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Antibiotics
Volume 13
Issue 12
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Antibiotics, Volume 13, Issue 12 (December 2024) – 131 articles

Cover Story (view full-size image): Periprosthetic joint infection (PJI) is an increasingly common and deleterious complication after joint replacement surgery, requiring surgery and prolonged antibiotic therapy. Vancomycin is commonly used for PJI caused by staphylococci, but our findings show that standard dosing regimens often fail to achieve therapeutic levels. Our study thus highlights the limitations of vancomycin therapy and emphasizes the importance of individualized dosing and regular monitoring. Alternative agents, such as daptomycin and dalbavancin, which do not require as extensive monitoring, could perhaps be used to improve outcomes after PJI. View this paper
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19 pages, 4130 KiB  
Article
Identification and Bioactivity Analysis of a Novel Bacillus Species, B. maqinnsis sp. nov. Bos-x6-28, Isolated from Feces of the Yak (Bos grunniens)
by Qiang Ma, Xin Xiang, Yan Ma, Guangzhi Li, Xingyu Liu, Boai Jia, Wenlin Yang, Hengxia Yin and Benyin Zhang
Antibiotics 2024, 13(12), 1238; https://doi.org/10.3390/antibiotics13121238 - 23 Dec 2024
Viewed by 626
Abstract
Background: The identification of novel bacterial species from the intestines of yaks residing on the Qinghai–Tibet Plateau is pivotal in advancing our understanding of host–microbiome interactions and represents a promising avenue for microbial drug discovery. Methods: In this study, we conducted a polyphasic [...] Read more.
Background: The identification of novel bacterial species from the intestines of yaks residing on the Qinghai–Tibet Plateau is pivotal in advancing our understanding of host–microbiome interactions and represents a promising avenue for microbial drug discovery. Methods: In this study, we conducted a polyphasic taxonomic analysis and bioactive assays on a Bacillus strain, designated Bos-x6-28, isolated from yak feces. Results: The findings revealed that strain Bos-x6-28 shares a high 16S rRNA gene sequence similarity (98.91%) with B. xiamenensis HYC-10T and B. zhangzhouensis DW5-4T, suggesting close phylogenetic affinity. Physiological and biochemical characterizations demonstrated that Bos-x6-28 could utilize nine carbon sources, including D-galactose, inositol, and fructose, alongside nine nitrogen sources, such as threonine, alanine, and proline. Analysis of biochemical markers indicated that Bos-x6-28’s cell wall hydrolysates contained mannose, glucose, and meso-2,6-diaminopimelic acid, while menaquinone-7 (MK-7), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylglycerol (DPG) were found in the cell membrane. The primary cellular fatty acids included C16:0 (28.00%), cyclo-C17:0 (19.97%), C14:0 (8.75%), cyclo-C19:0 (8.52%), iso-C15:0 (5.49%), anteiso-C15:0 (4.61%), and C12:0 (3.15%). Whole-genome sequencing identified a genome size of 3.33 Mbp with 3353 coding genes. Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses confirmed Bos-x6-28 as a novel species, hereby named B. maqinnsis Bos-x6-28 (MCCC 1K09379). Further genomic analysis unveiled biosynthetic gene clusters encoding bioactive natural compounds, including β-lactones, sactipeptides, fengycin, and lichenysin analogs. Additionally, in vitro assays demonstrated that this strain exhibits antibacterial and cytotoxic activities. Conclusions: These findings collectively indicate the novel Bacillus species B. maqinnsis Bos-x6-28 as a promising source for novel antibiotic and antitumor agents. Full article
(This article belongs to the Special Issue Antimicrobial and Anti-Infective Activity of Natural Products, 2nd Edition)
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10 pages, 468 KiB  
Article
Study on the Efficacy and Safety of Tedizolid in Japanese Patients
by Kazuhiro Ishikawa, Yasumasa Tsuda and Nobuyoshi Mori
Antibiotics 2024, 13(12), 1237; https://doi.org/10.3390/antibiotics13121237 - 23 Dec 2024
Viewed by 879
Abstract
Background/Objective: Tedizolid (TZD), an oxazolidinone, causes fewer adverse events than linezolid (LZD). However, studies on the long-term efficacy and safety of TZD, particularly in patients with hematological malignancies (HMs), remain limited. This study aimed to evaluate the safety of long-term TZD use [...] Read more.
Background/Objective: Tedizolid (TZD), an oxazolidinone, causes fewer adverse events than linezolid (LZD). However, studies on the long-term efficacy and safety of TZD, particularly in patients with hematological malignancies (HMs), remain limited. This study aimed to evaluate the safety of long-term TZD use in Japanese patients, including those with HM. Methods: We retrospectively reviewed the medical records of patients aged 15 years and older who received TZD treatment at St. Luke’s International Hospital between 2018 and 2023. Patient demographics, treatment duration, adverse events, and clinical outcomes were analyzed. Results: Data from 35 patients and 40 treatment episodes were analyzed, including 13 episodes in patients with HM, of whom 65.0% were male, with a median age of 69.0 years (IQR: 24.5 years). The median treatment duration was 13.5 days (IQR: 46.8), with a maximum of 203 days. TZD was switched from other anti-MRSA agents in 82.5% of cases, including 42.5% from LZD. One patient discontinued TZD due to liver dysfunction, attributed to concomitant medication use. Clinical cure rates were significantly higher in the non-HM group compared to the HM group (88.9% vs. 38.5%). The 90-day mortality rate differed notably between the HM and non-HM groups (69.2% and 3.7%). Despite 100% microbiological eradication, infection-related mortality rates were 3.7% in the non-HM and 38.5% in the HM group. No reported cases of optic neuritis, Clostridioides difficile colitis, or major bleeding; Conclusions: TZD appears to be safe for long-term use, regardless of HM status, with no major complications observed in this cohort. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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8 pages, 209 KiB  
Brief Report
Efficacy of Cefiderocol Against Endophthalmitis Isolates
by Brennan Schilling, Michael Hii, Hazel Q. Shanks, Eric G. Romanowski, Jonathan B. Mandell, Robert M. Q. Shanks and Michael Zegans
Antibiotics 2024, 13(12), 1236; https://doi.org/10.3390/antibiotics13121236 - 23 Dec 2024
Viewed by 729
Abstract
Background/Objectives: Endophthalmitis is an intraocular microbial infection that can lead to permanent blindness, even with prompt anti-microbial therapy. Multi-drug-resistant organisms are on the rise, potentially limiting the efficacy of current empiric antibiotic therapies of intravitreal ceftazidime and vancomycin. Cefiderocol is a recent FDA- [...] Read more.
Background/Objectives: Endophthalmitis is an intraocular microbial infection that can lead to permanent blindness, even with prompt anti-microbial therapy. Multi-drug-resistant organisms are on the rise, potentially limiting the efficacy of current empiric antibiotic therapies of intravitreal ceftazidime and vancomycin. Cefiderocol is a recent FDA- and EMA-approved antibiotic for multi-drug-resistant Gram-negative bacteria. Methods: To better understand its potential utility in the treatment of ocular infections, the MIC of cefiderocol was compared to ceftazidime and amikacin in endophthalmitis bacterial isolates using Epsilometer testing. Because vancomycin is commonly given concomitantly as part of empiric endophthalmitis treatment, possible synergistic and antagonistic effects of concomitant vancomycin and cefiderocol were also evaluated. Results: Cefiderocol was found to have lower MIC values compared to ceftazidime for Pseudomonadales or Enterobacterales species. When comparing the MICs of cefiderocol and vancomycin, there appeared to be no antagonism between the two antibiotics. Conclusions: This is the first report exploring the use of cefiderocol in endophthalmitis strains. The results of this study show this is a promising antibiotic for multi-drug-resistant Gram-negative organisms but further research is needed to investigate its intraocular safety profile. Full article
(This article belongs to the Collection Antibiotics in Ophthalmology Practice)
12 pages, 1674 KiB  
Article
Comparative Genome Analysis of Canine Frederiksenia canicola Isolates
by Marianna Domán, Krisztina Pintér, Boglárka Dóra Pollák, Ágnes Pintér, Enikő Wehmann, Miklós Tenk and Tibor Magyar
Antibiotics 2024, 13(12), 1235; https://doi.org/10.3390/antibiotics13121235 - 22 Dec 2024
Viewed by 1084
Abstract
Background/Objectives: The One Health approach is crucial for managing and controlling the spread of antimicrobial resistance. Frederiksenia canicola is a recently identified bacterial species that seems to be a component of the oral microbiota of dogs; however, its pathogenic nature is questionable. [...] Read more.
