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Antibiotics, Volume 12, Issue 6 (June 2023) – 136 articles

Cover Story (view full-size image): As part of our search for new antimicrobials and antibiotic enhancers, a series of naphthyl- and biphenyl-substituted polyamine conjugates have been synthesized. The structurally diverse library of compounds incorporated variation in the capping end groups and in the length of polyamine cores. Longer chain variants containing naphthyl capping groups exhibited more pronounced intrinsic antimicrobial properties against methicillin-resistant Staphylococcus aureus and the fungus Cryptococcus neoformans. Closer mechanistic study of one of these analogues identified it as a bactericide. In contrast to the previously reported diarylacyl-substituted polyamines, several examples in the current set were able to enhance the antibiotic action of doxycycline and/or erythromycin towards the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli. View this paper
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17 pages, 703 KiB  
Review
The Epidemiology of Animal-Associated Methicillin-Resistant Staphylococcus aureus
by Martyna Kasela, Mateusz Ossowski, Ewelina Dzikoń, Katarzyna Ignatiuk, Łukasz Wlazło and Anna Malm
Antibiotics 2023, 12(6), 1079; https://doi.org/10.3390/antibiotics12061079 - 20 Jun 2023
Cited by 5 | Viewed by 2255
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) remains an important etiological factor of human and animal infectious diseases, causing significant economic losses not only in human healthcare but also in the large-scale farming sector. The constantly changing epidemiology of MRSA observed globally affects animal welfare and [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) remains an important etiological factor of human and animal infectious diseases, causing significant economic losses not only in human healthcare but also in the large-scale farming sector. The constantly changing epidemiology of MRSA observed globally affects animal welfare and raises concerns for public health. High MRSA colonization rates in livestock raise questions about the meaning of reservoirs and possible transmission pathways, while the prevalence of MRSA colonization and infection rates among companion animals vary and might affect human health in multiple ways. We present the main findings concerning the circulation of animal-associated MRSA (AA-MRSA) in the environment and factors influencing the direction, mechanisms, and routes of its transmission. Studies have shown it that S. aureus is a multi-host bacterial pathogen; however, its adaptation mechanisms enabling it to colonize and infect both animal and human hosts are still rarely discussed. Finally, we elaborate on the most successful strategies and programs applied limiting the circulation of AA-MRSA among animals and humans. Although MRSA strains colonizing animals rarely infect humans, they undergo host-adaptive evolution enabling them to spread and persist in human populations. Full article
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10 pages, 1996 KiB  
Article
Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant Pseudomonas aeruginosa in an In Vitro Cystic Fibrosis Sputum Model
by Vaughn D. Craddock, Evan L. Steere, Hannah Harman and Nicholas S. Britt
Antibiotics 2023, 12(6), 1078; https://doi.org/10.3390/antibiotics12061078 - 20 Jun 2023
Viewed by 1467
Abstract
Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those [...] Read more.
Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed (p = 0.033) and Cmin (p = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin (p = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF. Full article
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12 pages, 1556 KiB  
Communication
The Use of Phage Cocktail and Various Antibacterial Agents in Combination to Prevent the Emergence of Phage Resistance
by Hoang Minh Duc, Yu Zhang, Son Minh Hoang, Yoshimitsu Masuda, Ken-Ichi Honjoh and Takahisa Miyamoto
Antibiotics 2023, 12(6), 1077; https://doi.org/10.3390/antibiotics12061077 - 20 Jun 2023
Cited by 4 | Viewed by 2138
Abstract
Bacterial food poisoning cases due to Salmonella and E. coli O157:H7 have been linked with the consumption of a variety of food products, threatening public health around the world. This study describes the combined effects of a phage cocktail (STG2, SEG5, and PS5), [...] Read more.
Bacterial food poisoning cases due to Salmonella and E. coli O157:H7 have been linked with the consumption of a variety of food products, threatening public health around the world. This study describes the combined effects of a phage cocktail (STG2, SEG5, and PS5), EDTA, nisin, and polylysine against the bacterial cocktail consisting of S. typhimurium, S. enteritidis, and E. coli O157:H7. Overall, phage cocktail (alone or in combination with nisin or/and polylysine) not only showed great antibacterial effects against bacterial cocktail at different temperatures (4 °C, 24 °C, and 37 °C), but also totally inhibited the emergence of phage resistance during the incubation period. These results suggest that the combination of phages with nisin or/and polylysine has great potential to simultaneously control S. typhimurium, S. enteritidis, and E. coli O157:H7. Full article
(This article belongs to the Special Issue Bacteriophages: Biology, Therapy and Application)
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16 pages, 2728 KiB  
Article
Ether Derivatives of Naringenin and Their Oximes as Factors Modulating Bacterial Adhesion
by Anna Duda-Madej, Joanna Kozłowska, Dagmara Baczyńska and Paweł Krzyżek
Antibiotics 2023, 12(6), 1076; https://doi.org/10.3390/antibiotics12061076 - 19 Jun 2023
Cited by 1 | Viewed by 1494
Abstract
Because of the close connection between adhesion and many vital cellular functions, the search for new compounds modulating the adhesion of bacteria belonging to the intestinal microbiota is a great challenge and a clinical need. Based on our previous studies, we discovered that [...] Read more.
Because of the close connection between adhesion and many vital cellular functions, the search for new compounds modulating the adhesion of bacteria belonging to the intestinal microbiota is a great challenge and a clinical need. Based on our previous studies, we discovered that O-lkyl naringenin derivatives and their oximes exhibit antimicrobial activity against antibiotic-resistant pathogens. The current study was aimed at determining the modulatory effect of these compounds on the adhesion of selected representatives of the intestinal microbiota: Escherichia coli, a commensal representative of the intestinal microbiota, and Enterococcus faecalis, a bacterium that naturally colonizes the intestines but has disease-promoting potential. To better reflect the variety of real-life scenarios, we performed these studies using two different intestinal cell lines: the physiologically functioning (“healthy”) 3T3-L1 cell line and the disease-mimicking, cancerous HT-29 line. The study was performed in vitro under static and microfluidic conditions generated by the Bioflux system. We detected the modulatory effect of the tested O-alkyl naringenin derivatives on bacterial adhesion, which was dependent on the cell line studied and was more significant for E. coli than for E. faecalis. In addition, it was noticed that this activity was affected by the concentration of the tested compound and its structure (length of the carbon chain). In summary, O-alkyl naringenin derivatives and their oximes possess a promising modulatory effect on the adhesion of selected representatives of the intestinal microbiota. Full article
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19 pages, 1182 KiB  
Review
CRISPR-Cas9 System: A Prospective Pathway toward Combatting Antibiotic Resistance
by Muhammad Uzair Javed, Muhammad Tahir Hayat, Hamid Mukhtar and Kalman Imre
Antibiotics 2023, 12(6), 1075; https://doi.org/10.3390/antibiotics12061075 - 19 Jun 2023
Cited by 4 | Viewed by 3094
Abstract
Antibiotic resistance is rising to dangerously high levels throughout the world. To cope with this problem, scientists are working on CRISPR-based research so that antibiotic-resistant bacteria can be killed and attacked almost as quickly as antibiotic-sensitive bacteria. Nuclease activity is found in Cas9, [...] Read more.
