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Macrophyte overgrowth in eutrophic lakes can hasten the decline of shallow water bodies, yet the impact of macrophyte deposition on sediment phosphorus (P) accumulation in the ice-on season remains unclear. Comparative analyses of P variations among 13 semi-connected sub-lakes in Wuliangsu Lake in China, a typical MDE lake, considered external flow and macrophyte decomposition as driving forces. Sediment P fractions and water total phosphorus (TP) were analyzed at 35 sampling points across three ice-on season stages, along with macrophyte TP content to assess debris contributions. Our findings reveal that phosphorus accumulation occurs during the ice-on season in the MDE lake, with an average TP content increase of 16 mg/kg. However, we observed a surprisingly small sediment nutrient accumulation ratio (ΔTP/ΔTN=0.006) compared to macrophyte nutrient levels before decomposition. Further analysis of the dominant species, Potamogeton pectinatus, indicates that a significant portion (55%) of macrophyte phosphorus is released before the ice-on season. This highlights the critical importance of timing macrophyte harvesting to precede the phosphorus leaching process, which has implications for lake management and ecosystem restoration efforts. Additionally, our research demonstrates similar transformations among different sediment fractions as previously reported. Macrophyte debris decomposition likely serves as the primary source of Residual P (Res-P) or TP accumulation. In addition, Ca-bound P (Ca-P) generally showed a decrease, which mainly caused by its transformation to Fe/Al-bound P (Fe/Al-P), Exchange-P (Ex-P), and sometimes to Res-P. However, we emphasize the significant impacts of flow dynamics on Ca-P transport and transformations. Its hydrodynamic action increases water dissolved oxygen, which accelerates the transformation of Ca-P to more easily released Fe/Al-P and Ex-P. Furthermore, hydrodynamic transport also leads to upstream Ca-P transport to downstream. This underscores the necessity of considering flow dynamics when estimating phosphorus variations and formulating phosphorus restoration strategies.
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Eutrofização , Lagos , Fósforo , Estações do Ano , Fósforo/análise , Fósforo/metabolismo , Ecossistema , China , Sedimentos Geológicos , Monitoramento Ambiental , GeloRESUMO
This paper discusses the framework of China's food safety standards and provides a brief overview of the problems and developmental characteristics of food safety in China. The composition and characteristics of China's food safety standards are revealed by an analysis of the changes in China's general food standards, an overview of the characteristics of the hygiene requirements in the production and operation process, and an introduction to food product and test method standards. In conclusion, Chinese food safety standards are still being improved, but they must also be effectively implemented and followed up in real time in order to continuously improve the quality of food and reduce food safety incidents. © 2024 Society of Chemical Industry.
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Inocuidade dos Alimentos , ChinaRESUMO
This study aimed to build a population pharmacokinetic (PopPK) model for contezolid tablet (MRX-I) in healthy subjects and adults with complicated skin and soft-tissue infections (cSSTIs) to further evaluate the efficacy and safety of contezolid and recommend the optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. PopPK analysis was performed using a nonlinear mixed-effects model (NONMEM) to examine the effects of age, body weight, sex, liver and renal functions, albumin, food, dosage strength, and subject type on the PK parameters of contezolid. PK/PD analysis was combined with the MIC of contezolid, clinical/microbiological efficacy, and nonclinical study data. Adverse events (AEs) and study drug-related AEs reported were summarized to examine the relationship between contezolid exposure level and safety measures. A two-compartment model was built. An exponential model was used to describe the interindividual variation. A proportional model was used to describe the intraindividual variation of PK parameters. Good clinical and microbiological efficacy are expected for the infections caused by S. aureus when contezolid is administered at 600 mg or 800 mg every 12 h (q12h). The area under the concentration-time curve from 0 to 24 h at steady state and maximum concentration of drug in serum at steady state of contezolid did not show significant association with the incidence of any AE. The dosing regimen of contezolid at 800 mg q12h administered postprandially for 7 to 14 days is expected to achieve satisfactory clinical and microbiological efficacy in cSSTIs, which is slightly better than that of 600 mg contezolid. This administration has been added to the prescribing information of contezolid tablets.
