Antibiotics

7 pages, 315 KiB

Open AccessArticle

Role of parC Mutations at Position 84 on High-Level Delafloxacin Resistance in Methicillin-Resistant Staphylococcus aureus

by Silvia Bolaños, Cesar Acebes, Óscar Martínez-Expósito, José Antonio Boga, Javier Fernández and Carlos Rodríguez-Lucas

Antibiotics 2024, 13(7), 641; https://doi.org/10.3390/antibiotics13070641 - 11 Jul 2024

Abstract

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates [...] Read more.

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present. Full article

(This article belongs to the Special Issue Mechanisms of Resistance to Antibacterial Agents in Staphylococcus and Enterococcus)

16 pages, 4452 KiB

Open AccessReview

Humanized Mouse Models of Bacterial Infections

by Katya McDonald, Adryiana Rodriguez and Gowrishankar Muthukrishnan

Antibiotics 2024, 13(7), 640; https://doi.org/10.3390/antibiotics13070640 - 11 Jul 2024

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Abstract

Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues to rise, posing serious risks to controlling global disease outbreaks. To develop novel and more effective treatment and vaccination [...] Read more.

Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues to rise, posing serious risks to controlling global disease outbreaks. To develop novel and more effective treatment and vaccination programs, there is a need for clinically relevant small animal models. Since multiple bacterial species have human-specific tropism for numerous virulence factors and toxins, conventional mouse models do not fully represent human disease. Several human disease characteristic phenotypes, such as lung granulomas in the case of Mycobacterium tuberculosis infections, are absent in standard mouse models. Alternatively, certain pathogens, such as Salmonella enterica serovar typhi and Staphylococcus aureus, can be well tolerated in mice and cleared quickly. To address this, multiple groups have developed humanized mouse models and observed enhanced susceptibility to infection and a more faithful recapitulation of human disease. In the last two decades, multiple humanized mouse models have been developed to attempt to recapitulate the human immune system in a small animal model. In this review, we first discuss the history of immunodeficient mice that has enabled the engraftment of human tissue and the engraftment methods currently used in the field. We then highlight how humanized mouse models successfully uncovered critical human immune responses to various bacterial infections, including Salmonella enterica serovar Typhi, Mycobacterium tuberculosis, and Staphylococcus aureus. Full article

(This article belongs to the Special Issue Staphylococcal Biology and Pathogenesis)

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17 pages, 1532 KiB

Open AccessArticle

Antimicrobial Resistance Profile, Whole-Genome Sequencing and Core Genome Multilocus Sequence Typing of B. anthracis Isolates in Croatia from 2001 to 2022

by Gordan Kompes, Sanja Duvnjak, Irena Reil, Željko Mihaljević, Boris Habrun, Miroslav Benić, Luka Cvetnić, Silvio Špičić and Antonela Bagarić

Antibiotics 2024, 13(7), 639; https://doi.org/10.3390/antibiotics13070639 - 11 Jul 2024

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Abstract

Bacillus anthracis, the causative agent of anthrax disease, is a worldwide threat to livestock, wildlife and public health. It is also considered one of the most important pathogens of bioterrorism. Rapid and reliable diagnosis and administration of antimicrobials are essential for effective [...] Read more.

Bacillus anthracis, the causative agent of anthrax disease, is a worldwide threat to livestock, wildlife and public health. It is also considered one of the most important pathogens of bioterrorism. Rapid and reliable diagnosis and administration of antimicrobials are essential for effective anthrax treatment. In this study, we determined the in vitro susceptibilities of 40 isolates of B. anthracis isolated in Croatia over the recent two decades to 18 antimicrobials. Whole-genome sequencing was performed, and bioinformatics tools were used to determine virulence factors and antimicrobial resistance genes. Core genome-based multilocus sequence typing was used for isolate comparison and phylogenetic analysis. All isolates were susceptible to all antimicrobials recommended for post-exposure prophylaxis or anthrax therapy. Susceptibility was found to all other tested antimicrobials that are an alternative for primary therapy. We found two beta-lactamase genes, but their expression is not sufficient to confer resistance. In all isolates used in this study, we found 21 virulence genes, 8 of which are responsible for toxin and capsule production. As far as phylogenetic analysis is concerned, the B. anthracis isolates from Croatia are categorised into two clades. The first is clade A, subclade Trans Eurasia, and the other is clade B, subclade B2. Full article

(This article belongs to the Special Issue Detection of Bacteria and Antibiotics Surveillance in Livestock)

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13 pages, 1435 KiB

Open AccessArticle

Prevalence and Phage-Based Biocontrol of Methicillin-Resistant Staphylococcus aureus Isolated from Raw Milk of Cows with Subclinical Mastitis in Vietnam

by Hoang Minh Son and Hoang Minh Duc

Antibiotics 2024, 13(7), 638; https://doi.org/10.3390/antibiotics13070638 - 10 Jul 2024

Viewed by 381

Abstract

S. aureus, particularly methicillin-resistant S. aureus, has been recognized as a main cause of bovine mastitis and food poisoning. This study investigated the prevalence, antibiotic resistance, and phage-based biocontrol of S. aureus and methicillin-resistant S. aureus isolated from raw milk of [...] Read more.

S. aureus, particularly methicillin-resistant S. aureus, has been recognized as a main cause of bovine mastitis and food poisoning. This study investigated the prevalence, antibiotic resistance, and phage-based biocontrol of S. aureus and methicillin-resistant S. aureus isolated from raw milk of cows with subclinical mastitis. The results showed that the prevalence of S. aureus and methicillin-resistant S. aureus was 12% (48/400) and 1.5% (6/400), respectively. The S. aureus isolates were highly resistant to penicillin (72.92%), erythromycin (43.75%), and tetracycline (39.58%). Out of 48 S. aureus isolates, 6 were identified as methicillin-resistant strains. Among them, one isolate was found to harbor the sea gene. A total of 5 phages were recovered from 50 pork and 50 chicken meat samples, 1 from pork and 4 from chicken meat samples. Phage PSA2 capable of lysing all 6 methicillin-resistant isolates was selected for characterization. The use of phage PSA2 completely inactivated methicillin-resistant S. aureus SA33 in raw milk at both 24 °C and 4 °C, indicating its potential as a promising antibacterial agent in controlling methicillin-resistant S. aureus in raw milk and treating bovine mastitis. Full article

(This article belongs to the Special Issue Exploring Antimicrobial Resistance in Foodborne Pathogens: Microbiological Perspectives)

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14 pages, 1996 KiB

Open AccessArticle

Cytocompatibility and Antibiofilm Activity of Calcium Hydroxide Mixed with Cyperus articulatus Essential Oil and Bio-C Temp Bioceramic Intracanal Medicament

by Cláudia Fernandes de Magalhães Silveira, Carlos Eduardo da Silveira Bueno and Angélica Zaninelli Schreiber

Antibiotics 2024, 13(7), 637; https://doi.org/10.3390/antibiotics13070637 - 10 Jul 2024

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Abstract

Calcium hydroxide represents the most commonly used intracanal dressing between sessions; however, it may not be effective against all types of microorganisms. Several compounds of plant origin have attracted increasing attention from researchers in recent years. The objective of this study was to [...] Read more.

