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Antibiotics
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ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment
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ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment

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 October 2025) | Viewed by 3339

Special Issue Editor

Dr. Carlo Pallotto

E-Mail Website
Guest Editor
Infectious Diseases Clinic, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
Interests: antimicrobial resistance; difficult-to-treat infections; endocarditis; antimicrobial stewardship; infection of the central nervous system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

ESKAPE and MDRO pathogens are still a growing concern, with an estimated enormous mortality in next decades. New antibiotics are going to be available and others are progressing in the pipeline. The appropriate use of these antibiotics should be a cornerstone of our daily activities in order to preserve them and to reduce the clinical and economical impact of antibiotic resistance.

Several questions are still open in the field of antibiotic treatment: role of combination therapy, treatment duration, antibiotics administration, and place in therapy of BLIC and new antibiotics, among many others.

This Special Issue will contribute to answering these and other arising questions about the treatment of ESKAPE and other MDRO infections.

Dr. Carlo Pallotto
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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 2900 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.

Keywords

  • ESKAPE
  • MDRO
  • Escherichia coli
  • Staphylococcus aureus
  • Klebsiella pneumoniae
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • Enterococcus faecalis
  • Enterococcus faecium
  • Stenotrophomonas maltophilia
  • Enterobacter cloacae
  • antimicrobial stewardship

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Published Papers (4 papers)

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Research

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16 pages, 397 KB  
Article
The Cost of Resource Use Relative to the Development of the Antimicrobial Stewardship Program in a Tertiary Cancer Setting in Qatar
by Dina Abushanab, Diala Alhaj Moustafa, Anas Hamad, Bhagyasree Adampally Sankar, Ziad G. Nasr, Hussam Alsoub and Daoud Al-Badriyeh
Antibiotics 2025, 14(12), 1204; https://doi.org/10.3390/antibiotics14121204 - 1 Dec 2025
Abstract
Background: Infection is a typical consequence of cancer treatment due to its immunosuppressive nature, where the high use of antimicrobials raises the risk of antimicrobial resistance (AMR). The primary objective of an antimicrobial stewardship program (ASP) is to optimize antimicrobial use, reduce the [...] Read more.
Background: Infection is a typical consequence of cancer treatment due to its immunosuppressive nature, where the high use of antimicrobials raises the risk of antimicrobial resistance (AMR). The primary objective of an antimicrobial stewardship program (ASP) is to optimize antimicrobial use, reduce the emergence of AMR, and ensure cost containment. This study sought to assess the difference in cost of resource use with the ASP in the specialized hematology/oncology setting in Qatar, before and after ASP maturity. Methods: From the perspective of the public healthcare hospital, the research investigated the difference in the cost of resource use between the developed ASP and the preliminary ASP at the National Center for Cancer Care and Research (NCCCR), Qatar. The preliminary ASP was defined as the 12 months following the establishment of the ASP (i.e., May 2015 to April 2016), while the developed ASP was defined as the last 12 months of a 5-year ASP implementation (i.e., February 2019 to January 2020). Patient records were retrospectively reviewed. The overall difference in cost of resource use was based on cost savings, cost avoidance, and operational cost measures. Results: A total of 186 patients were included in the study, with 81 in the preliminary ASP and 105 in the developed ASP. While total resource utilization costs rose by 17% in the developed ASP, per-patient analysis revealed lower resource costs of Qatari Riyal (QAR) 1390 (USD 381) compared to QAR 1546 (USD 423) in the preliminary period. The developed ASP achieved reductions in antimicrobial consumption (−55.9%) and costs (−80.9%), along with a total cost avoidance of QAR 11,969,651 (USD 3,288,366). Overall, the program resulted in a net annual reduction of QAR 13,205,840 (USD 3,618,038), which equates to QAR 180,910 (USD 49,564) saved per patient. Conclusions: At the NCCCR, Qatar, it seems that running the ASP for five years, with presumed development in its practices, was associated with reductions in antimicrobial costs, operational expenses, and overall resource spending. Full article
(This article belongs to the Special Issue ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment)
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14 pages, 1820 KB  
Article
Broad-Spectrum Gramicidin S Derivatives with Potent Activity Against Multidrug-Resistant Gram-Negative ESKAPE Pathogens
by John T. Kalyvas, Yifei Wang, Ornella Romeo, John R. Horsley and Andrew D. Abell
Antibiotics 2025, 14(5), 423; https://doi.org/10.3390/antibiotics14050423 - 22 Apr 2025
Cited by 2 | Viewed by 1468
Abstract
Background/Objectives: Multidrug-resistant Gram-negative ESKAPE pathogens, including E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, pose a significant global health threat. Gramicidin S, a potent cyclic antimicrobial peptide, is largely ineffective against these bacteria, and its high haemolytic toxicity [...] Read more.
Background/Objectives: Multidrug-resistant Gram-negative ESKAPE pathogens, including E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, pose a significant global health threat. Gramicidin S, a potent cyclic antimicrobial peptide, is largely ineffective against these bacteria, and its high haemolytic toxicity limits its clinical usage. This study reports on several novel gramicidin S analogues with improved efficacy and safety profiles against multidrug-resistant Gram-negative bacteria. Methods: A total of 19 gramicidin S derivatives were synthesised using Fmoc-based solid-phase peptide synthesis with targeted substitutions to enhance cationicity and modulate hydrophobicity. Minimum inhibitory concentrations (MICs) were determined against standard Gram-negative and Gram-positive strains. Haemolytic toxicity and in vitro nephrotoxicity were evaluated using human red blood cells and HEK-293 cells, respectively. All peptides were characterised by RP-HPLC and HRMS. Results: The selective incorporation of DArg and Trp significantly enhanced activity against Gram-negative bacteria while reducing cytotoxicity. Peptide 8 improved the therapeutic index (TI) against E. coli by 10-fold (MIC: 8 µg/mL; TI: 4.10) compared to gramicidin S (MIC: 32 µg/mL; TI: 0.38). Peptide 9 exhibited an 8-fold potency increase against K. pneumoniae and a 25-fold TI improvement. Peptide 19 enhanced activity against P. aeruginosa 8-fold over gramicidin S, while peptide 7 showed a 27-fold TI enhancement. All active peptides retained broad-spectrum activity against S. aureus, including MRSA. Conclusions: The findings highlight the critical role of balancing hydrophobicity and cationicity to overcome species-specific resistance mechanisms. Our gramicidin S analogues demonstrate potent broad-spectrum activity with significantly reduced toxicity compared to the parent peptide, providing a robust platform for the development of new antibiotics against ESKAPE bacterial pathogens. Full article
(This article belongs to the Special Issue ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment)
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Review

