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Pathogens
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Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications
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Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3216

Special Issue Editors

Dr. Giuseppe Pipitone

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Guest Editor
Infectious Disease Unit, ARNAS Civico-Di Cristina Hospital, Piazza Leotta, 5, Palermo, Italy
Interests: sepsis; critical illness; antimicrobial stewardship
Special Issues, Collections and Topics in MDPI journals
Dr. Alberto Enrico Maraolo

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Guest Editor
Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
Interests: One Health; drug resistance; microbiome
Special Issues, Collections and Topics in MDPI journals
Dr. Luigi Principe

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Guest Editor
Microbiology and Virology Unit, Great Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
Interests: antibiotic; resistance; microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

this Special Issue, "Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications", will highlight the pressing threat posed by drug-resistant microorganisms to global health. Antimicrobial abuse and misuse have led to an increase in drug resistance in bacteria, viruses, fungi, and parasites. This Special Issue will investigate novel treatment approaches to combating resistances, as well as diagnostics for the early and precise identification of resistant strains. This Special Issue will consider the intricacy of resistance mechanisms, including hereditary and environmental components, and their consequences for public health policy and therapeutic procedures. The socioeconomic cost of medication resistance will also be discussed, with an emphasis on how differences in healthcare infrastructure and resource availability can worsen the problem's effects worldwide. We must aim to maintain the effectiveness of current therapies and encourage the sustainable use of antibiotics globally by conducting interdisciplinary research.

Dr. Giuseppe Pipitone
Dr. Alberto Enrico Maraolo
Dr. Luigi Principe
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. Pathogens 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.

Keywords

  • antibiotics
  • multi-drug-resistant microorganisms
  • difficult-to-treat infections

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Published Papers (4 papers)