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Farmacologia Clínica , Infecções dos Tecidos Moles , Adulto , Antibacterianos/farmacologia , China , Humanos , Oxazolidinonas , Piridonas , Infecções dos Tecidos Moles/tratamento farmacológico , Staphylococcus aureusRESUMO
OBJECTIVES: Contezolid is a novel oxazolidinone antibacterial agent for managing infections caused by aerobic and anaerobic Gram-positive bacteria including methicillin-resistant strains. A Phase III, multicentre, randomized, double-blind, active-controlled trial evaluated the efficacy and safety of contezolid versus linezolid in adults with complicated skin and soft tissue infections (cSSTIs). METHODS: Adult patients with cSSTI were randomized in a ratio of 1:1 to receive contezolid 800â mg or linezolid 600â mg q12h for 7-14â days. Clinical cure rate and safety were assessed at the test of cure (TOC) visit in the full analysis set (FAS) and clinical evaluable (CE) population. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference of clinical cure rates greater than -10%. Chinadrugtrials.org.cn registration identifier: CTR20150855. RESULTS: Clinical cure rates at TOC indicated non-inferiority of contezolid 800â mg to linezolid 600â mg q12h for patients in the FAS with clinical evaluation, FAS, and CE populations: 92.8% (271/292) versus 93.4% (284/304) (difference -0.6%, 95% CI: -4.7% to 3.5%), 81.4% (271/333) versus 84.5% (284/336) (difference -3.1%, 95% CI: -8.8% to 2.6%) and 90.5% (267/295) versus 90.1% (282/313) (difference 0.4%, 95% CI: -4.3% to 5.1%). Contezolid and linezolid showed similar efficacy for the cSSTIs caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus. Contezolid demonstrated significant lower incidence of leucopenia (0.3% versus 3.4%) and thrombocytopenia (0% versus 2.3%) than linezolid. The frequency of treatment-emergent adverse events was comparable between the two groups. CONCLUSIONS: Contezolid 800â mg q12h is as effective as linezolid for treatment of cSSTIs in adults, but safer than linezolid in terms of haematological abnormalities.
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Staphylococcus aureus Resistente à Meticilina , Oxazolidinonas , Infecções dos Tecidos Moles , Adulto , Antibacterianos/efeitos adversos , Método Duplo-Cego , Humanos , Linezolida/efeitos adversos , Oxazolidinonas/efeitos adversos , Piridonas , Infecções dos Tecidos Moles/microbiologia , Resultado do TratamentoRESUMO
AIMS: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic (PPK)/pharmacodynamic analysis. METHODS: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of a 0.5-g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 72 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment and the cumulative fraction of response against Streptococcus pneumoniae and Staphylococcus aureus was calculated by Monte Carlo simulation. RESULTS: The data best fitted a 2-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L) and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4 ± 6.5% in severe renal impairment patients and 66.1 ± 16.8% in healthy controls. PPK/pharmacodynamic modelling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g every 48 hours (q48h) was the optimal dosing regimen in severe renal impairment patients, evidenced by higher probability of target attainment (92.7%) and cumulative fraction of response (>99%) at nemonoxacin minimum inhibitory concentration ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if minimum inhibitory concentration = 1 mg/L. CONCLUSION: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.
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Quinolonas , Staphylococcus aureus , Antibacterianos , Humanos , Testes de Sensibilidade Microbiana , Método de Monte CarloRESUMO
PURPOSES: To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin. METHODS: Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted in 18 healthy Chinese subjects. Both CMS formulas met the requirements of European Pharmacopoeia 9.2 with 12.1% difference in the two major active components (CMS A and CMS B). The PK parameters after a single intravenous infusion of CMS at 2.5 mg/kg were calculated and the steady-state plasma colistin concentrations (Css,avg) following multiple dosing, once every 12 h for 7 days, were simulated with the non-compartment model. RESULTS: The systemic exposure (AUC0-inf) of CMS were 59.49 ± 5.90 h·µg/mL and 51.09 ± 4.70 h·µg/mL, and the AUC0-inf of colistin were 15.39 ± 2.63 h·µg/mL and 12.36 ± 2.10 h·µg/mL for CTTQ and Parkedale, respectively. The ratios (90% CI) of geometric mean of AUC0-inf of CTTQ to Parkedale were 116.38% (112.95%, 119.91%) and 124.49% (120.76%, 128.35%) for CMS and colistin, respectively. The predicted Css,avg (95% CI) were 0.92 (0.85, 0.99) µg/mL and 0.74 (0.69, 0.79) µg/mL for CTTQ and Parkedale, respectively. CONCLUSION: The difference in component content in the two CMS formulas had a significant (P < 0.001) impact on the systemic exposure of colistin in human, thus, warranted essential considerations in clinical applications.
