6000张抗菌药物处方专项点评分析及监管措施的探讨

目的:对我院门诊不合理使用抗菌药物处方进行分析,提高我院合理使用抗菌药物水平,探讨不合理使用抗菌药的原因及合理使用抗菌药的监管措施。方法:利用本院抗菌药处方信息系统,抽取2016年1月~12月抗菌药物处方,每月抽查抗菌药处方500张,包括16个科室共6000张进行处方点评,将药物选择不适宜;药物选择起点高,用法用量不适宜;溶液的浓度不适宜;溶媒量不适宜;联合用药是不适宜,诊断不规范,无适应症用药,重复用药,疗程偏长汇总分析。结果:不合理处方涉及16个科室,1160张不合理抗菌药处方,占抽取处方的19.33%,不合理处方包括十方面的内容,共1340处,占总抽查处方的22.33%。结论:我院门诊抗菌药物使用存在不合理性,不合理抗菌药处方占总抽查处方的百分率偏高,抗菌药物专项点评有利于发现科室存在的普遍问题,提出干预措施为持续改进提供参考。     

凝结芽孢杆菌活菌片预防小儿肺炎继发性腹泻疗效观察

目的观察和评价凝结芽孢杆菌活菌片（商品名：爽舒宝）与抗菌药联用预防小儿肺炎继发性腹泻的临床疗效。方法将164例肺炎患儿随机分为预防组和对照组,预防组84例,对照组80例,两组均给予抗菌药及对症支持治疗。其中预防组在治疗的同时序贯（间隔2～3h）应用凝结芽孢杆菌活菌片,出现腹泻继续服用;对照组单用抗菌药,出现腹泻用凝结芽孢杆菌活菌片治疗。对两组继发性腹泻的发生率、腹泻持续天数、肺炎治疗的总疗程、腹痛和肠鸣音异常等症状和体征进行统计分析。结果预防组继发腹泻10例,发生率11．9％,对照组继发腹泻41例,发生率51．3％,两组相比差异具有统计学意义（P〈0．01）;预防组腹泻持续时间和治疗疗程显著短于对照组（P〈0．05）;预防组患儿腹痛、肠鸣音异常和脱水等症状和体征发生率均少于对照组（P〈0．05）。结论凝结芽孢杆菌活菌片与抗菌药序贯应用治疗肺炎,能显著降低继发性腹泻的发生率,缩短疗程,值得临床推广。     

Leukolysis reaction in the diagnosis of allergy to antibacterial preparations in pulmonology]

The experiment included 109 patients with non-specific pathological processes in the lungs. i.e. 21 cases with acute and 55 cases with chronic pneumonia and 33 cases with bronchial asthma with or without chronic pneumonia. Clinically intolerance of the antibacterial drugs was observed in 39 patients and increased leucolysis (above 15 per cent) was observed sometimes more frequently. Only with the use of penicillin the difference was 1.6 times. Out of 39 patients with clinical signs of allergy to antibiotics or sulphanilamide only 20 showed the signs of increased leucolysis on the use of the respective drug. No correlation between the percentage of the leucolysis cases due to antibiotics or sulphanilamides and the clinical signs of their intolerance was observed. The use of such drugs by a person or even only his presence in the hospital often induced increased leucolysis which may be considered as an indication of the person sensibilization to them.     

New approaches in the treatment of bacterial infections

Recently, several new drugs for the treatment of bacterial infections have been developed. Quinupristin/dalfopristin, moxifloxacin and gatifloxacin have been approved throughout the world for clinical use. Levofloxacin has been approved for the treatment of community-acquired pneumonia caused by penicillin-resistant Streptococcus pnuemoniae. The Food and Drug Administration has approved linezolid for clinical use, and new drug applications for gemifloxacin and telithromycin were filed. Other new targets have surfaced in the quest for novel antibacterial agents.     