Calcium hydroxide represents the most commonly used intracanal dressing between sessions; however, it may not be effective against all types of microorganisms. Several compounds of plant origin have attracted increasing attention from researchers in recent years. The objective of this study was to evaluate the cytocompatibility and antimicrobial activity of calcium hydroxide associated with the essential oil of Cyperus articulatus and the new bioceramic intracanal medicament Bio-C Temp^®. Five experimental groups were designed: group Ca–C. articulatus essential oil; group CHPG-calcium hydroxide associated with propylene glycol; group CHCa-essential oil of C. articulatus associated with calcium hydroxide; and group U-UltraCal^® XS; group BCT-Bio-C Temp^®. The control group was a culture medium. Cytocompatibility was assessed by the methyltetrazolium (MTT) assay after exposure of the Saos-2 human osteoblast-like cell line to dilutions of commercial products/associations for 24 h and 72 h. The antimicrobial activity against mature Enterococcus faecalis biofilm was evaluated by the crystal violet assay. All commercial products/associations showed a cell viability similar to or even higher than the control group (p > 0.05) for both periods evaluated. C. articulatus essential oil associated or not with calcium hydroxide showed better antibiofilm capacity. C. articulatus associated or not with calcium hydroxide showed superior cytocompatibility and antimicrobial capacity, representing a promissory intracanal medicament. Full article

(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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12 pages, 1001 KiB

Open AccessArticle

Is Antimicrobial Stewardship Policy Effectively Implemented in Polish Hospitals? Results from Antibiotic Consumption Surveillance before and during the COVID-19 Pandemic

by Urszula Durlak, Cezary Kapturkiewicz, Anna Różańska, Mateusz Gajda, Paweł Krzyściak, Filip Kania and Jadwiga Wójkowska-Mach

Antibiotics 2024, 13(7), 636; https://doi.org/10.3390/antibiotics13070636 - 10 Jul 2024

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Abstract

Background: The COVID-19 pandemic posed numerous challenges to public health systems, particularly in antimicrobial stewardship. This study aimed to assess antibiotic consumption before and during the COVID-19 pandemic to evaluate the effectiveness of the implemented antimicrobial stewardship program. Methods: This retrospective study was [...] Read more.

Background: The COVID-19 pandemic posed numerous challenges to public health systems, particularly in antimicrobial stewardship. This study aimed to assess antibiotic consumption before and during the COVID-19 pandemic to evaluate the effectiveness of the implemented antimicrobial stewardship program. Methods: This retrospective study was carried out at the University Hospital in Krakow, Poland, between 1 January 2019 and 31 December 2020. A total of 80,639 patients were enrolled. Antibiotic usage was measured as the percentage of patients receiving antibiotics and the number of days of therapy (DOTs). The World Health Organization (WHO) methodology and Anatomical Therapeutic Chemical (ATC) codes and AWaRe classification were utilized. The analyzed ATC antibiotic groups included penicillins (J01CA, J01CE, J01CF, J01CR, excluding piperacillin/tazobactam), piperacillin with tazobactam-beta-lactamase inhibitor (J01CR05), third- and fourth-generation cephalosporins (J01DD, J01DE), carbapenems (J01DH), macrolides (J01FA), fluoroquinolones (J01M), colistin (J01XB01), metronidazole (J01XD01) and others (J01DF, J01DI, J01E, J01G, J01XA, J01A). In the AWaRe classification, Access, Watch and Reserve groups of antibiotics were included. Results: In 2020, 79.2% of COVID-19 patients and 40.1% of non-COVID-19 patients were treated with antibiotics, compared to 28.8% in 2019. Also, in 2020, the antibiotic consumption in non-ICU COVID-19 patients was twice as high as in non-COVID-19 patients: 50.9 vs. 38.5 DOTs/100 patient days (pds). Conversely, in the ICU, antibiotic consumption in COVID-19 patients was 112.1 DOTs/100 pds compared to 248.9 DOTs/100 pds in non-COVID-19 patients. Significant increases were observed in the usage of third- and fourth-generation cephalosporins in 2020. The analysis according to the AWaRe system revealed the highest usage of the Watch group—ranging from 61.9% to 78.7%—and very high usage of the Reserve group—from 5.8% to 11.1%—in non COVID-19 and COVID-19 patients, respectively. Conclusions: Our findings highlight substantial issues with antibiotic use both before and during the COVID-19 pandemic. The results underscore the urgent need for improved antimicrobial stewardship policy implementation. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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18 pages, 871 KiB

Open AccessArticle

Adherence to Antibiotic Prescription Guidelines in Four Community Hospitals in Germany

by Joachim Peter Biniek, Frank Schwab, Karolin Graf and Ralf-Peter Vonberg

Antibiotics 2024, 13(7), 635; https://doi.org/10.3390/antibiotics13070635 - 10 Jul 2024

Viewed by 286

Abstract

This retrospective study aimed to assess and compare guideline adherence and treatment costs in the management of urinary tract infections (UTIs) and bloodstream infections (BSIs) in German tertiary hospitals from January 2019 to December 2020. The study analyzed 586 patient records, with 65% [...] Read more.

This retrospective study aimed to assess and compare guideline adherence and treatment costs in the management of urinary tract infections (UTIs) and bloodstream infections (BSIs) in German tertiary hospitals from January 2019 to December 2020. The study analyzed 586 patient records, with 65% diagnosed with UTIs and 35% with BSIs. Antibiotic treatment was given to 98% of patients, but only 65% received microbiological diagnostics. Bacterial growth was observed in 86% of patients with cultures taken, with Escherichia coli being the leading pathogen. The treatment was intravenous in 63% of cases, with Ceftriaxone as the leading antibiotic agent. The guideline adherence was found to be low, at 33%. Multivariable logistic regression analysis revealed that patients with urogenital risk factors (OR = 1.589; p < 0.001) and increasing age (OR = 1.01; p = 0.007) were significantly more likely to receive guideline-concordant treatment for UTIs and BSIs. Additionally, complicating factors such as diabetes and renal dysfunction were associated with higher adherence rates, underscoring the importance of targeted antibiotic stewardship interventions. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship Intervention: Importance for Clinical Practice and Health Policy)

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19 pages, 1328 KiB

Open AccessReview

From Herd Health to Public Health: Digital Tools for Combating Antibiotic Resistance in Dairy Farms

by Andra-Sabina Neculai-Valeanu, Adina-Mirela Ariton, Ciprian Radu, Ioana Porosnicu, Catalina Sanduleanu and Gabriela Amariții

Antibiotics 2024, 13(7), 634; https://doi.org/10.3390/antibiotics13070634 - 9 Jul 2024

Viewed by 419

Abstract

The emergence of antimicrobial resistance (AMR) is a significant threat to global food security, human health, and the future of livestock production. Higher rates of antimicrobial use in dairy farming and the sheer lack of new antimicrobials available for use focused attention on [...] Read more.

