Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Antibiotic safety among neonates and paediatrics in a public hospital: KwaZulu-Natal

Background: The World Health Organization (WHO) guidelines recommend the empiric treatment of infections before definitive treatment begins. However, ethical concerns limit the availability of clinical trials in neonates and paediatrics to fully ascertain the safety profile of antibiotics in these populations. Aim: This study aimed to quantify the use of antibiotics among neonates and paediatrics and commented on the use, rationale and appropriateness of antibiotics prescribed. Setting: A secondary level public sector hospital located in Durban, KwaZulu-Natal. Methods: Demographic and treatment information of neonates and paediatrics were collected retrospectively from January 2022 to June 2022. Data were obtained from patient files and extracted for analysis using Microsoft Excel®. Analytical and descriptive statistics were used to analyse patient demographics and treatment variables. Results: A total of 568 antibiotics, issued to 389 patients, were reviewed. Penicillins (40.1%), aminoglycosides (24.3%) and combination penicillin-beta-lactam inhibitors (23.3%) were identified as the most frequently prescribed antibiotics for inpatients. Most antibiotics prescribed to inpatients were for complications associated with pre-term birth (66.9%). Combination penicillin-beta-lactam inhibitors (34.7%), penicillins (29.5%) and cephalosporins (29.5%) were the most frequently prescribed antibiotics to outpatients. A correlation was found between the route of administration and the duration of therapy; the intravenous route (63.6%) was preferred over the oral route (36.4%) for administration. Conclusion: Many broad-spectrum antibiotics were prescribed, thus increasing the risk of resistance. Antibiotics were being prescribed according to the guidelines; however, there is still a need for therapeutic drug monitoring to ensure the continuation of rational drug use. Contribution: There was evidence of rational use of antibiotics in the public hospital (KwaZulu-Natal), in keeping with economic and availability factors.

Universal strategies and methodologies in broad-spectrum antiviral drug discovery / 药学学报

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

Analysis on effect of antimicrobial stewardship based on information technology for 6 years / 中华急诊医学杂志

Objective:To evaluate the effectiveness of antimicrobial stewardship based on self-developed antibiotic clinical decision support system (aCDSS) in the inpatients at a tertiary hospital for consecutive 6 years, and to provide reference for rational use and antimicrobial stewardship.Methods:aCDSS was self-designed based on information technology and applied in clinical use in our hospital from 2015. Data of inpatient information and antibacterial use from January 2015 to December 2020 were collected from HIS and aCDSS. A retrospective study was conducted in all inpatients on the utilization rate and antibiotic use density.Results:Since 2015, with the comprehensive implementation of antimicrobial stewardship based on the aCDSS,there was a significant decline on the annual rate of antibiotic usage from 44.18% in 2015 to 38.70% in 2020, as well as on the usage rate of extended-spectrum antimicrobial agents including carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors, tigecycline, broad-spectrum cephalosporins, fluoroquinolones, as well as glycopeptide and antifungal drugs. Compared with 2015, the usage of carbapenems, tigecycline and broad-spectrum β-lactam/β-lactamase inhibitors was declined nearly 50% in 2020, and the density of carbapenems and tigecycline were decreased by 29.6% and 7.1%, respectively in 2020. On the other side, the utilization rate and use density of narrow-spectrum cephalosporins continued to increase by year, the use density of narrow-spectrum cephalosporins accounting for 28.2% of all antibiotics in 2020.Conclusions:With the comprehensive implementation of aCDSS, the utilization rate and density of broad-spectrum and high-priced antibacterial drugs in our hospital have decreased continuously to decline in the past 6 years, while the proportion of narrow-spectrum antimicrobials has increased year by year, indicating that the structure of antimicrobial use has been continuously optimized and that antimicrobial stewardship based on the information technology have achieved remarkable results.