Background/Objectives: The One Health approach is crucial for managing and controlling the spread of antimicrobial resistance. Frederiksenia canicola is a recently identified bacterial species that seems to be a component of the oral microbiota of dogs; however, its pathogenic nature is questionable. Methods: In this study, the antibacterial susceptibility of F. canicola isolates was determined using the disk diffusion and broth microdilution methods. Genome-wide comparative analyses were performed to identify the genetic factors driving virulence and antimicrobial drug resistance (e.g., virulence factors, antimicrobial resistance genes (ARGs) and prophage-related sequences). Results: Most of the F. canicola isolates lacked virulence-associated genes. F. canicola is likely resistant to clindamycin, lincomycin and neomycin, but susceptible to penicillin, erythromycin and enrofloxacin. Antimicrobial resistance genes were not found in the F. canicola genomes, but prophage-related sequences were identified, suggesting its potential in the transfer of genes associated with drug resistance between bacteria in the oral microbiome. Conclusions: F. canicola is presumably a commensal organism with low virulence potential, as evidenced by the absence of virulence-associated genes. As F. canicola can colonize a wide range of hosts, including humans, further investigation with a greater number of isolates is needed to better understand the role of F. canicola in disease development and the spread of drug resistance. Full article
(This article belongs to the Section Genetic and Biochemical Studies of Antibiotic Activity and Resistance)
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20 pages, 3137 KiB  
Article
Bacterial Pathogen Profiles and Antibiotic Resistance in Pediatric Leukemia Patients: Insights for Optimizing Infection Management in Immunocompromised Children
by Cristina Elena Singer, Alin Iulian Silviu Popescu, Renata Maria Văruț, Mihaela Popescu, Dira Loredana, Kristina Radivojevic and Petrescu Ileana Octavia
Antibiotics 2024, 13(12), 1234; https://doi.org/10.3390/antibiotics13121234 - 22 Dec 2024
Viewed by 786
Abstract
Background: This study investigates bacterial etiology and antibiotic resistance in pediatric leukemia patients to determine the impact of chronic pathology on treatment efficacy. Methods: Thirty cases of children aged 1–16 years (18 boys, 12 girls) were analyzed, identifying 13 pathogens, including 8 [...] Read more.
Background: This study investigates bacterial etiology and antibiotic resistance in pediatric leukemia patients to determine the impact of chronic pathology on treatment efficacy. Methods: Thirty cases of children aged 1–16 years (18 boys, 12 girls) were analyzed, identifying 13 pathogens, including 8 Gram-positive and 5 Gram-negative bacteria. Results: Among the patients, 11 girls presented with acute lymphoblastic leukemia (ALL) type B, while one boy and one girl had acute myeloid leukemia, and, as for boys, three had ALL type T and two had pre-B ALL. The most common pathogens were methicillin-resistant Staphylococcus aureus (MRSA, 11 patients), methicillin-sensitive Staphylococcus aureus (MSSA, 6 patients), Klebsiella spp., and Staphylococcus epidermidis. Due to the patients’ compromised health, most required intensive care and strong antibiotic regimens, including linezolid, vancomycin, and ertapenem, which showed limited resistance. Conclusions: These findings highlight the critical importance of understanding bacterial resistance patterns to guide effective treatments in vulnerable populations. Knowing specific resistance profiles can be lifesaving, allowing for tailored therapies that improve survival rates in children with leukemia facing serious bacterial infections. Focusing on the dual aspects of pediatric patients and multidrug-resistant bacterial infections, this study aims to highlight the importance of addressing these factors together to enhance therapeutic approaches in vulnerable populations. Full article
(This article belongs to the Special Issue Antibiotic Resistance: From the Bench to Patients, 2nd Edition)
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10 pages, 914 KiB  
Article
Impact of Haemoadsorption Therapy on Short Term Mortality and Vasopressor Dependency in Severe Septic Shock with Acute Kidney Injury: A Retrospective Cohort Study
by Danny Epstein, Karawan Badarni and Yaron Bar-Lavie
Antibiotics 2024, 13(12), 1233; https://doi.org/10.3390/antibiotics13121233 - 22 Dec 2024
Viewed by 884
Abstract
Background/Objectives: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a major challenge in ICUs. This study evaluated whether combining haemoadsorption therapy with continuous renal replacement therapy (CRRT) reduces ICU and short-term mortality in patients with severe [...] Read more.
Background/Objectives: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a major challenge in ICUs. This study evaluated whether combining haemoadsorption therapy with continuous renal replacement therapy (CRRT) reduces ICU and short-term mortality in patients with severe septic shock and acute kidney injury (AKI) requiring CRRT. Methods: A single-centre retrospective cohort study was conducted at Rambam Health Care Campus, Haifa, Israel, from January 2018 to February 2024. Data were collected from ICU patients with severe septic shock and AKI requiring CRRT. Patients were divided into two groups: those receiving haemoadsorption therapy with CRRT and those receiving CRRT alone. Primary and secondary endpoints included ICU, 30 and 60-day mortality, vasopressor dependency index (VDI), and lactate levels. Results: Out of 545 patients with septic shock, 133 developed AKI requiring CRRT, and 76 met the inclusion criteria. The haemoadsorption group (n = 47) showed significant reductions in blood lactate levels and VDI after 24 h compared to the CRRT alone group (n = 29). ICU mortality was significantly lower in the haemoadsorption group (34.0% vs. 65.5%, p = 0.008), as was 30 and 60-day mortality (34.0% vs. 62.1%, p = 0.02, and 48.9% vs. 75.9%, p = 0.002). Multivariate analysis confirmed haemoadsorption therapy as independently associated with lower ICU and 30-day but not 60-day mortality. Conclusions: Haemoadsorption therapy combined with CRRT in patients with severe septic shock and AKI requiring CRRT is associated with improved lactate clearance, reduced vasopressor requirements, and lower ICU and 30-day mortality. Further high-quality randomized controlled trials are needed to confirm these findings. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship and Infection Prevention in Intensive Care Unit)
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22 pages, 11558 KiB  
Article
Chemical Composition and Antibacterial Effect of Clove and Thyme Essential Oils on Growth Inhibition and Biofilm Formation of Arcobacter spp. and Other Bacteria
by Leona Hofmeisterová, Tomáš Bajer, Maciej Walczak and David Šilha
Antibiotics 2024, 13(12), 1232; https://doi.org/10.3390/antibiotics13121232 - 20 Dec 2024
Viewed by 702
Abstract
Background: In recent years, significant resistance of microorganisms to antibiotics has been observed. A biofilm is a structure that significantly aids the survival of the microbial population and also significantly affects its resistance. Methods: Thyme and clove essential oils (EOs) were subjected to [...] Read more.