The emergence of antimicrobial resistance (AMR) is a significant threat to global food security, human health, and the future of livestock production. Higher rates of antimicrobial use in dairy farming and the sheer lack of new antimicrobials available for use focused attention on the question of how the dairy production sector contributed to the development of AMR and paved the path toward taking action to curtail it on the targeted type of farms. This paper aims to provide an introduction to a phenomenon that has gained considerable attention in the recent past due to its ever-increasing impact, the use of antimicrobial drugs, the emergence of antimicrobial resistance (AMR) on dairy farms, and seeks to discuss the possibilities of approaches such as digital health monitoring and precision livestock farming. Using sensors, data, knowledge, automation, etc., digital health monitoring, as well as Precision Livestock Farming (PLF), is expected to enhance health control and minimize disease and antimicrobial usage. The work presents a literature review on the current status and trends of AMR in dairy farms, an understanding of the concept of digital health monitoring and PLF, and the presentation and usefulness of digital health monitoring and PLF in preventing AMR. The study also analyses the strengths and weaknesses of adopting and incorporating digital technologies and artificial intelligence for dairy farming and presents areas for further study and level of use. Full article

(This article belongs to the Special Issue Antibiotics Use in Farms, 2nd Edition)

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9 pages, 380 KiB

Open AccessArticle

Hospitalized COVID-19 Patients with Urinary Tract Infection in Iran: Candida Species Distribution and Antifungal Susceptibility Patterns

by Zeinab Soleimani Shiyadeh, Shirin Farahyar, Laleh Vahedi Larijani, Justin Beardsley, Noura Nouri, Shahram Mahmoudi, Shahla Roudbar Mohammadi, Célia Fortuna Rodrigues and Maryam Roudbary

Antibiotics 2024, 13(7), 633; https://doi.org/10.3390/antibiotics13070633 - 8 Jul 2024

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Abstract

Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the [...] Read more.

Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the emergence of multidrug-resistant strains, poses significant challenges for effective treatment and further investigations. In this study, urine samples were collected from 70 COVID-19 patients with UTIs in sterile containers for microbiology examination. After microscopic observation, the isolates were identified both by phenotypic and molecular techniques such as multiplex PCR. Antifungal susceptibility testing (AFST) against fluconazole (Flu), itraconazole (Itr), and amphotericin B (AMB) was performed according to CLSI M27/S4 standard methods, with the frequency of isolates including Candida albicans (n = 20, 51.3%), Candida tropicalis (n = 15, 38.4%), Nakaseomyces glabrata (previously Candida glabrata) (n = 2, 5.1%), Pichia kudriavzevii (previously Candida krusei), and Candida parapsilosis (n = 1, 2.5%). All isolates of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis were sensitive to amphotericin B, while C. kruzei was resistant to AMB. Around 70% of C. albicans isolates were sensitive to Flu; 20% of C. tropicalis were resistant to itraconazole, while 33% were resistant to fluconazole. C. albicans and C. tropicalis were the main causes of candiduria in infected cases and both Flu and AMB showed good results in AFST in these species. Performing drug susceptibility testing for clinical isolates of Candida spp. provided guidance for appropriate management and control, and timely antifungal treatment. Full article

(This article belongs to the Special Issue Drug Repositioning in Antimicrobial Therapy, 2nd Edition)

12 pages, 831 KiB

Open AccessArticle

Differences in the Dwell Time of Peripherally Inserted Central Catheters between Patients with Catheter Colonization and Those Developing Central Line-Associated Bloodstream Infection: A Single Centre Retrospective Cohort Study

by Vassiliki C. Pitiriga, Elsa Campos, John Bakalis, George Saroglou and Athanasios Tsakris

Antibiotics 2024, 13(7), 632; https://doi.org/10.3390/antibiotics13070632 - 8 Jul 2024

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Abstract

Substantial knowledge gaps exist concerning the varying durations of peripherally inserted central catheter (PICC) placements that lead to either central line-associated bloodstream infection (CLABSI) or catheter colonization. We aimed to compare PICCs dwell time between patients who developed CLABSIs due to multidrug-resistant microorganisms [...] Read more.

Substantial knowledge gaps exist concerning the varying durations of peripherally inserted central catheter (PICC) placements that lead to either central line-associated bloodstream infection (CLABSI) or catheter colonization. We aimed to compare PICCs dwell time between patients who developed CLABSIs due to multidrug-resistant microorganisms (MDROs) and patients with catheter colonization by MDROs. Data from 86 patients admitted consecutively to a tertiary-care hospital from 2017 to 2020 were retrospectively analyzed. The mean dwell time was 25.73 ± 16.19 days in the PICC-CLABSI group and 16.36 ± 10.28 days in the PICC-colonization group (p = 0.002). The mean dwell time was 17.38 ± 9.5 days in the PICC-MDRO group and 22.48 ± 15.64 days in the PICC-non-MDRO group (p = 0.005). Within the PICC-CLABSI group, the mean dwell time for CLABSIs caused by MDROs was 21.50 ± 12.31 days, compared to 27.73 ± 16.98 days for CLABSIs caused by non-MDROs (p = 0.417). Within the PICC-colonization group, the mean dwell time was 15.55 ± 7.73 days in PICCs colonized by MDROs and 16.92 ± 11.85 days in PICCs colonized by non-MDROs (p = 0.124). The findings of the present study suggest that CLABSIs caused by MDROs in PICCs are associated with a shorter mean catheter dwell time compared to those caused by non-MDROs, underscoring the importance of considering infections by MDROs when evaluating PICC dwell times. Full article

(This article belongs to the Special Issue Antibiotics Resistance and Molecular Epidemiology of Carbapenem-Resistance Bacteria)

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20 pages, 6296 KiB

Open AccessArticle

New Fe₃O₄-Based Coatings with Enhanced Anti-Biofilm Activity for Medical Devices

by Ioana Adelina Pirușcă, Paul Cătălin Balaure, Valentina Grumezescu, Stefan-Andrei Irimiciuc, Ovidiu-Cristian Oprea, Alexandra Cătălina Bîrcă, Bogdan Vasile, Alina Maria Holban, Ionela C. Voinea, Miruna S. Stan, Roxana Trușcă, Alexandru Mihai Grumezescu and George-Alexandru Croitoru

Antibiotics 2024, 13(7), 631; https://doi.org/10.3390/antibiotics13070631 - 7 Jul 2024

Viewed by 585

Abstract

With the increasing use of invasive, interventional, indwelling, and implanted medical devices, healthcare-associated infections caused by pathogenic biofilms have become a major cause of morbidity and mortality. Herein, we present the fabrication, characterization, and in vitro evaluation of biocompatibility and anti-biofilm properties of [...] Read more.

With the increasing use of invasive, interventional, indwelling, and implanted medical devices, healthcare-associated infections caused by pathogenic biofilms have become a major cause of morbidity and mortality. Herein, we present the fabrication, characterization, and in vitro evaluation of biocompatibility and anti-biofilm properties of new coatings based on Fe₃O₄ nanoparticles (NPs) loaded with usnic acid (UA) and ceftriaxone (CEF). Sodium lauryl sulfate (SLS) was employed as a stabilizer and modulator of the polarity, dispersibility, shape, and anti-biofilm properties of the magnetite nanoparticles. The resulting Fe₃O₄ functionalized NPs, namely Fe₃O₄@SLS, Fe₃O₄@SLS/UA, and Fe₃O₄@SLS/CEF, respectively, were prepared by co-precipitation method and fully characterized by XRD, TEM, SAED, SEM, FTIR, and TGA. They were further used to produce nanostructured coatings by matrix-assisted pulsed laser evaporation (MAPLE) technique. The biocompatibility of the coatings was assessed by measuring the cell viability, lactate dehydrogenase release, and nitric oxide level in the culture medium and by evaluating the actin cytoskeleton morphology of murine pre-osteoblasts. All prepared nanostructured coatings exhibited good biocompatibility. Biofilm growth inhibition ability was tested at 24 h and 48 h against Staphylococcus aureus and Pseudomonas aeruginosa as representative models for Gram-positive and Gram-negative bacteria. The coatings demonstrated good biocompatibility, promoting osteoblast adhesion, migration, and growth without significant impact on cell viability or morphology, highlighting their potential for developing safe and effective antibacterial surfaces. Full article