Preparation and identification of a broad-spectrum antibody targeting hemagglutinin protein of influenza A virus / 中华微生物学和免疫学杂志

Objective:To prepare and identify a broad-spectrum antibody FHA3 targeting influenza A virus hemagglutinin (HA).Methods:According to the single-chain antibody fragment (scFv) sequence, the heavy chain (VH) and light chain (VL) variable regions of FHA3 were amplified by PCR and a recombinant plasmid pFRT-IgG1κ-FHA3 was constructed by linking the expression vector pFRT-IgG1κ. FHA3 was expressed in the ExpiCHO system and purified by affinity purification. The binding activity of FHA3 to influenza A virus HA was detected by ELISA. The neutralizing activity of FHA3 was detected in vitro by infecting host cells with pseudovirus. Results:SDS-PAGE showed that high-purity FHA3 was obtained. FHA3 could bind to H1N1 HA, H2N2 HA, H3N2 HA, H5N1 HA, H7N9 HA and H9N2 HA in a concentration-dependent manner. FHA3 had good neutralizing activity in vitro that was it could effectively block the invasion of H5N1 and H7N9 pseudoviruses into target cells at a low concentration of 5 μg/ml and H1N1 pseudovirus at 0.012 5 μg/ml. Conclusions:A broad spectrum antibody targeting HA protein of influenza A virus with neutralizing activity in vitro was obtained.

Effect of compound houttuynia mixture on influenza virus in vitro / 药学学报

Compound houttuynia mixture belongs to OTC class A medicine, which is made from Houttuynia cordata, Scutellaria baicalensis, Radix Isatidis, Forsythia, and Lonicera. As a kind of compound preparation of traditional Chinese medicine, houttuynia cordata mixture has extensive pharmacological effects, for example, clearing away heat and detoxifying, thus it is used for the sore throat, acute pharyngitis, and tonsillitis with wind-heat syndrome. In this study, the antiviral activity against influenza viruses and the primary mechanism of compound houttuynia mixture was evaluated. The antiviral effect of compound houttuynia mixture was determined by cytopathic effects (CPE), Western blot, quantitive reverse transcription PCR (qRT-PCR), and virus titer assays. The effect of houttuynia mixture on the replication cycle of influenza virus was evaluated by time-of-addition assay. In conclusion, the results showed that the compound houttuynia mixture had a broad-spectrum effect against influenza virus, including the international common influenza virus strains, the drug-resistant strains and the highly pathogenic avian influenza viruses H5N1 and H7N9. It mainly impairs the early stage of the viral replication.

Effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids in feces of very low birth weight infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids (SCFAs) in feces of very low birth weight (VLBW) infants.@*METHODS@#A total of 29 VLBW infants who were admitted to the Neonatal Diagnosis and Treatment Center of Children's Hospital Affiliated to Chongqing Medical University from June to December 2020 were enrolled as subjects for this prospective study. According to the course of treatment with broad-spectrum antibiotics, they were divided into two groups: ≤7 days (@*RESULTS@#There was a significant reduction in Chao index of the intestinal flora in the ≤7 days group and the >7 days group from week 2 to week 4 (@*CONCLUSIONS@#The course of treatment with broad-spectrum antibiotics can affect the abundance, colonization, and evolution of intestinal flora and the content of their metabolites SCFAs in VLBW infants. The indication and treatment course for broad-spectrum antibiotics should be strictly controlled in clinical practice.

Recent advances in the research of broad-spectrum antiviral agents / 药学学报

Viral infections have always threatened human health. Broad-spectrum antiviral agents (BSAs) can either target host proteins that are essential for viral replication, or act on multiple viruses or multiple genotypes of the same virus. More importantly, BSAs could reduce the possibility of drug resistance. From the perspective of medicinal chemistry, this review summarizes recent advances in the research of broad-spectrum antiviral drugs with privileged structures or targeting specific targets in the viral life cycle.

