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Pharmaceuticals
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Multi-Drug Resistance
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Multi-Drug Resistance

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 9540

Special Issue Editor

Dr. Na Xie

E-Mail Website
Guest Editor
West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Interests: multi-drug resistance; cancer; infection

Special Issue Information

Dear Colleagues,

Drug resistance is an unavoidable consequence of the use of drugs, which is a major challenge, notably in cancer and infection. Multi-drug resistance (MDR), which is characterized by cross-resistance to a wide variety of drugs with distinct structures and mechanisms of action, has emerged as a major threat to global public health security. Deciphering the multidisciplinary and interdisciplinary characteristics of MDR in cancer and infection allows the development of novel precision medicine treatment modalities that can overcome different and well-defined drug resistance mechanisms. This Special Issue aims to provide up-to-date research, reviews and commentary on the mechanisms of MDR in the treatment of cancer and infection, new diagnostic and therapeutic tools against multi-drug-resistant tumors or bacteria, as well as potential therapeutic strategies to overcome MDR.

Dr. Na Xie
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 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. Pharmaceuticals 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

  • multi-drug resistance
  • cancer
  • infection
  • mechanism
  • therapeutic medicine
  • diagnostic tools
  • clinical translation

Published Papers (6 papers)

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Research

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16 pages, 1423 KiB  
Article
Pre- and Post-COVID-19 Antimicrobial Resistance Pattern of Pathogens in an Intensive Care Unit
by Andreea-Loredana Golli, Ovidiu Mircea Zlatian, Monica Laura Cara and Mădălina Olteanu
Pharmaceuticals 2024, 17(4), 407; https://doi.org/10.3390/ph17040407 - 22 Mar 2024
Viewed by 656
Abstract
We aimed to determine the trend of the antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU) in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 [...] Read more.
We aimed to determine the trend of the antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU) in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. Positive bacterial culture data from 1695 samples from the pre-COVID-19 period and 1562 samples from the post-COVID-19 period were obtained. The most frequently isolated bacteria in both periods were Staphylococcus aureus and Klebsiella spp. The resistance rates of Klebsiella spp. Significantly increased against colistin (0.38% to 20.51%), gentamicin (44.62% to 64.85%), and aztreonam (56.35% to 3.60%). There was a significant increase in the resistance rate against colistin for E. coli strains (4.69% to 32.46%) and for Acinetobacter sp. strains (3.37% to 18.09%). More than 50% of the Staphylococcus aureus strains were MRSA, with statistically significant increases in the antimicrobial resistance rate against doxycycline (40.08% to 51.72%), linezolid (0.22% to 3.13%), rifampicin (53.16% to 64.93%), and teicoplanin (26.31% to 53.40%). The study revealed a significantly increasing trend in the antimicrobial resistance rate of Gram-negative pathogens against certain antibiotics, including those used only in cases where there are no other therapeutic options. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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14 pages, 3803 KiB  
Article
Collaterally Sensitive β-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant Staphylococcus aureus (MRSA) Biofilms
by Hamna Batool Hashmi, Muhammad Asad Farooq, Muhammad Hashim Khan, Abdulrahman Alshammari, Alanoud T. Aljasham, Sheikh Abdur Rashid, Nauman Rahim Khan, Irum Batool Hashmi, Muhammad Badar and Mohammad S. Mubarak
Pharmaceuticals 2023, 16(5), 687; https://doi.org/10.3390/ph16050687 - 02 May 2023
Cited by 1 | Viewed by 1615
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three β-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms. When used individually, none of the drugs exhibited significant antibacterial activity against MRSA in a planktonic state. At the same time, the combination of meropenem, piperacillin, and tazobactam showed a 41.7 and 41.3% reduction in planktonic bacterial cell growth, respectively. These drugs were further assessed for biofilm inhibition and removal. The combination of meropenem, piperacillin, and tazobactam caused 44.3% biofilm inhibition, while the rest of the combinations did not show any significant effects. Results also revealed that piperacillin and tazobactam exhibited the best synergy against the pre-formed biofilm of MRSA, with 46% removal. However, adding meropenem to the piperacillin and tazobactam combination showed a slightly reduced activity towards the pre-formed biofilm of MRSA and removed 38.7% of it. Although the mechanism of synergism is not fully understood, our findings suggest that these three β-lactam drugs can be used in combination as very effective therapeutic agents for the treatment of pre-existing MRSA biofilms. The in vivo experiments on the antibiofilm activity of these drugs will pave the way for applying such synergistic combinations to clinics. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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10 pages, 651 KiB  
Communication
Cost-Effectiveness of Targeted Prophylaxis among Allogenic Stem Cell Transplant Recipients
