://doi.org/10.3390/antibiotics12030608 - 18 Mar 2023
Viewed by 517
Abstract
Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used [...] Read more.
Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans. Full article
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Review
Evidence-Based Treatment of Pseudomonas aeruginosa Infections: A Critical Reappraisal
Antibiotics 2023, 12(2), 399; https://doi.org/10.3390/antibiotics12020399 - 16 Feb 2023
Cited by 1 | Viewed by 3305
Abstract
Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due [...] Read more.
Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due to MDR/XDR P. aeruginosa. P. aeruginosa has inherent resistance to many drug classes, the capacity to form biofilms, and most importantly, the ability to quickly acquire resistance to ongoing treatments. Based on the presence of risk factors for MDR/XDR infections and local epidemiology, where large proportions of strains are resistant to classic beta-lactams, the recommended empirical treatment for suspected P. aeruginosa infections is based on ceftolozane-tazobactam or ceftazidime-avibactam. Where local epidemiology indicates low rates of MDR/XDR and there are no risk factors, a third or fourth generation cephalosporin can be used in the context of a “carbapenem-sparing” strategy. Whenever feasible, antibiotic de-escalation is recommended after antimicrobial susceptibility tests suggest that it is appropriate, and de-escalation is based on different resistance mechanisms. Cefiderocol and imipenem-cilastatin-relebactam withstand most resistance mechanisms and may remain active in cases with resistance to other new antibiotics. Confronting the growing threat of MDR/XDR P. aeruginosa, treatment choices should be wise, sparing newer antibiotics when dealing with a suspected/confirmed susceptible P. aeruginosa strain and choosing the right option for MDR/XDR P. aeruginosa based on specific types and resistance mechanisms. Full article
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Other

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Case Report
Intravenous Fosfomycin: A Potential Good Partner for Cefiderocol. Clinical Experience and Considerations
Antibiotics 2023, 12(1), 49; https://doi.org/10.3390/antibiotics12010049 - 28 Dec 2022
Cited by 1 | Viewed by 688
Abstract
Multidrug resistant Gram-negative bacteremia represents a therapeutic challenge clinicians have to deal with. This concern becomes more difficult when causing germs are represented by carbapenem resistant Acinetobacter baumannii or difficult-to-treat Pseudomonas aeruginosa. Few antibiotics are available against these cumbersome bacteria, although literature [...] Read more.
Multidrug resistant Gram-negative bacteremia represents a therapeutic challenge clinicians have to deal with. This concern becomes more difficult when causing germs are represented by carbapenem resistant Acinetobacter baumannii or difficult-to-treat Pseudomonas aeruginosa. Few antibiotics are available against these cumbersome bacteria, although literature data are not conclusive, especially for Acinetobacter. Cefiderocol could represent a valid antibiotic choice, being a molecule with an innovative mechanism of action capable of overcoming common resistance pathways, whereas intravenous fosfomycin may be an appropriate partner either enhancing cefiderocol activity or avoiding resistance development. Here we report two patients with MDR Gram negative bacteremia who were successfully treated with a cefiderocol/fosfomycin combination. Full article
Systematic Review
Efficacy of Tuberculosis Treatment in Patients with Drug-Resistant Tuberculosis with the Use of Bedaquiline: The Experience of the Russian Federation
Antibiotics 2022, 11(11), 1622; https://doi.org/10.3390/antibiotics11111622 - 14 Nov 2022
Cited by 1 | Viewed by 1038
Abstract
In the conditions of the continued growth of multiple- and extensive drug-resistant tuberculosis, use of the new highly effective anti-tuberculosis drugs in this patient category is of great relevance. The aim of the study was determination the efficacy of treatment in patients with [...] Read more.