(This article belongs to the Special Issue Nanomaterials as Antimicrobial Agents for Biomedical Applications)

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26 pages, 10235 KiB

Open AccessArticle

In Vitro Evaluation of Colistin Conjugated with Chitosan-Capped Gold Nanoparticles as a Possible Formulation Applied in a Metered-Dose Inhaler

by Narumon Changsan, Apichart Atipairin, Poowadon Muenraya, Rutthapol Sritharadol, Teerapol Srichana, Neelam Balekar and Somchai Sawatdee

Antibiotics 2024, 13(7), 630; https://doi.org/10.3390/antibiotics13070630 - 6 Jul 2024

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Abstract

Inhaled colistin is used to treat pneumonia and respiratory infections through nebulization or dry powder inhalers. Nevertheless, the development of a metered-dose inhaler (MDI) for colistin, which could enhance patient convenience and treatment efficacy, has not yet been developed. Colistin is known for [...] Read more.

Inhaled colistin is used to treat pneumonia and respiratory infections through nebulization or dry powder inhalers. Nevertheless, the development of a metered-dose inhaler (MDI) for colistin, which could enhance patient convenience and treatment efficacy, has not yet been developed. Colistin is known for its ability to induce cellular toxicity. Gold nanoparticles (AuNPs) can potentially mitigate colistin toxicity. Therefore, this study aimed to evaluate the antimicrobial effectiveness of colistin conjugated with chitosan-capped gold nanoparticles (Col-CS-AuNPs) and their potential formulation for use with MDIs to deliver the aerosol directly to the deep lung. Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and elemental analysis were used to characterize the synthesized Col-CS-AuNPs. Drug release profiles fitted with the most suitable release kinetic model were evaluated. An MDI formulation containing 100 µg of colistin per puff was prepared. The aerosol properties used to determine the MDI performance included the fine particle fraction, mass median aerodynamic diameter, and geometric standard deviation, which were evaluated using the Andersen Cascade Impactor. The delivered dose uniformity was also determined. The antimicrobial efficacy of the Col-CS-AuNP formulation in the MDI was assessed. The chitosan-capped gold nanoparticles (CS-AuNPs) and Col-CS-AuNPs had particle sizes of 44.34 ± 1.02 and 174.50 ± 4.46 nm, respectively. CS-AuNPs effectively entrapped 76.4% of colistin. Col-CS-AuNPs exhibited an initial burst release of up to 60% colistin within the first 6 h. The release mechanism was accurately described by the Korsmeyer–Peppas model, with an R² > 0.95. The aerosol properties of the Col-CS-AuNP formulation in the MDI revealed a high fine particle fraction of 61.08%, mass median aerodynamic diameter of 2.34 µm, and geometric standard deviation of 0.21, with a delivered dose uniformity within 75–125% of the labeled claim. The Col-CS-AuNP MDI formulation completely killed Escherichia coli at 5× and 10× minimum inhibitory concentrations after 6 and 12 h of incubation, respectively. The toxicity of CS-AuNP and Col-CS-AuNP MDI formulations in upper and lower respiratory tract cell lines was lower than that of free colistin. The stability of the Col-CS-AuNP MDI formulation was maintained for at least 3 months. The Col-CS-AuNP MDI formulation effectively eradicated bacteria over a 12-h period, showing promise for advancing lung infection treatments. Full article

(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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30 pages, 756 KiB

Open AccessReview

Novel Antibiotics for Gram-Negative Nosocomial Pneumonia

by Maria Panagiota Almyroudi, Aina Chang, Ioannis Andrianopoulos, Georgios Papathanakos, Reena Mehta, Elizabeth Paramythiotou and Despoina Koulenti

Antibiotics 2024, 13(7), 629; https://doi.org/10.3390/antibiotics13070629 - 5 Jul 2024

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Abstract

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate [...] Read more.

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit ‘critical illness’ physiology that affects drug efficacy. Full article

(This article belongs to the Special Issue Antimicrobial Treatment of Lower Respiratory Tract Infections)

15 pages, 2748 KiB

Open AccessArticle

Screening and Evaluation of Potential Efflux Pump Inhibitors with a Seaweed Compound Diphenylmethane-Scaffold against Drug-Resistant Escherichia coli

by Wen-Jung Lu, Yu-Wei Lian, Chun-Ju Chang, Hsuan-Ju Lin, Chian-Yun Huang, Pang-Hung Hsu and Hong-Ting Lin

Antibiotics 2024, 13(7), 628; https://doi.org/10.3390/antibiotics13070628 - 5 Jul 2024

Viewed by 503

Abstract

Drug-resistant efflux pumps play a crucial role in bacterial antibiotic resistance. In this study, potential efflux pump inhibitors (EPIs) with a diphenylmethane scaffold were screened and evaluated against drug-resistant Escherichia coli. Twenty-four compounds were docked against the drug-binding site of E. coli [...] Read more.

Drug-resistant efflux pumps play a crucial role in bacterial antibiotic resistance. In this study, potential efflux pump inhibitors (EPIs) with a diphenylmethane scaffold were screened and evaluated against drug-resistant Escherichia coli. Twenty-four compounds were docked against the drug-binding site of E. coli multidrug transporter AcrB, and 2,2-diphenylethanol (DPE), di-p-tolyl-methanol (DPT), and 4-(benzylphenyl) acetonitrile (BPA) were screened for their highest binding free energy. The modulation assay was further used for EPI evaluation, revealing that DPE, DPT, and BPA could reduce the drug IC₅₀ value in E. coli strains overexpressing AcrB, indicating their modulation activity. Only DPE and BPA enhanced intracellular dye accumulation and inhibited the efflux of ethidium bromide and erythromycin. In addition, DPE and BPA showed an elevated post-antibiotic effect on drug-resistant E. coli, and they did not damage the permeability of the bacterial outer membrane. The cell toxicity test showed that DPE and BPA had limited human-cell toxicity. Therefore, DPE and BPA demonstrate efflux pump inhibitory activity, and they should be further explored as potential enhancers to improve the effectiveness of existing antibiotics against drug-resistant E. coli. Full article

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14 pages, 1424 KiB

Open AccessReview

Surveillance of Antimicrobial Resistance in the ECOWAS Region: Setting the Scene for Critical Interventions Needed

by Ahmed Taha Aboushady, Olivier Manigart, Abdourahmane Sow, Walter Fuller, Abdoul-Salam Ouedraogo, Chinelo Ebruke, François-Xavier Babin, Laetitia Gahimbare, Issiaka Sombié and John Stelling

Antibiotics 2024, 13(7), 627; https://doi.org/10.3390/antibiotics13070627 - 5 Jul 2024

Viewed by 472

Abstract

Antimicrobial resistance poses a significant challenge to public health globally, leading to increased morbidity and mortality. AMR surveillance involves the systematic collection, analysis, and interpretation of data on the occurrence and distribution of AMR in humans, animals, and the environment for action. The [...] Read more.