Background: In recent years, significant resistance of microorganisms to antibiotics has been observed. A biofilm is a structure that significantly aids the survival of the microbial population and also significantly affects its resistance. Methods: Thyme and clove essential oils (EOs) were subjected to chemical analysis using gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with a flame ionization detector (GC-FID). Furthermore, the antimicrobial effect of these EOs was tested in both the liquid and vapor phases using the volatilization method. The effect of the EOs on growth parameters was monitored using an RTS-8 bioreactor. However, the effect of the EOs on the biofilm formation of commonly occurring bacteria with pathogenic potential was also monitored, but for less described and yet clinically important strains of Arcobacter spp. Results: In total, 37 and 28 compounds were identified in the thyme and clove EO samples, respectively. The most common were terpenes and also derivatives of phenolic substances. Both EOs exhibited antimicrobial activity in the liquid and/or vapor phase against at least some strains. The determined antimicrobial activity of thyme and clove oil was in the range of 32–1024 µg/mL in the liquid phase and 512–1024 µg/mL in the vapor phase, respectively. The results of the antimicrobial effect are also supported by similar conclusions from monitoring growth curves using the RTS bioreactor. The effect of EOs on biofilm formation differed between strains. Biofilm formation of Pseudomonas aeruginosa was completely suppressed in an environment with a thyme EO concentration of 1024 µg/mL. On the other hand, increased biofilm formation was found, e.g., in an environment of low concentration (1–32 µg/mL). Conclusions: The potential of using natural matrices as antimicrobials or preservatives is evident. The effect of these EOs on biofilm formation, especially Arcobacter strains, is described for the first time. Full article
(This article belongs to the Special Issue Microbial Biofilms: Identification, Resistance and Novel Drugs)
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11 pages, 4054 KiB  
Article
The Effect of Medium-Chain Triglycerides Oil on Candida albicans and Streptococcus mutans in Planktonic and Mucosal Models
by Hiba Rashid Alyami, Yan Wu, Abdulwahab Aljughaiman, Ting Li, Abdullah Almulhim, Joseph M. Bliss and Jin Xiao
Antibiotics 2024, 13(12), 1231; https://doi.org/10.3390/antibiotics13121231 - 20 Dec 2024
Viewed by 1099
Abstract
Despite MCT oil’s potential antimicrobial benefits for gastrointestinal health, its effects on disrupting cariogenic pathogens on oral mucosal surfaces remain underexplored. This study evaluated the impact of MCT oil on the adhesion and invasion of Candida albicans and Streptoccocus mutans using planktonic and [...] Read more.
Despite MCT oil’s potential antimicrobial benefits for gastrointestinal health, its effects on disrupting cariogenic pathogens on oral mucosal surfaces remain underexplored. This study evaluated the impact of MCT oil on the adhesion and invasion of Candida albicans and Streptoccocus mutans using planktonic and mucosal models. First, a planktonic model was used to assess the impact of various concentrations of MCT on the growth of S. mutans and C. albicans. Subsequently, a mucosal model was established by seeding TR-146 human buccal mucosal epithelial cells on a 3 µm porous transwell membrane, forming an epithelial barrier. MCT oil was then applied to the epithelial barriers in different durations (10, 30, and 60 min). Subsequently, C. albicans and S. mutans were introduced in the transwell and their adherence to the epithelial cells and their transmigration through the barriers was assessed using colony-forming unit counts and the barrier integrity was assessed by trans epithelial electrical resistance (TEER). Furthermore, cytotoxicity of MCT oil on mucosal cells was assessed by AlamarBlue assay. We found that higher MCT concentrations (90% and 100%) significantly inhibited C. albicans and S. mutans growth in planktonic conditions. Additionally, MCT oil reduced S. mutans adhesion to epithelial cells, highlighting its potential to interfere with bacterial attachment and colonization to oral mucosa. However, the oil had limited effects on C. albicans adhesion and transmigration. MCT demonstrated no cytotoxic effects on the viability of epithelial cells. The study findings highlight the potential benefits of MCT oil, particularly in oral bacterial inhibition, for oral health applications. Full article
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21 pages, 2370 KiB  
Article
Phenotypic and Genomic Characterization of ESBL- and AmpC-β-Lactamase-Producing Enterobacterales Isolates from Imported Healthy Reptiles
by Franziska Unger, Tobias Eisenberg, Ellen Prenger-Berninghoff, Ursula Leidner, Torsten Semmler and Christa Ewers
Antibiotics 2024, 13(12), 1230; https://doi.org/10.3390/antibiotics13121230 - 20 Dec 2024
Viewed by 1047
Abstract
Background/Objectives: Reptiles are known reservoirs for members of the Enterobacterales. We investigated antimicrobial resistance (AMR) patterns, the diversity of extended-spectrum-/AmpC-β-lactamases (ESBL/AmpC) genes and the genomic organization of the ESBL/AmpC producers. Methods: A total of 92 shipments with 184 feces, skin, and urinate [...] Read more.
Background/Objectives: Reptiles are known reservoirs for members of the Enterobacterales. We investigated antimicrobial resistance (AMR) patterns, the diversity of extended-spectrum-/AmpC-β-lactamases (ESBL/AmpC) genes and the genomic organization of the ESBL/AmpC producers. Methods: A total of 92 shipments with 184 feces, skin, and urinate samples of live healthy reptiles were obtained during border inspections at Europe’s most important airport for animal trade and screened for AMR bacteria by culture, antimicrobial susceptibility testing, and whole genome sequencing (WGS) of selected isolates. Results: In total, 668 Enterobacterales isolates with phenotypic evidence for extended-spectrum-/AmpC-β-lactamases (ESBL/AmpC) were obtained, from which Klebsiella (n = 181), Citrobacter (n = 131), Escherichia coli (n = 116), Salmonella (n = 69), and Enterobacter (n = 52) represented the most common groups (other genera (n = 119)). Seventy-nine isolates grew also on cefotaxime agar and were confirmed as ESBL (n = 39) or AmpC (n = 39) producers based on WGS data with respective genes localized on chromosomes or plasmids. Isolates of E. coli contained the most diverse set of ESBL genes (n = 29), followed by Klebsiella (n = 9), Citrobacter, and Enterobacter (each n = 1). Contrarily, AmpC genes were detected in E. coli and Citrobacter (n = 13 each), followed by Enterobacter (n = 12) and Klebsiella (n = 4). Isolates of Salmonella with ESBL/AmpC genes were not found, but all genera contained a variety of additional AMR phenotypes and/or genotypes. MLST revealed 36, 13, 10, and nine different STs in E. coli, Klebsiella, Citrobacter, and Enterobacter, respectively. Conclusions: A significant fraction of the studied Enterobacterales isolates possessed acquired AMR genes, including some high-risk clones. All isolates were obtained from selective media and also wild-caught animals carried many AMR genes. Assignment of AMR to harvesting modes was not possible. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Genes and Antimicrobial Resistant Pathogens in Wildlife)
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16 pages, 1009 KiB  
Article
Bioactive Compounds Isolated from a Marine Sponge Selectively Inhibit Neisseria gonorrhoeae
by Omar E. Christian, Dreyona A. Perry, Alaa I. Telchy, Preston N. Walton and Daniel Williams
Antibiotics 2024, 13(12), 1229; https://doi.org/10.3390/antibiotics13121229 - 19 Dec 2024
Viewed by 1033
Abstract
Background/Objectives: Neisseria gonorrhoeae is the third most common sexually transmitted infection (STI), which may become untreatable soon if resistance continues to drastically increase. Due to increases in resistance to recommended antibiotics, alternative sources of novel compounds to combat this threat are being explored. Interestingly, [...] Read more.
