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Antibiotics, Volume 12, Issue 3 (March 2023) – 206 articles

Cover Story (view full-size image): Escherichia coli resistant to extended-spectrum cephalosporins (ESC-EC) are a major antimicrobial resistance threat. Furthermore, since they typically carry highly mobile plasmid-borne resistance genes and now have a global distribution in animal, human, and environmental sources, the highly complex epidemiology of ESC-EC infection requires a One Health approach to effectively design control and preventive measures. Here, we present the steps taken to assemble a database with phenotypic and genetic information on 10,763 ESC-EC isolates from multiple sources (humans, livestock, companion animals, wildlife, and environmental) in eight European countries under the framework of the DiSCoVeR Joint Research Project funded by the One Health European Joint Programme (OH-EJP), along with its strengths and limitations. View this paper
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9 pages, 6167 KiB  
Case Report
Mycobacterium marinum: A Challenging Cause of Protracted Tenosynovitis
by Pernille Grand Moestrup, Maiken Stilling, Christian Morberg Wejse and Victor Naestholt Dahl
Antibiotics 2023, 12(3), 629; https://doi.org/10.3390/antibiotics12030629 - 22 Mar 2023
Cited by 1 | Viewed by 3020
Abstract
Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons [...] Read more.
Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons on the second phalanx of his right hand. He was initially treated with steroid injections without any effect. Followingly, ulceration and an abscess developed on the dorsal site of the hand. At this point, it came to the physician’s knowledge that the patient had been cleaning an aquarium before onset of symptoms. After progression to massive tenosynovitis, the patient was admitted and underwent multiple surgical debridements. Briefly, after the first surgery, an interferon-γ release assay was positive, and treatment for M. marinum with rifampicin and azithromycin was initiated after eight months of symptoms. Later, a surgical biopsy showed acid-fast bacilli, and a polymerase chain reaction confirmed the diagnosis of M. marinum. In this case story, we highlight the difficulties of diagnosing and managing this complicated infection, describe the considerable morbidity associated with it, and suggest that local tissue concentrations could be useful to improve clinical outcomes, as these concentrations are potentially suboptimal. Full article
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62 pages, 5604 KiB  
Review
Design and Synthesis of Novel Antimicrobial Agents
by Zeinab Breijyeh and Rafik Karaman
Antibiotics 2023, 12(3), 628; https://doi.org/10.3390/antibiotics12030628 - 22 Mar 2023
Cited by 15 | Viewed by 6091
Abstract
The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics’ availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World [...] Read more.
The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics’ availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World Health Organization (WHO) recognized 12 families of bacteria that present the greatest harm to human health, where options of antibiotic therapy are extremely limited. Therefore, this paper reviews possible new ways for the development of novel classes of antibiotics for which there is no pre-existing resistance in human bacterial pathogens. By utilizing research and technology such as nanotechnology and computational methods (such as in silico and Fragment-based drug design (FBDD)), there has been an improvement in antimicrobial actions and selectivity with target sites. Moreover, there are antibiotic alternatives, such as antimicrobial peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, and cannabinoids. Additionally, drug repurposing (such as with ticagrelor, mitomycin C, auranofin, pentamidine, and zidovudine) and synthesis of novel antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, and pyrazole derivatives) represent novel approaches to treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown to be an excellent platform to design a new generation of antimicrobial agents with better efficacy against multidrug-resistant bacteria. Ultimately, to combat resistant bacteria and to stop the spread of resistant illnesses, regulations and public education regarding the use of antibiotics in hospitals and the agricultural sector should be combined with research and technological advancements. Full article
(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)
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15 pages, 1921 KiB  
Article
Artificial Neural Network Prediction of Antiadhesion and Antibiofilm-Forming Effects of Antimicrobial Active Mushroom Extracts on Food-Borne Pathogens
by Jovana Vunduk, Anita Klaus, Vesna Lazić, Maja Kozarski, Danka Radić, Olja Šovljanski and Lato Pezo
Antibiotics 2023, 12(3), 627; https://doi.org/10.3390/antibiotics12030627 - 22 Mar 2023
Cited by 2 | Viewed by 1320
Abstract
The problem of microbial biofilms has come to the fore alongside food, pharmaceutical, and healthcare industrialization. The development of new antibiofilm products has become urgent, but it includes bioprospecting and is time and money-consuming. Contemporary efforts are directed at the pursuit of effective [...] Read more.
The problem of microbial biofilms has come to the fore alongside food, pharmaceutical, and healthcare industrialization. The development of new antibiofilm products has become urgent, but it includes bioprospecting and is time and money-consuming. Contemporary efforts are directed at the pursuit of effective compounds of natural origin, also known as “green” agents. Mushrooms appear to be a possible new source of antibiofilm compounds, as has been demonstrated recently. The existing modeling methods are directed toward predicting bacterial biofilm formation, not in the presence of antibiofilm materials. Moreover, the modeling is almost exclusively targeted at biofilms in healthcare, while modeling related to the food industry remains under-researched. The present study applied an Artificial Neural Network (ANN) model to analyze the anti-adhesion and anti-biofilm-forming effects of 40 extracts from 20 mushroom species against two very important food-borne bacterial species for food and food-related industries—Listeria monocytogenes and Salmonella enteritidis. The models developed in this study exhibited high prediction quality, as indicated by high r2 values during the training cycle. The best fit between the modeled and measured values was observed for the inhibition of adhesion. This study provides a valuable contribution to the field, supporting industrial settings during the initial stage of biofilm formation, when these communities are the most vulnerable, and promoting innovative and improved safety management. Full article
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13 pages, 1825 KiB  
Article
Evaluation of Efflux-Mediated Resistance and Biofilm formation in Virulent Pseudomonas aeruginosa Associated with Healthcare Infections
by Paul A. Akinduti, Onome W. George, Hannah U. Ohore, Olusegun E. Ariyo, Samuel T. Popoola, Adenike I. Adeleye, Kazeem S. Akinwande, Jacob O. Popoola, Solomon O. Rotimi, Fredrick O. Olufemi, Conrad A. Omonhinmin and Grace I. Olasehinde
Antibiotics 2023, 12(3), 626; https://doi.org/10.3390/antibiotics12030626 - 22 Mar 2023
Cited by 6 | Viewed by 1611
Abstract
Pseudomonas aeruginosa is a significant pathogen identified with healthcare-associated infections. The present study evaluates the role of biofilm and efflux pump activities in influencing high-level resistance in virulent P. aeruginosa strains in clinical infection. Phenotypic resistance in biotyped Pseudomonas aeruginosa (n = [...] Read more.