Antimicrobial resistance poses a significant challenge to public health globally, leading to increased morbidity and mortality. AMR surveillance involves the systematic collection, analysis, and interpretation of data on the occurrence and distribution of AMR in humans, animals, and the environment for action. The West African Health Organization, part of the Economic Community of West African States (ECOWAS), is committed to addressing AMR in the region. This paper examines the status of AMR surveillance in ECOWAS countries using available WHO data from the TrACSS survey and GLASS enrollments. The analysis reveals that while progress has been made, significant challenges remain. Twelve of the fifteen ECOWAS countries are enrolled in GLASS, and ten have developed national action plans (NAPs) for AMR. However, there is a need to ensure all countries fully implement their NAPs, continue reporting to GLASS, and use the data for evidence-based actions and decision making. Surveillance systems for AMR and antimicrobial consumption/use vary across countries with some demonstrating limited capacity. All countries, except Cabo Verde, reported having a reference laboratory for AMR testing. Strengthening laboratory capabilities, data management and use, and multisectoral coordination are crucial for effective AMR surveillance and response. Based on the findings and the regional context, it is essential to prioritize capacity building, data utilization, and the adoption of standardized guidelines for AMR surveillance. Collaboration among ECOWAS countries, the WAHO, and international partners is essential to address AMR comprehensively. Ensuring a consistent supply of essential antimicrobial medications and reagents is vital. Full article

(This article belongs to the Special Issue Successful Antimicrobial Stewardship Approaches to Address Nosocomial Infections)

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14 pages, 2123 KiB

Open AccessArticle

Antibiotic Resistance in Acetic Acid Bacteria Originating from Vinegar

by Sun-Hee Kim, Hyun-Wook Jang, Jin-Ju Park, Dong-Geon Nam, Su-Jeong Lee, Soo-Hwan Yeo and So-Young Kim

Antibiotics 2024, 13(7), 626; https://doi.org/10.3390/antibiotics13070626 - 5 Jul 2024

Viewed by 488

Abstract

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use [...] Read more.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study. Full article

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38 pages, 3295 KiB

Open AccessReview

Coatings Based on Essential Oils for Combating Antibiotic Resistance

by Anita Ioana Visan and Irina Negut

Antibiotics 2024, 13(7), 625; https://doi.org/10.3390/antibiotics13070625 - 4 Jul 2024

Viewed by 279

Abstract

In the current era of widespread antimicrobial resistance, the utilization of essential oils (EOs) derived from plants has emerged as a promising alternative in combating pathogens that have developed resistance to antibiotics. This review explores the therapeutic potential of essential oils as valuable [...] Read more.

In the current era of widespread antimicrobial resistance, the utilization of essential oils (EOs) derived from plants has emerged as a promising alternative in combating pathogens that have developed resistance to antibiotics. This review explores the therapeutic potential of essential oils as valuable tools in restoring the efficacy of antibiotics, highlighting their unique ability to affect bacteria in multiple ways and target various cellular systems. Despite the challenge of elucidating their precise mode of action, EOs have shown remarkable results in rigorous testing against a diverse range of bacteria. This review explores the multifaceted role of EOs in combating bacterial microorganisms, emphasizing their extraction methods, mechanisms of action, and comparative efficacy against synthetic antibiotics. Key findings underscore the unique strategies EOs deploy to counter bacteria, highlighting significant differences from conventional antibiotics. The review extends to advanced coating solutions for medical devices, exploring the integration of EO formulations into these coatings. Challenges in developing effective EO coatings are addressed, along with various innovative approaches for their implementation. An evaluation of these EO coatings reveals their potential as formidable alternatives to traditional antibacterial agents in medical device applications. This renaissance in exploring natural remedies emphasizes the need to combine traditional wisdom with modern scientific advancements to address the urgent need for effective antimicrobial solutions in the post-antibiotic era. Full article

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14 pages, 918 KiB

Open AccessArticle

Mutations in embB406 Are Associated with Low-Level Ethambutol Resistance in Canadian Mycobacterium tuberculosis Isolates

by Morgan Hiebert, Meenu K. Sharma, Melissa Rabb, Lisa Karlowsky, Kiana Bergman and Hafid Soualhine

Antibiotics 2024, 13(7), 624; https://doi.org/10.3390/antibiotics13070624 - 4 Jul 2024

Viewed by 585

Abstract

In Mycobacterium tuberculosis, molecular predictions of ethambutol resistance rely primarily on the detection of mutations within embB. However, discordance between embB406 mutations and gold standard phenotypic drug sensitivity testing (DST) questions the significance of embB406 mutations used in molecular [...] Read more.

In Mycobacterium tuberculosis, molecular predictions of ethambutol resistance rely primarily on the detection of mutations within embB. However, discordance between embB406 mutations and gold standard phenotypic drug sensitivity testing (DST) questions the significance of embB406 mutations used in molecular DST. This study tabulates embB mutations found in Canadian M. tuberculosis isolates and evaluates the impact of specific mutations on ethambutol resistance. The National Reference Centre for Mycobacteriology culture collection (n = 2796) was screened for isolates with embB mutations. Phenotypic DST was performed on the BACTEC™ MGIT™ 960 at ethambutol concentrations of 2–5 μg/mL. Whole genome sequencing was used for drug resistance predictions, phylogenomics and single nucleotide polymorphism analysis. Detection of resistance-associated embB mutations corresponded to a positive predictive value of 64.3%, negative predictive value of 99.2%, 98.7% specificity, and 73.3% sensitivity compared to phenotypic DST. Two embB406 mutation subtypes (Gly406Asp, Gly406Ala) were found among 16 isolates, of which 12 were sensitive at 5 µg/mL ethambutol with variable resistance between 2–4 µg/mL. A novel frameshift mutation in regulator embR (Gln258fs) was found in nine isolates. Mutations in embB406 were associated with low-level ethambutol resistance undetectable at the recommended critical concentration (5 μg/mL). These novel mutations may exacerbate variability in ethambutol resistance. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Drug-Resistant Mycobacterium tuberculosis)

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16 pages, 3291 KiB

Open AccessReview

Medical Device-Associated Infections Caused by Biofilm-Forming Microbial Pathogens and Controlling Strategies

by Akanksha Mishra, Ashish Aggarwal and Fazlurrahman Khan

Antibiotics 2024, 13(7), 623; https://doi.org/10.3390/antibiotics13070623 - 4 Jul 2024

Viewed by 736

Abstract

Hospital-acquired infections, also known as nosocomial infections, include bloodstream infections, surgical site infections, skin and soft tissue infections, respiratory tract infections, and urinary tract infections. According to reports, Gram-positive and Gram-negative pathogenic bacteria account for up to 70% of nosocomial infections in intensive [...] Read more.