Background/Objectives: Neisseria gonorrhoeae is the third most common sexually transmitted infection (STI), which may become untreatable soon if resistance continues to drastically increase. Due to increases in resistance to recommended antibiotics, alternative sources of novel compounds to combat this threat are being explored. Interestingly, marine sponges have proven to produce a plethora of bioactive compounds that display anticancer, antiviral, antifungal, and antibacterial activity. Methods: In this study, the extracts of the sponge collected from Saint Thomas, US Virgin Islands were examined to determine their antibacterial activity against E. coli, S. aureus, and N. gonorrhoeae. Results: The ethyl acetate sponge extracts significantly inhibited growth of N. gonorrhoeae, while none inhibited S. aureus and E. coli. The bioassay-guided purification of the ethyl acetate extract resulted in the isolation of 6-desmethyl-6-ethylspongosoritin A (1) and plakortone B (2). To determine if the pure sponge metabolite could improve the efficacy of ceftriaxone against a high-level ceftriaxone (HTX)-resistant gonococcal strain, an antibiotic checkerboard assay was done by combining various concentrations of either precursor fractions or the purified compound 2 with ceftriaxone. Plakortone B (2) and ceftriaxone acted in synergy against gonococcal strains and inhibited growth by increasing membrane permeability when exposed for 4 h and 24 h. Conclusions: This suggests that marine sponges may serve as a source for novel bioactive compounds against antibiotic-resistant strains of N. gonorrhoeae, as well as improve the efficacy of currently prescribed antibiotics. Full article
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17 pages, 2651 KiB  
Review
Classical and Modern Models for Biofilm Studies: A Comprehensive Review
by Zhihe Yang, Sadaf Aiman Khan, Laurence J. Walsh, Zyta M. Ziora and Chaminda Jayampath Seneviratne
Antibiotics 2024, 13(12), 1228; https://doi.org/10.3390/antibiotics13121228 - 18 Dec 2024
Viewed by 1091
Abstract
Biofilms are structured microbial communities that adhere to various abiotic and biotic surfaces, where organisms are encased in an exo-polysaccharide matrix. Organisms within biofilms use various mechanisms that help them resist external challenges, such as antibiotics, rendering them more resistant to drugs. Therefore, [...] Read more.
Biofilms are structured microbial communities that adhere to various abiotic and biotic surfaces, where organisms are encased in an exo-polysaccharide matrix. Organisms within biofilms use various mechanisms that help them resist external challenges, such as antibiotics, rendering them more resistant to drugs. Therefore, researchers have attempted to develop suitable laboratory models to study the physical features of biofilms, their resistance mechanisms against antimicrobial agents, and their gene and protein expression profiles. However, current laboratory models suffer from various limitations. In this comprehensive review, we have summarized the various designs that have been used for laboratory biofilm models, presenting their strengths and limitations. Additionally, we have provided insight into improving these models to more closely simulate real-life scenarios, using newly developed techniques in additive manufacturing, synthetic biology, and bioengineering. Full article
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25 pages, 6694 KiB  
Review
Microbial Colonization, Biofilm Formation, and Malodour of Washing Machine Surfaces and Fabrics and the Evolution of Detergents in Response to Consumer Demands and Environmental Concerns
by Patricia Osta-Ustarroz, Allister J. Theobald and Kathryn A. Whitehead
Antibiotics 2024, 13(12), 1227; https://doi.org/10.3390/antibiotics13121227 - 18 Dec 2024
Viewed by 1164
Abstract
Bacterial attachment and biofilm formation are associated with the contamination and fouling at several locations in a washing machine, which is a particularly complex environment made from a range of metal, polymer, and rubber components. Microorganisms also adhere to different types of clothing [...] Read more.
Bacterial attachment and biofilm formation are associated with the contamination and fouling at several locations in a washing machine, which is a particularly complex environment made from a range of metal, polymer, and rubber components. Microorganisms also adhere to different types of clothing fibres during the laundering process as well as a range of sweat, skin particles, and other components. This can result in fouling of both washing machine surfaces and clothes and the production of malodours. This review gives an introduction into washing machine use and surfaces and discusses how biofilm production confers survival properties to the microorganisms. Microbial growth on washing machines and textiles is also discussed, as is their potential to produce volatiles. Changes in consumer attitudes with an emphasis on laundering and an overview regarding changes that have occurred in laundry habits are reviewed. Since it has been suggested that such changes have increased the risk of microorganisms surviving the laundering process, an understanding of the interactions of the microorganisms with the surface components alongside the production of sustainable detergents to meet consumer demands are needed to enhance the efficacy of new antimicrobial cleaning agents in these complex and dynamic environments. Full article
(This article belongs to the Section Antibiofilm Strategies)
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13 pages, 3921 KiB  
Article
Treatment of Periprosthetic Joint Infection with Intravenous Vancomycin: Do We Hit the Target?
by Rasmus Haglund, Ulrika Tornberg, Ann-Charlotte Claesson, Eva Freyhult and Nils P. Hailer
Antibiotics 2024, 13(12), 1226; https://doi.org/10.3390/antibiotics13121226 - 18 Dec 2024
Viewed by 999
Abstract
Background/objectives: Vancomycin is commonly used in the treatment of periprosthetic joint infection (PJI), and trough concentrations are measured to ascertain that they are within the therapeutic range. It has not been investigated what proportion of vancomycin concentrations during treatment of PJI patients [...] Read more.
Background/objectives: Vancomycin is commonly used in the treatment of periprosthetic joint infection (PJI), and trough concentrations are measured to ascertain that they are within the therapeutic range. It has not been investigated what proportion of vancomycin concentrations during treatment of PJI patients is accurately within this range, how many dose adjustments are commonly needed, and which patient factors predispose towards aberrations from the desired range. Method: In this single-center cohort study, we investigated vancomycin trough concentrations in 108 patients with surgically treated PJI who received IV administered vancomycin treatment post-operatively. Patients were identified in our local arthroplasty register, and data beyond what was available in the register were collected from electronic medical charts. Results: Of the final study cohort, 41% were women, and the median age was 71 (IQR 63–79) years. Most patients had PJI of the hip (73%), the majority (54%) underwent a debridement, antibiotics and implant retention (DAIR) procedure prior to vancomycin treatment, and 39% received vancomycin-loaded bone cement during the preceding revision procedure. Of 791 vancomycin trough measurements, only 58.2% were within the target range of 15–20 mg/L, 18.5% were below, and 23.4% were above. A total of 71% of all patients required at least one dose adjustment, and the median length of vancomycin treatment was 8 days. We observed positive correlations of vancomycin trough concentrations with both age (Spearman’s rho = 0.35, p < 0.001) and pre-treatment creatinine concentrations (Spearman’s rho = 0.34, p < 0.001), but no statistically significant difference between patients who had received vancomycin-loaded bone cement and those who had not. Conclusions: In our PJI patients, a high proportion of vancomycin trough concentrations were outside the therapeutic range, despite adherence to local and national guidelines. We can also confirm that caution needs to be exerted in patients of advanced age and those with compromised kidney function. Alternative broad-spectrum antibiotics that do not require as extensive therapeutic drug monitoring should be further explored. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)
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14 pages, 1383 KiB  
Article
Does a Specific Sequential Combination of Antiseptic Solutions for Chemical Debridement in Periprosthetic Joint Infection Improve Outcomes vs. Solution Alone? An In Vivo Study
by Miguel Márquez-Gómez, Marta Díaz-Navarro, Andrés Visedo, Lourdes Prats-Peinado, Patricia Muñoz, Javier Vaquero, María Guembe and Pablo Sanz-Ruíz
Antibiotics 2024, 13(12), 1225; https://doi.org/10.3390/antibiotics13121225 - 17 Dec 2024
Viewed by 796
Abstract
Background: Chemical debridement is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of [...] Read more.