Spectrum of pathogens in hospital infections in onco-urologic patients and their sensitivity to antibacterial drugs

Retrospective examination of case records and laboratory findings related to 155 patients discharged from the Urological Department of the All-Union Oncology Research Centre, Academy of Medical Sciences of the USSR within a period of 3 months showed that 41.9 per cent of the oncourological patients had infectious processes requiring antibacterial therapy. Among 80 infectious episodes 62 or 77.5 per cent were of intrahospital origin. There was a relationship of the frequency of the infections to localization of the tumor process, a patient's age, the treatment character and some diagnostic and treatment procedures. 70 per cent of the hospital infections were urinary and 15 per cent referred to suppuration of the operative wounds. The predominant causative agents of the complications were Pseudomonas spp., Klebsiella tribe, Proteus spp. and Enterococci with the highest levels of resistance to antibacterial drugs. The drugs of choice for treating the infections in that group of the patients were ofloxacin and cefotaxime. Aminoglycosides, semisynthetic penicillins, cephalosporins and urological antiseptics were used in accordance with antibioticograms. In the treatment of severe gram-negative infections dioxydin was used. Since hospital infections in oncourological patients are usually caused by hospital multiple resistant strains of microorganisms, often present in associations, the adequate antibacterial therapy requires constant bacteriological surveillance providing not only the choice of the most efficient drug but also early correction of the therapy after the pathogen change.     

The future of new oral antibiotics including the quinolones.

It is estimated that more than 110 million dollars'' worth of oral antibiotics will have been sold in Canada in 1987. In the next few years several new oral antimicrobial agents will reach the market, including beta-lactamase inhibitors, cephalosporins, monobactams, erythromycins and quinolones. Most of these new agents have a broader spectrum of antibacterial activity than the presently available oral antibiotics. A few have a longer half-life and can be administered once a day. The new oral drugs, especially the quinolones and possibly beta-lactams, will now be used to treat infections that in the past could be treated only parenterally. Exacerbations of pulmonary infections due to Pseudomonas aeruginosa in cystic fibrosis can now be successfully treated at home with the new quinolones. Osteomyelitis, arthritis, pneumonia and pyelonephritis will most likely be treated at home in the future. In severe infections patients will be admitted to hospital for short courses of parenteral therapy, followed by oral treatment. If used appropriately the new oral agents may lead to new approaches to the treatment of infectious diseases.     

A Method of Determining Patterns of Use of Antibacterial Drugs

A hospital chart review system using standard IBM punch cards was designed to review patterns of use of antibacterial drugs in a large Canadian general hospital. Review of the charts of 4894 patients during an eight-month period showed that this method provided an inexpensive and accurate summary of many of the details of use of antibacterial drugs, including indications accepted for drug use, specific drugs selected, the manner in which the drugs were used and the precautions taken to avoid adverse reactions. This method of review should be valuable in delineating drug misuse and overuse, and hence in the continuing education of the physician.     

Targeting mesenchymal stem cell therapy for severe pneumonia patients

Pneumonia is the inflammation of the lungs and it is the world’s leading cause of death for children under 5 years of age.The latest coronavirus disease 2019(COVID-19)virus is a prominent culprit to severe pneumonia.With the pandemic running rampant for the past year,more than 1590000 deaths has occurred worldwide up to December 2020 and are substantially attributable to severe pneumonia and induced cytokine storm.Effective therapeutic approaches in addition to the vaccines and drugs under development are hence greatly sought after.Therapies harnessing stem cells and their derivatives have been established by basic research for their versatile capacity to specifically inhibit inflammation due to pneumonia and prevent alveolar/pulmonary fibrosis while enhancing antibacterial/antiviral immunity,thus significantly alleviating the severe clinical conditions of pneumonia.In recent clinical trials,mesenchymal stem cells have shown effectiveness in reducing COVID-19-associated pneumonia morbidity and mortality;positioning these cells as worthy candidates for combating one of the greatest challenges of our time and shedding light on their prospects as a nextgeneration therapy to counter future challenges.     