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Antibacterianos/farmacocinética , Colistina/farmacocinética , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/química , Colistina/administração & dosagem , Colistina/química , Estudos Cross-Over , Composição de Medicamentos/métodos , Feminino , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Masculino , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Adulto JovemRESUMO
BACKGROUND: Isavuconazole is a broad-spectrum triazole for the treatment of invasive fungal disease (IFD). OBJECTIVE: To investigate the clinical experience with isavuconazole in Chinese individuals. PATIENTS/METHODS: Participants were Chinese healthy volunteers from a Phase I pharmacokinetics (PK) and safety study of single/multiple doses of isavuconazole (n = 36) and Chinese patients from the global Phase III SECURE study that assessed safety and efficacy of isavuconazole vs voriconazole for IFD treatment (n = 26). RESULTS: No clinically relevant differences in PK were found between Chinese and Western participants, although exposure was increased in Chinese volunteers. Treatment-emergent adverse events (TEAEs) were reported in 75.0% of healthy volunteers, many of which were infusion-related. No serious AEs were reported. In SECURE, findings in Chinese patients (n = 26) were similar to the global population. For patients who received ≥1 dose of study drug, allcause mortality from first dose to Day 42 was 10.0% (1/10) with isavuconazole and 25.0% (4/16) with voriconazole (treatment difference [95% confidence interval, CI]: -15.0% [-43.2%, 13.2%]). Overall response at the end of treatment for patients with proven/probable IFD was 25.0% and 16.7% with isavuconazole and voriconazole, respectively (treatment difference [95% CI] -8.3% [-60.2%, 43.5%]). Isavuconazole was associated with lower incidence of hepatobiliary, eye, skin, subcutaneous tissue and psychiatric disorders compared with voriconazole and lower incidence of treatment-related TEAEs, serious TEAES or death overall. CONCLUSIONS: Although further research is required, this study demonstrated a favourable risk-benefit profile of isavuconazole in Chinese patients.
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Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Voluntários Saudáveis/estatística & dados numéricos , Nitrilas/farmacocinética , Nitrilas/uso terapêutico , Piridinas/farmacocinética , Piridinas/uso terapêutico , Triazóis/farmacocinética , Triazóis/uso terapêutico , Administração Intravenosa , Administração Oral , Povo Asiático , China , Experimentação Humana , Humanos , Infecções Fúngicas Invasivas/etnologia , Nitrilas/efeitos adversos , Piridinas/efeitos adversos , Resultado do Tratamento , Triazóis/efeitos adversosRESUMO
BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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Monitoramento de Medicamentos , Vancomicina , Adulto , Povo Asiático , Criança , China , Humanos , Recém-Nascido , Sociedades , Vancomicina/uso terapêuticoAssuntos
Oxazolidinonas , Dermatopatias Bacterianas , Infecções dos Tecidos Moles , Adulto , Humanos , Linezolida/efeitos adversos , Infecções dos Tecidos Moles/tratamento farmacológico , Piridonas , Antibacterianos/efeitos adversos , Método Duplo-Cego , Resultado do Tratamento , Dermatopatias Bacterianas/tratamento farmacológicoRESUMO
OBJECTIVES: Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting. METHODS: Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days. Clinical cure was assessed at the test of cure (TOC) visit (8-15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than -10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135. RESULTS: Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference -1.0%, 95% CI -6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI -4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups. CONCLUSIONS: Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified.
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Antibacterianos/administração & dosagem , Aztreonam/administração & dosagem , Cefalosporinas/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Vancomicina/administração & dosagem , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Aztreonam/efeitos adversos , Cefalosporinas/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dermatopatias Bacterianas/complicações , Infecções dos Tecidos Moles/complicações , Resultado do Tratamento , Vancomicina/efeitos adversos , Adulto Jovem , CeftarolinaRESUMO
BACKGROUND: Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. METHODS: We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. RESULTS: The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.