Pseudomonas aeruginosa is a significant pathogen identified with healthcare-associated infections. The present study evaluates the role of biofilm and efflux pump activities in influencing high-level resistance in virulent P. aeruginosa strains in clinical infection. Phenotypic resistance in biotyped Pseudomonas aeruginosa (n = 147) from diagnosed disease conditions was classified based on multiple antibiotic resistance (MAR) indices and analysed with logistic regression for risk factors. Efflux pump activity, biofilm formation, and virulence factors were analysed for optimal association in Pseudomonas infection using receiver operation characteristics (ROC). Age-specificity (OR [CI] = 0.986 [0.946–1.027]), gender (OR [CI] = 1.44 [0.211–9.827]) and infection sources (OR [CI] = 0.860 [0.438–1.688]) were risk variables for multidrug resistance (MDR)-P. aeruginosa infection (p < 0.05). Biofilm formers caused 48.2% and 18.5% otorrhea and wound infections (95% CI = 0.820–1.032; p = 0.001) respectively and more than 30% multidrug resistance (MDR) strains demonstrated high-level efflux pump activity (95% CI = 0.762–1.016; p = 0.001), protease (95% CI = 0.112–0.480; p = 0.003), lipase (95% CI = 0.143–0.523; p = 0.001), and hemolysin (95% CI = 1.109–1.780; p = 0.001). Resistance relatedness of more than 80% and 60% to cell wall biosynthesis inhibitors (ceftazidime, ceffproxil, augumentin, ampicillin) and, DNA translational and transcriptional inhibitors (gentamicin, ciprofloxacin, ofloxacin, nitrofurantoin) were observed (p < 0.05). Strong efflux correlation (r = 0.85, p = 0.034) with MDR strains, with high predictive performances in efflux pump activity (ROC-AUC 0.78), biofilm formation (ROC-AUC 0.520), and virulence hierarchical-clustering. Combine activities of the expressed efflux pump and biofilm formation in MDR-P. aeruginosa pose risk to clinical management and infection control. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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36 pages, 24719 KiB  
Review
A Comprehensive Review on Chemical Synthesis and Chemotherapeutic Potential of 3-Heteroaryl Fluoroquinolone Hybrids
by Halyna Hryhoriv, Sergiy M. Kovalenko, Marine Georgiyants, Lyudmila Sidorenko and Victoriya Georgiyants
Antibiotics 2023, 12(3), 625; https://doi.org/10.3390/antibiotics12030625 - 21 Mar 2023
Cited by 4 | Viewed by 2118
Abstract
Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for [...] Read more.
Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for chemical modification, with subsequent useful changes in the pharmacokinetics and pharmacodynamics of the initial molecules. This review summarizes the chemical and pharmacological results of fluoroquinolones hybridization by introducing different heterocyclic moieties into position 3 of the core system. It analyses the synthetic procedures and approaches to the formation of heterocycles from the fluoroquinolone carboxyl group and reveals the most convenient ways for such procedures. Further, the results of biological activity investigations for the obtained hybrid pharmacophore systems are presented. The latter revealed numerous promising molecules that can be further studied to overcome the problem of resistance to antibiotics, to find novel anticancer agents and more. Full article
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16 pages, 820 KiB  
Article
Reporting Antimicrobial-Related Adverse Drug Events in Jordan: An Analysis from the VigiBase Database
by Nizar Mahmoud Mhaidat, Sayer Al-Azzam, Hayaa Abdallah Banat, Jaber Mohammad Jaber, Mohammad Araydah, Osama Y. Alshogran and Mamoon A. Aldeyab
Antibiotics 2023, 12(3), 624; https://doi.org/10.3390/antibiotics12030624 - 21 Mar 2023
Cited by 1 | Viewed by 2163
Abstract
This study aims to assess the reporting of antimicrobial-related adverse drug events (ADEs) in Jordan between 2003 and 2022. Data regarding the antimicrobial-related ADEs were extracted from the WHO’s global database (VigiBase) by the Rational Drug Use and Pharmacovigilance Department at the Jordan [...] Read more.
This study aims to assess the reporting of antimicrobial-related adverse drug events (ADEs) in Jordan between 2003 and 2022. Data regarding the antimicrobial-related ADEs were extracted from the WHO’s global database (VigiBase) by the Rational Drug Use and Pharmacovigilance Department at the Jordan Food and Drug Administration (JFDA). A total of 279 Individual Case Safety Reports (ICSRs) were recorded. The number of ICSRs increased from 2019 onwards (219 out of 279 cases). This increase in the reported ADEs was influenced by the actions of the JFDA, including the introduction of electronic reporting forms, updating the national pharmacovigilance guidelines, which encouraged adverse drug reactions reporting, the implementation of the AMR-national action plan, the encouragement to report due to COVID-19 vaccine, and the continuous awareness campaigns and training programs. Skin and subcutaneous tissue disorders (n = 105; 19.48%) were the most reported antimicrobial-related ADEs. The highest number of ADEs was reported for tetracyclines (n = 101; 18.74%) followed by fluoroquinolones (n = 54; 10.02%), third-generation cephalosporines (n = 48; 8.9%), and carbapenems (n = 42; 7.79%). From the top 10 consumed antibiotics, the number of ADEs in patients who consumed Watch group antibiotics (97 ADEs) was higher than those who consumed Access group antibiotics (28 ADEs). The findings highlight the need to monitor and rationalize the use of Watch antibiotics. Enhanced reporting of antimicrobial-related adverse drug reactions is needed to inform antimicrobial stewardship and improve the pharmacovigilance system in Jordan. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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13 pages, 2312 KiB  
Article
The Antimicrobial Peptide Octopromycin Suppresses Biofilm Formation and Quorum Sensing in Acinetobacter baumannii
by Dinusha Chathurangi Rajapaksha, Shan Lakmal Edirisinghe, Chamilani Nikapitiya, Ilson Whang and Mahanama De Zoysa
Antibiotics 2023, 12(3), 623; https://doi.org/10.3390/antibiotics12030623 - 21 Mar 2023
Cited by 6 | Viewed by 2151
Abstract
Acinetobacter baumannii is an opportunistic bacterial pathogen that causes severe infections in immunocompromised individuals. A. baumannii forms biofilm and produces extracellular matrix, which supports bacteria to survive under harsh conditions and be resistant to antibacterial treatments. In the present study, we investigated the [...] Read more.
Acinetobacter baumannii is an opportunistic bacterial pathogen that causes severe infections in immunocompromised individuals. A. baumannii forms biofilm and produces extracellular matrix, which supports bacteria to survive under harsh conditions and be resistant to antibacterial treatments. In the present study, we investigated the biofilm and quorum-sensing inhibitory effects of antimicrobial peptide, octopromycin in A. baumannii. Field emission-scanning electron microscopy results clearly showed significantly reduced biofilm mass and caused a collapse in biofilm architecture at the minimum inhibitory concentration (50 µg/mL) and minimum bactericidal concentration (200 µg/mL) of octopromycin. Antibiotic-resistant persister cells of A. baumannii were successfully killed by octopromycin treatment, and it inhibited violacein production in Chromobacterium violaceum in a concentration-dependent manner. Octopromycin also inhibited alginate production, surface movements (swarming and swimming), and twitching motility of A. baumannnii, confirming its anti-quorum-sensing activity. Multiple metabolic pathways, two-component regulation systems, quorum-sensing, and antibiotic synthesis-related pathways in A. baumannii biofilms were strongly affected by octopromycin treatment. The collective findings indicate that the antibacterial peptide octopromycin may control A. baumannii biofilms through multi-target interactions. Octopromycin could be a desirable therapeutic option for the prevention and control of A. baumannii infections. Full article
(This article belongs to the Special Issue Antimicrobial Peptides from Natural Sources to Synthetic Optimization)
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16 pages, 3200 KiB  
Article
Vernonia polyanthes Less. (Asteraceae Bercht. & Presl), a Natural Source of Bioactive Compounds with Antibiotic Effect against Multidrug-Resistant Staphylococcus aureus
by Jordana Damasceno Gitirana de Santana, Oscar Alejandro Santos-Mayorga, Jônatas Rodrigues Florencio, Mirella Chrispim Cerqueira de Oliveira, Luísa Maria Silveira de Almeida, Julianna Oliveira de Lucas Xavier, Danielle Cristina Zimmermann-Franco, Gilson Costa Macedo, Adriana Lúcia Pires Ferreira, Orlando Vieira de Sousa, Ademar Alves da Silva Filho and Maria Silvana Alves
Antibiotics 2023, 12(3), 622; https://doi.org/10.3390/antibiotics12030622 - 21 Mar 2023
Viewed by 1473
Abstract
Vernonia polyanthes is a medicinal plant used to treat many disorders, including infectious diseases. This study investigated the chemical constituents and the antibacterial activity of V. polyanthes leaf rinse extract (Vp-LRE). The chemical characterization of Vp-LRE was established using ultra-high performance liquid chromatography [...] Read more.