Hospital-acquired infections, also known as nosocomial infections, include bloodstream infections, surgical site infections, skin and soft tissue infections, respiratory tract infections, and urinary tract infections. According to reports, Gram-positive and Gram-negative pathogenic bacteria account for up to 70% of nosocomial infections in intensive care unit (ICU) patients. Biofilm production is a main virulence mechanism and a distinguishing feature of bacterial pathogens. Most bacterial pathogens develop biofilms at the solid-liquid and air-liquid interfaces. An essential requirement for biofilm production is the presence of a conditioning film. A conditioning film provides the first surface on which bacteria can adhere and fosters the growth of biofilms by creating a favorable environment. The conditioning film improves microbial adherence by delivering chemical signals or generating microenvironments. Microorganisms use this coating as a nutrient source. The film gathers both inorganic and organic substances from its surroundings, or these substances are generated by microbes in the film. These nutrients boost the initial growth of the adhering bacteria and facilitate biofilm formation by acting as a food source. Coatings with combined antibacterial efficacy and antifouling properties provide further benefits by preventing dead cells and debris from adhering to the surfaces. In the present review, we address numerous pathogenic microbes that form biofilms on the surfaces of biomedical devices. In addition, we explore several efficient smart antiadhesive coatings on the surfaces of biomedical device-relevant materials that manage nosocomial infections caused by biofilm-forming microbial pathogens. Full article

(This article belongs to the Special Issue Combating Biofilm-Related Infections: Novel Therapeutics and Strategies)

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12 pages, 1492 KiB

Open AccessArticle

Antiparasitic Activity of Isolated Fractions from Parthenium incanum Kunth against the Hemoflagellate Protozoan Trypanosoma cruzi

by David Alejandro Hernández-Marín, Rocio Castro-Rios, Abelardo Chávez-Montes, Sandra L. Castillo-Hernández, Joel Horacio Elizondo-Luevano, Martín Humberto Muñoz-Ortega and Eduardo Sánchez-García

Antibiotics 2024, 13(7), 622; https://doi.org/10.3390/antibiotics13070622 - 4 Jul 2024

Viewed by 395

Abstract

This study focused on isolating, identifying, and evaluating the trypanocidal potential against the hemoflagellate protozoan Trypanosoma cruzi of compounds from Parthenium incanum (Mariola), a plant used in traditional Mexican medicine to treat stomach and liver disorders. P. incanum has a wide distribution in [...] Read more.

This study focused on isolating, identifying, and evaluating the trypanocidal potential against the hemoflagellate protozoan Trypanosoma cruzi of compounds from Parthenium incanum (Mariola), a plant used in traditional Mexican medicine to treat stomach and liver disorders. P. incanum has a wide distribution in Mexico. This study found that methanolic extracts of P. incanum, obtained by static maceration and successive reflux, had promising results. The fractions were compared using thin-layer chromatography (TLC) and those that showed similarities were mixed. A bioguided assay was performed with Staphylococcus aureus ATCC 25923, using agar diffusion and bioautography techniques to determine the preliminary biological activity. The fractions with antimicrobial activity were purified using a preparative thin-layer chromatography (PTLC) plate, obtaining the bioactive bandages that were subjected to a trypanocidal evaluation against the Ninoa strain of T. cruzi in its epimastigote stage. This revealed an IC₅₀ of up to 45 ± 2.5 µg/mL, in contrast to the values obtained from the crude extracts of less than 100 µg/mL. The TLC, Fourier-transform infrared spectroscopy (FT-IR), and high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) techniques were used to identify the compounds, demonstrating the presence of sesquiterpene lactones, parthenin, and coronopolin. We concluded that these compounds have the potential to inhibit T. cruzi growth. Full article

(This article belongs to the Special Issue Antiprotozoal Activity of Natural Products: 2nd Edition)

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17 pages, 7141 KiB

Open AccessArticle

FTY720 Reduces the Biomass of Biofilms in Pseudomonas aeruginosa in a Dose-Dependent Manner

by Abdurahman A. Niazy, Rhodanne Nicole A. Lambarte, Terrence S. Sumague, Mary Grace B. Vigilla, Najla M. Bin Shwish, Ranan Kamalan, Eid Khulaif Daeab and Nami M. Aljehani

Antibiotics 2024, 13(7), 621; https://doi.org/10.3390/antibiotics13070621 - 4 Jul 2024

Viewed by 502

Abstract

Pseudomonas aeruginosa, a nosocomial pathogen, has strong biofilm capabilities, representing the main source of infection in the human body. Repurposing existing drugs has been explored as an alternative strategy to combat emerging antibiotic-resistant pathogens. Fingolimod hydrochloride (FTY720), an immunomodulatory drug for multiple [...] Read more.

Pseudomonas aeruginosa, a nosocomial pathogen, has strong biofilm capabilities, representing the main source of infection in the human body. Repurposing existing drugs has been explored as an alternative strategy to combat emerging antibiotic-resistant pathogens. Fingolimod hydrochloride (FTY720), an immunomodulatory drug for multiple sclerosis, has shown promising antimicrobial effects against some ESKAPE pathogens. Therefore, the effects of FTY720 on the biofilm capabilities of Pseudomonas aeruginosa were investigated in this study. It was determined that FTY720 inhibited the growth of P. aeruginosa PAO1 at 100 µM. The significant reduction in PAO1 cell viability was observed to be dose-dependent. Additional cytotoxicity analysis on human cell lines showed that FTY720 significantly reduced viabilities at sub-inhibitory concentrations of 25–50 µM. Microtiter assays and confocal analysis confirmed reductions in biofilm mass and thickness and the cell survivability ratio in the presence of FTY720. Similarly, virulence production and biofilm-related gene expression (rhlA, rhlB, pilA, pilI, fliC, fliD and algR) were determined. The results demonstrate that pigment production was affected and quantitative real-time PCR analysis showed a variable degree of reduced gene expression in response to FTY720 at 12.5–50 µM. These findings suggest that FTY720 could be repurposed as an alternative antibiofilm agent against Pseudomonas aeruginosa. Full article

(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)

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16 pages, 5510 KiB

Open AccessArticle

Chitosan-Integrated Curcumin–Graphene Oxide/Copper Oxide Hybrid Nanocomposites for Antibacterial and Cytotoxicity Applications

by Anandhavelu Sanmugam, Logesh Kumar Sellappan, Abbishek Sridharan, Swathy Manoharan, Ananda Babu Sairam, Abdulrahman I. Almansour, Subha Veerasundaram, Hyun-Seok Kim and Dhanasekaran Vikraman

Antibiotics 2024, 13(7), 620; https://doi.org/10.3390/antibiotics13070620 - 3 Jul 2024

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Abstract

This study deals with the facile synthesis of a single-pot chemical technique for chitosan–curcumin (CUR)-based hybrid nanocomposites with nanostructured graphene oxide (GO) and copper oxide (CuO) as the antibacterial and cytotoxic drugs. The physicochemical properties of synthesized hybrid nanocomposites such as CS-GO, CS-CuO, [...] Read more.

This study deals with the facile synthesis of a single-pot chemical technique for chitosan–curcumin (CUR)-based hybrid nanocomposites with nanostructured graphene oxide (GO) and copper oxide (CuO) as the antibacterial and cytotoxic drugs. The physicochemical properties of synthesized hybrid nanocomposites such as CS-GO, CS-CuO, CS-CUR-GO, and CS-CUR-GO/CuO were confirmed with various advanced tools. Moreover, the in vitro drug release profile of the CS-CUR-GO/CuO nanocomposite exhibited sustained and controlled release during different time intervals. Also, the antibacterial activity of the CS-CUR-GO/CuO hybrid nanocomposite presented the maximum bactericidal effect against Staphylococcus aureus and Escherichia coli pathogens. The hybrid nanocomposites revealed improved cytotoxicity behaviour against cultured mouse fibroblast cells (L929) via cell adhesion, DNA damage, and proliferation. Thus, the chitosan-based hybrid nanocomposites offer rich surface area, biocompatibility, high oxidative stress, and bacterial cell disruption functionalities as a potential candidate for antibacterial and cytotoxicity applications. Full article

(This article belongs to the Special Issue Essential Oil of the Plants: Chemical Composition, Antimicrobial Activity, and Biological Applications)

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27 pages, 871 KiB

Open AccessReview

Quorum Quenching Approaches against Bacterial-Biofilm-Induced Antibiotic Resistance

by Patrizia D’Aquila, Elisabetta De Rose, Giada Sena, Angelo Scorza, Bonaventura Cretella, Giuseppe Passarino and Dina Bellizzi

Antibiotics 2024, 13(7), 619; https://doi.org/10.3390/antibiotics13070619 - 3 Jul 2024

Viewed by 362

Abstract

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising [...] Read more.