Background: Chemical debridement is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of solutions. In an in vitro study, our group recently demonstrated that sequential combination debridement (SCD) with 3% acetic acid (AA) followed by 10% povidone iodine (PI) and 5 mM hydrogen peroxide (H2O2) was the best strategy for reducing bacterial load. The present study aimed to validate these findings in an in vivo model. Results: The median (IQR) log CFU/mL was lower in the group of mice treated with SCD (2.85 [0.00–3.72]) than in the Bactisure™ group (4.02 [3.41–4.72], p = 0.02). While this reduction was also greater than in the PI group (3.99 [1.11–4.33]), the difference did not reach statistical significance (p = 0.19). Cell viability assays showed no differences between treatments. S. aureus bacteremia was detected in 10% of mice treated with SCD, compared to 30% in the PI group and 10% in the Bactisure™ group. The difference was not statistically significant (p = 0.36). Conclusion: Our findings confirm that SCD significantly reduced bacterial load in an in vivo S. aureus PJI model, showing superior anti-biofilm activity compared to Bactisure™ and comparable performance to PI alone. These results highlight SCD’s potential to serve as a standardized chemical debridement protocol, combining enhanced efficacy with clinical applicability. Methods: We tested SCD with 3% AA for 3 min, 10% PI for 3 min, and H2O2 for 3 min in a 7-day Staphylococcus aureus (ATCC29213)-based murine femur PJI model and compared the results with single treatments of 10% PI for 3 min or Bactisure™ solution for 3 min. A sterile steel implant with local administration of saline solution for 3 min was used as a non-infected control. After completing irrigation procedures, under anesthesia, mice were euthanized, and implants were analyzed for CFU/mL counts and cell viability rates. Blood cultures were obtained pre-euthanasia to detect bacteremia. Full article
(This article belongs to the Special Issue Antimicrobial Therapeutics for Bone and Periprosthetic Joint Infection)
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15 pages, 2636 KiB  
Article
High-Risk Lineages of Hybrid Plasmids Carrying Virulence and Carbapenemase Genes
by Valeria V. Shapovalova, Polina S. Chulkova, Vladimir A. Ageevets, Varvara Nurmukanova, Irina V. Verentsova, Asya A. Girina, Irina N. Protasova, Victoria S. Bezbido, Victor I. Sergevnin, Irina V. Feldblum, Larisa G. Kudryavtseva, Sergey N. Sharafan, Vladislav V. Semerikov, Marina L. Babushkina, Inna R. Valiullina, Nikita S. Chumarev, Guzel S. Isaeva, Natalya A. Belyanina, Irina U. Shirokova, Tatiana M. Mrugova, Elena I. Belkova, Svetlana D. Artemuk, Aleksandra A. Meltser, Marina V. Smirnova, Tatyana N. Akkonen, Nataliya A. Golovshchikova, Oleg V. Goloshchapov, Alexey B. Chukhlovin, Lubov N. Popenko, Elena Y. Zenevich, Aleksandr A. Vlasov, Galina V. Mitroshina, Marina S. Bordacheva, Irina V. Ageevets, Ofeliia S. Sulian, Alisa A. Avdeeva, Vladimir V. Gostev, Irina A. Tsvetkova, Maria A. Yakunina, Ekaterina U. Vasileva, Alina D. Matsvay, Dmitry I. Danilov, Yulia A. Savochkina, German A. Shipulin and Sergey V. Sidorenkoadd Show full author list remove Hide full author list
Antibiotics 2024, 13(12), 1224; https://doi.org/10.3390/antibiotics13121224 - 17 Dec 2024
Viewed by 1011
Abstract
Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli [...] Read more.
Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli (E. coli) isolated from Russian hospitals. Methods: We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 Kpn and 5 E. coli) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022. Results: The plasmid analysis identified 18 clusters that showed high concordance with replicon typing, with all clusters having a major replicon type. The majority of plasmids in the IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar)-like cluster (79.16%) carried both antibiotic resistance genes (e.g., blaNDM-1 and blaOXA-48) and virulence factors (VFs) such as siderophore genes. We hypothesized that hybrid plasmids could play a critical role in the dissemination of antibiotic resistance genes and VFs. Comparative analyses with global plasmid databases revealed high-risk lineages of hybrid plasmids that are predominantly spread throughout Russia at present. Conclusions: Our findings underscore the importance of monitoring plasmid backbones for clinical management, surveillance, and infection control activities. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)
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10 pages, 256 KiB  
Review
The Role of Rifampin in Prosthetic Joint Infections: Efficacy, Challenges, and Clinical Evidence
by Jakrapun Pupaibool
Antibiotics 2024, 13(12), 1223; https://doi.org/10.3390/antibiotics13121223 - 17 Dec 2024
Viewed by 1011
Abstract
Rifampin is a crucial antibiotic in the management of prosthetic joint infections (PJI), particularly due to its effectiveness against staphylococcal bacteria and its ability to penetrate and disrupt biofilms. This review evaluates rifampin’s role by examining its mechanism of action, clinical efficacy, and [...] Read more.
Rifampin is a crucial antibiotic in the management of prosthetic joint infections (PJI), particularly due to its effectiveness against staphylococcal bacteria and its ability to penetrate and disrupt biofilms. This review evaluates rifampin’s role by examining its mechanism of action, clinical efficacy, and integration into treatment regimens based on recent evidence and guidelines. Rifampin’s synergistic effects with other antibiotics, such as β-lactams and vancomycin, enhance bacterial eradication, and some evidence shows that it improves patient outcomes. However, evidence supporting its use is limited by the scarcity of robust human clinical trials, and challenges such as potential drug interactions and resistance development necessitate careful management. Ongoing research is needed to refine its use and address existing limitations in clinical practice. Full article
(This article belongs to the Special Issue Prevention, Diagnostic and Antimicrobial Treatment of Periprosthetic Joint Infection—Proven Meets Innovative, Complementary Approaches)
14 pages, 3162 KiB  
Article
Goondicones A–H: Spiro-Isoindolinone Heartworm Anthelmintics from an Australian Pasture-Soil-Derived Streptomyces sp.
by Jianying Han, David F. Bruhn, Cynthia T. Childs, Yovany Moreno, Angela A. Salim, Taizong Wu and Robert J. Capon
Antibiotics 2024, 13(12), 1222; https://doi.org/10.3390/antibiotics13121222 - 17 Dec 2024
Viewed by 734
Abstract
Background/Objectives: There is an urgent need for new and improved anthelmintics that are not constrained by existing resistance pathways and that can safeguard the health and welfare of animals. Methods: An integrated platform of chemical, bioassay, and cultivation profiling applied to a library [...] Read more.
Background/Objectives: There is an urgent need for new and improved anthelmintics that are not constrained by existing resistance pathways and that can safeguard the health and welfare of animals. Methods: An integrated platform of chemical, bioassay, and cultivation profiling applied to a library of microbes isolated from Australian livestock pasture soil was used to detect and guide the production, isolation, characterization, identification, and evaluation of new natural products with anthelmintic properties. Results: A global natural products social (GNPS) molecular network analysis of 110 Australian pasture-soil-derived microbial extracts prioritized for antiparasitic activity identified unique molecular families in the extract of Streptomyces sp. S4S-00185A06, a strain selectively active against Dirofilaria immitis microfilariae. UPLC-DAD analysis identified metabolites with unique UV-vis chromophores and unprecedented molecular formulas. A chemical investigation of Streptomyces sp. S4S-00185A06 yielded goondicones A–H (1–8) as new examples of a rare class of spiro-isoindolinones, with structures assigned on the basis of detailed spectroscopic analysis, ECD calculations, and biosynthetic considerations. Conclusions: While goondicones 1–8 exhibit little to no in vitro inhibitory activity against Gram-positive, Gram-negative, and/or fungal pathogens, human carcinoma cells, or the livestock gastrointestinal parasite Haemonchus contortus L1–L3 larvae, 5 and 6 (and, to a lesser extent, 1) inhibit the motility of heartworm Dirofilaria immitis microfilaria (IC50 10–11 μM). A structure activity relationship analysis based on the co-metabolites 1–8 suggests that (i) an 8-OH is preferable to 8–oxo moiety, (ii) 20-NMe and 3-OH moieties are essential, and (iii) C-9 epimerization exerts no discernible impact on in vitro potency. Full article
(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)
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9 pages, 1031 KiB  
Communication
Characterization of Metallo β-Lactamase Producing Enterobacterales Isolates with Susceptibility to the Aztreonam/Avibactam Combination
by Brunella Posteraro, Flavio De Maio, Teresa Spanu, Maria Alejandra Vidal Pereira, Francesca Romana Fasano and Maurizio Sanguinetti
Antibiotics 2024, 13(12), 1221; https://doi.org/10.3390/antibiotics13121221 - 17 Dec 2024
Viewed by 933
Abstract
Background/Objectives: Metallo-β-lactamases (MBLs) in Enterobacterales and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT [...] Read more.