Antibiotic resistance is rising to dangerously high levels throughout the world. To cope with this problem, scientists are working on CRISPR-based research so that antibiotic-resistant bacteria can be killed and attacked almost as quickly as antibiotic-sensitive bacteria. Nuclease activity is found in Cas9, which can be programmed with a specific target sequence. This mechanism will only attack pathogens in the microbiota while preserving commensal bacteria. This article portrays the delivery methods used in the CRISPR-Cas system, which are both viral and non-viral, along with its implications and challenges, such as microbial dysbiosis, off-target effects, and failure to counteract intracellular infections. CRISPR-based systems have a lot of applications, such as correcting mutations, developing diagnostics for infectious diseases, improving crops productions, improving breeding techniques, etc. In the future, CRISPR-based systems will revolutionize the world by curing diseases, improving agriculture, and repairing genetic disorders. Though all the drawbacks of the technology, CRISPR carries great potential; thus, the modification and consideration of some aspects could result in a mind-blowing technique to attain all the applications listed and present a game-changing potential. Full article
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13 pages, 334 KiB  
Perspective
Insights on Current Strategies to Decolonize the Gut from Multidrug-Resistant Bacteria: Pros and Cons
by Natalia Roson-Calero, Clara Ballesté-Delpierre, Javier Fernández and Jordi Vila
Antibiotics 2023, 12(6), 1074; https://doi.org/10.3390/antibiotics12061074 - 19 Jun 2023
Cited by 5 | Viewed by 2113
Abstract
In the last decades, we have witnessed a steady increase in infections caused by multidrug-resistant (MDR) bacteria. These infections are associated with higher morbidity and mortality. Several interventions should be taken to reduce the emergence and spread of MDR bacteria. The eradication of [...] Read more.
In the last decades, we have witnessed a steady increase in infections caused by multidrug-resistant (MDR) bacteria. These infections are associated with higher morbidity and mortality. Several interventions should be taken to reduce the emergence and spread of MDR bacteria. The eradication of resistant pathogens colonizing specific human body sites that would likely cause further infection in other sites is one of the most conventional strategies. The objective of this narrative mini-review is to compile and discuss different strategies for the eradication of MDR bacteria from gut microbiota. Here, we analyse the prevalence of MDR bacteria in the community and the hospital and the clinical impact of gut microbiota colonisation with MDR bacteria. Then, several strategies to eliminate MDR bacteria from gut microbiota are described and include: (i) selective decontamination of the digestive tract (SDD) using a cocktail of antibiotics; (ii) the use of pre and probiotics; (iii) fecal microbiota transplantation; (iv) the use of specific phages; (v) engineered CRISPR-Cas Systems. This review intends to provide a state-of-the-art of the most relevant strategies to eradicate MDR bacteria from gut microbiota currently being investigated. Full article
17 pages, 1686 KiB  
Review
Treatment of Periodontal Infections, the Possible Role of Hydrogels as Antibiotic Drug-Delivery Systems
by Adelaide Mensah, Aoife M. Rodgers, Eneko Larrañeta, Lyndsey McMullan, Murtaza Tambuwala, John F. Callan and Aaron J. Courtenay
Antibiotics 2023, 12(6), 1073; https://doi.org/10.3390/antibiotics12061073 - 19 Jun 2023
Cited by 4 | Viewed by 2553
Abstract
With the advancement of biomedical research into antimicrobial treatments for various diseases, the source and delivery of antibiotics have attracted attention. In periodontal diseases, antibiotics are integral in positive treatment outcomes; however, the use of antibiotics is with caution as the potential for [...] Read more.
With the advancement of biomedical research into antimicrobial treatments for various diseases, the source and delivery of antibiotics have attracted attention. In periodontal diseases, antibiotics are integral in positive treatment outcomes; however, the use of antibiotics is with caution as the potential for the emergence of resistant strains is of concern. Over the years, conventional routes of drug administration have been proven to be effective for the treatment of PD, yet the problem of antibiotic resistance to conventional therapies continues to remain a setback in future treatments. Hydrogels fabricated from natural and synthetic polymers have been extensively applied in biomedical sciences for the delivery of potent biological compounds. These polymeric materials either have intrinsic antibacterial properties or serve as good carriers for the delivery of antibacterial agents. The biocompatibility, low toxicity and biodegradability of some hydrogels have favoured their consideration as prospective carriers for antibacterial drug delivery in PD. This article reviews PD and its antibiotic treatment options, the role of bacteria in PD and the potential of hydrogels as antibacterial agents and for antibiotic drug delivery in PD. Finally, potential challenges and future directions of hydrogels for use in PD treatment and diagnosis are also highlighted. Full article
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21 pages, 691 KiB  
Review
Use of Newer and Repurposed Antibiotics against Gram-Negative Bacteria in Neonates
by Angeliki Kontou, Maria Kourti, Elias Iosifidis, Kosmas Sarafidis and Emmanuel Roilides
Antibiotics 2023, 12(6), 1072; https://doi.org/10.3390/antibiotics12061072 - 19 Jun 2023
Cited by 5 | Viewed by 2124
Abstract
Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and [...] Read more.
Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem/cilastatin–relebactam), although old antibiotics such as colistin, tigecycline, and fosfomycin are also encompassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarce, with few clinical trials enrolling neonates for the evaluation of the efficacy, safety, and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population. Full article
(This article belongs to the Special Issue Antibiotics and Neonatal Sepsis: Challenges and Opportunities)
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12 pages, 782 KiB  
Article
Effect of Phenylalanine–Arginine Beta-Naphthylamide on the Values of Minimum Inhibitory Concentration of Quinolones and Aminoglycosides in Clinical Isolates of Acinetobacter baumannii
by Stefany Plasencia-Rebata, Saul Levy-Blitchtein, Juana del Valle-Mendoza, Wilmer Silva-Caso, Isaac Peña-Tuesta, William Vicente Taboada, Fernando Barreda Bolaños and Miguel Angel Aguilar-Luis
Antibiotics 2023, 12(6), 1071; https://doi.org/10.3390/antibiotics12061071 - 18 Jun 2023
Cited by 1 | Viewed by 2075
Abstract
(1) Background: Acinetobacter baumannii has become the most important pathogen responsible for nosocomial infections in health systems. It expresses several resistance mechanisms, including the production of β-lactamases, changes in the cell membrane, and the expression of efflux pumps. (2) Methods: A. baumannii was [...] Read more.
