Antibiotics-Basel最新文献

Background: Cutaneous wounds are common in outpatient care, but national patterns of who manages them and how antimicrobials are used remain unclear. Objectives: To characterize outpatient specialty involvement and antimicrobial use for acute and chronic cutaneous wound visits in the United States. Methods: We conducted a retrospective cross-sectional analysis of 2011-2019 National Ambulatory Medical Care Survey (NAMCS) data. Cutaneous wound visits were identified using prespecified ICD-9-CM and ICD-10-CM codes and classified as acute (open or traumatic wounds and burns) or chronic (pressure injuries and lower-limb ulcers). Survey weights were applied to estimate national visit volumes, specialty shares, and antimicrobial utilization patterns. Results: We identified 45.1 million cutaneous wound visits, representing 0.8% of all outpatient visits, of which about two thirds were acute and one third chronic. Primary care physicians accounted for the largest share of wound visits, while dermatologists managed 3.9% of overall wound visits, 2.4% of acute visits, and 7.4% of chronic visits. Among 156.6 million medications recorded at wound visits, antimicrobials represented 13.1% overall, 14.9% in acute visits, and 10.2% in chronic visits. Cephalexin accounted for 32.1% of antimicrobial medications overall and 39.2% in acute visits, whereas chronic wound visits had a more heterogeneous antimicrobial profile that included topical mupirocin, cephalexin, trimethoprim-sulfamethoxazole, and topical nystatin. Conclusions: Outpatient cutaneous wound care in the United States is delivered predominantly by primary care clinicians and relies heavily on a small set of systemic and topical antimicrobials, highlighting opportunities to strengthen antimicrobial stewardship and expand dermatology's role in chronic wound management.

Background/Objectives: The aim of this study is to investigate how the joint, the number and the type of prior revision surgeries influence the diagnostic thresholds for synovial cell count for patients who undergo their first total hip or knee arthroplasty revision compared to re-revisions, as different cutoffs might substantially influence treatment courses. Methods: In this retrospective single-center register analysis, data from 214 revised THAs (total hip arthroplasties) and TKAs (total knee arthroplasties) were collected, of which 103 (48.1%) have so far undergone at least one revision surgery. Diagnosis was based on the EBJIS criteria, and we identified 163 (76.2%) septic and 51 (23.8%) aseptic cases. Data on synovial cell count were collected and analyzed for their diagnostic accuracy and optimal cutoffs. For re-revisions, a covariate-adjusted ROC (receiver operating characteristic) for the joint, type of previous surgery and number of surgeries was created. Results: We found no significant differences in cell counts between patients before first revision compared to those undergoing re-revision for septic (p = 0.40) and aseptic indications (p = 0.84). The overall diagnostic accuracy was high for all re-revision cases, with a sensitivity of 0.86, specificity of 0.91, AUC (area under the curve) of 0.92, at an optimal cutoff value of 2439.50 G/L. As for re-revised hip joints, the optimal cutoffs were higher compared to knee joints (2439.5 G/L vs. 2626.5 G/L, hip AUC = 0.90, knee AUC = 0.93, p = 0.14). Furthermore, the AUCs for cell count differed significantly depending on the type of previous surgery in re-revision (p = 0.03). The covariate-adjusted analysis showed no significant differences compared to the unadjusted analysis. Conclusions: Cell count remains reliable for diagnosing periprosthetic joint infection in patients with prior revisions, with minor threshold variations from the EBJIS (European Bone and Joint Infection Society) criteria. While the type of preceding revision affects accuracy, the diagnostic value remains consistently high overall.

