Antibiotics-Basel最新文献

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.

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.

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.

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.

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.

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., bla_NDM-1 and bla_OXA-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.

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.

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.

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.

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.