Vernonia polyanthes is a medicinal plant used to treat many disorders, including infectious diseases. This study investigated the chemical constituents and the antibacterial activity of V. polyanthes leaf rinse extract (Vp-LRE). The chemical characterization of Vp-LRE was established using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS), and glaucolide A was identified through 1H and 13C nuclear magnetic resonance (NMR) and mass fragmentation. The cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The antibacterial activity was assessed by minimal inhibitory concentration and minimal bactericidal concentration. Interactions between ligands and beta-lactamase were evaluated via molecular docking. UHPLC/Q-TOF-MS detected acacetin, apigenin, chrysoeriol, isorhamnetin, isorhamnetin isomer, kaempferide, 3′,4′-dimethoxyluteolin, 3,7-dimethoxy-5,3′,4′-trihydroxyflavone, piptocarphin A and glaucolide A. Vp-LRE (30 µg/mL) and glaucolide A (10 and 20 μg/mL) were cytotoxic against RAW 264.7 cells. Glaucolide A was not active, but Vp-LRE inhibited the Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Salmonella Choleraesuis and Typhimurium, with a bacteriostatic effect. The compounds (glaucolide A, 3′,4′-dimethoxyluteolin, acacetin and apigenin) were able to interact with beta-lactamase, mainly through hydrogen bonding, with free energy between −6.2 to −7.5 kcal/mol. These results indicate that V. polyanthes is a potential natural source of phytochemicals with a significant antibiotic effect against MRSA strains. Full article
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15 pages, 1085 KiB  
Article
Risk Factors, Genetic Diversity, and Antimicrobial Resistance of Staphylococcus spp. Isolates in Dogs Admitted to an Intensive Care Unit of a Veterinary Hospital
by Jordana Almeida Santana, Amanda Oliveira Paraguassu, Ranielle Stephanie Toledo Santana, Rafael Gariglio Clark Xavier, Patricia Maria Colleto Freitas, Flavia Figueira Aburjaile, Vasco Ariston de Carvalho Azevedo, Bertram Brenig, Anders Miki Bojesen and Rodrigo Otávio Silveira Silva
Antibiotics 2023, 12(3), 621; https://doi.org/10.3390/antibiotics12030621 - 21 Mar 2023
Cited by 2 | Viewed by 1709
Abstract
Intensive Care Units (ICU) usually provide an excellent environment for the selection of pathogens associated with hospital-acquired infections (HAI), leading to increased mortality and hospitalization costs. Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a major cause of HAI in dogs worldwide, but the risk factors [...] Read more.
Intensive Care Units (ICU) usually provide an excellent environment for the selection of pathogens associated with hospital-acquired infections (HAI), leading to increased mortality and hospitalization costs. Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a major cause of HAI in dogs worldwide, but the risk factors and dynamics of colonization by MRSP are largely unknown. This study aimed to evaluate the risk factors associated with the acquisition of MRSP in dogs admitted to an ICU, and to report the antimicrobial resistance profiles and genetic relatedness of MRSP isolates. Sterile swabs from the nostril, axilla, and rectum were collected daily during the hospitalization of 54 dogs. Samples were subjected to Mannitol Salt Agar, and colonies were identified by MALDI-ToF, polymerase chain reaction (PCR), and sequencing of the rpoB gene. Antimicrobial susceptibility testing and PCR detection of mecA were performed. Staphylococcus spp. was isolated from 94% of the dogs, and the most frequently isolated species was S. pseudintermedius (88.2%). Carriage of multidrug resistant (MDR) staphylococci was observed in 64.4% of the dogs, and approximately 39% had methicillin-resistant Staphylococcus sp. (MRS), of which 21.6% had MRSP and 1.9% had methicillin-resistant S. aureus (MRSA). The acquisition of MRSP during ICU hospitalization was associated with sex (female), age (>7 years), and dogs that had previously been treated with antimicrobials. Animals colonized by MRSP resistant to ≥9 antimicrobial classes had longer hospital stays than those colonized by other MRS strains. Among the 13 MRSP isolates that were subjected to whole-genome sequencing, ten were classified as ST71. A single nucleotide polymorphism (SNP) analysis revealed three clones, including one that was detected in infected dogs outside the ICU. This study indicates novel risk factors associated with colonization by MRSP. The detection of the same MRSP clone causing HAI outside the ICU reinforces the need for improved infection prevention and control practices at veterinary hospitals in general and at the ICU in particular. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Companion Animals II)
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11 pages, 857 KiB  
Article
Vancomycin Sequestration in ST Filters: An In Vitro Study
by Frédéric J. Baud, Pascal Houzé, Jean-Herlé Raphalen, Pascal Philippe and Lionel Lamhaut
Antibiotics 2023, 12(3), 620; https://doi.org/10.3390/antibiotics12030620 - 21 Mar 2023
Viewed by 967
Abstract
Background. Sequestration of vancomycin in ST® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST® interaction was assessed using the in vitro NeckEpur® technology. Method. ST150® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were [...] Read more.
Background. Sequestration of vancomycin in ST® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST® interaction was assessed using the in vitro NeckEpur® technology. Method. ST150® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were assessed in duplicate: (i) continuous diafiltration (CDF): 4 L/h, (ii) continuous dialysis (CD): 2.5 L/h post-filtration. Results. The mean initial vancomycin concentration in the central compartment (CC) was 51.4 +/− 5.0 mg/L. The mean percentage eliminated from the CC over 6 h was 91 +/− 4%. The mean clearances from the CC by CDF and CD were 2.8 and 1.9 L/h, respectively. The mean clearances assessed using cumulative effluents were 4.4 and 2.2 L/h, respectively. The mean percentages of the initial dose eliminated in the effluents from the CC by CDF and CD were 114 and 108% with no detectable sequestration of vancomycin in both modes of elimination. Discussion. Significant sequestration adds a clearance to that provided by CDF and CD. The study provides multiple evidence from the CC, the filter, and the effluents of the lack of an increase in total clearance in comparison with the flow rates without significant sequestration in the ST® filter comparing cumulative effluents to the initial dose in the CC. Conclusions. There is no evidence ST® filters directly sequestrate vancomycin. Full article
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17 pages, 3599 KiB  
Article
Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents
by Youri Cortat, Miroslava Nedyalkova, Kevin Schindler, Parth Kadakia, Gozde Demirci, Sara Nasiri Sovari, Aurelien Crochet, Stefan Salentinig, Marco Lattuada, Olimpia Mamula Steiner and Fabio Zobi
Antibiotics 2023, 12(3), 619; https://doi.org/10.3390/antibiotics12030619 - 20 Mar 2023
Cited by 6 | Viewed by 2164
Abstract
In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug [...] Read more.
