Antibiotics-Basel最新文献

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.

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.

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-10^T and B. zhangzhouensis DW5-4^T, 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.

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.

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.

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.

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.

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.

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.

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.