Research and development of antiviral drugs against new coronavirus 2019-nCoV / 中国临床药理学与治疗学

At the end of 2019,an outbreak of 2019 new coronavirus infectious disease (COVID-19) in Wuhan spread rapidly in China and reported cases in other countries.The number of infected cases and deaths quickly exceeded Severe Acute Respiratory Syndrome (SARS) in a short period of time,resulting in incalculable losses to China.Chinese researchers have quickly identified the pathogen,2019-nCoV (or SARS-CoV-2 or HCoV-19) and carried out the research and development of antiviral drugs at different levels.This article briefly reviews the current advancement of research and development of new therapeutics against 2019-nCoV infection.Given that the progress of research and development of antiviral drugs against the emerging and reemerging pathogens is relatively backwarded,we suggest that the research and development of antivirals against pathogens with pandemic or epidemic potential should be carried out in advance before the occurrence of the outbreaks. At the national level,we should promote the research and development of broad-spectrum antivirals and clinical trials to combat the pathogens with epidemic risk.

Acute thrombocytopenia due to meropenem: a case report

Meropenem is a broad spectrum antibacterial drug from the carbapenem family. It is commonly used as an empirical antimicrobial in severe infections like pneumonia, intra-abdominal infections, septicaemia, meningitis etc. Severe adverse effects with meropenem are rare (<1 %) which include hypersensitivity and hematologic adverse effects. In the literature, few cases have been reported of meropenem induced thrombocytopenia that has shown the immune mechanism by which thrombocytopenia occurs. Drug induced thrombocytopenia (DITP) can be a life threatening condition if not diagnosed and managed properly. As meropenem is being widely used in hospitals nowadays, it is important to be aware of the rare but serious adverse effects it causes.

Hemivulvectomía radical por gangrena de fournier en mujer con antecedente de radioterapia pélvica / Radical hemivulvectomy due to Fournier's gangrene in a woman with a history of pelvic radiotherapy

RESUMEN La Gangrena de Fournier es una infección necrotizante que afecta al área genitourinaria, perineal y perianal. Se trata de una infección muy grave con una rápida evolución a estadios avanzados y una elevada tasa de morbimortalidad asociada. Sin embargo, con frecuencia tiende a ser infradiagnosticada. Es vital en su manejo un diagnóstico basado en la sospecha clínica e inicio del tratamiento quirúrgico precoz con desbridamiento y exéresis de los tejidos afectos. Además, es crucial la asociación de antibioterapia de amplio espectro y el apoyo nutricional de soporte en el pronóstico de dicha entidad. En este artículo se revisa un caso clínico de Gangrena de Fournier, en una paciente con antecedentes de osteítis púbica y cistitis derivadas del tratamiento mediante radioterapia pélvica, diagnosticado y tratado con una hemivulvectomía radical, antibioterapia y lavados quirúrgicos en nuestro Hospital.

ABSTRACT The Fournier's Gangrene is a necrotizing infection which is located in the perineal area. It´s a severe infection, which involves a quick evolution to advanced stages where a high morbimortality rate is associated. However, it often tends to be underdiagnosed in early stages. The most important in the diagnosis is a high clinical suspicion and subsequent surgical treatment which is base on a desbridalment and exeresis of the affected tissues. In addition, the association of broad-spectrum antibiotic therapy and nutritional support are crucial. This report reviews a clinical case of Fournier's Gangrene, in a patient with a history of radiation induced cystitis and pubic osteitis after pelvic radiotherapy, diagnosed and treated with a radical hemivulvectomy, antibiotic therapy and lavages in our Hospital.

Estudio de prescripción-indicación en pacientes con antimicrobianos de amplio espectro en medicina interna de un hospital del Ecuador / Pharmacotherapeutic Follow-up in Patients with Broad-spectrum Antimicrobial in Internal Medicine of a Hospital in Ecuador / Estudo de prescrição-indicação em pacientes com antimicrobianos de amplo espectro em medicina interna de um hospital do Equador