(1) Background: Acinetobacter baumannii has become the most important pathogen responsible for nosocomial infections in health systems. It expresses several resistance mechanisms, including the production of β-lactamases, changes in the cell membrane, and the expression of efflux pumps. (2) Methods: A. baumannii was detected by PCR amplification of the blaOXA-51-like gene. Antimicrobial susceptibility to fluoroquinolones and aminoglycosides was assessed using the broth microdilution technique according to 2018 CLSI guidelines. Efflux pump system activity was assessed by the addition of a phenylalanine–arginine beta-naphthylamide (PAβN) inhibitor. (3) Results: A total of nineteen A. baumannii clinical isolates were included in the study. In an overall analysis, in the presence of PAβN, amikacin susceptibility rates changed from 84.2% to 100%; regarding tobramycin, they changed from 68.4% to 84.2%; for nalidixic acid, they changed from 73.7% to 79.0%; as per ciprofloxacin, they changed from 68.4% to 73.7%; and, for levofloxacin, they stayed as 79.0% in both groups. (4) Conclusions: The addition of PAβN demonstrated a decrease in the rates of resistance to antimicrobials from the family of quinolones and aminoglycosides. Efflux pumps play an important role in the emergence of multidrug-resistant A. baumannii strains, and their inhibition may be useful as adjunctive therapy against this pathogen. Full article
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12 pages, 1585 KiB  
Article
Insight into the Clonal Lineage and Antimicrobial Resistance of Staphylococcus aureus from Vascular Access Infections before and during the COVID-19 Pandemic
by Chih-Chen Kao, Chi-Hsiang Lai, Min-Yi Wong, Tsung-Yu Huang, Yuan-Hsi Tseng, Chu-Hsueh Lu, Chien-Chao Lin and Yao-Kuang Huang
Antibiotics 2023, 12(6), 1070; https://doi.org/10.3390/antibiotics12061070 - 18 Jun 2023
Viewed by 1163
Abstract
Patients receiving hemodialysis are at risk of vascular access infections (VAIs) and are particularly vulnerable to the opportunistic pathogen Staphylococcus aureus. Hemodialysis patients were also at increased risk of infection during the COVID-19 pandemic. Therefore, this study determined the change in the [...] Read more.
Patients receiving hemodialysis are at risk of vascular access infections (VAIs) and are particularly vulnerable to the opportunistic pathogen Staphylococcus aureus. Hemodialysis patients were also at increased risk of infection during the COVID-19 pandemic. Therefore, this study determined the change in the molecular and antibiotic resistance profiles of S. aureus isolates from VAIs during the pandemic compared with before. A total of 102 S. aureus isolates were collected from VAIs between November 2013 and December 2021. Before the pandemic, 69 isolates were collected, 58%, 39.1%, and 2.9% from arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs), respectively. The prevalence of AVG and TCC isolates changed to 39.4% and 60.6%, respectively, of the 33 isolates during the pandemic. Sequence type (ST)59 was the predominant clone in TCC methicillin-resistant S. aureus (MRSA) and AVG-MRSA before the pandemic, whereas the predominant clone was ST8 in AVG-MRSA during the pandemic. ST59 carrying the ermB gene was resistant to clindamycin and erythromycin. By contrast, ST8 carrying the msrA gene was exclusively resistant to erythromycin. The ST distribution for different VAIs changed from before to during the pandemic. The change in antibiotic resistance rate for different VAIs was closely related to the distribution of specific STs. Full article
(This article belongs to the Special Issue Rational Use of Antibiotics in Bloodstream Infection)
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19 pages, 1312 KiB  
Article
Staphylococcus aureus Small-Colony Variants from Airways of Adult Cystic Fibrosis Patients as Precursors of Adaptive Antibiotic-Resistant Mutations
by Guillaume Millette, David Lalonde Séguin, Charles Isabelle, Suzanne Chamberland, Jean-François Lucier, Sébastien Rodrigue, André M. Cantin and François Malouin
Antibiotics 2023, 12(6), 1069; https://doi.org/10.3390/antibiotics12061069 - 17 Jun 2023
Cited by 6 | Viewed by 1520
Abstract
Prototypic Staphylococcus aureus and their small-colony variants (SCVs) are predominant in cystic fibrosis (CF), but the interdependence of these phenotypes is poorly understood. We characterized S. aureus isolates from adult CF patients over several years. Of 18 S. aureus-positive patients (58%), 13 [...] Read more.
Prototypic Staphylococcus aureus and their small-colony variants (SCVs) are predominant in cystic fibrosis (CF), but the interdependence of these phenotypes is poorly understood. We characterized S. aureus isolates from adult CF patients over several years. Of 18 S. aureus-positive patients (58%), 13 (72%) were positive for SCVs. Characterization included genotyping, SCCmec types, auxotrophy, biofilm production, antibiotic susceptibilities and tolerance, and resistance acquisition rates. Whole-genome sequencing revealed that several patients were colonized with prototypical and SCV-related clones. Some clonal pairs showed acquisition of aminoglycoside resistance that was not explained by aminoglycoside-modifying enzymes, suggesting a mutation-based process. The characteristics of SCVs that could play a role in resistance acquisition were thus investigated further. For instance, SCV isolates produced more biofilm (p < 0.05) and showed a higher survival rate upon exposure to ciprofloxacin and vancomycin compared to their prototypic associated clones. SCVs also developed spontaneous rifampicin resistance mutations at a higher frequency. Accordingly, a laboratory-derived SCV (ΔhemB) acquired resistance to ciprofloxacin and gentamicin faster than its parent counterpart after serial passages in the presence of sub-inhibitory concentrations of antibiotics. These results suggest a role for SCVs in the establishment of persistent antibiotic-resistant clones in adult CF patients. Full article
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33 pages, 1951 KiB  
Review
Gut Microbiota and Antibiotic Treatments for the Main Non-Oncologic Hepato-Biliary-Pancreatic Disorders
by Federica Di Vincenzo, Alberto Nicoletti, Marcantonio Negri, Federica Vitale, Lorenzo Zileri Dal Verme, Antonio Gasbarrini, Francesca Romana Ponziani and Lucia Cerrito
Antibiotics 2023, 12(6), 1068; https://doi.org/10.3390/antibiotics12061068 - 17 Jun 2023
Cited by 3 | Viewed by 2051
Abstract
The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a [...] Read more.