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Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Vancomicina/uso terapêutico , China , HumanosRESUMO
This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n = 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n = 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean ± SD) at steady state (Cmax_ss) were 9.60 ± 1.84 and 11.04 ± 2.18 µg/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0-24_ss) were 44.03 ± 8.62 and 65.82 ± 10.78 µg · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ± 1.47, 8.17 ± 1.76, and 9.96 ± 2.23 µg/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0-24_ss values were 40.46 ± 9.52, 54.17 ± 12.10, and 71.34 ± 17.79 µg · h/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was ≤1 mg/liter. It is suggested that all of the studied intravenous nemonoxacin dosing regimens should have favorable clinical and microbiological efficacies in future clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.).
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Antibacterianos/farmacocinética , Quinolonas/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Quinolonas/farmacologiaRESUMO
Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at assessing the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, double-blind, placebo-controlled, dose escalating safety and tolerability study in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square crossover pharmacokinetic study in 12 subjects. The study revealed that nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related adverse events (AEs) were mild, transient, and confined to local irritation at the injection site. The pharmacokinetic study revealed that after the administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum plasma drug concentration (Cmax) values were 4.826 µg/ml, 7.152 µg/ml, and 11.029 µg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC0-72 h) were 17.05 µg · h/ml, 39.30 µg · h/ml, and 61.98 µg · h/ml. The mean elimination half-life (t1/2) was 11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear dose-response relationship between the AUC0-72 h and AUC0-∞. These findings provide further support for the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.).
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Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Quinolonas/efeitos adversos , Quinolonas/farmacocinética , Administração Intravenosa , Antibacterianos/administração & dosagem , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Quinolonas/administração & dosagemRESUMO
OBJECTIVE: The aim of this study was to develop and validate an ultra-performance liquid chromatographic (UPLC) method with photodiode array detector for the measurement of vancomycin in human serum samples for therapeutic drug monitoring or other applications. METHODS: The method included the extraction of vancomycin in serum by deproteinization with acetonitrile. The analyses were carried out using an ACQUITY UPLC BEH C(18) column (2.1 × 50 mm, 1.7 µm) using acetonitrile and 0.005 M KH(2)PO(4) buffer (pH 2.5) as the mobile phase at a flow rate of 0.3 mL/min, with photodiode array detection at 230 nm. The method was validated for extraction recovery, inter- and intraday precision (relative standard deviation, RSD%), and accuracy and stability of vancomycin in serum. Both the established UPLC method and fluorescence polarization immunoassay (FPIA) were used to measure the prepared quality control (QC) samples (1.0, 7.0, 35.0, 75.0 mg/L) to validate the accuracy of UPLC. Furthermore, both methods were subsequently used to assay the vancomycin concentration in 172 clinical serum samples collected from patients receiving vancomycin in the hospitals localized in Shanghai (China) and 32 control samples from United Kingdom National External Quality Assessment Service (UK NEQAS). RESULTS: The retention time of vancomycin was 2.6 minutes. The calibration curve for UPLC was linear over the range 1.0-100.0 mg/L (R(2) > 0.999). The method was fully validated in terms of recovery, selectivity, accuracy, precision, and various conditions. The absolute difference% and RSD% of the prepared QC samples assayed by UPLC were all better than the results by FPIA. A paired t test of the results of the prepared QC samples indicated that the results of all the QC samples had significant difference (P < 0.05), except for the 7.0 mg/L QC samples, which suggested that UPLC was more accurate for the samples containing low or high concentration of vancomycin. A correlation with the Deming model provided a good linear relation between the results of the 2 methods applied to 172 samples, with equation of UPLC = 0.99 × FPIA - 0.19 (R(2)= 0.923), and the agreement of the 2 methods was illustrated using Bland-Altman plot with a mean difference (UPLC - FPIA) of -0.428 mg/L and 95% confidence interval of -8.33 to 7.47 mg/L, respectively. A Student t test comparing results obtained by the UPLC method and group mean results of control samples from UK NEQAS were not significant (P = 0.057). CONCLUSIONS: A short analysis time, small amount of serum needed, high specificity, and accuracy make the UPLC method developed in this study appropriate and practical for vancomycin therapeutic drug monitoring and could be applied to other nonserum applications or where requiring superior validation parameters such as for pharmacokinetic/pharmacodynamic studies.