Resumen Introducción: desde hace varios años existe preocupación por el incremento específico en el consumo de antimicrobianos por los problemas que estos generan. Por tal motivo se decidió diseñar un programa de atención farmacéutica en pacientes hospitalizados en servicios abiertos para evitar el desarrollo de problemas relacionados con medicamentos asociados con antimicrobianos. Materiales y métodos: se realizó un estudio retrospectivo de utilización de medicamentos, del tipo prescripción-indicación en una muestra de estudio de 25 pacientes que recibieron antimicrobianos de amplio espectro en el área de medicina interna del hospital José María Velasco Ibarra desde abril hasta julio del 2016. Resultados: el 76 % de los pacientes fueron mujeres. La patología más frecuente que requirió la utilización de antimicrobianos fue la infección de vías urinarias complicada (48 %): el 24 % de los pacientes recibió más de un antibiótico de amplio espectro y el más utilizado fue el imipenem/cilastatina (34.4 %), seguido de la piperacilina/tazobactam y el cefepime, ambas con un 28.1 % y la vancomicina (9.4 %). El 48 % de las prescripciones fueron inadecuadas, se detectó la presencia de PRM en el 84 % de los pacientes. Conclusión: el diseño de un programa de atención farmacéutica en pacientes hospitalizados garantiza la identificación, prevención y/o solución de los problemas relacionados con medicamentos, su uso adecuado y la calidad de la atención.

Abstract Introduction: For several years there has been concern about the specific increase in the consumption of antimicrobials due to the problems they generate. For this reason it was decided design a pharmaceutical care program for hospitalized patients in open services to avoid the development of problems related to antimicrobial-associated drugs. Materials and methods: A retrospective study was conducted on the use of medications, of the prescription-indication type in a study sample of 25 patients who received broad-spectrum antimicrobials in the internal medicine area of the José María Velasco Ibarra Hospital from April to July. 2016. Results: 76 % of the patients were women; The most frequent pathology that required the use of antimicrobials was complicated urinary tract infection (48 %>); 24 % of patients received more than one broad spectrum antibiotic and the most widely used was imipenem/cilastatin (34.4 %), followed by piperacillin / tazobactam and cefepime, both with 28.1 % and vancomycin (9.4 %); 48 % of the prescriptions were inadequate, the presence of PRM was detected in 84 % of the patients. Conclusion: The design of a pharmaceutical care program in hospitalized patients guarantees the identification, prevention and / or solution of the problems related to medicines, their proper use and the quality of care.

Resumo Introdução: desde há vários anos existe preocupação pelo incremento específico no consumo de antimicrobianos pelos problemas que estes geram. Por tal motivo decidiu-se desenhar um programa de atenção farmacêutica em pacientes hospitalizados em serviços abertos para evitar o desenvolvimento de problemas relacionados com medicamentos associados a antimicrobianos. Materiais e métodos: realizou-se um estudo retrospectivo de utilização de medicamentos, do tipo prescrição-indicação em uma amostra de estudo de 25 pacientes que receberam antimicrobianos de amplo espectro na área de medicina interna do Hospital José María Velasco Ibarra desde abril até julho de 2016. Resultados: o 76 % dos pacientes foram mulheres; a patologia mais frequente que requereu a utilização de antimicrobianos foi a infeção de vias urinárias complicada (48 %); o 24 % dos pacientes recebeu mais de um antibiótico de amplo espectro e o mais utilizado foi o imipeném/cilastatina (34.4 %), seguido da piperacilina/tazobactam e o cefepima, ambas as duas com um 28.1 % e a vancomicina (9.4 %>); o 48 % das prescrições foram inadequadas, detectou-se a presença de PRM no 84 % dos pacientes. Conclusão: o desenho de um programa de atenção farmacêutica em pacientes hospitalizados garante a identificação, prevenção e/ou solução dos problemas relacionados com medicamentos, o uso adequado dos mesmos, e a qualidade da atenção.