In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics. Full article
(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)
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14 pages, 324 KiB  
Article
Antimicrobial Resistance Molecular Mechanisms of Helicobacter pylori in Jordanian Children: A Cross-Sectional Observational Study
by Salma Burayzat, Mohammad Al-Tamimi, Mohammad Barqawi, Mustafa Sabri Massadi, Jumanah Abu-Raideh, Hadeel Albalawi, Ashraf I. Khasawneh, Nisreen Himsawi and Maha Barber
Antibiotics 2023, 12(3), 618; https://doi.org/10.3390/antibiotics12030618 - 20 Mar 2023
Cited by 1 | Viewed by 1578
Abstract
Background: H. pylori antimicrobial resistance causes increasing treatment failure rates among H. pylori gastritis in children. This study investigates the molecular mechanisms of H. pylori antimicrobial resistance among Jordanian children. Methods: Demographic, clinical, and laboratory data were recorded for children referred to Prince Hamzah [...] Read more.
Background: H. pylori antimicrobial resistance causes increasing treatment failure rates among H. pylori gastritis in children. This study investigates the molecular mechanisms of H. pylori antimicrobial resistance among Jordanian children. Methods: Demographic, clinical, and laboratory data were recorded for children referred to Prince Hamzah Hospital. Clarithromycin, Metronidazole, and Levofloxacin susceptibility were tested via E-test. Clarithromycin-related mutations were investigated using Real-Time (RT)-PCR and Levofloxacin resistance was analyzed with DNA sequencing of the gyrA gene. Results: 116 children were recruited, including 55.2% females and 55.2% in the age range of 10.1 to 14 years. A total of 82.7% were naïve to eradication therapy. H. pylori positivity was 93.9%, 89.6%, 61.7%, and 84.3% according to Rapid Urease Test, histology, culture, and RT-PCR, respectively. Resistance rates were 25.9% for Clarithromycin, 50% for Metronidazole, and 6.9% for Levofloxacin via E-test. A2142G or A2143G or a combination of both mutations concerning Clarithromycin resistance were documented in 26.1% of samples, while mutations in gyrA gen-related to Levofloxacin resistance were reported in 5.3% of samples. Antibiotic resistance was significantly affected by abdominal pain, anemia, hematemesis, and histological findings (p < 0.05). Conclusion: H. pylori resistance was documented for Metronidazole and Clarithromycin. RT-PCR for H. pylori identification and microbial resistance determination are valuable alternatives for cultures in determining antimicrobial susceptibility. Full article
11 pages, 1160 KiB  
Article
Molecular Characterization and Epidemiology of Antibiotic Resistance Genes of β-Lactamase Producing Bacterial Pathogens Causing Septicemia from Tertiary Care Hospitals
by Mohammad Riaz Khan, Sadiq Azam, Sajjad Ahmad, Qaisar Ali, Zainab Liaqat, Noor Rehman, Ibrar Khan, Metab Alharbi and Abdulrahman Alshammari
Antibiotics 2023, 12(3), 617; https://doi.org/10.3390/antibiotics12030617 - 20 Mar 2023
Cited by 1 | Viewed by 1543
Abstract
Septicemia is a systematic inflammatory response and can be a consequence of abdominal, urinary tract and lung infections. Keeping in view the importance of Gram-negative bacteria as one of the leading causes of septicemia, the current study was designed with the aim to [...] Read more.
Septicemia is a systematic inflammatory response and can be a consequence of abdominal, urinary tract and lung infections. Keeping in view the importance of Gram-negative bacteria as one of the leading causes of septicemia, the current study was designed with the aim to determine the antibiotic susceptibility pattern, the molecular basis for antibiotic resistance and the mutations in selected genes of bacterial isolates. In this study, clinical samples (n = 3389) were collected from potentially infected male (n = 1898) and female (n = 1491) patients. A total of 443 (13.07%) patients were found to be positive for bacterial growth, of whom 181 (40.8%) were Gram-positive and 262 (59.1%) were Gram-negative. The infected patients included 238 males, who made up 12.5% of the total number tested, and 205 females, who made up 13.7%. The identification of bacterial isolates revealed that 184 patients (41.5%) were infected with Escherichia coli and 78 (17.6%) with Pseudomonas aeruginosa. The clinical isolates were identified using Gram staining biochemical tests and were confirmed using polymerase chain reaction (PCR), with specific primers for E. coli (USP) and P. aeruginosa (oprL). Most of the isolates were resistant to aztreonam (ATM), cefotaxime (CTX), ampicillin (AMP) and trimethoprim/sulfamethoxazole (SXT), and were sensitive to tigecycline (TGC), meropenem (MEM) and imipenem (IPM), as revealed by high minimum inhibitory concentration (MIC) values. Among the antibiotic-resistant bacteria, 126 (28.4%) samples were positive for ESBL, 105 (23.7%) for AmpC β-lactamases and 45 (10.1%) for MBL. The sequencing and mutational analysis of antibiotic resistance genes revealed mutations in TEM, SHV and AAC genes. We conclude that antibiotic resistance is increasing; this requires the attention of health authorities and clinicians for proper management of the disease burden. Full article
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12 pages, 3587 KiB  
Article
Polyphosphate Ester-Type Transporters Improve Antimicrobial Properties of Oxytetracycline
by Mariya Kozak, Anna Stasiuk, Vasyl Vlizlo, Dmytro Ostapiv, Yulia Bodnar, Nataliia Kuz’mina, Natalia Figurka, Natalia Nosova, Roman Ostapiv, Igor Kotsumbas, Sergiy Varvarenko and Volodymyr Samaryk
Antibiotics 2023, 12(3), 616; https://doi.org/10.3390/antibiotics12030616 - 20 Mar 2023
Cited by 3 | Viewed by 1765
Abstract
Prolonged use of antibiotics can cause toxicity in human and animal cells and lead to the development of antibiotic resistance. The development of drug delivery systems for enhanced antibacterial properties of antibiotics could reduce toxic effects and minimize the development of resistance. The [...] Read more.
Prolonged use of antibiotics can cause toxicity in human and animal cells and lead to the development of antibiotic resistance. The development of drug delivery systems for enhanced antibacterial properties of antibiotics could reduce toxic effects and minimize the development of resistance. The aim of this study was to evaluate the effectiveness of oxytetracycline in complexes with new polyphosphate ester-type transporters and to investigate the antimicrobial effect of these complexes on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth in vitro. Two polyphosphate ester-type transporters with different molecular weights were synthesized, and oxytetracycline was attached through the phosphorus groups. To determine the sensitivities of microorganisms, oxytetracycline hydrochloride and oxytetracycline complexes with polyphosphate ester-type transporters (P4 and P6) were added to liquid and solid media with E. coli, P. aeruginosa, and S. aureus in different doses. Oxytetracycline in complex with polyphosphate ester-type transporters at low doses (2.3 to 3.8 μg/disk or μg/mL) in both solid and liquid media inhibits the growth of S. aureus more effectively than oxytetracycline alone. The maximum influence on E. coli growth on solid media is observed at a dose of 8 μg/disk of oxytetracycline in combination with both P4 and P6 polyphosphate ester-type transporters. P. aeruginosa growth under the influence of oxytetracycline in combination with polyphosphate-ester type transporters in a liquid medium depends on the dose of antibiotic and the day of cultivation. Full article
(This article belongs to the Special Issue The Global Need for New Antimicrobial and Antibiofilm Agents)
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10 pages, 1112 KiB  
Article
Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study
by Johanne Gade Lilleøre, Andrea René Jørgensen, Martin Bruun Knudsen, Pelle Hanberg, Kristina Öbrink-Hansen, Sara Kousgaard Tøstesen, Kjeld Søballe, Maiken Stilling and Mats Bue
Antibiotics 2023, 12(3), 615; https://doi.org/10.3390/antibiotics12030615 - 20 Mar 2023
Viewed by 1101
Abstract
Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic [...] Read more.
Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. For the low piperacillin target (8 µg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 µg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered. Full article
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8 pages, 738 KiB  
Communication
Comparison of Broth Microdilution, Disk Diffusion and Strip Test Methods for Cefiderocol Antimicrobial Susceptibility Testing on KPC-Producing Klebsiella pneumoniae
by Federica Bovo, Tiziana Lazzarotto, Simone Ambretti and Paolo Gaibani
Antibiotics 2023, 12(3), 614; https://doi.org/10.3390/antibiotics12030614 - 20 Mar 2023
Cited by 2 | Viewed by 1745
Abstract
The aim of this study was to compare the reference broth microdilution (BMD) method with the Disk Diffusion (DD) test and strip test against a collection of 75 well-characterized Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) clinical strains to assess cefiderocol (CFD) antimicrobial [...] Read more.
The aim of this study was to compare the reference broth microdilution (BMD) method with the Disk Diffusion (DD) test and strip test against a collection of 75 well-characterized Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) clinical strains to assess cefiderocol (CFD) antimicrobial activity. Whole-genome sequencing was performed on KPC-Kp strains by Illumina iSeq100 platform. The Categorical Agreement (CA) between the BMD method and DD test was 92% (69/75) with a Major Error (ME) of 16.7% (6/36). Additionally, the CA between the BMD method and test strip was 90.7% (68/75) with a Very Major Error (VME) of 17.9% (7/39) and 82.7% (62/75) between the strip test and DD with a ME of 30.2%. KPC-Kp strains showing resistance to CFD were 27 out of 75 (36%) by three methods. Specifically, 51.9% (14/27) of KPC-Kp resistant to CFD harbored blaKPC-3, while 48.1% (13/27) harbored mutated blaKPC-3. Moreover, KPC-Kp strains carrying a mutated blaKPC-3 gene exhibited high MIC values (p value < 0.001) compared to wild-type blaKPC-3. In conclusion, the DD test resulted as a valid alternative to the BMD method to determine the in vitro susceptibility to CFD, while the strip test exhibited major limitations. Full article
(This article belongs to the Special Issue Carbapenem-Resistant Enterobacterales: Development of New Antibiotics)
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11 pages, 735 KiB  
Article
Antimicrobial Resistant Pathogens Detected in Raw Pork and Poultry Meat in Retailing Outlets in Kenya
by Patrick Muinde, John Maina, Kelvin Momanyi, Victor Yamo, John Mwaniki and John Kiiru
Antibiotics 2023, 12(3), 613; https://doi.org/10.3390/antibiotics12030613 - 20 Mar 2023
Cited by 1 | Viewed by 3084
Abstract
There is increasing proof of bacterial resistance to antibiotics all over the world, and this puts the effectiveness of antimicrobials that have been essential in decreasing disease mortality and morbidity at stake. The WHO has labeled some classes of antimicrobials as vitally important [...] Read more.
There is increasing proof of bacterial resistance to antibiotics all over the world, and this puts the effectiveness of antimicrobials that have been essential in decreasing disease mortality and morbidity at stake. The WHO has labeled some classes of antimicrobials as vitally important to human health. Bacteria from animals are thought to be reservoirs of resistance genes that can be transferred to humans through the food chain. This study aimed to identify the resistance patterns of bacteria from pork and poultry meat samples purchased from leading retail outlets in Kenya. Of the 393 samples collected, 98.4% of pork and 96.6% of poultry were contaminated with high levels of bacteria. Among the 611 bacterial isolates recovered, 38.5% were multi-drug resistant. This resistance was noted for critically essential antimicrobials (according to the WHO) such as rifampicin (96%), ampicillin (35%), cefotaxime (9%), cefepime (6%), and ciprofloxacin (6%). Moreover, there was high resistance to key antimicrobials for veterinary medicine such as tetracycline (39%), sulfamethoxazole (33%), and trimethoprim (30%). It is essential to spread awareness about the judicious use of antibiotics and take preventive measures to reduce disease burden. Full article
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13 pages, 286 KiB  
Article
Prevalence and Predictors of Antibiotic Self-Medication in Sudan: A Descriptive Cross-Sectional Study
by Mohamed A. Hussain, Ahmed O. Mohamed, Omalhassan A. Abdelkarim, Bashir A. Yousef, Asma A. Babikir, Maysoon M. Mirghani, Entsar A. Mohamed, Wadah Osman, Ramzi A. Mothana and Rashid Elhag
Antibiotics 2023, 12(3), 612; https://doi.org/10.3390/antibiotics12030612 - 20 Mar 2023
Cited by 3 | Viewed by 2217
Abstract
Background: Self-medication with antibiotics (SMA) is one of the common factors which precipitate antimicrobial resistance, yet if effective implementations are amended it can be effortlessly controlled. The present study aimed to estimate the prevalence and predictors of SMA in Sudan. Methods: The study [...] Read more.
Background: Self-medication with antibiotics (SMA) is one of the common factors which precipitate antimicrobial resistance, yet if effective implementations are amended it can be effortlessly controlled. The present study aimed to estimate the prevalence and predictors of SMA in Sudan. Methods: The study adopted a cross-sectional study design conducted in all Sudan states between June and December 2021. Multi-stage stratified cluster sampling was used. A semi-structured questionnaire was used for data collection. Descriptive statistics were used to present the data. Binary logistic regression was computed to investigate the possible factors which associated with SMA. Results: Out of 1492 participants surveyed, 71.3% utilize antibiotics as self-medication. The derived reasons for SMA were convenience (63.3%) and cost-saving (34.8%). Tonsillitis was the most common ailment behind SMA (55.5%). Log-binominal regression revealed that non-insured and low level of education participants were more likely to predict SMA. Regarding the practice, 40% changed the dose and/or antibiotics mainly owing to improvement (53.7%) or worsening of the condition (37.9%). The most commonly used antibiotic was amoxicillin/clavulanic acid (32.5%). Conclusions: Two out of three individuals in Sudan practice SMA mainly to manage upper respiratory tract ailments. Thus, the necessity of implementing an antimicrobial stewardship program throughout the country, as well as implementing effective legislation to prohibit dispensing antibiotics without prescription is urgently required. Full article
14 pages, 280 KiB  
Article
Teicoplanin-Resistant Coagulase-Negative Staphylococci: Do the Current Susceptibility Testing Methods Reliably Detect This Elusive Phenotype?
by Adriana D. Balasiu and Colin R. MacKenzie
Antibiotics 2023, 12(3), 611; https://doi.org/10.3390/antibiotics12030611 - 19 Mar 2023
Cited by 1 | Viewed by 1672
Abstract
Coagulase-negative staphylococci (CoNS), members of the skin commensal microbiota, are increasingly associated with local or systemic infections due to a shift in patient populations in recent decades. Subsequently, more CoNS strains have been subjected to antibiotic susceptibility testing (AST), thus leading to the [...] Read more.