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13 pages, 672 KB  
Review
Pharmacokinetics/Pharmacodynamics-Based Repositioning of Cefmetazole and Flomoxef in Extended-Spectrum β-Lactamase-Producing Enterobacterales Treatment: An Injectable Carbapenem-Sparing and Outpatient Strategy
by Takahiro Kato, Yusuke Yagi, Takumi Maruyama and Yukihiro Hamada
Antibiotics 2025, 14(8), 737; https://doi.org/10.3390/antibiotics14080737 - 23 Jul 2025
Cited by 1 | Viewed by 1478
Abstract
Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. [...] Read more.
Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article
(This article belongs to the Special Issue ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment)
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Other

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10 pages, 3128 KB  
Case Report
Cefiderocol as a Successful Therapy for Osteomyelitis Due to XDR Pseudomonas aeruginosa: A Case Report and Literature Review
by Alice Mulè, Anna Cambianica, Alberto Matteelli, Silvia Lorenzotti, Angelica Lenzi, Francesco Rossini, Alessio Sollima, Susanna Capone and Francesco Castelli
Antibiotics 2025, 14(12), 1199; https://doi.org/10.3390/antibiotics14121199 - 28 Nov 2025
Viewed by 93
Abstract
Background: Carbapenem-resistant Enterobacterales and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa are a growing public health issue. Cefiderocol demonstrated activity against β-lactamase-producing Gram-negative bacteria (GNB). However, bone PharmacoKinetics (PK) data is lacking. Here, we report a case of post-traumatic chronic osteomyelitis caused by extensively [...] Read more.
Background: Carbapenem-resistant Enterobacterales and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa are a growing public health issue. Cefiderocol demonstrated activity against β-lactamase-producing Gram-negative bacteria (GNB). However, bone PharmacoKinetics (PK) data is lacking. Here, we report a case of post-traumatic chronic osteomyelitis caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa which was successfully treated with cefiderocol. Moreover, we conducted a non-systematic review of the available literature. Case Report: We described the case of a 64-year-old man who was admitted to a traumatology ward after a work accident caused crushing of his left foot. Microbiological tests on intraoperative biopsies demonstrated XDR P. aeruginosa and K. oxytoca. Despite the administrations of different antibiotics regimens and multiple surgical revisions, the patient developed chronic osteomyelitis. To prevent amputation, cefiderocol was prescribed for six weeks, resulting in a complete clinical resolution of osteomyelitis. Review of the Literature: We performed a non-systematic review of the literature searching the public databases PubMed and Google Scholar. We identified nine case reports. In most patients (60%) the cause of osteomyelitis was post-surgical, and all the reported cases were healthcare associated. Osteomyelitis treatment required both antimicrobial therapy and surgery in all the cases described. Cefiderocol was often prescribed in association with other antibiotics (70%). Clinical cure was described in all the reported cases. Conclusions: This study highlights that cefiderocol is safe and efficacious to treat osteomyelitis caused by carbapenem-resistant GNB. However, evidence is limited to a few case reports. Full article
(This article belongs to the Special Issue ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment)
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