Background/Objectives: Metallo-β-lactamases (MBLs) in Enterobacterales and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates. Methods: AZT-AVI, along with other clinically relevant antimicrobials, was tested against thirteen MBL-producing clinical isolates of Enterobacterales (nine Klebsiella pneumoniae, three Enterobacter cloacae, and one Providencia stuartii) using whole-genome sequencing (WGS) for genetic characterization. Results: AZT-AVI demonstrated full susceptibility across all isolates, whereas aztreonam alone was ineffective. The newer β-lactam/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam were inactive in 100% and 92.3% of isolates, respectively. WGS-based analysis revealed multiple resistance mechanisms consistent with MDR phenotypes, including high-risk K. pneumoniae clones (ST147 and ST11). Conclusions: AZT-AVI is effective against MDR MBL-producing Enterobacterales, highlighting its therapeutic potential for challenging infections. While WGS does not replace phenotypic testing, it provides valuable insights for antimicrobial stewardship and the monitoring of resistance gene dissemination. Full article
(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)
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18 pages, 2881 KiB  
Article
A Screen of Traditional Chinese Medicinal Plant Extracts Reveals 17 Species with Antimicrobial Properties
by Garrett L. Ellward, Macie E. Binda, Dominika I. Dzurny, Michael J. Bucher, Wren R. Dees and Daniel M. Czyż
Antibiotics 2024, 13(12), 1220; https://doi.org/10.3390/antibiotics13121220 - 17 Dec 2024
Viewed by 1518
Abstract
Background/Objectives: Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global health and economic security. Many clinical isolates of these pathogens have become completely resistant to current antibiotics, making treatment nearly impossible. Herbal remedies, such as those found in Traditional Chinese Medicine (TCM), have been practiced for thousands of years and successfully used to treat a wide range of ailments, including infectious diseases. Surprisingly, despite this extensive knowledge of folk medicine, no plant-derived antibacterial drugs are currently approved for clinical use. As such, the objective of this study is to evaluate the antimicrobial properties of extracts derived from TCM plants. Methods: This study explores a comprehensive library comprising 664 extracts from 132 distinct TCM plant species for antimicrobial properties against gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria using liquid and solid in vitro assays. Results: Intriguingly, our results reveal 17 plant species with potent antimicrobial properties effective primarily against gram-positive organisms, including Streptococcus aureus and epidermidis. A literature search revealed that nearly 100 purified compounds from the identified TCM plants were previously isolated and confirmed for their antimicrobial properties, collectively inhibiting 45 different bacterial species. Conclusions: Our results indicate that phytobiotics from the identified plants could serve as potential candidates for novel antimicrobials. Full article
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27 pages, 1698 KiB  
Systematic Review
Bacterial Infections, Trends, and Resistance Patterns in the Time of the COVID-19 Pandemic in Romania—A Systematic Review
by Dan Dumitru Vulcanescu, Iulia Cristina Bagiu, Cecilia Roberta Avram, Licinia Andrada Oprisoni, Sonia Tanasescu, Teodora Sorescu, Razvan Susan, Monica Susan, Virgiuliu Bogdan Sorop, Mircea Mihai Diaconu, Tiberiu Liviu Dragomir, Octavia Oana Harich, Razvan Mihai Horhat, Stefania Dinu and Florin George Horhat
Antibiotics 2024, 13(12), 1219; https://doi.org/10.3390/antibiotics13121219 - 14 Dec 2024
Viewed by 1313
Abstract
Background: The COVID-19 pandemic has intensified concerns over bacterial infections and antimicrobial resistance, particularly in Romania. This systematic review explores bacterial infection patterns and resistance during the pandemic to address critical gaps in knowledge. Methods: A systematic review, following PRISMA guidelines, was conducted [...] Read more.
Background: The COVID-19 pandemic has intensified concerns over bacterial infections and antimicrobial resistance, particularly in Romania. This systematic review explores bacterial infection patterns and resistance during the pandemic to address critical gaps in knowledge. Methods: A systematic review, following PRISMA guidelines, was conducted using databases such as PubMed and Scopus, focusing on studies of bacterial infections from 2020 to 2022. Articles on bacterial infections in Romanian patients during the pandemic were analyzed for demographic data, bacterial trends, and resistance profiles. Results: A total of 87 studies were included, detailing over 20,000 cases of bacterial infections. The review found that Gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae, were the most frequently identified pathogens, alongside Gram-positive Staphylococcus aureus and Enterococcus spp. Multidrug resistance (MDR) was noted in 24% of the reported strains, with common resistance to carbapenems and cephalosporins. Conclusions: The pandemic has amplified the complexity of managing bacterial infections, particularly in critically ill patients. The rise in MDR bacteria underscores the need for stringent antimicrobial stewardship and infection control measures. Continuous monitoring of bacterial trends and resistance profiles will be essential to improve treatment strategies in post-pandemic healthcare settings. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens)
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13 pages, 647 KiB  
Article
Prevalence of Antimicrobial Resistance Among the WHO’s AWaRe Classified Antibiotics Used to Treat Urinary Tract Infections in Diabetic Women
by Ahmad Hamdan, Mohannad N. AbuHaweeleh, Leena Al-Qassem, Amira Kashkoul, Izzaldin Alremawi, Umna Hussain, Sara Khan, Menatalla M. S. ElBadway, Tawanda Chivese, Habib H. Farooqui and Susu M. Zughaier
Antibiotics 2024, 13(12), 1218; https://doi.org/10.3390/antibiotics13121218 - 14 Dec 2024
Viewed by 951
Abstract
Background and Objectives: Diabetes is linked to a higher risk of urinary tract infections (UTIs) in women, often leading to recurrent antibiotic treatments. Frequent antibiotic use for UTIs can contribute to antimicrobial resistance (AMR), a critical public health threat that increases treatment [...] Read more.
Background and Objectives: Diabetes is linked to a higher risk of urinary tract infections (UTIs) in women, often leading to recurrent antibiotic treatments. Frequent antibiotic use for UTIs can contribute to antimicrobial resistance (AMR), a critical public health threat that increases treatment failure. This study investigated the prevalence of AMR and its associated factors among women with UTIs, comparing those with and without diabetes. Results: The study population had a mean age of 52 years (SD = 23) for the women without diabetes and 68 years (SD = 14) for those with diabetes. Resistance was highest for cefazolin and levofloxacin in the Access and Watch antibiotic groups, while ciprofloxacin was the most frequently prescribed antibiotic. AMR prevalence was 35.7% among the women with diabetes and 21.3% among those without. After adjustment, AMR was significantly associated with both uncomplicated diabetes (OR 1.14, 95% CI 1.08–1.21) and complicated diabetes (OR 1.54, 95% CI 1.45–1.64), as well as with higher numbers of prescribed antibiotics (OR 277.39, 95% CI 253.79–303.17). Methods: Using a cross-sectional cohort from the Physionet database, we analyzed data on 116,902 female participants treated for UTIs, including their antibiotic exposure, diabetes status, comorbidities, and hospital admission details. Antimicrobials were classified per the WHO’s AWaRe criteria. The primary outcome was AMR identified in urine cultures, and the association with diabetes status was evaluated using multivariable logistic regression. Conclusions: Our findings highlight the need for focused antimicrobial stewardship in women with diabetes to reduce the AMR rates in this vulnerable group. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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17 pages, 2840 KiB  
Article
Evaluation of Metronidazole Resistance of Vaginal Swab Isolates from South African Women Treated for Bacterial Vaginosis
by Timo Schwebs, Ann-Katrin Kieninger, Lenka Podpera Tisakova, Vera Oberbauer, Rocío Berdaguer, Andile Mtshali, Gugulethu Mzobe, Anne Rompalo, Adrian Mindel, Marothi Letsoalo, Nigel Garrett, Sinaye Ngcapu and Lorenzo Corsini
Antibiotics 2024, 13(12), 1217; https://doi.org/10.3390/antibiotics13121217 - 14 Dec 2024
Viewed by 954
Abstract
Background/Objectives: The high recurrence rate of bacterial vaginosis (BV) after antibiotic treatment is at least partially attributed to resistant bacteria. The CAPRISA 083 (CAP083) study investigated the influence of metronidazole (MTZ) treatment on the vaginal microbiome in 56 South African women diagnosed [...] Read more.