2008-2012年484株肺炎克雷伯菌耐药性分析及耐药机制的初步研究

目的回顾性分析近五年来医院住院及门诊病原菌感染患者中肺炎克雷伯菌的分离趋势,探讨其对常规抗菌药物的耐药性变迁和相关耐药机制。方法采用法国梅里埃公司的Vitek-2 Compact全自动微生物分析仪进行细菌鉴定及药敏试验,部分菌株采用微量生化管鉴定,部分药敏试验采用琼脂扩散法（KB）,药敏结果判读按照美国临床和实验室标准化协会（CLSI）制定的标准判读,纸片法表型确证试验检测超广谱β-内酰胺酶（ESBLs）,改良Hodge试验检测碳青霉烯酶表型,EDTA双纸片法检测金属酶表型。结果五年间484株肺炎克雷伯菌部分药物耐药率正逐年上升,其常见药物平均耐药率如下：阿米卡星（3.0%）,复方新诺明（31.1%）,头孢三嗪（14.5%）,环丙沙星（18.7%）,氯霉素（21.6%）,特治星（6.3%）,头孢他啶（22.0%）,头孢噻肟（23.6%）,舒普深（4.2%）,呋喃妥英（26.9%）,美罗培南（2.1%）,ESBLs阳性99株（20.4%）,改良Hodge试验检测碳青霉烯酶表型阳性5株,EDTA双纸片法检测金属酶表型阳性2株。结论部分药物耐药率逐年上升的有复方新诺明、环丙沙星、头孢他啶、头孢噻肟;耐药率较低的有美罗培南、阿米卡星、舒普深、特治星、头孢三嗪。应加强细菌耐药性监测,以及耐碳青霉烯酶筛查试验,为临床提供用药参考。     

A Pipeline for Screening Small Molecules with Growth Inhibitory Activity against Burkholderia cenocepacia

Infections with the bacteria Burkholderia cepacia complex (Bcc) are very difficult to eradicate in cystic fibrosis patients due the intrinsic resistance of Bcc to most available antibiotics and the emergence of multiple antibiotic resistant strains during antibiotic treatment. In this work, we used a whole-cell based assay to screen a diverse collection of small molecules for growth inhibitors of a relevant strain of Bcc, B. cenocepacia K56-2. The primary screen used bacterial growth in 96-well plate format and identified 206 primary actives among 30,259 compounds. From 100 compounds with no previous record of antibacterial activity secondary screening and data mining selected a total of Bce bioactives that were further analyzed. An experimental pipeline, evaluating in vitro antibacterial and antibiofilm activity, toxicity and in vivo antibacterial activity using C. elegans was used for prioritizing compounds with better chances to be further investigated as potential Bcc antibacterial drugs. This high throughput screen, along with the in vitro and in vivo analysis highlights the utility of this experimental method to quickly identify bioactives as a starting point of antibacterial drug discovery.     