In the conditions of the continued growth of multiple- and extensive drug-resistant tuberculosis, use of the new highly effective anti-tuberculosis drugs in this patient category is of great relevance. The aim of the study was determination the efficacy of treatment in patients with multidrug- and extensive drug-resistant tuberculosis using bedaquiline based on studies published in the Russian Federation. Materials and methods: The authors analyzed data published in studies from 2014 to 2022; 41 publications were included in total and 17 articles corresponded to the study design. The results of treatment of 1404 tuberculosis patients with MDR/XDR TB were described. Bedaquiline was used according to the standard scheme with a description of the treatment results after 24–26 weeks. Treatment efficacy was estimated according to accepted criteria. Results of the study: The analysis showed that the treatment efficacy on conversion was achieved in 79.5% of cases (95% Cl 76.5–82.3), and recovery was observed in 82.0% of cases (95% Cl 78.6–85.1). Departure from the therapy was observed in rare cases (9.8%; 95% Cl 7.9–12.2). Deaths were recorded in 6.5% of cases (95% Cl 4.9–8.3), which were associated with the severe disease and concomitant pathology in 74.3%. The development of adverse events was noted in half of the patients (55.7%); however, bedaquiline cancellation occurred in a few cases (7.0%; 95% Cl 3.0–13.0). From analyzing data in patients with MDR and XDR TB, the efficacy of treatment was 89.9% (95% Cl 85.9–93.2) and 71.9% (95% Cl 66.2–77.1), respectively. Conclusion: Use of bedaquiline in treatment makes it possible to achieve recovery of patients with MDR/XDR TB in 82.0% of cases with patients dropping out of treatment in 9.8%. At the same time, in patients with MDR TB, recovery was achieved in 89.9% of cases, while in patients with XDR TB, 71.9% of cases recovered. Full article
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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: Comparison between EUCAST broth microdilution and MIC Strip test in defining isavuconazole in vitro susceptibility against Candida and rare yeast clinical isolates
Authors: Laura Trovato
Affiliation: U.O.C. Laboratory Analysis Unit, A.O.U. “Policlinico-Vittorio Emanuele”, Via S.Sofia 78, Catania 95123, Italy
Abstract: Introduction: Isavuconazole is a new broad-spectrum triazole, with significant in vitro activity against yeasts. Due both to the growing rate of invasive fungal infections and the possible finding of drug resistance in relevant clinical isolates, studies on this antifungal drug continue to be encouraged. Isavuconazole in vitro susceptibility can be evaluated through broth microdilution as a reference method. Considering possible difficulties in equipping such methods in a laboratory diagnostic routine, a commercial MIC Strip test has been designed. This study aims to implement literary data about isavuconazole in vitro activity against Candida and rare yeast clinical isolates and compare EUCAST broth microdilution and MIC Strip test in defining isavuconazole in vitro susceptibility. Materials and methods: The study involved 629 yeast isolates from positive blood cultures (January 2017-December 2021). The identified species were C. albicans (283), C. glabrata (53), C. krusei (23), C. tropicalis (68), C. parapsilosis complex (151), C. famata (6), C. guilliermondii (12), S. cerevisiae (12), C. neoformans (5), S. capitata (12), and Rhodotorula species (4). All the isolates were tested for isavuconazole in vitro susceptibility with EUCAST microdilution and MIC Strip methods. Statistical and microbiological calculations were also performed. Finally, proposed cut-off values (P-ECOFF) were calculated using ECOFFinder software. Results: The total essential agreement between the two methods had a percentage of 99.3%, while some differences had emerged relatively to distinction by species. Among Candida species, C. albicans showed an essential agreement of 99.2%, while C. glabrata one was 98.1%. C. krusei and C. parapsilosis complex essential agreement was 100%. Also C. famata, C. guilliermondii and C. incospicua showed an essential agreement equal to 100%. The lowest value was detected for C. tropicalis (95.6%). For rare yeast species such as S. capitata, Rhodotorula species, C. neoformans and S. cerevisiae essential agreement values were equal to 100%. P-ECOFFs were calculated for C. albicans (0.125 mg/L), C. parapsilosis complex (16 mg/L), C. krusei (16 mg/L) and C. tropicalis (16 mg/L). Discussion: The essential agreement between broth microdilution and MIC Strip test was high, so we can consider that both methods are useful in testing isavuconazole in vitro susceptibility. Our data about E-COFF were just preliminary because E-COFF establishment requires huge studies with a major number of isolates and research centres. Further studies could lead to either definitive E-COFF or clinical breakpoints, which represent the most important categorization tool of the laboratory data, allowing a better insertion of an antimicrobial drug in clinical practice.

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