Background/Objectives: The increase in incidences of multidrug resistance exacerbates tuberculosis-related global health challenges and underscores a call for more efforts for development of new antitubercular drugs, including the use of medicinal plants, especially those that have been used for generations by traditional healers. Despite reports of antimicrobial activity and chemical profiling of Kirkia wilmsii (K. wilmsii) extracts, chemical structures of the bioactive agents have not been elucidated. Here, we used a combination of bioactivity-guided fractionation, mass spectrometry, and nuclear magnetic resonance to purify and elucidate the chemical structure of antimycobacterial agents contained in leaf and twig extracts for K. wilmsii. Results: After overnight extraction with acetone and 90 g of dry twigs and leaves produced 5.38 g (6%) and 4.56 g (5%) of product, which displayed moderate antimycobacterial activity of 0.5 and 1 mg/mL, respectively. The antimycobacterial activity was increased six- and three-fold, respectively, after the crude extracts were subjected to solvent-solvent partitioning. Due to many bioactive fractions being obtained after silica gel chromatography purification, fraction 5 of twig extract was prioritized for further purification due to its low minimum inhibitory concentration (MIC) (0.25 mg/mL) and cytotoxicity (20%, in THP-1 cells). Sequential purification of the fraction 5 (twig extract) extracts through the C18 cartridge and high-performance liquid chromatography (HPLC) produced four fractions, which were subjected to structural elucidation. The high-resolution mass spectrometric analyses revealed that the first two eluting peaks had the same mass ion of 441.0822 m/z (M - H^-), which corresponded to catechin monogallate, and so were the last two eluting peaks, which had a mass ion of 539.0932 m/z (M - H^-), corresponding to catechin digallate. Further analyses by ¹H, ¹³C, and 2D NMR confirmed the chemical structures of compounds eluting in the first two peaks on HPLC as structural isomers of catechin 3'-monogallate and catechin 4'-monogallate (MIC not determined). Similarly, compounds eluting in the last two peaks were identified as structural isomers catechin 3'-digallate and catechin 4'-digallate, with an MIC of 250 µg/mL against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv and an MBC of 500 μg/mL against M. smegmatis. Conclusions: To the best of our knowledge, this study is the first to report the structure of catechin 3'- and 4'-digallate, their antimycobacterial activity, and the existence of acyl migration involving galloyl 3' and 4'-hydroxyl groups of catechin ring B.

Background: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria (MRGN). At present, few data are available on the pharmacokinetics of this substance in critically ill patients, particularly for the treatment of central nervous system infections. Patients and Methods: Here, we reported on a 22-year-old male patient after severe open head trauma. Initial screening revealed colonization with 4MRGN A. baumannii (OXA-23) (perianal) and 4MRGN K. pneumoniae (KPC) (tracheal). Unfortunately, he developed ventriculitis (4MRGN A. baumannii). According to microbiological testing, the patient with normal renal function received 3 × 2 g/d i.v. cefiderocol as a prolonged infusion (3 h) and colistin 3 × 3 Mio. IU/d i.v. for 2 weeks. In addition to serum trough levels, drug monitoring was performed in the cerebrospinal fluid (CSF) via external ventricular drainage (24 h aliquots). Results: Serum and CSF specimens analyzed by liquid chromatography-mass spectroscopy (LC-MS) in the presence of severe meningeal inflammation yielded average CSF concentrations of cefiderocol from 5.48 to 8.40 (median 6.98) μg/mL and a concentration ratio C_{CSF mean}/C_{serum trough} from 0.38 to 0.76 (median 0.48). The cefiderocol levels in the CSF were sufficient for eradication of A. baumannii. A subsequent CSF infection with K. pneumoniae (found initially in screening and resistant to cefiderocol) after completed treatment with cefiderocol was successfully treated with gentamicin (intrathecally) and ceftazidime/avibactam (i.v.). However, the patient died due to a Candida tropicalis infection detected in the CSF on day 71. Conclusions: Our results indicate that standard dosages of cefiderocol are sufficient for treatment of CNS infections in the presence of a severe disruption of the blood-CSF barrier.

Background/Objectives: The high prevalence of fluoroquinolone-resistant E. coli in healthy children represents a significant public-health risk, facilitating the spread of antimicrobial resistance and increasing the potential for difficult-to-treat extraintestinal infections with severe clinical outcomes. This study aimed to investigate the prevalence of fluoroquinolone resistance in multidrug-resistant E. coli isolated from presumptively healthy children in St. Petersburg, Russia, with a particular focus on fluoroquinolone resistance determinants. Methods: Phenotypic AST was performed on 307 E. coli isolates from fecal pediatric samples, comprising 230 isolates from 2012 to 2013 and 77 isolates from 2021 to 2022. A subset (n = 47) of MDR isolates underwent whole-genome sequencing. Results: The frequency of MDR E. coli strains rose significantly from 15.7% to 32.5% over the study period. The most significant increases in resistance among E. coli strains were to third-generation cephalosporins (CTX, CTZ) and fluoroquinolones (CIP), rising fourfold over a decade. Based on phenotypic resistance profiles of MDR E. coli to quinolones, the highest resistance rates were observed for MFX (80.9%) followed by NAL (74.5%), LVX (44.7%) and CIP (40.4%). Genotypic analysis revealed distinct pathways: low-level NAL resistance required only an S83 mutation in gyrA, whereas low-level MFX resistance was predominantly conferred by a plasmid-borne qnr gene. In contrast, resistance to CIP and LVX involved at least three QRDR mutations: S83L and D87N/Y in gyrA, and S80I in parC. Notably, our study showed the predominance of the ST131 and ST38 clones in E. coli isolated from pediatric samples. Conclusions: Our findings suggest that the efficacy of moxifloxacin for empirical treatment of infections caused by MDR E. coli might be severely compromised. Overall, the current study highlights that the pediatric gut microbiota serves as a reservoir for resistant E. coli with the expansion of multidrug-resistant clones independently of direct antibiotic selection pressure.