The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a wide range of diseases, from non-neoplastic ones to tumorigenesis. The continuous bidirectional metabolic communication between gut and hepato-pancreatic district, through bile ducts and portal vein, leads to a continuous interaction with translocated bacteria and their products. Chronic liver disease and pancreatic disorders can lead to reduced intestinal motility, decreased bile acid synthesis and intestinal immune dysfunction, determining a compositional and functional imbalance in gut microbiota (dysbiosis), with potentially harmful consequences on the host’s health. The modulation of the gut microbiota by antibiotics represents a pioneering challenge with striking future therapeutic opportunities, even in non-infectious diseases. In this setting, antibiotics are aimed at harmonizing gut microbial function and, sometimes, composition. A more targeted and specific approach should be the goal to pursue in the future, tailoring the treatment according to the type of microbiota modulation to be achieved and using combined strategies. Full article
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12 pages, 1306 KiB  
Review
Aurachins, Bacterial Antibiotics Interfering with Electron Transport Processes
by Sebastian Kruth and Markus Nett
Antibiotics 2023, 12(6), 1067; https://doi.org/10.3390/antibiotics12061067 - 17 Jun 2023
Cited by 1 | Viewed by 1895
Abstract
Aurachins are farnesylated quinolone alkaloids of bacterial origin and excellent inhibitors of the respiratory chain in pro- and eukaryotes. Therefore, they have become important tool compounds for the investigation of electron transport processes and they also serve as lead structures for the development [...] Read more.
Aurachins are farnesylated quinolone alkaloids of bacterial origin and excellent inhibitors of the respiratory chain in pro- and eukaryotes. Therefore, they have become important tool compounds for the investigation of electron transport processes and they also serve as lead structures for the development of antibacterial and antiprotozoal drugs. Especially aurachin D proved to be a valuable starting point for structure-activity relationship studies. Aurachin D is a selective inhibitor of the cytochrome bd oxidase, which has received increasing attention as a target for the treatment of infectious diseases caused by mycobacteria. Moreover, aurachin D possesses remarkable activities against Leishmania donovani, the causative agent of leishmaniasis. Aurachins are naturally produced by myxobacteria of the genus Stigmatella as well as by some Streptomyces and Rhodococcus strains. The recombinant production of these antibiotics turned out to be challenging due to their complex biosynthesis and their inherent toxicity. Recently, the biotechnological production of aurachin D was established in E. coli with a titer which is higher than previously reported from natural producer organisms. Full article
(This article belongs to the Topic Antimicrobial Agents and Nanomaterials)
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17 pages, 6090 KiB  
Article
Using Targeted Nano-Antibiotics to Improve Antibiotic Efficacy against Staphylococcus aureus Infections
by Hung Le, Emmanuelle Dé, Didier Le Cerf and Carole Karakasyan
Antibiotics 2023, 12(6), 1066; https://doi.org/10.3390/antibiotics12061066 - 16 Jun 2023
Cited by 1 | Viewed by 2278
Abstract
The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, [...] Read more.
The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, ciprofloxacin and levofloxacin, into polymer-based nano-carriers (nano-antibiotics), with the goal of increasing their local bioavailability at bacterial infection sites. The formulations were optimized to achieve maximal drug loading. The surfaces of nano-antibiotics were modified with anti-staphylococcal antibodies as ligand molecules to target S. aureus pathogens. The interaction of nano-antibiotics with the bacterial cells was investigated via fluorescent confocal microscopy. Conventional tests (MIC and MBC) were used to examine the antibacterial properties of nano-antibiotic formulations. Simultaneously, a bioluminescence assay model was employed, revealing the rapid and efficient assessment of the antibacterial potency of colloidal systems. In comparison to the free-form antibiotic, the targeted nano-antibiotic exhibited enhanced antimicrobial activity against both the planktonic and biofilm forms of S. aureus. Furthermore, our data suggested that the efficacy of a targeted nano-antibiotic treatment can be influenced by its antibiotic release profile. Full article
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26 pages, 20249 KiB  
Article
Design, Synthesis, and Structure–Activity Relationship Studies of New Quinone Derivatives as Antibacterial Agents
by Juan Andrades-Lagos, Javier Campanini-Salinas, América Pedreros-Riquelme, Jaime Mella, Duane Choquesillo-Lazarte, P. P. Zamora, Hernán Pessoa-Mahana, Ian Burbulis and David Vásquez-Velásquez
Antibiotics 2023, 12(6), 1065; https://doi.org/10.3390/antibiotics12061065 - 16 Jun 2023
Cited by 1 | Viewed by 2660
Abstract
Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so [...] Read more.
Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so it is necessary to develop new agents with novel chemical structures and/or mechanisms of action. In response to this, our group takes up the challenge of designing a new family of pyrimidoisoquinolinquinones displaying antimicrobial activities against multidrug-resistant Gram-positive bacteria. Accordingly, the objective of this study was to establish the necessary structural requirements to obtain compounds with high antibacterial activity, along with the parameters controlling antibacterial activity. To achieve this goal, we designed a family of compounds using different strategies for drug design. Forty structural candidates were synthesized and characterized, and antibacterial assays were carried out against high-priority bacterial pathogens. A variety of structural properties were modified, such as hydrophobicity and chain length of functional groups attached to specific carbon positions of the quinone core. All the synthesized compounds inhibited Gram-positive pathogens in concentrations ranging from 0.5 to 64 µg/mL. Two derivatives exhibited minimum inhibitory concentrations of 64 µg/mL against Klebsiella pneumoniae, while compound 28 demonstrated higher potency against MRSA than vancomycin. Full article
(This article belongs to the Special Issue Molecular Methods in Antibiotics Discovery)
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13 pages, 899 KiB  
Review
The Impact of COVID-19 Pandemic on ESBL-Producing Enterobacterales Infections: A Scoping Review
by Ha Thi Thao Mai and J. Luis Espinoza
Antibiotics 2023, 12(6), 1064; https://doi.org/10.3390/antibiotics12061064 - 16 Jun 2023
Cited by 5 | Viewed by 3329
Abstract
Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy [...] Read more.
Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy to spread and can cause difficult-to-treat infections. Here, we summarize the available evidence on the impact of the COVID-19 pandemic on infections caused by ESBL-PE. Using specific criteria and keywords, we searched PubMed, MEDLINE, and EMBASE for articles published up to 30 March 2023 on potential changes in the epidemiology of ESBL-E since the beginning of the COVID-19 pandemic. We identified eight studies that documented the impact of COVID-19 on ESBL-E. Five studies were focused on assessing the frequency of ESBL-PE in patient-derived specimens, and three studies investigated the epidemiological aspects of ESBL-PE infections in the context of the COVID-19 pandemic. Some of the studies that were focused on patient specimens reported a decrease in ESBL-PE positivity during the pandemic, whereas the three studies that involved patient data (1829 patients in total) reported a higher incidence of ESBL-PE infections in patients hospitalized for COVID-19 compared with those with other conditions. There are limited data on the real impact of the COVID-19 pandemic on the epidemiology of ESBL-PE infections; however, patient-derived data suggest that the pandemic has exacerbated the spread of these pathogens. Full article
(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)
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12 pages, 1168 KiB  
Article
Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against Klebsiella pneumoniae by MALDI-TOF MS
by Camila Mörschbächer Wilhelm, Everton Inamine, Andreza Francisco Martins and Afonso Luís Barth
Antibiotics 2023, 12(6), 1063; https://doi.org/10.3390/antibiotics12061063 - 16 Jun 2023
Cited by 1 | Viewed by 2163
Abstract
Introduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to [...] Read more.
Introduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to determine synergism in vitro in microbiology laboratories. Objective: To develop a method to determine the synergism of ATM and CZA by MALDI-TOF MS (SynMALDI). Method: Klebsiella pneumoniae (n = 22) isolates with blaNDM and/or blaKPC genes were tested. The time–kill curve assay was performed for four isolates (three positives for blaNDM and blaKPC and one positive for blaNDM only). For SynMALDI, each isolate was incubated for 3 h in 4 tubes containing brain–heart infusion broth with the following: (1) no antibiotic; (2) ATM at 64 mg/L; (3) CZA at 10/4 mg/L; and (4) ATM at 64 mg/L plus CZA at 10/4 mg/L. After incubation, the bacterial protein extract was analyzed by MALDI-TOF MS, and the relative growth (RG) was determined for each isolate, considering intensities of the peaks of the bacterium incubated with antibiotic (tubes 2, 3, and 4) to the same bacterium incubated without antibiotic (tube 1), as follows: RG = IntensityWith antibiotic/IntensityWithout antibiotic. The combination was determined as synergistic when there was an RG decrease of 0.3 in the antibiotic combination in relation to the RG of the most active antibiotic alone. Results: The combination of ATM plus CZA proved to be synergic by time–kill curve assay. All isolates tested with the SynMALDI method also presented synergism. Conclusions: Detection of synergism for ATM plus CZA combination can be determined by MALDI-TOF MS, providing fast results in order to improve patient treatment. Full article
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11 pages, 1380 KiB  
Article
Evidence of Antibiotic Resistance and Virulence Factors in Environmental Isolates of Vibrio Species
by Rajkishor Pandey, Simran Sharma and Kislay Kumar Sinha
Antibiotics 2023, 12(6), 1062; https://doi.org/10.3390/antibiotics12061062 - 16 Jun 2023
Cited by 2 | Viewed by 1961
Abstract
The outbreak of waterborne diseases such as cholera and non-cholera (vibriosis) is continuously increasing in the environment due to fecal and sewage discharge in water sources. Cholera and vibriosis are caused by different species of Vibrio genus which are responsible for acute diarrheal [...] Read more.
The outbreak of waterborne diseases such as cholera and non-cholera (vibriosis) is continuously increasing in the environment due to fecal and sewage discharge in water sources. Cholera and vibriosis are caused by different species of Vibrio genus which are responsible for acute diarrheal disease and soft tissue damage. Although incidences of cholera and vibriosis have been reported from the Vaishali district of Bihar, India, clinical or environmental strains have not been characterized in this region. Out of fifty environmental water samples, twelve different biochemical test results confirmed the presence of twenty Vibrio isolates. The isolates were found to belong to five different Vibrio species, namely V. proteolyticus, V. campbellii, V. nereis, V. cincinnatiensis, and V. harveyi. From the identified isolates, 65% and 45% isolates were found to be resistant to ampicillin and cephalexin, respectively. Additionally, two isolates were found to be resistant against six and four separately selected antibiotics. Furthermore, virulent hlyA and ompW genes were detected by PCR in two different isolates. Additionally, phage induction was also noticed in two different isolates which carry lysogenic phage in their genome. Overall, the results reported the identification of five different Vibrio species in environmental water samples. The isolates showed multiple antibacterial resistance, phage induction, and virulence gene profile in their genome. Full article
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21 pages, 1248 KiB  
Review
Antimicrobial Resistance and Clonal Lineages of Escherichia coli from Food-Producing Animals
by Adriana Silva, Vanessa Silva, José Eduardo Pereira, Luís Maltez, Gilberto Igrejas, Patrícia Valentão, Virgílio Falco and Patrícia Poeta
Antibiotics 2023, 12(6), 1061; https://doi.org/10.3390/antibiotics12061061 - 15 Jun 2023
Cited by 13 | Viewed by 3311
Abstract
Escherichia coli are one of the most important pathogenic bacteria readily found in the livestock and widely studied as an indicator that carries drug-resistant genes between humans, animals, and the environment. The use of antimicrobials in the food chain, particularly in food-producing animals, [...] Read more.
Escherichia coli are one of the most important pathogenic bacteria readily found in the livestock and widely studied as an indicator that carries drug-resistant genes between humans, animals, and the environment. The use of antimicrobials in the food chain, particularly in food-producing animals, is recognized as a significant contributor to the development and spread of antimicrobial resistance (AMR) and resistance genes can be transferred from the farm through the food-chain. The objective of this review is to highlight the background of the antimicrobials use in food-producing animals, more specifically, to study clonal lineages and the resistance profiles observed in E. coli, as well as in extended spectrum beta-lactamases (ESBL) producing E. coli, in a set of food-production animals with greater relevance in food consumption, such as pigs, poultry, cattle, fish farming and rabbits. Regarding the prevalence of ESBL-producing E. coli among farm animals, high-to-moderate prevalence was observed, and the highest resistance rates to tetracycline and ampicillin was detected in different farms in all geographic regions. Worldwide pandemic clones and high-risk zoonotic E. coli clones have been identified in most food-producing animals, and some of these clones are already disseminated in different niches, such as the environment and humans. A better understanding of the epidemiology of E. coli and ESBL-producing E. coli in livestock is urgently needed. Animal production is one of the major causes of the antibiotic resistance problem worldwide and a One Health approach is needed. Full article
(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)
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17 pages, 3074 KiB  
Article
Antimicrobial Resistance Profiles and Co-Existence of Multiple Antimicrobial Resistance Genes in mcr-Harbouring Colistin-Resistant Enterobacteriaceae Isolates Recovered from Poultry and Poultry Meats in Malaysia
by Md. Rezaul Karim, Zunita Zakaria, Latiffah Hassan, Nik Mohd Faiz and Nur Indah Ahmad
Antibiotics 2023, 12(6), 1060; https://doi.org/10.3390/antibiotics12061060 - 15 Jun 2023
Cited by 5 | Viewed by 2073
Abstract
The co-existence of the colistin resistance (mcr) gene with multiple drug-resistance genes has raised concerns about the possibility of the development of pan-drug-resistant bacteria that will complicate treatment. This study aimed to investigate the antibiotic resistance profiles and co-existence of antibiotic [...] Read more.