Background/Objectives: The high recurrence rate of bacterial vaginosis (BV) after antibiotic treatment is at least partially attributed to resistant bacteria. The CAPRISA 083 (CAP083) study investigated the influence of metronidazole (MTZ) treatment on the vaginal microbiome in 56 South African women diagnosed with BV. To explore the etiology of recurrent BV in this cohort, we retrospectively analyzed vaginal swabs collected in CAP083 before and after MTZ treatment. Methods: We isolated over 1200 bacterial strains, including Gardnerella, Lactobacillus, Prevotella, and Fannyhessa, and determined the minimum inhibitory concentration (MIC) of MTZ and the resistance status according to CLSI and EUCAST guidelines. Results: At baseline, 64% (CLSI) of Gardnerella isolates were resistant to MTZ, rising to 80% after MTZ treatment by the 12-week visit. Lactobacillus species consistently exhibited resistance of 100%, while Fannyhessea vaginae maintained resistance rates of 78–91% across visits. Prevotella strains varied, showing two susceptible isolates at baseline and one resistant isolate at the 6-week visit. Susceptible and resistant Gardnerella isolates were often isolated from the same swab, and 70% (CLSI) of participants had at least one resistant Gardnerella strain already at baseline. Sensitive Gardnerella isolates were not a predictor of an MTZ-mediated reduction in Gardnerella abundance. Conclusions: Our data indicate that the 23% cure rate in CAP083 was associated with a combination of a high share of MTZ-resistant bacteria at baseline, a potentially insufficient MTZ dose regimen, and a constantly high average abundance of Gardnerella. Future research should explore novel therapeutic strategies to enhance treatment efficacy and combat antibiotic resistance. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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17 pages, 863 KiB  
Article
Identification of Factors Determining Patterns of Serum C-Reactive Protein Level Reduction in Response to Treatment Initiation in Patients with Drug-Susceptible Pulmonary Tuberculosis
by Agnija Kivrane, Viktorija Ulanova, Solveiga Grinberga, Eduards Sevostjanovs, Anda Viksna, Iveta Ozere, Ineta Bogdanova, Ilze Simanovica, Inga Norvaisa, Leonora Pahirko, Dace Bandere and Renate Ranka
Antibiotics 2024, 13(12), 1216; https://doi.org/10.3390/antibiotics13121216 - 14 Dec 2024
Viewed by 850
Abstract
Background: Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well [...] Read more.
Background: Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well established. Objectives: This study evaluated the impact of patients’ baseline characteristics and anti-TB drug plasma exposure on the early reduction in serum CRP levels and its relationship with treatment response. Methods: We enrolled 42 patients with drug-susceptible pulmonary TB, who received a standard six-month regimen. The plasma concentrations of four anti-TB drugs were analysed using LC-MS/MS. Clinically relevant data, including serum CRP levels before and 10–12 days after treatment initiation (CRP10–12d), were obtained from electronic medical records and patient questionnaires. Results: In 10–12 days, the median serum CRP level decreased from 21.9 to 6.4 mg/L. Lower body mass index, positive sputum-smear microscopy results, and lung cavitations at diagnosis were related to higher biomarker levels at both time points; smoking had a more pronounced effect on serum CRP10–12d levels. Variability in anti-TB drug plasma exposure did not significantly affect the reduction in serum CRP levels. The serum CRP10–12d levels, or fold change from the baseline, did not predict the time to sputum culture conversion. Conclusions: Disease severity and patient characteristics may influence the pattern of early CRP reduction, while anti-TB drug plasma exposure had no significant effect at this stage. These early changes in serum CRP levels were not a predictor of response to anti-TB therapy. Full article
(This article belongs to the Special Issue Antibiotics and Infectious Respiratory Diseases, 2nd Edition)
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8 pages, 569 KiB  
Article
Increased Antibiotic Susceptibility of Gram-Positive Bacteria in Cerebrospinal Fluid Compared to Broth
by Jennifer S. Wirth, Marija Djukic, Katrin Biesner, Utz Reichard, Roland Nau and Jana Seele
Antibiotics 2024, 13(12), 1215; https://doi.org/10.3390/antibiotics13121215 - 14 Dec 2024
Viewed by 844
Abstract
Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens [...] Read more.
Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Methods: Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller–Hinton broth (Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis) or brain–heart infusion (Streptococcus pneumoniae). Results: Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were either lower in CSF than in broth or equal in CSF and broth. The difference between MICs in CSF and broth was prominent with gentamicin, levofloxacin, linezolid (staphylococci), and vancomycin (staphylococci and pneumococcus), whereas it was absent with ampicillin (E. faecalis), penicillin G (S. pneumoniae), linezolid (enterococcus and pneumococcus), and vancomycin (enterococcus). In no case was the MIC or MBC higher in CSF than in broth. Conclusions: Several antibiotics possess an antibacterial effect in CSF at lower concentrations than the MICs determined in broth, i.e., MICs in broth underestimate in situ susceptibility in CSF. Full article
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17 pages, 631 KiB  
Article
Pooled Antibiotic Susceptibility Testing Performs Within CLSI Standards for Validation When Measured Against Broth Microdilution and Disk Diffusion Antibiotic Susceptibility Testing of Cultured Isolates
by Emery Haley, Frank R. Cockerill, Rick L. Pesano, Richard A. Festa, Natalie Luke, Mohit Mathur, Xiaofei Chen, Jim Havrilla and David Baunoch
Antibiotics 2024, 13(12), 1214; https://doi.org/10.3390/antibiotics13121214 - 14 Dec 2024
Viewed by 945
Abstract
Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay [...] Read more.
Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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23 pages, 2893 KiB  
Article
Synthesis of Temporin-SHa Retro Analogs with Lysine Addition/Substitution and Antibiotic Conjugation to Enhance Antibacterial, Antifungal, and Anticancer Activities
by Shahzad Nazir, Arif Iftikhar Khan, Rukesh Maharjan, Sadiq Noor Khan, Muhammad Adnan Akram, Marc Maresca, Farooq-Ahmad Khan and Farzana Shaheen
Antibiotics 2024, 13(12), 1213; https://doi.org/10.3390/antibiotics13121213 - 13 Dec 2024
Viewed by 712
Abstract
In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (1), which is [...] Read more.