Background: Antibiotics are essential for treating infections; however, they disrupt the microbiome and key microbiome-dependent functions. Clinical evidence is mixed for probiotic supplementation following antibiotics due to product heterogeneity and inconsistencies in evaluating biological mechanisms that drive clinical consequences. Accordingly, this study investigates the effects of a multi-species synbiotic on gut microbiome composition and function, and gut barrier integrity, during and following antibiotics. Methods: In a randomized, placebo-controlled trial designed to assess proof-of-mechanism, healthy adult participants received a daily synbiotic (53.6 billion AFU multi-species probiotic and 400 mg Indian pomegranate extract; DS-01) or matching placebo for 91 days. All participants also received ciprofloxacin (500 mg orally twice daily) and metronidazole (500 mg orally three times daily) for the first 7 days. Samples were collected at baseline and Days 7, 14, 49, and 91. Endpoints included fecal microbiome composition, fecal acetate and butyrate levels, urinary Urolithin A (UroA), serum p-cresol sulfate (pCS), gut barrier integrity, and safety. Results: The multi-species synbiotic significantly increased the alpha-diversity of Bifidobacterium and Lactobacillus at all timepoints compared to placebo, including short-term (Day 7, p < 0.0001) and end-of-study (Day 91, p < 0.001). The multi-species synbiotic enhanced recovery of native beneficial microbes, including butyrate-producing species and a novel Oscillospiraceae species (UMGS1312 sp900550625, p < 0.001). Beneficial microbiome-dependent metabolites increased, including fecal butyrate (119%, p < 0.05), fecal acetate (62%, p < 0.01), and UroA (13,008%, p < 0.05), whereas detrimental metabolite pCS decreased (68%, p < 0.05) compared to placebo. Functionally, the multi-species synbiotic improved gut barrier integrity rapidly (Day 7; 305%, p < 0.05) and over the long-term (Day 91; 161%, p < 0.05) compared to placebo. Conclusions: During and after antibiotics, this multi-species synbiotic promotes recovery of gut microbiome diversity and native beneficial microbes, microbiome metabolite recovery, and gut barrier function, all of which underpin antibiotic-associated gastrointestinal symptoms.

Background: Blue laser light has been the subject of research regarding the inactivation of microorganisms as a possible alternative to chemical treatment methods for a number of years. In dentistry, blue light could be used, for example, in the treatment of periodontitis/peri-implantitis, as well as in endodontics and against caries. It could serve as an alternative or supplement to traditional chemical and/or invasive methods. The antimicrobial effectiveness of a blue laser in relation to the speed of treatment is investigated using three different microbial test organisms in order to identify possible species differences. Methods: The test organisms Enterococcus faecalis, Streptococcus mutans, and Candida albicans were applied to smooth zirconium discs and treated twice with a diode laser at 445 nm wavelength with a traversing speed of 1, 2, and 4 mm/s. The antimicrobial effect was analysed based on the resulting colony-forming units on agar plates. The temperature was measured during the treatment. Preliminary tests were carried out using the MTT dye test to determine relevant setting parameters and the required energy dose. Results: Statistically significant differences were found between the negative control and the treated samples for all three tested organisms, with a maximum viability reduction of 1.8 log₁₀ CFU/mL for Enterococcus faecalis, 2.5 log₁₀ CFU/mL for Streptococcus mutans, and 1.0 log₁₀ CFU/mL for Candida albicans at 1 mm/s traversing speed, regarding estimated marginal means (p < 0.001). The temperature on the substrate surface reached 30 to 42 °C for all samples evaluated. Conclusions: Blue laser light (445 nm) demonstrates antimicrobial activity, which increases with prolonged exposure. Further research is needed to assess all key influencing parameters and define possible clinical applications.

