-
BMC Microbiology Jun 2024Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism...
BACKGROUND
Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation.
METHODS
Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis.
RESULTS
Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria.
CONCLUSION
This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.
Topics: Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination; Microbial Sensitivity Tests; Anti-Bacterial Agents; Metabolomics; Humans; Genomics; Phenotype; Staphylococcal Infections; Bacterial Proteins; Transcriptome; Gene Expression Profiling; Multiomics
PubMed: 38877418
DOI: 10.1186/s12866-024-03364-8 -
Chemosphere Aug 2024The phyto-Fenton process, which generates hydroxyl radicals through Fenton and Fenton-like reactions using plant-derived hydrogen peroxide (HO) and ferrous iron (Fe...
The phyto-Fenton process, which generates hydroxyl radicals through Fenton and Fenton-like reactions using plant-derived hydrogen peroxide (HO) and ferrous iron (Fe (II)) can degrade organic pollutants. Duckweed, an aquatic plant, is promising for a co-beneficial phytoremediation process that combines wastewater treatment and biomass production for biofuel feedstock. However, the phyto-Fenton process using duckweed has not been extensively studied. Because sulfamethoxazole (SMX), a major antibiotic, is distributed widely and is an emerging contaminant, its effective removal from contaminated water is necessary. The present study investigated the possibility of the simultaneous efficient removal of SMX from polluted water and biomass production for fuel feedstock by the phyto-Fenton process using duckweed. This is the first attempt to demonstrate the co-benefits of SMX removal and biomass production using duckweed. Intracellular HO was produced using four duckweeds, Lemna aequinoctialis, L. minor, Landolina punctata, and Spirodela polyrhiza, in the range of 16.7-24.6 μ mol g-1 fresh weight, and extracellular HO was released into the water phase. Consequently, duckweed could be used as an HO supply source for the phyto-Fenton process. Specifically, 0.5 g fresh duckweed almost completely eliminated 1 mg L SMX after 5 d in 50 mL sterile modified Hoagland solution containing 10 mM Fe (II). Fe (II)-dependent elimination of SMX indicated the occurrence of phyto-Fenton reaction. The phyto-Fenton process using duckweed effectively removed SMX. S. polyrhiza duckweed similarly removed 1 mg L SMX even in sewage effluent containing other organic contaminants. During this treatment, duckweed biomass was generated at 7.95 g dry weight m d, which was converted into methane at 353 normal liters CH kg volatile solids by anaerobic digestion. For the first time, this study clearly demonstrates the potential for simultaneous SMX removal and biomass production from SMX-contaminated wastewater using duckweed.
Topics: Sulfamethoxazole; Wastewater; Biomass; Hydrogen Peroxide; Biodegradation, Environmental; Araceae; Iron; Water Pollutants, Chemical; Waste Disposal, Fluid; Biofuels
PubMed: 38866331
DOI: 10.1016/j.chemosphere.2024.142592 -
JAMA Network Open Jun 2024Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear.
OBJECTIVE
To assess the safety and efficacy of peceleganan spray for the treatment of wound infections.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022.
INTERVENTIONS
Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189).
MAIN OUTCOMES AND MEASURES
The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions.
RESULTS
Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.
Topics: Humans; Male; Female; Middle Aged; Adult; Wound Infection; Anti-Infective Agents, Local; China; Silver Sulfadiazine; Treatment Outcome; Aged; Anti-Bacterial Agents
PubMed: 38861260
DOI: 10.1001/jamanetworkopen.2024.15310 -
PLoS Neglected Tropical Diseases Jun 2024Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity...
Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center.
BACKGROUND
Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity (VA) outcomes, and factors associated with VA loss in patients with active OT following antiparasitic treatment.
METHODOLOGY/PRINCIPAL FINDINGS
A retrospective chart review of patients with active OT treated with antiparasitic drugs between 2010 and 2020 was performed. Outcome measures included clinical characteristics, interval VA, and predictive factors associated with loss of VA ≤ 20/50 at 6 months post-treatment. Ninety-two patients (95 eyes) were enrolled. The median follow-up time was 10.9 months (IQR 4.9-31.8 months). The median age at presentation was 35.9 years, 51% were male, and 92.4% had unilateral OT. Eleven patients (12%) were immunocompromised (HIV infection, eight patients; receiving immunosuppressive agents, three patients). Patients mainly presented with primary retinitis without previous scar (62%), posterior pole lesion (56%), and lesion size of ≤ 2-disc area (75%). Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients. Oral trimethoprim/sulfamethoxazole monotherapy was the primary short-term antiparasitic drug prescribed (85%). At the final visit, 21% of all affected eyes suffered VA ≤ 20/200. The cumulative incidence of recurrent OT at three years was 33.9% (95% CI, 19.7%-54.2%). Immunocompromised patients [adjusted odds ratio (aOR) 4.9, p = 0.041], macular lesion (aOR 5.4, p = 0.032), and initial VA ≤ 20/200 (aOR 9.1, p = 0.014) were predictive of having VA ≤ 20/50 at 6 months post-treatment.