Coagulase-negative staphylococci (CoNS), members of the skin commensal microbiota, are increasingly associated with local or systemic infections due to a shift in patient populations in recent decades. Subsequently, more CoNS strains have been subjected to antibiotic susceptibility testing (AST), thus leading to the increased detection of teicoplanin resistance. However, data concerning teicoplanin resistance among CoNS strains remain limited, heterogeneous, and inconclusive. We collected 162 consecutive CoNS strains identified using Vitek-2 as teicoplanin-resistant and tested them with a range of AST methods. The results of standard and high inoculum broth microdilution (sBMD; hBMD), agar dilution (AD) after 24 h and 48 h incubation, standard and macrogradient diffusion strip (sGDT, MET), screening agar, and disc diffusion were compared to assess their robustness and to establish a diagnostic algorithm to detect teicoplanin resistance. sBMD was used as the reference method, and the lowest number of strains were teicoplanin-resistant using this method. sGDT and disc diffusion generated similar results to sBMD. Compared with sBMD, AD-24 h generated the lowest number of false teicoplanin-resistant strains, followed by hBMD, AD-48 h, and Vitek-2. sGDT, a fast, easy, affordable method in diagnostic settings, generated the highest rate of false teicoplanin-susceptible strains. Vitek-2 testing produced the highest number of teicoplanin-resistant strains. Only in two strains was the initial Vitek-2 teicoplanin resistance confirmed using five other AST methods. In conclusion, the different antibiotic susceptibility testing methods generated inconsistent, inconclusive, and discrepant results, thus making it difficult to establish a diagnostic algorithm for suspected teicoplanin resistance. Teicoplanin testing proved to be challenging and easily influenced by technical factors. This study aimed not only to raise awareness of teicoplanin resistance testing but also of the need for future studies focusing on the clinical efficacy of teicoplanin in relation to its susceptibility results. Full article
17 pages, 1463 KiB  
Article
Assessment of the Microbiological Acceptability of White Cheese (Akkawi) in Lebanon and the Antimicrobial Resistance Profiles of Associated Escherichia coli
by Nasri Daher Hussein, Jouman W. Hassan, Marwan Osman, Khaled El-Omari, Samer A. Kharroubi, Imad Toufeili and Issmat I. Kassem
Antibiotics 2023, 12(3), 610; https://doi.org/10.3390/antibiotics12030610 - 19 Mar 2023
Cited by 4 | Viewed by 2418
Abstract
Dairy foods are a staple in Lebanon, a low- and middle-income country that has been experiencing serious challenges to food safety and antimicrobial stewardship among other issues. The microbiological acceptability of dairy products has been of increasing concern. This is partially due to [...] Read more.
Dairy foods are a staple in Lebanon, a low- and middle-income country that has been experiencing serious challenges to food safety and antimicrobial stewardship among other issues. The microbiological acceptability of dairy products has been of increasing concern. This is partially due to the failing economy and prolonged power outages that affect the quality of raw material and disrupt the dairy cold chain, respectively. Therefore, we assessed the microbiological acceptability of Akkawi, a popular white-brined cheese in Lebanon. For this purpose, we quantified the densities of Escherichia coli (a fecal indicator) and Staphylococcus aureus in cheeses collected from Lebanese retail stores. Additionally, we evaluated the antibiotic resistance profiles of the E. coli isolated from the cheese. E. coli and S. aureus were detected in 40 (80%) and 16 (32%) of the 50 cheese samples, respectively. Notably, 40 (80%) and 16 (32%) of the samples exceeded the maximum permissible limit of E. coli and S. aureus, respectively. A high percentage of the 118 E. coli isolated from the cheeses showed resistance to clinically and agriculturally important antibiotics, while 89 (75%) isolates were classified as multidrug-resistant (MDR). Given that Akkawi can be consumed without cooking, our findings highlight serious food safety and antimicrobial resistance problems that require immediate interventions. Full article
(This article belongs to the Special Issue Non-antibiotic Approaches to Control Food-Borne Pathogens)
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11 pages, 3951 KiB  
Article
Effect of Dielectric Barrier Discharge Plasma against Listeria monocytogenes Mixed-Culture Biofilms on Food-Contact Surfaces
by Min Gyu Song, Pantu Kumar Roy, Eun Bi Jeon, So Hee Kim, Min Soo Heu, Jung-Suck Lee, Jae-Suk Choi, Jin-Soo Kim and Shin Young Park
Antibiotics 2023, 12(3), 609; https://doi.org/10.3390/antibiotics12030609 - 19 Mar 2023
Cited by 3 | Viewed by 1670
Abstract
Listeria monocytogenes is a major foodborne pathogen. Various methods can be used to control biofilms formed by foodborne pathogens. Recently, the food industry has become interested in plasma, which can be used as a non-thermal technology with minimum changes to product quality. In [...] Read more.
Listeria monocytogenes is a major foodborne pathogen. Various methods can be used to control biofilms formed by foodborne pathogens. Recently, the food industry has become interested in plasma, which can be used as a non-thermal technology with minimum changes to product quality. In this study, the effects of dielectric barrier discharge (DBD) plasma on L. monocytogenes mixed-culture biofilms formed on stainless steel (SS), latex hand glove (HG), and silicone rubber (SR) were investigated. DBD plasma effectuated reductions of 0.11–1.14, 0.28–1.27 and 0.37–1.55 log CFU/cm2, respectively. Field emission scanning electron microscopy (FE-SEM) demonstrated that DBD plasma cuts off intercellular contact and induces cell decomposition to prevent the development of biological membranes. It was confirmed that the formed biofilms collapsed and separated into individual bacteria. Our findings suggest that DBD plasma can be used as an alternative non-heating sterilization technology in the food industry to reduce biofilm formation on bacterial targets. Full article
(This article belongs to the Special Issue Antimicrobial Resistance of Foodborne Bacteria and Food Safety)
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24 pages, 2303 KiB  
Review
Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review
by Ali A. Rabaan, Tarek Sulaiman, Shamsah H. Al-Ahmed, Zainab A. Buhaliqah, Ali A. Buhaliqah, Buthina AlYuosof, Mubarak Alfaresi, Mona A. Al Fares, Sara Alwarthan, Mohammed S. Alkathlan, Reem S. Almaghrabi, Abdulmonem A. Abuzaid, Jaffar A. Altowaileb, Maha Al Ibrahim, Eman M. AlSalman, Fatimah Alsalman, Mohammad Alghounaim, Ahmed S. Bueid, Awad Al-Omari and Ranjan K. Mohapatra
Antibiotics 2023, 12(3), 608; https://doi.org/10.3390/antibiotics12030608 - 18 Mar 2023
Cited by 7 | Viewed by 4676
Abstract
Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used [...] Read more.
Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans. Full article
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7 pages, 1197 KiB  
Case Report
Late-Onset Bleb-Related Endophthalmitis Caused by Moraxella nonliquefaciens: A Case Report
by Su-Chin Shen and Kuan-Jen Chen
Antibiotics 2023, 12(3), 607; https://doi.org/10.3390/antibiotics12030607 - 18 Mar 2023
Cited by 1 | Viewed by 1230
Abstract
Moraxella species are Gram-negative coccobacilli that typically colonize the flora of the human upper respiratory tract and have low pathogenic potential. There are limited case reports implicating the organisms as the cause of endocarditis, bacteremia, septic arthritis, ocular infection, and meningitis. In cases [...] Read more.