Broad spectrum antibiotic use among in-patients at a hospital in Nairobi, Kenya

Background: Antimicrobial resistance is an increasingly serious threat to global public health. While the use of antibiotics is an important contributing factor, there are gaps regarding this in our region. This study aimed to describe the use of nine broad spectrum antibiotics among in-patients of The Nairobi Hospital (TNH) so as to identify opportunities for quality improvement.Methods: This was a retrospective review of the use of meropenem, ertapenem, imipenem, cefepime, piperacillin, gentamicin, amikacin, vancomycin and teicoplanin among in-patients of TNH from 1st January 2018 to 31st March 2018. Demographic and clinical data of all in-patients who were prescribed these antibiotics during the study period were retrieved from patient files.Results: There were 301 study participants with a median age (range) of 30years (1day-74years), of whom 161 (53.5%) were male. More than half of the participants were admitted for less than one week and had at least one co-morbidity. Meropenem was the most commonly prescribed study antibiotic 123 (40.9%) followed by amikacin 89 (29.6%). Respiratory tract infections 125 (41.5%) were the predominant indications. Meropenem had the longest mean duration of administration, 6.5days while the aminoglycosides were administered for a relatively shorter duration of about 4.8days. Cultures were done on 187 (62.1%) patients though it is only samples of 45 patients that grew an organism, E. coli and Klebsiella sp being the most frequently isolated organisms.Conclusions: There’s a need to strongly intensify implementation of restriction strategies for Meropenem use and introduction of education programs on antimicrobial stewardship targeting all prescribers.

Research on the mechanism of gut microbiota in reducing blood glucose of db/db diabetic mice by broad-spectrum antibiotics / 医学研究生学报

Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group: broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d)); Control group: 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01); Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db / db diabetic mice, and the alterations of gut microbiota may play an essential role in the process of reducing blood glucose by broad-spectrum antibiotics.

Susceptibility of boll weevil to ready-to-use insecticide mixtures / Suscetibilidade do bicudo-do-algodoeiro a misturas de inseticidas prontas para uso

Boll weevil is the major cotton pest in Brazil, and insecticides are widely recommended against it. We determined the susceptibility of boll weevil to insecticides either in single or in mixture ready-to-use formulations, which are registered to spray cotton fields under the hypothesis that mixtures are more toxic to the target pest. Concentration-mortality curves were determined to adult species, simultaneously through dried residues and ingestion. Ten insecticide formulations were studied with five in mixture (lambda-cyhalothrin + thiamethoxam, lambda-cyhalothrin + chlorantraniliprole, thiamethoxam + chlorantraniliprole, and fenitrothion + esfenvalerate) and their five respective single formulations. Cotton leaf discs and cotyledons were dipped into insecticide dilutions prepared by diluting the commercial products into distilled water. Adult mortality was assessed 48 hours after caging adults on treated and untreated materials. The LC50s-concentrations varied from 0.004 to 0.114 g a.i./L, with a relative potency between single and mixture ones, varying from 1.37- to 29.59-fold. Furthermore, lambda-cyhalothrin and thiamethoxam in single formulation were the most toxic insecticides to boll weevil. Among insecticide mixtures, only lambda-cyhalothrin + chlorantraniliprole resulted in a synergic effect; whereas the remaining mixtures showed an antagonistic effect. Therefore, except for the mixture of lambda-cyhalothrin + chlorantraniliprole, the remaining mixtures did not enhance toxicity against the boll weevil and should be recommended only when aimed at different purposes.(AU)