CONCLUSIONS
Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole. Severe VA loss was observed in one-fifth of eyes following treatment with lesion resolution. Immunocompromised patients, eyes with macular lesions, and poor initial VA were associated with poor VA outcomes.
Topics: Humans; Toxoplasmosis, Ocular; Male; Retrospective Studies; Adult; Female; Thailand; Visual Acuity; Middle Aged; Tertiary Care Centers; Young Adult; Immunocompromised Host; Antiparasitic Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Adolescent; Treatment Outcome; Southeast Asian People
PubMed: 38843299
DOI: 10.1371/journal.pntd.0012232 -
World Journal of Urology May 2024To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center... (Comparative Study)
Comparative Study
BACKGROUND
To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX).
METHODS
Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF).
RESULTS
Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively.
CONCLUSION
The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.
Topics: Humans; Male; Fosfomycin; Ciprofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Antibiotic Prophylaxis; Aged; Middle Aged; Prostate; Anti-Bacterial Agents; Drug Therapy, Combination; Biopsy; Retrospective Studies; Rectum; Postoperative Complications
PubMed: 38806739
DOI: 10.1007/s00345-024-05048-4 -
Narra J Apr 2024Second-degree burn, the most common among burn degrees, underscores the importance of timely and proper treatment in influencing prognosis. Nutmeg (), renowned for its...
Second-degree burn, the most common among burn degrees, underscores the importance of timely and proper treatment in influencing prognosis. Nutmeg (), renowned for its potent antibacterial and antifungal properties, also serves as an effective antiseptic for open wounds. The aim of this study was to identify the phytochemical constituents of nutmeg essential oil and analyze the wound healing effect of nutmeg cream on second-degree burns in an animal model. An experimental study with a completed randomized design was conducted on strain Wistar rats with second-degree burn. This study had four groups and each group consisting of four rats: B (burn-treated base cream), B+N (burn-treated 3% nutmeg cream), B+SSD (burn-treated silver sulfadiazine (BSS)), and B+N+SSD (burn-treated 3% nutmeg cream and SSD in a 1:1 ratio). The phytochemical analysis of nutmeg essential oil was conducted by gas chromatography and mass spectroscopy (GC-MS). The burn diameter and burn wound healing percentage were measured from day 0 to 18. One-way ANOVA followed by post hoc analysis using the least significant difference (LSD) was employed to analysis the effect. The phytochemical analysis of nutmeg essential oil found that myristicin, terpinene-4-ol, terpinene, safrole and terpinolene were the most abundant putative compounds in nutmeg essential oil. On day 0, the average burn wound diameters were 1.4 cm in all groups and increases were observed in all groups on day 3. The wound diameter decreased until day 18 with the smallest burn wound diameter was found in the B+N group (0.86±0.37 cm), followed by B+SSD (0.93±0.29 cm). The B+SSD group exhibited the highest percentage of burn wound healing (56.80±14.05%), which was significantly different from the base cream (<0.05). The percentage of burn wound healing in rats given 3% nutmeg cream was 41.88±13.81%, suggesting that nutmeg cream could promote burn wound healing in rats induced by second-degree burns.
Topics: Animals; Myristica; Wound Healing; Burns; Rats, Wistar; Rats; Disease Models, Animal; Oils, Volatile; Skin Cream; Male; Gas Chromatography-Mass Spectrometry; Anti-Infective Agents, Local; Silver Sulfadiazine
PubMed: 38798873
DOI: 10.52225/narra.v4i1.621 -
The Science of the Total Environment Aug 2024Biochars and organoclays have been proposed as efficient adsorbents to reduce the mobility of agrochemicals in soils. However, following their application to soils,...