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Research

11 pages, 4918 KB  
Article
Genomic Characterization of a Carbapenem-Resistant Acinetobacter pittii Strain Harboring Chromosome-Borne blaNDM-1 from China
by Wenjuan Liu, Haixia Wang, Weijian Zhu, Xiaobin Li, Ying He and Wen Su
Pathogens 2025, 14(10), 1037; https://doi.org/10.3390/pathogens14101037 - 13 Oct 2025
Viewed by 423
Abstract
New Delhi metallo-beta-lactamase (NDM)-producing Acinetobacter spp. have been reported worldwide and become a global threat to clinics. This study aimed to characterize the genomic features of the carbapenem-resistant Acinetobacter pittii strain AP8900 harboring chromosome-borne blaNDM-1. The genome of strain AP8900 was [...] Read more.
New Delhi metallo-beta-lactamase (NDM)-producing Acinetobacter spp. have been reported worldwide and become a global threat to clinics. This study aimed to characterize the genomic features of the carbapenem-resistant Acinetobacter pittii strain AP8900 harboring chromosome-borne blaNDM-1. The genome of strain AP8900 was fully sequenced using Illumina and PacBio platforms. Genome analyses revealed that the chromosome-borne blaNDM-1 of strain AP8900 was located on the Tn125 bracketed by two copies of ISAba125 in the same orientation. So far, only five strains of A. pittii with complete genomes harboring chromosome-borne blaNDM-1 were found (four from China and one from the USA), all carrying nearly identical Tn125 carried by the strain AP8900. Furthermore, the Tn125 of strain AP8900 in this study was also distributed in other species, mainly Acinetobacter spp. Notably, the Tn125 carried by AP8900 also found in Proteus mirabilis, Klebsiella pneumoniae, and Morganella morganii. In addition, two antibiotic resistance plasmids were found in strain AP8900, and the configuration “sul2- glmM” was found on both pAP8900-1 (ISAba1-sul2-glmM-ISVsa3-IS1006) and pAP8900-2 (∆ISAba2-sul2-glmM-IS17). This study delivers comprehensive insights into the characteristics and diversity of chromosome-borne blaNDM-1 in A. pittii. The complete genome of A. pittii AP8900 strain from southern China provides important data for the analysis of antimicrobial resistance in this region. Full article
(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)
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13 pages, 1676 KB  
Article
Detection and Impact of Staphylococcus aureus Small Colony Variants in Chronic Wounds: A Pilot Study
by Eleanna Carris, Klara C. Keim, Landrye Reynolds-Reber, Isaiah K. George, Nicholas Sanford, Rocio Navarro-Garcia, Taylor D. Lenzmeier and Allie Clinton Smith
Pathogens 2025, 14(10), 1023; https://doi.org/10.3390/pathogens14101023 - 9 Oct 2025
Viewed by 486
Abstract
A unique phenotype of S. aureus called S. aureus small-colony variants (SA-SCVs) are a consequential contributor to multiple infectious processes. SA-SCVs are distinguishable from wild-type S. aureus (WT-SA) by their small size, slowed growth rate, and altered biochemical reactions; these changes make SA-SCV [...] Read more.
A unique phenotype of S. aureus called S. aureus small-colony variants (SA-SCVs) are a consequential contributor to multiple infectious processes. SA-SCVs are distinguishable from wild-type S. aureus (WT-SA) by their small size, slowed growth rate, and altered biochemical reactions; these changes make SA-SCV more difficult to detect from clinical specimens using routine diagnostics. While the clinical environment of chronic wound infections has the potential to stimulate the production of SA-SCVs, studies investigating detection of SA-SCVs in chronic wounds have not been previously conducted. Chronic wound specimens found to harbor S. aureus via qPCR screening, and screened for recent aminoglycoside treatment and/or co-infected with Pseudomonas aeruginosa, were collected from a specialty wound care clinic in April 2019. In-house enrichment methods alongside culture-dependent and independent diagnostics were utilized to recover and identify SA-SCVs from these chronic wounds. Our investigation determined difficulties in recovering and identifying SA-SCVs during routine diagnostic procedures, and the potential clinical impact of wounds harboring SA-SCVs related to antimicrobial susceptibility. Full article
(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)
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12 pages, 247 KB  
Article
Restoring Control: Real-World Success with Imipenem–Relebactam in Critical MDR Infections—A Multicenter Observational Study
by Andrea Marino, Giuseppe Pipitone, Emmanuele Venanzi Rullo, Federica Cosentino, Rita Ippolito, Roberta Costa, Sara Bagarello, Ylenia Russotto, Chiara Iaria, Bruno Cacopardo and Giuseppe Nunnari
Pathogens 2025, 14(7), 685; https://doi.org/10.3390/pathogens14070685 - 11 Jul 2025
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Abstract
Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but [...] Read more.
Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article
(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)
14 pages, 2554 KB  
Article
Antibacterial Evaluation of Tricyclic Antidepressants Against S. aureus and the Possible Pathways of the Mechanism of Action
by Vitória Pessoa de Farias Cabral, Daniel Sampaio Rodrigues, Lívia Gurgel do Amaral Valente Sá, Lara Elloyse Almeida Moreira, Cecília Rocha da Silva, João Batista de Andrade Neto, Érica Rayanne Mota da Costa, Thais Lima Ferreira, Leilson Carvalho de Oliveira, Beatriz Oliveira de Souza, Dávylla Rênnia Saldanha Pinheiro, Bruno Coêlho Cavalcanti, Islay Lima Magalhães, Manoel Odorico de Moraes and Hélio Vitoriano Nobre Júnior
Pathogens 2025, 14(7), 613; https://doi.org/10.3390/pathogens14070613 - 20 Jun 2025
Cited by 1 | Viewed by 726
Abstract
The resistance of Staphylococcus aureus to conventional pharmacological treatments has gradually increased. Thus, new therapeutic strategies are needed. Three tricyclic antidepressants (TCAs), amitriptyline (AMT), nortriptyline (NOR), and clomipramine (CLO), stand out with potential in this regard. Thus, the objective of this study was [...] Read more.
The resistance of Staphylococcus aureus to conventional pharmacological treatments has gradually increased. Thus, new therapeutic strategies are needed. Three tricyclic antidepressants (TCAs), amitriptyline (AMT), nortriptyline (NOR), and clomipramine (CLO), stand out with potential in this regard. Thus, the objective of this study was to evaluate the antibacterial activity of TCAs against S. aureus. The methodology used broth microdilution, checkerboard, flow cytometry, fluorescence microscopy, and scanning electron microscopy (SEM) techniques. The results showed that the minimum inhibitory concentration (MIC) of AMT was 256 µg/mL, while the MIC of NOR was 128 µg/mL, and the MIC of CLO was between 64 and 128 µg/mL. The TCAs exhibited bactericidal activity. In the analysis of the association with oxacillin (OXA), AMT exhibited 75% synergism, while NOR and CLO obtained 62.5%. In combination with vancomycin (VAN), AMT and NOR presented 100% additive interactions, while CLO exhibited 62.5% indifferent interactions. The mechanism of TCAs, isolated and combined with OXA, was associated with a reduction in cell viability, resulting from their action on the bacterial genetic material and generation of oxidative stress. Furthermore, the action of the drugs produced intense morphological changes in the bacterial cells. In conclusion, TCAs are a potential alternative for antistaphylococcal therapy. Full article
(This article belongs to the Special Issue Drug Resistant Pathogens: Diagnosis, Treatment, and Global Health Implications)
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