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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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

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.