Moraxella species are Gram-negative coccobacilli that typically colonize the flora of the human upper respiratory tract and have low pathogenic potential. There are limited case reports implicating the organisms as the cause of endocarditis, bacteremia, septic arthritis, ocular infection, and meningitis. In cases of keratitis and conjunctivitis, Moraxella nonliquefaciens is not commonly isolated from the ocular surface. We present a case of a diabetic patient who developed late-onset bleb-related endophthalmitis caused by M. nonliquefaciens 4 years after glaucoma filtering surgery. Within one day, the patient presented with an acutely fulminant course with sudden visual loss, redness, and ocular pain. Appropriate antibiotic treatment and early vitrectomy resulted in a favorable final visual acuity of 20/100, which was his vision prior to infection. The use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass spectrometry (MALDI-TOF MS) enabled the rapid identification of the organism. Endophthalmitis caused by M. nonliquefaciens should be considered in patients who underwent glaucoma filtering surgery with antifibrotic agents. Full article
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12 pages, 605 KiB  
Systematic Review
Antibiotic Prophylaxis in One-Stage Revision of Septic Total Knee Arthroplasty: A Scoping Review
by Carlo Ciccullo, Thomas Neri, Luca Farinelli, Antonio Gigante, Rémi Philippot, Frederic Farizon and Bertrand Boyer
Antibiotics 2023, 12(3), 606; https://doi.org/10.3390/antibiotics12030606 - 18 Mar 2023
Viewed by 1870
Abstract
Background: Total knee replacement (TKA) is becoming a routine procedure in orthopedic surgery. One of the possible complications of this surgery is periprosthetic joint infection (PJI). The purpose of this study is to identify, through a literature review, which antibiotic is used as [...] Read more.
Background: Total knee replacement (TKA) is becoming a routine procedure in orthopedic surgery. One of the possible complications of this surgery is periprosthetic joint infection (PJI). The purpose of this study is to identify, through a literature review, which antibiotic is used as prophylaxis for septic one-stage revision TKA and what is the rationale for its use. Methods: We searched: MEDLINE, Embase, PsycINFO on Ovid, the Cochrane Library, and the Google Scholar Database. The searches were limited by date (January 2005 to September 2022) and to the English language. All types of original research were considered, including prospective or retrospective longitudinal studies, cross-sectional studies, and randomized trials. The specific search terms were ((antibiotic [MeSH]) AND (prophylaxis)) and (TKA OR TKR OR “Arthroplasty, Replacement, Knee” [MeSH] OR ((knee) adj2 (replace* OR arthroplasty* OR prosthe*))). Results: Despite our research efforts, we found no article capable of answering the question of which antibiotic to use as surgical prophylaxis for a septic revision one-stage TKA. Conclusions: Although the research results are inconclusive, we would recommend using the same antibiotic prophylaxis as for primary joint replacement, i.e., cefazolin, as it was recommended for its low side effect rate and relative effectiveness. Full article
(This article belongs to the Special Issue Antibiotics Prophylaxis for Knee Arthroplasty: Benefits and Problems)
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13 pages, 3440 KiB  
Article
Use of Medical-Grade Honey to Treat Clinically Infected Heel Pressure Ulcers in High-Risk Patients: A Prospective Case Series
by Georgios E. Papanikolaou, Georgios Gousios and Niels A. J. Cremers
Antibiotics 2023, 12(3), 605; https://doi.org/10.3390/antibiotics12030605 - 17 Mar 2023
Cited by 4 | Viewed by 5276
Abstract
Management of locally infected heel-pressure ulcers (HPUs) remains challenging, and given the increasing occurrence of infections resistant to antibiotic therapy and patients’ unwillingness to surgery, innovative and effective approaches must be considered. Medical-grade honey (MGH) could be an alternative therapeutic approach due to [...] Read more.
Management of locally infected heel-pressure ulcers (HPUs) remains challenging, and given the increasing occurrence of infections resistant to antibiotic therapy and patients’ unwillingness to surgery, innovative and effective approaches must be considered. Medical-grade honey (MGH) could be an alternative therapeutic approach due to its broad-spectrum antimicrobial activity and healing properties. This study aimed to present the high effectiveness and safety of MGH for the conservative treatment of clinically infected HPUs. In this case series, we have prospectively studied nine patients with local signs of infected HPUs. In all cases, HPUs persisted for more than 4 weeks, and previous treatments with topical antibiotics or antiseptic products were ineffective. All patients were at high-risk to develop HPU infection due to their advanced age (median age of 86 years), several comorbidities, and permanent immobility. All wounds were treated with MGH products (L-Mesitran), leading to infection resolution within 3–4 weeks and complete wound healing without complication. Considering the failure of previous treatments and the chronic nature of the wounds, MGH was an effective treatment. MGH-based products are clinically and cost-effective for treating hard-to-heal pressure ulcers such as HPUs. Thus, MGH can be recommended as an alternative or complementary therapy in wound healing. Full article
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9 pages, 250 KiB  
Article
Disc Diffusion and ComASP® Cefiderocol Microdilution Panel to Overcome the Challenge of Cefiderocol Susceptibility Testing in Clinical Laboratory Routine
by Gabriele Bianco, Matteo Boattini, Sara Comini, Giuliana Banche, Rossana Cavallo and Cristina Costa
Antibiotics 2023, 12(3), 604; https://doi.org/10.3390/antibiotics12030604 - 17 Mar 2023
Cited by 5 | Viewed by 1780
Abstract
Cefiderocol susceptibility testing represents a major challenge for clinical microbiology. Although disc diffusion showed robustness to test cefiderocol susceptibility, large areas of technical uncertainty (ATU) are reported by current EUCAST breakpoints. Herein, we evaluated the in vitro activity of cefiderocol on a collection [...] Read more.
Cefiderocol susceptibility testing represents a major challenge for clinical microbiology. Although disc diffusion showed robustness to test cefiderocol susceptibility, large areas of technical uncertainty (ATU) are reported by current EUCAST breakpoints. Herein, we evaluated the in vitro activity of cefiderocol on a collection of 286 difficult-to-treat Gram-negative isolates using disc diffusion and ComASP® cefiderocol microdilution panel. Broth microdilution (BMD) in iron-depleted Mueller–Hinton broth was used as reference method. Following the EUCAST guidelines, disc diffusion allowed to determine cefiderocol susceptibility (susceptible or resistant) in 78.6%, 88.1%, 85.4% and 100% of Enterobacterales, P. aeruginosa, A. baumannii and S. maltophilia isolates tested, respectively. ComASP® cefiderocol panel showed 94% and 84% of overall categorical agreement and essential agreement. Only one very major error and two major errors were observed, for MIC values nearly close to the resistance breakpoint (2 mg/L). Overall, 20.5% of the carbapenemase-producing Enterobacterales that achieved ATU results by the disc diffusion method tested resistant by both ComASP® panel and reference BMD. Conversely, all VIM-producing P. aeruginosa showed MIC values in the susceptible range (≤2 mg/L). Lastly, only six out of seven (85.7%) A. baumannii isolates showing inhibition zones <17 mm tested resistant by both ComASP® panel and the reference BMD suggesting that inhibition zone <17 mm are not unequivocally suggestive of resistance. Our results, although obtained on a limited number of isolates, suggest that the combination of disc diffusion with a ComASP® cefiderocol microdilution panel could be a viable solution to overcome the challenge of cefiderocol susceptibility testing in routine microbiology laboratories. Full article
20 pages, 2621 KiB  
Article
Serving Two Masters: Effect of Escherichia coli Dual Resistance on Antibiotic Susceptibility
by Olusola Jeje, Akamu J. Ewunkem, Liesl K. Jeffers-Francis and Joseph L. Graves, Jr.