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Antibacterianos/sangue , Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Soro/química , Vancomicina/sangue , Estudos de Casos e Controles , Imunoensaio de Fluorescência por Polarização , Humanos , Controle de Qualidade , Sensibilidade e EspecificidadeRESUMO
The decomposition of macrophytes plays a crucial role in the nutrient cycles of macrophyte-dominated eutrophication lakes. While research on plant decomposition mechanisms and microbial influences has rapid developed, it is curious that plant decomposition models have remained stagnant at the single-stage model from 50 years ago, without endeavor to consider any important factors. Our research conducted in-situ experiments and identified the optimal metrics for decomposition-related microbes, thereby establishing models for microbial impacts on decomposition rates (k_RDR). Using backward elimination in stepwise regression, we found that the optimal subset of independent variables-specifically Gammaproteobacteria-Q-L, Actinobacteriota-Q-L, and Ascomycota-Q-L-increased the adjusted R-squared (Ra2) to 0.93, providing the best modeling for decomposition rate (p = 0.002). Additionally, k_RDR can be modeled by synergic parameters of ACHB-Q-L, LDB-Q-L, and AB-Q-L for bacteria, and SFQ for fungi, albeit with a slightly lower Ra2 of 0.7-0.9 (p < 0.01). The primary contribution of our research lies in two key aspects. Firstly, we introduced optimal metrics for modeling microbes, opting for debris surface microbes over sediment microbes, and prioritizing absolute abundance over relative abundance. Secondly, our model represents a noteworthy advancement in debris modeling. Alongside elucidating the focus and innovative aspects of our work, we also addressed existing limitations and proposed directions for future research. SYNOPSIS: This study explores optimum metrics for decomposition-related microbes, offering precise microbial models for enhanced lake nutrient cycle simulation.
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Eutrofização , Lagos , Lagos/microbiologia , Lagos/química , Plantas , Monitoramento Ambiental , Bactérias/metabolismoRESUMO
Background: To investigate the association of marital status on cardiovascular death risk in lung cancer patients. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 2011 to 2015 (N = 118,293), the association between marital status and cardiovascular death (CVD) risk in patients with lung cancer was assessed by competing-risks regression models. Results: Unmarried status was associated with increased risk of cardiovascular death in lung cancer patients [hazard ratio (HR) = 1.398, 95 % confidence interval (CI): 1.268-1.542], which remained significant even after adjusting for potential covariates (HR = 1.407, 95 % CI: 1.276-1.551). Further unmarried subgroups analysis showed that the different unmarried status were associated with increased cardiovascular death risk as follows: single (HR = 1.397, 95 % CI: 1.236-1.1.580), separated (HR = 1.630, 95 % CI: 1.153-2.305), divorced (HR = 1.318, 95 % CI: 1.158-1.500), and widowed (HR = 1.561, 95 % CI: 1.393-1.749). Further subgroup analysis by sex revealed that compared to male lung cancer patients with married, CVD risk was significant increased in their counterparts with widowed (adjusted HR = 1.509, 95 % CI: 1.291-1.764, P<0.001), single (adjusted HR = 1.361, 95 % CI: 1.168-1.585, P<0.001) and divorced (adjusted HR = 1.353, 95 % CI: 1.177-1.555, P<0.001) rather than those with separated. However, similar phenomena was only observed in female lung cancer patients with widowed (adjusted HR = 1.414, 95 % CI: 1.220-1.640, P<0.001) and single (adjusted HR = 1.438, 95 % CI: 1.195-1.730, P<0.001). Conclusion: Unmarried status was associated with increased cardiovascular death risk in patients with lung cancer, which highlighted that more attention and humanistic/supportive care should be offered to unmarried lung cancer patients for improving the prognosis.