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising strategy pursued in recent years focuses on controlling and preventing this formation by targeting and inhibiting the Quorum Sensing (QS) system, whose central role in biofilm has been extensively demonstrated. Therefore, the research and development of Quorum Quenching (QQ) compounds, which inhibit QS, has gradually attracted the attention of researchers and has become a new strategy for controlling harmful microorganisms. Among these, a number of both natural and synthetic compounds have been progressively identified as able to interrupt the intercellular communication within a microbial community and the adhesion to a surface, thus disintegrating mature/preformed biofilms. This review describes the role played by QS in the formation of bacterial biofilms and then focuses on the mechanisms of different natural and synthetic QS inhibitors (QSIs) exhibiting promising antibiofilm ability against Gram-positive and Gram-negative bacterial pathogens and on their applications as biocontrol strategies in various fields. Full article

(This article belongs to the Special Issue Molecular Mechanism of Antibiotic Resistance in Microbial Biofilms)

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13 pages, 1803 KiB

Open AccessArticle

Culex quinquefasciatus Mosquitoes Resist Acquisition of Methicillin-Resistant Staphylococcus aureus: Insights from Field and Laboratory Studies

by Waseema Arif, Gowdham Thangaraj, Pushpa Srinivasan, Srikanth Srirama and Panneer Devaraju

Antibiotics 2024, 13(7), 618; https://doi.org/10.3390/antibiotics13070618 - 2 Jul 2024

Viewed by 447

Abstract

The emergence of antimicrobial resistance (AMR) in pathogens and their spillover into the environment have become a global public health menace. Insects can acquire these pathogens from the environment and would serve as mechanical and biological vectors. The current study assessed the ability [...] Read more.

The emergence of antimicrobial resistance (AMR) in pathogens and their spillover into the environment have become a global public health menace. Insects can acquire these pathogens from the environment and would serve as mechanical and biological vectors. The current study assessed the ability of Culex quinquefasciatus mosquitoes to acquire methicillin-resistant Staphylococcus aureus (MRSA) through the exposure of the mosquitoes to the pathogen via rearing water, blood feed, or a feeding membrane under laboratory conditions. In addition, mosquito immatures collected from their habitat in the vicinity of hospitals, veterinary dispensaries, and butcher shops at 15 study sites in Puducherry were screened for MRSA infection. All samples were subjected to the culture-based isolation of S. aureus from the surface and homogenate. The presence of the S. aureus-specific nuc gene and the genes that confer resistance to methicillin (mecA and mecC) were screened using PCR tests. MRSA was not evident either on the external surface or in the homogenate of the mosquitoes emerging from the larvae reared in the MRSA-spiked water or those fed with MRSA through blood or smeared membranes. Furthermore, the presence of MRSA was not evident in any of the field-caught mosquitoes. Hence, we conclude that C. quinquefasciatus mosquitoes are impervious to MRSA colonization. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)

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11 pages, 3368 KiB

Open AccessCommunication

Comparative Antimicrobial Resistance and Prevalence of Methicillin Resistance in Coagulase-Positive Staphylococci from Conventional and Organic Dairy Farms in South Korea

by Therese Ariane N. Neri, Hyunjung Park, Sujin Kang, Seung Hee Baek and In Sik Nam

Antibiotics 2024, 13(7), 617; https://doi.org/10.3390/antibiotics13070617 - 2 Jul 2024

Viewed by 504

Abstract

Bovine mastitis (BM) has caused huge economic and financial losses in the dairy industry worldwide, with Staphylococcus aureus as one of its major pathogens. BM treatment still relies on antibiotics and its extensive use often generates methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. [...] Read more.

Bovine mastitis (BM) has caused huge economic and financial losses in the dairy industry worldwide, with Staphylococcus aureus as one of its major pathogens. BM treatment still relies on antibiotics and its extensive use often generates methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. aureus (MuRSA). This study compared the antimicrobial resistance trend in coagulase-positive Stapholococci (CoPS) isolated from BM milk in conventional and organic dairy farms and checked prevalence of MRSA and MuRSA. A total of 163 presumptive Staphylococci were isolated, wherein 11 out of 74 from 4 conventional farms (CF1, CF2, CF3, CF4) and 17 out of 89 from 3 organic farms (OF1, OF2, OF3) exhibited coagulase activity. Multiplex-PCR amplification confirmed at least one coagulase-positive isolate from CF1, CF2, CF3, CF4, and OF1 as S. aureus, denoted by the presence of the nuc gene. Three isolates from CF2 contained the mecA gene, indicating MRSA prevalence, while the MuRSA gene marker, mupA, was not detected in any of the isolates. Antimicrobial testing showed that conventional farm isolates were more resistant to antibiotics, especially ampicillin and tetracycline. This suggests a risk of developing multidrug resistance in dairy farms if antibiotic use is not properly and strictly monitored and regulated. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Food Animals and Human — a One Health Perspective)

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13 pages, 911 KiB

Open AccessArticle

Efficacy and Safety of Ceftazidime–Avibactam Alone versus Ceftazidime–Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort

by Marco Fois, Andrea De Vito, Francesca Cherchi, Elena Ricci, Michela Pontolillo, Katia Falasca, Nicolò Corti, Agnese Comelli, Alessandra Bandera, Chiara Molteni, Stefania Piconi, Francesca Colucci, Paolo Maggi, Vincenzo Boscia, Aakash Fugooah, Sara Benedetti, Giuseppe Vittorio De Socio, Paolo Bonfanti and Giordano Madeddu

Antibiotics 2024, 13(7), 616; https://doi.org/10.3390/antibiotics13070616 - 2 Jul 2024

Viewed by 490

Abstract

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We [...] Read more.

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting. Full article

(This article belongs to the Special Issue Successful Antimicrobial Stewardship Approaches to Address Nosocomial Infections)

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22 pages, 6146 KiB

Open AccessArticle

The Antimicrobial Peptide Capitellacin: Chemical Synthesis of Analogues to Probe the Role of Disulphide Bridges and Their Replacement with Vinyl Sulphides

by Oscar A. Shepperson, Paul W. R. Harris, Margaret A. Brimble and Alan J. Cameron

Antibiotics 2024, 13(7), 615; https://doi.org/10.3390/antibiotics13070615 - 2 Jul 2024

Viewed by 399

Abstract

Capitellacin (1) is a 20-residue antimicrobial β-hairpin, produced by the marine polychaeta (segmented worms) Capitella teletai. Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin’s structure–activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library [...] Read more.