by Nour Shbaklo, Costanza Vicentini, Alessandro Busca, Luisa Giaccone, Chiara Dellacasa, Irene Dogliotti, Tommaso Lupia, Carla M. Zotti, Silvia Corcione and Francesco Giuseppe De Rosa
Pharmaceuticals 2023, 16(3), 466; https://doi.org/10.3390/ph16030466 - 21 Mar 2023
Cited by 4 | Viewed by 1313
Abstract
Bloodstream infections (BSI) are life-threatening complications for onco-hematologic patients. Fluoroquinolones prophylaxis (FQP) was recommended for patients with neutropenia. Later, it was correlated with increased resistance rates among this population and its role became debated. While the role of FQ prophylaxis is still being [...] Read more.
Bloodstream infections (BSI) are life-threatening complications for onco-hematologic patients. Fluoroquinolones prophylaxis (FQP) was recommended for patients with neutropenia. Later, it was correlated with increased resistance rates among this population and its role became debated. While the role of FQ prophylaxis is still being studied, its cost-effectiveness is also unknown. The objective of this study was to evaluate the costs and effects associated with two alternative strategies (FQP vs. no prophylaxis) for patients with hematological malignancies undergoing allogenic stem cell transplant (HSCT). A decision-tree model was built integrating retrospectively collected data from a single transplant center, part of a tertiary teaching hospital in Northern Italy. Probabilities, costs and effects were considered in the assessment of the two alternative strategies. Probabilities of colonization, BSIs, extended-spectrum beta lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) BSIs and mortality associated with infection, as well as median duration of length of stay (LOS) were calculated based on data collected between 2013 and 2021. The center applied the strategy of FQP between 2013 and 2016, and of no prophylaxis between 2016 and 2021. Data on 326 patients were collected during the considered time period. Overall, the rates of colonization, BSI, KPC/ESBL BSI, and mortality were 6.8% (95% confidence interval (CI) 2.7–13.5), 42% (9.9–81.4) and 20.72 (16.67–25.26), respectively. A mean bed-day cost of 132€ was estimated. Considering no prophylaxis vs. prophylaxis, the difference in costs ranged between additional 33.61 and 80.59€ per patient, whereas the difference in effects ranged between 0.11 and 0.03 life-years (LYs) lost (around 40 and 11 days). Given the small differences in terms of costs and effects between the two strategies, no prophylaxis seems an appropriate choice. Furthermore, this analysis did not consider the broader effect on hospital ecology of multiple doses of FQP, which could provide further support for the strategy of no prophylaxis. Our results suggest that the necessity for FQP in onco-hematologic setting should be determined based on local antibiotic resistance patterns. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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16 pages, 12450 KiB  
Article
Afatinib Reverses EMT via Inhibiting CD44-Stat3 Axis to Promote Radiosensitivity in Nasopharyngeal Carcinoma
by Huichao Huang, Fangling Huang, Xujun Liang, Ying Fu, Zhe Cheng, Yan Huang, Zhuchu Chen, Yankun Duan and Yongheng Chen
Pharmaceuticals 2023, 16(1), 37; https://doi.org/10.3390/ph16010037 - 27 Dec 2022
Cited by 1 | Viewed by 1783
Abstract
Background: Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its radiosensitive effects in nasopharyngeal carcinoma (NPC). However, the detailed mechanism of afatinib-mediated sensitivity to radiation is still obscure in NPC. Methods: Quantitative phosphorylated proteomics and bioinformatics analysis were performed to illustrate the global [...] Read more.
Background: Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its radiosensitive effects in nasopharyngeal carcinoma (NPC). However, the detailed mechanism of afatinib-mediated sensitivity to radiation is still obscure in NPC. Methods: Quantitative phosphorylated proteomics and bioinformatics analysis were performed to illustrate the global phosphoprotein changes. The activity of the CD44-Stat3 axis and Epithelial-Mesenchymal Transition (EMT)-linked markers were evaluated by Western blotting. Wound healing and transwell assays were used to determine the levels of cell migration upon afatinib combined IR treatment. Cell proliferation was tested by CCK-8 assay. A pharmacological agonist by IL-6 was applied to activate Stat3. The xenograft mouse model was treated with afatinib, radiation or a combination of afatinib and radiation to detect the radiosensitivity of afatinib in vivo. Results: In the present study, we discovered that afatinib triggered global protein phosphorylation alterations in NPC cells. Further, bioinformatics analysis indicated that afatinib inhibited the CD44-Stat3 signaling and subsequent EMT process. Moreover, functional assays demonstrated that afatinib combined radiation treatment remarkably impeded cell viability, migration, EMT process and CD44-Stat3 activity in vitro and in vivo. In addition, pharmacological stimulation of Stat3 rescued radiosensitivity and biological functions induced by afatinib in NPC cells. This suggested that afatinib reversed the EMT process by blocking the activity of the CD44-Stat3 axis. Conclusion: Collectively, this work identifies the molecular mechanism of afatinib as a radiation sensitizer, thus providing a potentially useful combination treatment and drug target for NPC radiosensitization. Our findings describe a new function of afatinib in radiosensitivity and cancer treatment. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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Review