Bicudo-do-algodoeiro é a principal praga do algodoeiro no Brasil, sendo o uso de inseticidas amplamente recomendado para o seu controle. A suscetibilidade do bicudo-do-algodoeiro foi determinada a inseticidas em formulação simples ou em misturas prontas para uso, as quais têm sido recomendadas para pulverizar campos de algodão sob a hipótese de serem mais tóxicas à praga alvo. Assim, curvas de concentração-mortalidade foram determinadas para adultos do bicudo contaminados, simultaneamente, via resíduo seco e ingestão dos inseticidas. Dez formulações foram estudadas, sendo cinco misturas (lambda-cialotrina + tiametoxam, lambda-cialotrina + clorantraniliprole, tiametoxam + clorantraniliprole e fenitrotiona + esfenvalerato) e suas respectivas cinco formulações simples. Folhas e cotilédones do algodoeiro foram mergulhados em diluições do inseticida preparadas com os produtos comerciais e água destilada. A mortalidade adulta foi avaliada 48 horas após o acondicionamento dos adultos em materiais tratados e não tratados. As concentrações de CL50s variaram de 0,004 a 0,114 g i.a./L, com potência relativa entre formulação simples e misturas, variando de 1,37 a 29,59 vezes. A lambda-cialotrina e o tiametoxam em formulações simples foram os inseticidas mais tóxicos para o bicudo. Entre as misturas, aquela preparada com lambda - cialotrina + clorantraniliprole resultou em um efeito sinérgico, enquanto as demais misturas mostraram um efeito antagonista. Portanto, exceto pela mistura de lambda-cialotrina + clorantraniliprole, as demais misturas não demonstraram maior toxicidade para o bicudo-do-algodoeiro e devem ser recomendadas somente quando objetivam finalidades diferentes.(AU)

Establishment of Scoring System for Risk Factors of Invasive Fungal Infection in Patients with Hematologic Diseases / 中国药房

OBJECTIVE:To establish a risk scoring system for identifying invasive fungal infection(IFI)patients with hematologic diseases. METHODS:Risk factors were investigated among 200 patients diagnosed with IFI and 200 control patients at the same time from Jan. 2008 to Dec. 2015. The single factor analysis and Logistic multivariate regression analysis were conducted for potential risk factors to screen and assign risk factors of IFI. The risk scoring system of IFI was established,the performance of scoring system was evaluated by receiver operating characteristic(ROC)curve. Using the scoring system,103 patients of validation group were scored during Jan. to Jun. in 2016.The incidence of IFI in each group was compared. 18 high-risk patients were intervened by the scoring system. RESULTS:Community acquired infection,the reduction of neutrophils,fungal infection history,corticosteroids and broad-spectrum antibiotics(Enzyme inhibitors,glycopeptides,quinolones,aminoglycosides and carbapenems)were risk factors of IFI(P<0.001),and the score of them were 17,10,39,14,14 according to the regression coefficients. IFI risk scoring system was divided into low,medium and high risk(scoring 0-30,31-40,≥41),AUC of ROC curve was 0.916. The incidence of IFI in low-risk,medium-risk and high risk groups were 3.0%,10.7% and 62.5%,high-risk group was significantly higher than low and medium-risk groups(P<0.05).The incidence of IFI was 16.7% in intervention group, there was statistical significance compared to high-risk group of validation group(P<0.05). CONCLUSIONS:This scoring system shows good ability to distinguish risk stratification. It can help clinicians identifying IFI high-risk groups and timely guiding timely intervention for patients.

Comparación de ceftazidima-amikacina contra imipenem en el tratamiento de fiebre neutropénica / Comparison of ceftazidime/amikacin vs imipenem in the treatment of neutropenic fever

Resumen: ANTECEDENTES: la fiebre neutropénica es una de las principales complicaciones del tratamiento oncológico y es causa importante de morbilidad y mortalidad; afecta a más de 80% de los pacientes con neoplasias hematológicas durante el primer ciclo de quimioterapia. El tratamiento consiste en antibióticos de amplio espectro con respuestas terapéuticas heterogéneas. OBJETIVO: determinar el tiempo promedio de la desaparición de la fiebre después de la administración de la primera dosis del antibiótico. MATERIAL Y MÉTODO: estudio prospectivo, aleatorizado, doble ciego, efectuado del 1 de mayo al 24 de septiembre de 2014, en el que los pacientes se distribuyeron al azar para recibir tratamiento con ceftazidima-amikacina o imipenem durante 10 días. Se registraron la temperatura y fiebre. Se tomaron hemocultivos previo al tratamiento y a las 48 horas en caso de persistencia de fiebre. Se registraron todos los hemocultivos con crecimiento bacteriano. RESULTADOS: se evaluaron 31 pacientes, de 17 a 61 años de edad (promedio de 33.6 ± 13.9); 15 pacientes recibieron ceftazidima-amikacina (48.4%) y 16 pacientes imipenem (51.6%). El tiempo promedio de remisión de la fiebre fue de 11.2 ± 16.3 vs 9.6 ± 14.8 horas (p = 0.6) en el grupo de ceftazidima-amikacina e imipenem, respectivamente. CONCLUSIONES: no hubo diferencia en el tiempo de mejoría clínica entre los pacientes tratados con imipenem o ceftazidima-amikacina. Ambos esquemas antimicrobianos fueron igual de eficaces para el tratamiento de la fiebre neutropénica secundaria a quimioterapia.