In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (1), which is known for its antimicrobial and anticancer activities. We synthesized new analogs of 1 using three strategies, i.e., retro analog preparation, lysine addition/substitution, and levofloxacin conjugation. Analogs were tested in terms of their antibacterial, antifungal, and anticancer activities. Analog 2, corresponding to retro analog of NST-2, was found to be more active but also more hemolytic, reducing its selectivity index and therapeutic potential. The addition of lysine (in analog 3) and lysine substitution (in analog 7) reduced the hemolytic effect resulting in safer peptides. Conjugation with levofloxacin on the lysine side chain (in analogs 4 and 5) decreased the hemolytic effect but unfortunately also the antimicrobial and anticancer activities of the analogs. Oppositely, conjugation with levofloxacin at the N-terminus of the peptide via the β-alanine linker (in analogs 6 and 8) increased their antimicrobial and anticancer activity but also their hemolytic effect, resulting in less safe/selective analogs. In conclusion, lysine addition/substitution and levofloxacin conjugation, at least at the N-terminal position through the β-alanine linker, were found to enhance the therapeutic potential of retro analogs of NST-2 whereas other modifications decreased the activity or increased the toxicity of the peptides. Full article
(This article belongs to the Section Antimicrobial Peptides)
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45 pages, 16580 KiB  
Review
Bisindole Compounds—Synthesis and Medicinal Properties
by Maria Marinescu
Antibiotics 2024, 13(12), 1212; https://doi.org/10.3390/antibiotics13121212 - 13 Dec 2024
Viewed by 1364
Abstract
The indole nucleus stands out as a pharmacophore, among other aromatic heterocyclic compounds with remarkable therapeutic properties, such as benzimidazole, pyridine, quinoline, benzothiazole, and others. Moreover, a series of recent studies refer to strategies for the synthesis of bisindole derivatives, with various medicinal [...] Read more.
The indole nucleus stands out as a pharmacophore, among other aromatic heterocyclic compounds with remarkable therapeutic properties, such as benzimidazole, pyridine, quinoline, benzothiazole, and others. Moreover, a series of recent studies refer to strategies for the synthesis of bisindole derivatives, with various medicinal properties, such as antimicrobial, antiviral, anticancer, anti-Alzheimer, anti-inflammatory, antioxidant, antidiabetic, etc. Also, a series of natural bisindole compounds are mentioned in the literature for their various biological properties and as a starting point in the synthesis of other related bisindoles. Drawing from these data, we have proposed in this review to provide an overview of the synthesis techniques and medicinal qualities of the bisindolic compounds that have been mentioned in recent literature from 2010 to 2024 as well as their numerous uses in the chemistry of materials, nanomaterials, dyes, polymers, and corrosion inhibitors. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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15 pages, 3605 KiB  
Article
Restoring Multidrug-Resistant Escherichia coli Sensitivity to Ampicillin in Combination with (−)-Epigallocatechin Gallate
by Anong Kiddee, Atchariya Yosboonruang, Achiraya Siriphap, Grissana Pook-In, Chittakun Suwancharoen, Acharaporn Duangjai, Ratsada Praphasawat, Masami Suganuma and Anchalee Rawangkan
Antibiotics 2024, 13(12), 1211; https://doi.org/10.3390/antibiotics13121211 - 13 Dec 2024
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Abstract
Multidrug-resistant (MDR) bacteria, especially Escherichia coli, are a major contributor to healthcare-associated infections globally, posing significant treatment challenges. This study explores the efficacy of (−)-epigallocatechin gallate (EGCG), a natural constituent of green tea, in combination with ampicillin (AMP) to restore the effectiveness [...] Read more.
Multidrug-resistant (MDR) bacteria, especially Escherichia coli, are a major contributor to healthcare-associated infections globally, posing significant treatment challenges. This study explores the efficacy of (−)-epigallocatechin gallate (EGCG), a natural constituent of green tea, in combination with ampicillin (AMP) to restore the effectiveness of AMP against 40 isolated MDR E. coli strains. Antimicrobial activity assays were conducted to determine the minimum inhibitory concentrations (MIC) of EGCG using the standard microdilution technique. Checkerboard assays were employed to assess the potential synergistic effects of EGCG combined with AMP. The pharmacodynamic effects of the combination were evaluated through time-kill assays. Outer membrane disruption was analyzed by measuring DNA and protein leakage and with assessments using N-phenyl-1-naphthylamine (NPN) and rhodamine 123 (Rh123) fluorescence dyes. Biofilm eradication studies involved biofilm formation assays and preformed biofilm biomass and viability assays. Scanning electron microscopy (SEM) was used to examine changes in cellular morphology. The results indicated that EGCG demonstrated activity against all isolates, with MICs ranging from 0.5 to 2 mg/mL, while AMP exhibited MIC values between 1.25 and 50 mg/mL. Importantly, the EGCG-AMP combination showed enhanced efficacy compared to either treatment alone, as indicated by a fractional inhibitory concentration index between 0.009 and 0.018. The most pronounced synergy was observed in 13 drug-resistant strains, where the MIC for EGCG dropped to 8 µg/mL (from 1 mg/mL alone) and that for AMP to 50 µg/mL (from 50 mg/mL alone), achieving a 125-fold and 1000-fold reduction, respectively. Time-kill assays revealed that the bactericidal effect of the EGCG-AMP combination occurred within 2 h. The mechanism of EGCG action includes the disruption of membrane permeability and biofilm eradication in a dose-dependent manner. SEM confirmed that the combination treatment consistently outperformed the individual treatments. This study underscores the potential of restoring AMP efficacy in combination with EGCG as a promising strategy for treating MDR E. coli infections. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms, 2nd Edition)
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10 pages, 1461 KiB  
Article
Prevalence of Vancomycin-Variable Enterococci from the Bloodstream in the Korea Global Antibiotic Resistance Surveillance System, 2017–2022
by Sung Young Lee, Ji-Hyun Nam, Jung Wook Kim, Soo Hyun Kim and Jung Sik Yoo
Antibiotics 2024, 13(12), 1210; https://doi.org/10.3390/antibiotics13121210 (registering DOI) - 12 Dec 2024
Viewed by 822
Abstract
Vancomycin-variable enterococci (VVE), though genetically containing van genes, are phenotypically sensitive to vancomycin. If VVE is undetected or does not grow on the vancomycin-resistant enterococci (VRE) selection medium, or both, it can acquire resistance upon exposure to vancomycin. This characteristic is clinically important [...] Read more.
Vancomycin-variable enterococci (VVE), though genetically containing van genes, are phenotypically sensitive to vancomycin. If VVE is undetected or does not grow on the vancomycin-resistant enterococci (VRE) selection medium, or both, it can acquire resistance upon exposure to vancomycin. This characteristic is clinically important for the treatment and prevention of VRE. This study aims to analyze the prevalence and characteristics of VVE in Korea through the Global Antibiotic Resistance Surveillance System (Kor-GLASS) and emphasize the importance of VVE. A total of 3342 enterococcal bloodstream isolates were collected through the Kor-GLASS between 2017 and 2022. Antibiotic susceptibility testing, van gene detection, and multilocus sequence typing were conducted with all the isolates. The trends in the domestic prevalence of VVE were analyzed and compared with global prevalence data. Among the isolates, 197 (5.9%), including 124 Enterococcus faecium and 73 E. faecalis, were identified as VVE. While the VRE incidence has declined in Korea since 2020, the VVE incidence is significantly rising. In Korea, only the vanA gene has been detected in both VRE and VVE, and no other van gene variants have been identified. Most of these isolates belong to CC17 (91.3%), with ST17, ST817, and ST80 as the predominant types. We have shown that continuous surveillance is essential in Korea due to the persistently high prevalence of VRE and the potential evolution of VVE into VRE. Consequently, it is critical to evaluate Enterococcus species isolated from domestic clinical settings for their phenotypic vancomycin resistance and the molecular detection of van genes, irrespective of the strain. Full article
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21 pages, 413 KiB  
Review
Perspectives on the Use of Echinocandins in the Neonatal Intensive Care Unit
by Niki Dermitzaki, Foteini Balomenou, Dimitra Gialamprinou, Vasileios Giapros, Dimitrios Rallis and Maria Baltogianni
Antibiotics 2024, 13(12), 1209; https://doi.org/10.3390/antibiotics13121209 (registering DOI) - 12 Dec 2024
Viewed by 848
Abstract
The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been [...] Read more.
The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile. Full article
(This article belongs to the Special Issue New Insights into Prevention, Diagnosis, and Treatment of Neonatal Sepsis and Short- and Long-Term Outcomes)
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