The co-existence of the colistin resistance (mcr) gene with multiple drug-resistance genes has raised concerns about the possibility of the development of pan-drug-resistant bacteria that will complicate treatment. This study aimed to investigate the antibiotic resistance profiles and co-existence of antibiotic resistance genes among the colistin-resistant Enterobacteriaceae isolates recovered from poultry and poultry meats. The antibiotic susceptibility to various classes of antibiotics was performed using the Kirby-Bauer disk diffusion method and selected antimicrobial resistance genes were detected using PCR in a total of 54 colistin-resistant Enterobacteriaceae isolates including Escherichia coli (E. coli) (n = 32), Salmonella spp. (n = 16) and Klebsiella pneumoniae (K. pneumoniae) (n = 6) isolates. Most of the isolates had multi-drug resistance (MDR), with antibiotic resistance against up to seven classes of antibiotics. All mcr-harbouring, colistin-resistant Enterobacteriaceae isolates showed this MDR (100%) phenotype. The mcr-1 harbouring E. coli isolates were co-harbouring multiple antibiotic resistance genes. The seven most commonly identified resistance genes (blaTEM, tetA, floR, aac-3-IV, aadA1, fosA, aac(6_)-lb) were detected in an mcr-1-harbouring E. coli isolate recovered from a cloacal swab. The mcr-5 harbouring Salmonella spp. isolate recovered from poultry meats was positive for blaTEM, tetA, floR, aac-3-IV, fosA and aac(6_)-lb genes. In conclusion, the colistin-resistant Enterobacteriaceae with mcr genes co-existing multiple clinically important antimicrobial resistance genes in poultry and poultry meats may cause potential future threats to infection treatment choices in humans and animals. Full article
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9 pages, 623 KiB  
Article
Whole Genome Sequencing and Phenotypic Analysis of Antibiotic Resistance in Filifactor alocis Isolates
by Rosa Romero-Martínez, Anushiravan Maher, Gerard Àlvarez, Rui Figueiredo, Rubén León and Alexandre Arredondo
Antibiotics 2023, 12(6), 1059; https://doi.org/10.3390/antibiotics12061059 - 15 Jun 2023
Cited by 1 | Viewed by 1401
Abstract
There is scarce knowledge regarding the antimicrobial resistance profile of F. alocis. Therefore, the objective of this research was to assess antimicrobial resistance in recently obtained F. alocis clinical isolates and to identify the presence of antimicrobial resistance genes. Isolates were obtained from [...] Read more.
There is scarce knowledge regarding the antimicrobial resistance profile of F. alocis. Therefore, the objective of this research was to assess antimicrobial resistance in recently obtained F. alocis clinical isolates and to identify the presence of antimicrobial resistance genes. Isolates were obtained from patients with periodontal or peri-implant diseases and confirmed by sequencing their 16S rRNA gene. Confirmed isolates had their genome sequenced by whole genome sequencing and their phenotypical resistance to nine antibiotics (amoxicillin clavulanate, amoxicillin, azithromycin, clindamycin, ciprofloxacin, doxycycline, minocycline, metronidazole, and tetracycline) tested by E-test strips. Antimicrobial resistance genes were detected in six of the eight isolates analyzed, of which five carried tet(32) and one erm(B). Overall, susceptibility to the nine antibiotics tested was high except for azithromycin in the isolate that carried erm(B). Moreover, susceptibility to tetracycline, doxycycline, and minocycline was lower in those isolates that carried tet(32). The genetic surroundings of the detected genes suggested their inclusion in mobile genetic elements that might be transferrable to other bacteria. These findings suggest that, despite showing high susceptibility to several antibiotics, F. alocis might obtain new antimicrobial resistance traits due to its acceptance of mobile genetic elements with antibiotic resistance genes in their genome. Full article
(This article belongs to the Special Issue Periodontitis: Prevention and Treatment)
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21 pages, 1341 KiB  
Review
The Research Status, Potential Hazards and Toxicological Mechanisms of Fluoroquinolone Antibiotics in the Environment
by Jia Du, Qinghua Liu, Ying Pan, Shaodan Xu, Huanxuan Li and Junhong Tang
Antibiotics 2023, 12(6), 1058; https://doi.org/10.3390/antibiotics12061058 - 15 Jun 2023
Cited by 15 | Viewed by 3255
Abstract
Fluoroquinolone antibiotics are widely used in human and veterinary medicine and are ubiquitous in the environment worldwide. This paper recapitulates the occurrence, fate, and ecotoxicity of fluoroquinolone antibiotics in various environmental media. The toxicity effect is reviewed based on in vitro and in [...] Read more.
Fluoroquinolone antibiotics are widely used in human and veterinary medicine and are ubiquitous in the environment worldwide. This paper recapitulates the occurrence, fate, and ecotoxicity of fluoroquinolone antibiotics in various environmental media. The toxicity effect is reviewed based on in vitro and in vivo experiments referring to many organisms, such as microorganisms, cells, higher plants, and land and aquatic animals. Furthermore, a comparison of the various toxicology mechanisms of fluoroquinolone antibiotic residues on environmental organisms is made. This study identifies gaps in the investigation of the toxic effects of fluoroquinolone antibiotics and mixtures of multiple fluoroquinolone antibiotics on target and nontarget organisms. The study of the process of natural transformation toward drug-resistant bacteria is also recognized as a knowledge gap. This review also details the combined toxicity effect of fluoroquinolone antibiotics and other chemicals on organisms and the adsorption capacity in various environmental matrices, and the scarcity of data on the ecological toxicology evaluation system of fluoroquinolone antibiotics is identified. The present study entails a critical review of the literature providing guidelines for the government to control the discharge of pollutants into the environment and formulate policy coordination. Future study work should focus on developing a standardized research methodology for fluoroquinolone antibiotics to guide enterprises in the design and production of drugs with high environmental biocompatibility. Full article
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13 pages, 3391 KiB  
Article
Critical-Illness: Combined Effects of Colistin and Vasoactive Drugs: A Pilot Study
by Rodopi Stamatiou, Anna Vasilaki, Dimitra Tzini, Vasiliki Tsolaki, Konstantina Zacharouli, Maria Ioannou, George Fotakopoulos, Markos Sgantzos and Demosthenes Makris
Antibiotics 2023, 12(6), 1057; https://doi.org/10.3390/antibiotics12061057 - 15 Jun 2023
Cited by 2 | Viewed by 1483
Abstract
Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and [...] Read more.
Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and improve blood flow to vital organs, which can be compromised in critically ill patients. The exact mechanism of colistin-induced muscle toxicity is of significant interest due to its potential intensive-care clinical implications. Colistin alone or in combination with vasoconstrictive agents was administrated in non-septic and LPS-induced septic animals for 10 days. Histopathological evaluation of the gastrocnemius muscle and dot-blot protein tissue analysis were performed. Increased intramuscular area, de-organization of the muscle fibers and signs of myopathy were observed in colistin-treated animals. This effect was ameliorated in the presence of vasoconstrictive drugs. Administration of colistin to septic animals resulted in a decrease of AMPK and cyclin-D1 levels, while it had no effect on caspase 3 levels. Vasoconstrictive drugs’ administration reversed the effects of colistin on AMPK and cyclin D1 levels. Colistin’s effects on muscle depend on septic state and vasoconstriction presence, highlighting the need to consider these factors when administering it in critically ill patients. Full article
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14 pages, 1482 KiB  
Article
Clinical Features and Outcomes of VAP Due to Multidrug-Resistant Klebsiella spp.: A Retrospective Study Comparing Monobacterial and Polybacterial Episodes
by Dalia Adukauskiene, Ausra Ciginskiene, Agne Adukauskaite, Despoina Koulenti and Jordi Rello
Antibiotics 2023, 12(6), 1056; https://doi.org/10.3390/antibiotics12061056 - 15 Jun 2023
Viewed by 1283
Abstract
VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university [...] Read more.
VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university hospital, aiming to compare both the clinical features and the 60-day ICU all-cause mortality of monobacterial and polybacterial MDR Klebsiella spp. VAP episodes. Of the 86 MDR Klebsiella spp. VAP episodes analyzed, 50 (58.1%) were polybacterial. The 60-day mortality was higher (p < 0.05) in polybacterial episodes: overall (50.0 vs. 27.8%), in the sub-group with less-severe disease (SOFA < 8) at VAP onset (45.5 vs. 15.0%), even with appropriate treatment (41.7 vs. 12.5%), and the sub-group of extended drug-resistant (XDR) Klebsiella spp. (46.4 vs. 17.6%). The ICU mortality (44.0 vs. 22.5%) was also higher in the polybacterial episodes. The monobacterial MDR Klebsiella spp. VAP was associated (p < 0.05) with prior hospitalization (61.1 vs. 40.0%), diabetes mellitus (30.6 vs. 5.8%), obesity (30.6 vs. 4.7%), prior antibiotic therapy (77.8 vs. 52.0%), prior treatment with cephalosporins (66.7 vs. 36.0%), and SOFA cardiovascular ≥ 3 (44.4 vs. 10.0%) at VAP onset. Patients with polybacterial VAP were more likely (p < 0.05) to be comatose (22.2 vs. 52.0%) and had a higher SAPS II score (median [IQR] 45.0 [35.25–51.1] vs. 50.0 [40.5–60.75]) at VAP onset. Polybacterial MDR Klebsiella spp. VAP had distinct demographic and clinical characteristics compared to monobacterial, and was associated with poorer outcomes. Full article
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12 pages, 439 KiB  
Article
The Impact of the COVID-19 Pandemic in Postoperative Neurosurgical Infections at a Reference Center in México
by José Luis Soto Hernández, Luis Esteban Ramírez González, Guadalupe Reyes Ramírez, Carolina Hernández Hernández, Natalia Rangel Torreblanca, Verónica Ángeles Morales, Karen Flores Moreno, Miguel Ramos Peek and Sergio Moreno Jiménez
Antibiotics 2023, 12(6), 1055; https://doi.org/10.3390/antibiotics12061055 - 15 Jun 2023
Cited by 1 | Viewed by 1050
Abstract
The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and [...] Read more.
The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and type of postoperative infections, the causative microorganisms and in-hospital mortality rates in a 4-year period, from the pre-pandemic year 2019 until 2022. A total of 4150 neurosurgical procedures were registered. In 2020 the total number of surgeries was reduced by 36% compared to 2019 OR = 0.689 (95% CI 0.566–0.834) p ≤ 0.001, transnasal/trans sphenoidal pituitary resections decreased by 53%, and spinal surgeries by 52%. The rate of neurosurgical infections increased from 3.5% in 2019 to 5.6% in 2020 (p = 0.002). Regarding the microorganisms that caused infections, gram positive cocci accounted for 43.5% of isolates, Klebsiella spp. and Pseudomonas spp. caused one third of the infections. No significant differences were found for in-hospital mortality nor patterns of resistance to antibiotics. The number of surgeries increased in the last two years, although the infection rate has returned to pre-pandemic levels. We observed a lower impact from subsequent waves of COVID-19 and despite an increase in the number of surgeries, the surgeries have not amounted to the full pre-pandemic levels. Full article
(This article belongs to the Special Issue Surgical Site Infections: Epidemiology, Microbiology and Prevention)
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16 pages, 1940 KiB  
Review
Diagnosis of Periprosthetic Joint Infection: The Utility of Biomarkers in 2023
by Mehmet Kursat Yilmaz, Ahmad Abbaszadeh, Saad Tarabichi, Ibrahim Azboy and Javad Parvizi
Antibiotics 2023, 12(6), 1054; https://doi.org/10.3390/antibiotics12061054 - 15 Jun 2023
Cited by 5 | Viewed by 2860
Abstract
Periprosthetic joint infection (PJI) is a rare yet devastating complication following total joint arthroplasty (TJA). Early and accurate diagnosis of PJI is paramount in order to maximize the chances of successful treatment. However, we are yet to identify a single “gold standard” test [...] Read more.