Capitellacin (1) is a 20-residue antimicrobial β-hairpin, produced by the marine polychaeta (segmented worms) Capitella teletai. Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin’s structure–activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library of capitellacin analogues was prepared to systematically study the influence of the two disulphide bridges on its structure and activity, and their replacement with a vinyl sulphide as a potential bioisostere. Upon studying the resulting peptides’ antimicrobial activity and secondary structure, the most terminal disulphide emerged as the most critical element for maintaining both bioactivity and the secondary structure, properties which were demonstrated to be closely interlinked. The removal of the innermost disulphide bridge or disulphide replacement with a vinyl sulphide emerged as strategies with which to tune the activity spectrum, producing selectivity towards E. coli. Additionally, an enantiomeric d-capitellacin analogue revealed mechanistic insights, suggesting that chirality may be an inherent property of capitellacin’s bacterial membrane target, or that a hitherto unknown secondary mechanism of action may exist. Additionally, we propose the Alloc protecting group as a more appropriate alternative to the common Dde group during fast-flow Fmoc-SPPS, in particular for short-chain diamino acids. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Edition)

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15 pages, 4406 KiB

Open AccessArticle

Treating Infected Non-Healing Venous Leg Ulcers with Medical-Grade Honey: A Prospective Case Series

by Georgios E. Papanikolaou, Georgios Gousios, Niels A. J. Cremers and Linsey J. F. Peters

Antibiotics 2024, 13(7), 614; https://doi.org/10.3390/antibiotics13070614 - 2 Jul 2024

Viewed by 677

Abstract

Venous leg ulcers (VLUs) are hard-to-heal wounds and are prone to microbial colonization. Innovative and improved therapies are thus required to resolve local infection and enhance the wound healing process. The objective of this study was to evaluate the effectiveness of medical-grade honey [...] Read more.

Venous leg ulcers (VLUs) are hard-to-heal wounds and are prone to microbial colonization. Innovative and improved therapies are thus required to resolve local infection and enhance the wound healing process. The objective of this study was to evaluate the effectiveness of medical-grade honey (MGH) for the treatment of clinically infected and non-healing VLUs. This prospective case series included nine patients with an average age of 83.4 years (range: 75–91 years) with a total of eleven VLUs, previously ineffectively treated with various products. Major risk factors for the appearance of VLUs were chronic venous insufficiency, advanced age, multiple comorbidities (particularly cardiovascular diseases), and impaired mobility. All wounds presented with local signs of infection. Upon presentation, treatment was commenced with a range of MGH-based products (L-Mesitran^®). Clinical signs of infection were eliminated by MGH after 2.2 weeks on average (range: 1–4 weeks), and wounds were completely healed after 7 weeks on average (range: 3–18 weeks). No further complications or recurrences were observed. MGH has a broad-spectrum antimicrobial activity and promotes rapid healing, thus improving patients’ quality of life. Moreover, MGH-based products are safe, easy to use, cost-effective, and can effectively treat VLUs alone or in combination with standard-of-care therapies. Full article

(This article belongs to the Special Issue Honey: A Sweet Solution to the Growing Problem of Antimicrobial Resistance, 2nd Volume)

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19 pages, 6392 KiB

Open AccessArticle

Unveiling the Antimicrobial, Anti-Biofilm, and Anti-Quorum-Sensing Potential of Paederia foetida Linn. Leaf Extract against Staphylococcus aureus: An Integrated In Vitro–In Silico Investigation

by Sirijan Santajit, Witawat Tunyong, Dararat Horpet, Asma Binmut, Thida Kong-Ngoen, Churaibhon Wisessaowapak, Techit Thavorasak, Pornpan Pumirat and Nitaya Indrawattana

Antibiotics 2024, 13(7), 613; https://doi.org/10.3390/antibiotics13070613 - 1 Jul 2024

Viewed by 650

Abstract

Antimicrobial resistance poses a global health threat, with Staphylococcus aureus emerging as a notorious pathogen capable of forming stubborn biofilms and regulating virulence through quorum sensing (QS). In the quest for novel therapeutic strategies, this groundbreaking study unveils the therapeutic potential of Paederia [...] Read more.

Antimicrobial resistance poses a global health threat, with Staphylococcus aureus emerging as a notorious pathogen capable of forming stubborn biofilms and regulating virulence through quorum sensing (QS). In the quest for novel therapeutic strategies, this groundbreaking study unveils the therapeutic potential of Paederia foetida Linn., an Asian medicinal plant containing various bioactive compounds, contributing to its antimicrobial activities, in the battle against S. aureus. Through a comprehensive approach, we investigated the effect of ethanolic P. foetida leaf extract on S. aureus biofilms, QS, and antimicrobial activity. The extract exhibited promising inhibitory effects against S. aureus including the biofilm-forming strain and MRSA. Real-time PCR analysis revealed significant downregulation of key virulence and biofilm genes, suggesting interference with QS. Biofilm assays quantified the extract’s ability to disrupt and prevent biofilm formation. LC-MS/MS analysis identified quercetin and kaempferol glycosides as potential bioactive constituents, while molecular docking studies explored their binding to the QS transcriptional regulator SarA. Computational ADMET predictions highlighted favorable intestinal absorption but potential P-glycoprotein interactions limiting oral bioavailability. While promising anti-virulence effects were demonstrated, the high molecular weights and excessive hydrogen bond donors/acceptors of the flavonoid glycosides raise concerns regarding drug-likeness and permeability. This integrated study offers valuable insights for developing novel anti-virulence strategies to combat antimicrobial resistance. Full article

(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products, 2nd Edition)

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11 pages, 2383 KiB

Open AccessArticle

Therapeutic Potential of Mangosteen Pericarp Extract-Loaded Liposomes against Superficial Skin Infection Caused by Staphylococcus pseudintermedius in a Murine Model

by Seong-Yeop Kim, Seong-Yong Park, Jung-Hwa Lee, Nayeong Kim, Ha-Na Oh, So-Young Yoo, Dae-Sung Lee and Je-Chul Lee

Antibiotics 2024, 13(7), 612; https://doi.org/10.3390/antibiotics13070612 - 1 Jul 2024

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Abstract

α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model [...] Read more.

α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model of superficial skin infection caused by S. pseudintermedius. α-MG-rich extract was purified from mangosteen pericarp and then complexed with γ-cyclodextrin (γ-CD), forming the inclusion complexes. Nanoliposomes containing MPE and γ-CD complexes were prepared by adding lecithin and casein. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of MPE-loaded liposomes were determined using agar dilution and broth microdilution methods. The therapeutic potential of MPE-loaded liposomes was evaluated in vivo on tape-stripped skin lesions infected with S. pseudintermedius. Purified MPE and MPE-loaded liposomes contained 402.43 mg/g and 18.18 mg/g α-MG, respectively. MPE-loaded liposomes showed antibacterial activity against clinical Staphylococcus isolates in vitro but did not show antibacterial activity against Gram-negative bacterial isolates. MPE-loaded liposomes demonstrated consistent MICs and MBCs against Staphylococcus isolates. These liposomes significantly reduced bacterial numbers and lesional sizes in a superficial skin infection model. Moreover, they reconstructed the epidermal barrier in skin lesions. The therapeutic concentrations of MPE-loaded liposomes did not induce cytotoxicity in canine progenitor epidermal keratinocyte cells. In conclusion, MPE-loaded liposomes hold promise for the development of a prospective topical formulation to treat superficial pyoderma in companion animals. Full article

(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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Antibiotics, Volume 13, Issue 7 (July 2024) – 70 articles

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