Background/Objectives: Multidrug-resistant (MDR) strains of Streptococcus suis are increasingly prevalent and present significant challenges in clinical management. Given that the development of new antibiotics is a resource-intensive process and time-consuming, there is an urgent need for alternative therapeutic strategies to address resistance in the short term. One promising approach is the use of combination therapy, which involves pairing potent antibiotics with agents that may be less effective on their own, to enhance therapeutic efficacy and potentially overcome resistance mechanisms. This study aimed to investigate the in vitro antibacterial activity of combining two classes of antibiotics with distinct mechanisms of action-cell wall synthesis inhibitors and protein synthesis inhibitors-against MDR S. suis strains isolated from diseased pigs. Methods: A total of 36 MDR S. suis strains were tested using a microbroth dilution checkerboard assay to determine the minimum inhibitory concentration (MIC) of four cell wall synthesis inhibitors -amoxicillin/clavulanic acid (AMC), ampicillin (AMP), penicillin G (PEN), and vancomycin (VAN)- in combination with four protein synthesis inhibitors -gentamicin (GEN), neomycin (NEO), tilmicosin (TMS), and tylosin (TYL). Time-kill curve assays were conducted to evaluate the in vitro bactericidal activity of synergistic antibiotic combinations (PEN-GEN and AMP-NEO) against Beta-lactam-resistant and Beta-lactam-susceptible MDR S. suis strains. Results: Checkerboard analysis revealed that penicillin-gentamicin combination exhibited the most effective synergistic activity against the MDR S. suis strains (10/19, 52.6%), with ∑FIC values of 0.25-1.06 and MIC reductions from resistant to susceptible levels. Time-kill assays further confirmed the synergistic bactericidal effect of the combination, demonstrating complete bacterial clearance within 6-9 h, markedly rapid bacterial killing compared to monotherapy. Conclusions: This study demonstrates that antibiotic combinations, particularly Beta-lactams combined with aminoglycosides, show synergistic activity against pig-isolated S. suis MDR strains. The PEN-GEN combination exhibited strong synergistic and bactericidal effects, supporting combination therapy as a potential strategy to address antimicrobial resistance. Further evaluation in diverse strain backgrounds and prudent antibiotic use are essential to confirm efficacy and limit the emergence of antibiotic resistance.

Background: Pancreatoduodenectomy (PD) remains the fundamental treatment for periampullary malignancies but is associated with considerable morbidity (20-50%) and mortality (2-7%). Bacteriobilia contributes to unfavourable postoperative outcomes. Current antibiotic prophylaxis recommendations endorse first-generation cephalosporins, which often fail to adequately target pathogens most frequently isolated from bile. To date, no specific guidelines for preoperative targeted antibiotic therapy have been established, although tailoring such strategies to the bile microbiome may improve surgical outcomes. This study aimed to characterize bile microbiology in patients undergoing PD for pancreatic ductal adenocarcinoma (PDAC), evaluating potential antibiotherapy regimens that provide effective coverage against the most frequently isolated pathogens.

Methods: A retrospective cohort analysis of 725 patients surgically treated for pancreatic tumours at a high-volume pancreatic surgery center between 2017 and 2022 was performed. To minimize heterogeneity, study was restricted to 138 patients who underwent PD with histopathological confirmed PDAC. Intraoperative bile cultures were assessed.

Results: Patients with bacteriobilia likewise experienced worse outcomes: higher 5-year mortality (OR 3.01, p = 0.007), greater overall postoperative pancreatic fistula (POPF) occurrence (OR 2.54, p = 0.044) and wound infections (OR 2.90, p = 0.038). Among bile microbiome the highest susceptibility rates were observed for combination of amoxicillin/clavulanic acid with gentamicin, while the lowest were noted for cephalosporin-metronidazole regimen (93.6% vs. 30.2%, respectively).

Conclusions: Bacteriobilia contributes to postoperative complications and serves as a predictor of poorer survival after PD. Standard perioperative antibiotic prophylaxis in PD is insufficient. Based on our findings, perioperative antibiotic therapy with amoxicillin/clavulanic acid and gentamicin combination appears to provide superior coverage and may improve postoperative morbidity and overall survival following PD.