Periprosthetic joint infection (PJI) is a rare yet devastating complication following total joint arthroplasty (TJA). Early and accurate diagnosis of PJI is paramount in order to maximize the chances of successful treatment. However, we are yet to identify a single “gold standard” test for the diagnosis of PJI. As a result, the diagnosis of PJI is often challenging. Currently, the 2018 ICM definition of PJI is the only validated diagnostic criteria available. This article will review the importance of serum and synovial biomarkers in the diagnosis of PJI. In addition, it will provide a brief overview of the emerging modalities for the identification of infections in this setting. Full article
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13 pages, 3038 KiB  
Article
Cranberry/Chondroitin Sulfate Co-precipitate as a New Method for Controlling Urinary Tract Infections
by Concetta Caglioti, Rossana Iannitti, Giada Ceccarelli, Laura Selan, Marco Artini, Rosanna Papa, Antonio Malvasi, Rosaria Gentile, Diletta Del Bianco, Florinda Apone, Paola Angelini, Federico Palazzetti and Bernard Fioretti
Antibiotics 2023, 12(6), 1053; https://doi.org/10.3390/antibiotics12061053 - 15 Jun 2023
Cited by 1 | Viewed by 2020
Abstract
Urinary tract infections (UTI), which are among the most frequent cases of infectious diseases, mainly affect women. The most common treatment approach involves the use of antibiotics, although this solution is not always the most suitable, mainly because of the resistance that bacterial [...] Read more.
Urinary tract infections (UTI), which are among the most frequent cases of infectious diseases, mainly affect women. The most common treatment approach involves the use of antibiotics, although this solution is not always the most suitable, mainly because of the resistance that bacterial strains develop. Proanthocyanidins are a class of polyphenols, abundantly contained in cranberry extracts, which have shown beneficial effects in the treatment of urinary tract infections, due to their anti-adhesive properties toward bacteria, with respect to the membranes of the cells of the urothelium and intestine, thus reducing their virulence. In this work, we demonstrate via microscopy and scattering measurements how a mixture of cranberry and chondroitin sulfate can form a crosslinked structure with barrier properties. By using a design of experiment (DOE), we optimized the mass ratio to obtain a precipitate between cranberry extract and chondroitin sulfate in the presence of N-acetylcysteine and hyaluronic acid. By using transepithelial electrical resistance (TEER) chambers, we confirmed the barrier properties of the best mixture obtained with the DOE. Lastly, the antibiofilm action was investigated against five strains of Escherichia coli with different antibiotic sensitivity. The precipitate displayed a variable inhibitory effect in biofilm formation with major effects in UTI with an antibiotic resistance profile. Full article
(This article belongs to the Section Plant-Derived Antibiotics)
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12 pages, 434 KiB  
Review
Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review
by Sylvain Diamantis, Catherine Chakvetadze, Astrid de Pontfarcy and Matta Matta
Antibiotics 2023, 12(6), 1052; https://doi.org/10.3390/antibiotics12061052 - 15 Jun 2023
Cited by 1 | Viewed by 1588
Abstract
Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our [...] Read more.
Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. Methodology: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. Results: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. Conclusions: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs. Full article
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8 pages, 250 KiB  
Editorial
Antimicrobial and Anti-Infective Activity of Natural Products—Gaining Knowledge from Novel Studies
by Elizabeth S. Fernandes, Isabella F. da Silva Figueiredo, Cinara R. A. V. Monteiro and Valério Monteiro-Neto
Antibiotics 2023, 12(6), 1051; https://doi.org/10.3390/antibiotics12061051 - 15 Jun 2023
Cited by 1 | Viewed by 1552
Abstract
Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of [...] Read more.
Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of research. In this context, studies covering the investigation of their ability to combat resistant microorganisms, either by neutralization or inactivation of pathogen resistance mechanisms and virulence properties, have gained attention. Herein, a collection of 19 manuscripts focused on the antimicrobial and anti-infective activity of natural products, including their mechanisms of action, in silico evidence of antimicrobial activity, synergistic associations with antibiotics, and other aspects, will be discussed. Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)
19 pages, 4248 KiB  
Article
Efficacy and Safety of Antibiotic Impregnated Microporous Nanohydroxyapatite Beads for Chronic Osteomyelitis Treatment: A Multicenter, Open-Label, Prospective Cohort Study
by Chittawee Jiamton, Adinun Apivatgaroon, Saree Aunaramwat, Banchai Chawalitrujiwong, Chaiwat Chuaychoosakoon, Sitthiphong Suwannaphisit, Choen Jirawison, Chonlathan Iamsumang, Pinkawas Kongmalai, Pawaris Sukvanich, Pongtep Na Nakorn, Worawit Ongbumrungphan, Pawin Rattanasumrit, Suthee Tharakulphan, Thanachai Thongtanworapat, Faungchat Thammarakcharoen, Autcharaporn Srion, Jintamai Suwanprateeb and Bancha Chernchujit
Antibiotics 2023, 12(6), 1049; https://doi.org/10.3390/antibiotics12061049 - 15 Jun 2023
Cited by 3 | Viewed by 2291
Abstract
Chronic osteomyelitis is still a serious health problem that causes disabling conditions and has an impact on the quality of life. The objective of this study was to determine the clinical efficacy and safety of localized antibiotics delivery via impregnated microporous nanohydroxyapatite (nHA-ATB) [...] Read more.
Chronic osteomyelitis is still a serious health problem that causes disabling conditions and has an impact on the quality of life. The objective of this study was to determine the clinical efficacy and safety of localized antibiotics delivery via impregnated microporous nanohydroxyapatite (nHA-ATB) beads for chronic osteomyelitis treatment. A total of 62 patients were enrolled in this study. After radical surgical debridement, the bone defect was filled with three types of antibiotics (vancomycin or gentamicin or fosfomycin) impregnated HA beads. The follow-up period was 48 weeks. It was found that the success rate was approximately 98% with a re-infection in only one patient. Quality of life of all patients after treatment improved significantly over time. Systemic exposure to vancomycin and gentamicin after beads implantation was limited and high local antibiotics concentrations were found in wound drainage fluid at 24, 48 and 72 h. Blood biochemistry measurements did not show any nephrotoxic or hepatotoxic effects. 20 adverse events were reported, but 90% of the events were resolved without having to remove the beads and the patients recovered. Satisfactory outcomes were observed in terms of success rate, quality of life and adverse effect. nHA-ATB beads impregnated by vancomycin or gentamicin or fosfomycin could potentially be employed as an alternative product of choice for localized antibiotics delivery in chronic osteomyelitis treatment. Full article
(This article belongs to the Special Issue Advances in Orthopedic Infection Management and Antibiotic Treatment)
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