Antibiotics 2023, 12(3), 603; https://doi.org/10.3390/antibiotics12030603 - 17 Mar 2023
Cited by 3 | Viewed by 1547
Abstract
The prevalence of multidrug-resistant bacteria and their increased pathogenicity has led to a growing interest in metallic antimicrobial materials and bacteriophages as potential alternatives to conventional antibiotics. This study examines how resistance to excess iron (III) influences the evolution of bacteriophage resistance in [...] Read more.
The prevalence of multidrug-resistant bacteria and their increased pathogenicity has led to a growing interest in metallic antimicrobial materials and bacteriophages as potential alternatives to conventional antibiotics. This study examines how resistance to excess iron (III) influences the evolution of bacteriophage resistance in the bacterium Escherichia coli. We utilized experimental evolution in E. coli to test the effect of the evolution of phage T7 resistance on populations resistant to excess iron (III) and populations without excess iron resistance. Phage resistance evolved rapidly in both groups. Dual-resistant (iron (III)/phage) populations were compared to their controls (excess iron (III)-resistant, phage-resistant, no resistance to either) for their performance against each stressor, excess iron (III) and phage; and correlated resistances to excess iron (II), gallium (III), silver (I) and conventional antibiotics. Excess iron (III)/phage-resistant populations demonstrated superior 24 h growth compared to all other populations when exposed to increasing concentrations of iron (II, III), gallium (III), ampicillin, and tetracycline. No differences in 24 h growth were shown between excess iron (III)/phage-resistant and excess iron (III)-resistant populations in chloramphenicol, sulfonamide, and silver (I). The genomic analysis identified selective sweeps in the iron (III) resistant (rpoB, rpoC, yegB, yeaG), phage-resistant (clpX →/→ lon, uvaB, yeaG, fliR, gatT, ypjF, waaC, rpoC, pgi, and yjbH) and iron (III)/phage resistant populations (rcsA, hldE, rpoB, and waaC). E. coli selected for resistance to both excess iron (III) and T7 phage showed some evidence of a synergistic effect on various components of fitness. Dual selection resulted in correlated resistances to ionic metals {iron (II), gallium (III), and silver (I)} and several conventional antibiotics. There is a likelihood that this sort of combination antimicrobial treatment may result in bacterial variants with multiple resistances. Full article
(This article belongs to the Section Bacteriophages)
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12 pages, 279 KiB  
Article
Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice
by Cristina Villanueva-Bueno, Elena Montecatine-Alonso, Francisco Jiménez-Parrilla, María González-López, Silvia Manrique-Rodríguez, Francisco Moreno-Ramos, Carme Cañete-Ramírez, Elisenda Dolz, Ana García-Robles, José Manuel Caro-Teller, María Teresa Moral-Pumarega, Elena Bergon-Sendin, María Teresa Gómez-Trevecedo Calvo, Carmen Gallego-Fernández, Concepción Álvarez del Vayo-Benito, Marta Mejías-Trueba, María Victoria Gil-Navarro and Paediatric Antimicrobial Defined Daily Dose Study Group (KiDDDs)
Antibiotics 2023, 12(3), 602; https://doi.org/10.3390/antibiotics12030602 - 17 Mar 2023
Viewed by 1371
Abstract
Background: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion [...] Read more.
Background: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. Methods: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. Results: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. Conclusion: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability. Full article
(This article belongs to the Special Issue Current Updates in Antimicrobial Resistance in Pediatric Patients)
12 pages, 1351 KiB  
Article
Direct Detection of KPC Peak from Positive Blood Cultures Using MALDI-TOF MS: Are We There Yet?
by Natália Kehl Moreira, Camila Mörschbächer Wilhelm, Aymê Duarte Echevarria, Fabiana Caroline Zempulski Volpato, Priscila Lamb Wink, Afonso Luís Barth and Juliana Caierão
Antibiotics 2023, 12(3), 601; https://doi.org/10.3390/antibiotics12030601 - 17 Mar 2023
Cited by 2 | Viewed by 1578
Abstract
Detecting carbapenemase-associated carbapenem resistance is a subject of major clinical and epidemiological concern as it influences therapeutic choice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed as a means to assess bacterial resistance mechanisms. We aimed to detect the [...] Read more.
Detecting carbapenemase-associated carbapenem resistance is a subject of major clinical and epidemiological concern as it influences therapeutic choice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed as a means to assess bacterial resistance mechanisms. We aimed to detect the KPC enzyme directly from positive blood cultures using MALDI-TOF MS. To do so, 102 clinical Enterobacteria were evaluated, including 59 blaKPC positives. Proteins were extracted using formic acid, isopropyl alcohol, and water (17:33:50) and spotted onto a steel target plate using the double-layer sinapinic acid technique. Two parameters were considered: (i) the visual detection of a clear peak with the expected KPC m/z and (ii) the evaluation of the relative intensity of the ions in the peak. A peak was observed in 56/59 blaKPC-positive isolates (94.9% sensitivity), with no false-positive results (100% specificity). When considering intensity, with a cut-off ≥120 (a.u.), sensitivity was 94.9% and specificity was 95.3%. We proposed a “buffer” zone, with intermediate values of intensity (115 to 125) reaching 100% sensitivity and specificity. The detection of KPC peaks directly from positive blood cultures using MALDI-TOF MS is feasible and rapid, which may improve appropriate patient therapy and antimicrobial stewardship. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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10 pages, 1522 KiB  
Communication
In Vitro Bacterial Competition of Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli against Coagulase-Negative Staphylococci from Bovine Mastitis Milk
by Anyaphat Srithanasuwan, Montira Intanon, Wasana Chaisri and Witaya Suriyasathaporn
Antibiotics 2023, 12(3), 600; https://doi.org/10.3390/antibiotics12030600 - 16 Mar 2023
Viewed by 1583
Abstract
Intramammary infection (IMI) from the environment and infected quarters can cause co-infection. The objective of this study was to determine the ability of coagulase-negative staphylococci (CNS) to survive in the same environment as Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli as [...] Read more.
Intramammary infection (IMI) from the environment and infected quarters can cause co-infection. The objective of this study was to determine the ability of coagulase-negative staphylococci (CNS) to survive in the same environment as Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli as major pathogens. In total, 15 and 242 CNS strains were used in Experiment I and Experiment II, respectively. Both experiments were separated into three conditions: culture with CNS 24 h before (PRIOR), after (AFTER), and at the same time (EQUAL). The lack of a clear zone, regardless of size, was determined to be the key to the survival of both. The CNS species’ percentages of survival against major pathogens were tested using Fisher’s exact test. Differences in the percentages of survival were evident among the CNS species in all conditions. For the PRIOR condition, all CNS mostly survived when living with major strains; however, S. chromogenes could degrade S. agalactiae. Although most CNS strains were degraded in the AFTER and EQUAL conditions, some strains of S. hominis and S. simulans could resist S. aureus and S. agalactiae. In conclusion, some specific strains of CNS are able to survive in an environment with major pathogens. Research into the survival strains may indicate that the concept of novel bacteria with bacteriolytic capabilities might be possible as a novel mastitis treatment. Full article
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