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26 pages, 1817 KiB  
Review
New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians
by Davide Carcione, Jari Intra, Lilia Andriani, Floriana Campanile, Floriana Gona, Silvia Carletti, Nicasio Mancini, Gioconda Brigante, Dario Cattaneo, Sara Baldelli, Mattia Chisari, Alessandra Piccirilli, Stefano Di Bella and Luigi Principe
Pharmaceuticals 2023, 16(9), 1304; https://doi.org/10.3390/ph16091304 - 15 Sep 2023
Viewed by 1908
Abstract
Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including [...] Read more.
Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including ceftobiprole, ceftaroline, dalbavancin, oritavancin, omadacycline, tedizolid, and delafloxacin. From a methodological standpoint, a comprehensive analysis on clinical trials, molecular structure, mechanism of action, microbiological targeting, clinical use, pharmacokinetic/pharmacodynamic features, and potential for therapeutic drug monitoring will be addressed. Each antibiotic paragraph is divided into specialized microbiological, clinical, and pharmacological sections, including detailed and appropriate tables. A better understanding of the latest promising advances in the field of therapeutic options could lead to the development of a better approach in managing antimicrobial therapy for multidrug-resistant Gram-positive pathogens, which increasingly needs to be better stratified and targeted. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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25 pages, 3152 KiB  
Review
Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins
by Yiyuan Feng, Sha Zhu, Tengwen Liu, Guoguo Zhi, Bingjie Shao, Jibin Liu, Baixue Li, Cen Jiang, Quansheng Feng, Peijie Wu and Dong Wang
Pharmaceuticals 2023, 16(8), 1114; https://doi.org/10.3390/ph16081114 - 07 Aug 2023
Cited by 1 | Viewed by 1345
Abstract
RNA-binding proteins (RBPs), being pivotal elements in both physiological and pathological processes, possess the ability to directly impact RNA, thereby exerting a profound influence on cellular life. Furthermore, the dysregulation of RBPs not only induces alterations in the expression levels of genes associated [...] Read more.
RNA-binding proteins (RBPs), being pivotal elements in both physiological and pathological processes, possess the ability to directly impact RNA, thereby exerting a profound influence on cellular life. Furthermore, the dysregulation of RBPs not only induces alterations in the expression levels of genes associated with cancer but also impairs the occurrence of post-transcriptional regulatory mechanisms. Consequently, these circumstances can give rise to aberrations in cellular processes, ultimately resulting in alterations within the proteome. An aberrant proteome can disrupt the equilibrium between oncogenes and tumor suppressor genes, promoting cancer progression. Given their significant role in modulating gene expression and post-transcriptional regulation, directing therapeutic interventions towards RBPs represents a viable strategy for combating drug resistance in cancer treatment. RBPs possess significant potential as diagnostic and prognostic markers for diverse cancer types. Gaining comprehensive insights into the structure and functionality of RBPs, along with delving deeper into the molecular mechanisms underlying RBPs in tumor drug resistance, can enhance cancer treatment strategies and augment the prognostic outcomes for individuals afflicted with cancer. Full article
(This article belongs to the Special Issue Multi-Drug Resistance)
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