RESUMO
To achieve the objective of "waste control by waste", in this study, a green aerogel adsorbent comprised of pomelo-peel cellulose and sodium alginate (PCC/SA) was prepared through dual-network crosslinking. The resulting 3D hierarchical porous structured PCC/SA aerogel exhibited good structural stability, and kept the morphological integrity during 10 days in a wide pH range (2-10), suggesting its potential for recycling in diverse complex environments. Besides, the superior adsorption capacities for methylene blue (MB) and Cu(II) were observed, with the qm values and adsorption equilibrium times were recorded to be 1299.59 mg/g (300 min) and 287.55 mg/g (120 min), correspondingly. Furthermore, the favorable reusability of the PCC/SA aerogel was also demonstrated, with the removal efficiency for MB remaining almost unchanged (about 94 %) after 10 adsorption-desorption cycles, while there was a slight reduction for Cu(II) from 85.28 % to 72.47 %. XPS and FTIR analysis revealed that electrostatic attraction, hydrogen bonding, cation exchange and coordination were the major adsorption mechanisms. Importantly, the PCC/SA aerogel can be naturally degraded in soil within 10 weeks. Therefore, the as-prepared aerogel bead derived from pomelo peel shows great promise as an adsorbent for wastewater treatment containing dye and heavy metal ions.
Assuntos
Celulose , Corantes , Géis , Metais Pesados , Celulose/química , Adsorção , Corantes/química , Géis/química , Metais Pesados/química , Metais Pesados/isolamento & purificação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Alginatos/química , Concentração de Íons de Hidrogênio , Azul de Metileno/química , Citrus/química , Porosidade , Purificação da Água/métodos , Cobre/química , CinéticaRESUMO
Hospital wastewater treatment systems (HWTSs) are a significant source and reservoir of antibiotic resistance genes (ARGs) and a crucial hub for transmitting ARGs from clinical to natural environments. However, there is a lack of research on the antibiotic resistome of clinical wastewater in HWTSs. In this study, we used metagenomics to analyze the prevalence and abundance of ARGs in five typical HWTSs. A total of 17 antibiotics from six categories were detected in the five HWTSs; ß-lactam antibiotics were found at the highest concentrations, with up to 4074.08 ng·L-1. We further found a total of 21 ARG types and 1106 subtypes of ARGs with the highest percentage of multi-drug resistance genes (evgS, msbA, arlS, and baeS). The most abundant last-resort ARGs were mcr, which were detected in 100 % of the samples. HWTSs effluent is a major pathway for the transmission of last-resort ARGs into urban wastewater networks. The removal of antibiotics, antibiotic-resistant bacteria, and ARGs from HWTSs was mainly achieved by tertiary treatment, i.e., chlorine disinfection, but antibiotics and ARGs were still present in the HWTSs effluent or even increased after treatment. Moreover, antibiotics and heavy metals (especially mercury) in hospital effluents can exert selective pressure for antibiotic resistance, even at low concentrations. Qualitative analyses based on metagenome-assembled genome analysis revealed that the putative hosts of the identified ARGs are widely distributed among Pseudomonas, Acidovorax, Flavobacterium, Polaromonas, and Arcobacter. Moreover, we further assessed the clinical availability of ARGs and found that multidrug ARGs had the highest clinical relevance values. This study provides new impulses for monitoring and removing antibiotics and ARGs in the hospital sewage treatment process.
Assuntos
Antibacterianos , Purificação da Água , Águas Residuárias , Genes Bacterianos , HospitaisRESUMO
BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou maisRESUMO
The aim of this paper was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of nemonoxacin, a novel nonfluorinated quinolone, against Streptococcus pneumoniae in vitro. A modified infection model was used to simulate the pharmacokinetics of nemonoxacin following scaling of single oral doses and multiple oral dosing. Four S. pneumoniae strains with different penicillin sensitivities were selected, and the drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid maximum-effect (Emax) model was used to analyze the relationship between PK/PD parameters and drug effect. Analysis indicated that the killing pattern of nemonoxacin shows a dualism which is mainly concentration dependent when the MIC is low and that the better PK/PD index should be the area under the concentration-time curve for the free, unbound fraction of the drug divided by the MIC (fAUC0-24/MIC), which means that giving the total daily amount of drug as one dose is appropriate under those conditions. When the MIC is high, the time (T) dependency is important and the valid PK/PD index should be the cumulative percentage of a 24-h period in which the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T>MIC), which means that to split the maximum daily dose into several separate doses will benefit the eradication of the bacteria. To obtain a 3-log10-unit decrease, the target values of fAUC0-24/MIC and f%T>MIC are 47.05 and 53.4%, respectively.