Abstract: BACKGROUND: Neutropenic fever is one of the major complications of cancer treatment and it is an important cause of morbidity and mortality. It occurs in more than 80% of patients with hematologic malignancies during the first cycle of chemotherapy. Treatment consists on broad-spectrum antibiotics with heterogeneous therapeutic responses. OBJECTIVE: To determine the average time for disappearance of fever after the administration of the first dose of antibiotics. MATERIAL AND METHOD: A prospective, randomized, double blind study was conducted. Patients were randomized to receive treatment with ceftazidime/amikacin or imipenem for 10 days. A record of temperature and fever was kept. Blood cultures prior to treatment and at 48 hours were taken in case of persistent fever. All blood cultures were recorded for bacterial growth. RESULTS: Were evaluated 31 patients with ages between 17 and 61 years (mean 33.6 ± 13.9). Fifteen patients received ceftazidime/amikacin (48.4%) and 16 patients imipenem (51.6%). The average time of remission of fever was 11.2±16.3 vs 14.8 ± 9.6 hours (p = 0.6) for the ceftazidime/amikacin and imipenem group, respectively. CONCLUSIONS: There was no difference about the time of clinical improvement among patients treated with imipenem or ceftazidime/amikacin. Both antimicrobials schemes were equally effective for the treatment of secondary neutropenic fever chemotherapy.

Conservative epitope of human papillomavirus type 31 L2 can induce broad-spectrum neutralizing antibodies / 基础医学与临床

Objective To detect the immunogenicity of conservative neutralizing epitope from human papilloma-virus type 31 ( HPV31) minor capsid protein L2, and analyze the neutralizing antibody spectrum of its immune sera.Methods Synthesize HPV31 L2 aa.17-40 peptide and conjugate with KLH by EDC.Immunize New Zeal-and white rabbits with HPV31 L2-KLH and Freud's Adjuvant.Analyze the neutralizing antibody titers of immune sera against HPVs from α4,α7,α9,α10 and β1 species by pseudovirus neutralization assay.Results In rabbits, HPV31 L2-KLH induced broad-spectrum neutralizing antibodies against at least 17 types of HPV, among which the neutralizing antibody titers against HPV31 are the highest, followed by that of HPV5/45/57. Conclusions The broad-spectrum neutralizing activity of the immune sera of HPV31 L2 is stimulated by conser-vative neutralizing epitope.The results lay the foundation of the development of broad-spectrum HPV vaccines based on HPV31 L2 neutralizing epitope.

Paclitaxel: A Landmark Natural Anticancer Drug / 世界科学技术-中医药现代化

As a most effective monomer composition from bark of Pacific Yew,paclitaxel and its derivatives are used in clinical practice as broad spectrum anticancer drugs.Since its discovery in the 1970 s,many researches had been carried out,mainly focusing on the modification,structure-activity relationship and pharmacological activity.The great successes pressed ahead the development of a series of taxol-like drugs,including taxol,docetaxel,cabazitaxel,larotaxel.Nowadays,studies of taxol are still the hotpots,which concentrated on the new source such as cultivation of tissue,fungus culture and new dosage forms.As the representative of drugs research from natural source,taxol is worth to be summarized of its history and ongoing development for looking forward to bring new innovation mentality in new drugs.