Biochars and organoclays have been proposed as efficient adsorbents to reduce the mobility of agrochemicals in soils. However, following their application to soils, these adsorbents undergo changes in their physicochemical properties over time due to their interaction with soil components. In this study, the adsorption capacity of a commercial biochar and a commercial organoclay for the antibiotic sulfamethoxazole (SFMX) and the pesticide ethofumesate (ETFM) was evaluated over aging periods of 3 months in the laboratory and 1 year in the field, subsequent to their application to a Mediterranean soil. The results showed that the adsorption of SFMX and ETFM in the soil amended with the adsorbents was greater than in the unamended soil, but for both chemicals, adsorption decreased with aging of the adsorbents in the soil. Characterization of the adsorbents before and after aging revealed physical blocking of adsorption sites by soil components. The loss of adsorption capacity of the adsorbents upon aging led to higher leaching of SFMX and ETFM in the soil containing field-aged adsorbents, although leaching remained lower than in unamended soil. Our findings reveal that, under the Mediterranean environment studied, the efficacy of the studied materials as adsorbents is maintained to a considerable extent for at least one year after their field application, which would have positive implications in their use for attenuating the dispersion of agricultural contaminants in the environment.
Topics: Sulfamethoxazole; Charcoal; Adsorption; Soil Pollutants; Soil; Clay
PubMed: 38797398
DOI: 10.1016/j.scitotenv.2024.173501 -
Molecules (Basel, Switzerland) May 2024Bioelectrochemical systems (BESs) are an innovative technology for the efficient degradation of antibiotics. () MR-1 plays a pivotal role in degrading sulfamethoxazole...
Bioelectrochemical systems (BESs) are an innovative technology for the efficient degradation of antibiotics. () MR-1 plays a pivotal role in degrading sulfamethoxazole (SMX) in BESs. Our study investigated the effect of BES conditions on SMX degradation, focusing on microbial activity. The results revealed that BESs operating with a 0.05 M electrolyte concentration and 2 mA/cm current density outperformed electrolysis cells (ECs). Additionally, higher electrolyte concentrations and elevated current density reduced SMX degradation efficiency. The presence of nutrients had minimal effect on the growth of MR-1 in BESs; it indicates that MR-1 can degrade SMX without nutrients in a short period of time. We also highlighted the significance of mass transfer between the cathode and anode. Limiting mass transfer at a 10 cm electrode distance enhanced MR-1 activity and BES performance. In summary, this study reveals the complex interaction of factors affecting the efficiency of BES degradation of antibiotics and provides support for environmental pollution control.
Topics: Sulfamethoxazole; Shewanella; Bioelectric Energy Sources; Electrodes; Biodegradation, Environmental; Anti-Bacterial Agents; Electrolysis; Electrochemical Techniques
PubMed: 38792137
DOI: 10.3390/molecules29102276 -
PloS One 2024Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP...
Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.
Topics: Fibroins; Hydrogen-Ion Concentration; Nanoparticles; Furosemide; Drug Delivery Systems; Polymethacrylic Acids; Drug Liberation; Drug Carriers; Particle Size; Animals; Humans; Spectroscopy, Fourier Transform Infrared
PubMed: 38781182
DOI: 10.1371/journal.pone.0303177 -
Malaria Journal May 2024Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages... (Observational Study)
Observational Study
BACKGROUND
Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages throughout the year. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa and a child-friendly dispersible tablet formulation has recently become available.
METHODS
This qualitative non-interventional observational study was conducted in Benin, Côte d'Ivoire, and Mozambique between February and June 2022. Prototype blister packs, dispensing boxes and job aids designed to support dispersible SP deployment for PMC were evaluated using focus group discussions (FGD) and semi-structured in-depth individual interviews (IDI) with health authorities, health personnel, community health workers (CHWs) and caregivers. The aim was to evaluate knowledge and perceptions of malaria and chemoprevention, test understanding of the tools and identify gaps in understanding, satisfaction, user-friendliness and acceptability, and assess the potential role of CHWs in PMC implementation. Interviews were transcribed and imported to ATLAS.ti for encoding and categorization. Thematic content analysis used deductive and inductive coding with cross-referencing of findings between countries and participants to enrich data interpretation. Continuous comparison across the IDI and FGD permitted iterative, collaborative development of materials.
RESULTS
Overall, 106 participants completed IDIs and 70 contributed to FGDs. Malaria was widely recognised as the most common disease affecting children, and PMC was viewed as a positive intervention to support child health. The role of CHWs was perceived differently by the target groups, with caregivers appreciating their trusted status in the community, whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria.
CONCLUSION
Simple modifications profoundly affected the perception of PMC and influenced acceptability. Iterative quantitative investigation resulted in PMC-specific materials suited to the local context and socio-cultural norms of the target population with the aim of increasing access to chemoprevention in children most at risk of severe malaria.
Topics: Mozambique; Benin; Malaria; Antimalarials; Chemoprevention; Humans; Cote d'Ivoire; Drug Combinations; Pyrimethamine; Sulfadoxine; Child, Preschool; Female; Male; Drug Packaging; Infant; Child; Adult
PubMed: 38773567
DOI: 10.1186/s12936-024-04977-0