盐酸坦索罗辛与宁米泰胶囊联合用药调控β-内酰胺酶相关基因及溶血和毒力基因表达

盐酸坦索罗辛(TSH)是一种选择性α₁肾上腺素受体阻滞剂,主要用于治疗良性前列腺增生症。宁泌泰胶囊(NMT)是根据中医理论建立的配方制剂,具有清热解毒、利尿排尿等功效,主要用于湿热蕴结淋淋、淋湿酸痛、尿血、下尿路感染与慢性前列腺炎。研究显示,TSH可与多种药物联合用于治疗微生物感染和抗生素耐药,显示出较好的治疗效果和应用前景;NMT对大肠杆菌、变形杆菌、淋病奈瑟菌、粪链球菌、金黄色葡萄球菌等多种致病菌也具有明显的抑菌和杀菌作用。提示这2种药物联合应用可能对临床细菌具有显著的抗菌活性。本研究采用比浊法,在肺炎克雷伯菌(K. pneumonia)、金黄色葡萄球菌(S. aureus)和枯草芽孢杆菌(B. subtilis)中,体外检测TSH与NMT联合应用的抗菌活性。研究发现,TSH与NMT联合应用表现出显著的抗菌活性,对3种菌株的体外抑制活性均强于单一治疗。建立感染动物模型,在体内检测TSH与NMT联合应用的抗菌活性。结果表明,2种药物联合使用对肺炎克雷伯菌肺部感染小鼠模型的治疗效果显著(P < 0.01),对枯草芽孢杆菌感染小鼠具有显著的治疗效果(P < 0.05),而对感染金黄色葡萄球菌的小鼠无明显影响。运用RT-PCR,研究β-内酰胺酶、溶血及毒力相关基因的表达,评价其抗菌机制。结果提示,2种药物联用于肺炎克雷伯菌的抗菌机制可能涉及上调或下调β-内酰胺酶相关基因(包括GES、VEB、PER-2和IMP),在枯草芽孢杆菌中抗菌机制可能涉及上调或下调溶血相关基因(yhdP、yhdT、yqhB和yugS);在金黄色葡萄球菌中,抗菌机制可能涉及上调或下调关键毒力基因(saeR、hla、sbi和mecA)。这些数据表明,TSH与NMT联合使用,通过调节β-内酰胺酶、溶血和毒力相关基因的转录水平表达,对3株菌株表现出显著的体外杀菌作用;并且该组合对体内感染肺炎克雷伯菌和枯草芽孢杆菌的小鼠模型具有更好的治疗作用。因此,TSH和NMT的联合治疗可能对细菌感染具有潜在的预防或治疗作用。     

Effectiveness of acipole in prevention of enteric dysbacteriosis due to antibacterial therapy]

Acipole (Lactobacillus acidophilus + Kefir greins) was used to manage antibiotic dysbacteriosis as an adverse reaction of antibacterial therapy. 120 patients treated with antibacterial drugs for acute pneumonia and exacerbations of chronic bronchitis were observed. 54 of them were treated under the routine regimen with antibiotics and 66 were additionally treated with the eubiotic acipole: 1 tablet (5 doses) 3 times a day 30 minutes before meal. Routine bacteriological examination of the feces was applied to all the patients. High frequency of bacteriologically revealed dysbacteriosis was stated. The therapy under the antibiotic + acipole regimen lowered the frequency of dysbacteriosis events and their severity. The fact that the use of acipole simultaneously with the routine antibacterial therapy prevented the development of dysbacteriosis clinical signs is of practical importance.     

Indwelling catheter infection

A “catheter team”, consisting of two hospital assistants specially trained to catheterize male patients, inserted indwelling catheters in 435 men over a two-year period. The infection rate was 33%; in the 200 patients not treated with antimicrobial drugs (study group) the rate was 37%, while in the 235 patients who were so treated (antibacterial group) the infection rate was 29%. Fifty percent of patients not treated were infected after 6.3 days, whereas in patients on antibacterial therapy a 50% infection rate was not reached until 14 days after insertion. Therefore, no antibacterial therapy is necessary if it is anticipated that the catheter will be necessary for less than four days. On the other hand, prophylactic antibacterial therapy would delay the onset of infection considerably if catheterization were expected to continue for more than four days. Sulfisoxazole was our drug of choice for prophylactic treatment.     

Pharmacogenetics of community-acquired pneumonia

The rate of acetylation of xenobiotics affects the course and prognosis of infectious diseases. The efficacy of antibiotic therapy of community-acquired pneumonia in RA-patients is lower than that in LA-ones. In order to ensure the best antimicrobial effect on the onset of the disease it is required to use regimens with the maximum permissible dose of antibacterial drugs in the regions where the rapid type prevails.     

Diazenedicarboxamides as inhibitors of D-alanine-D-alanine ligase (Ddl)

D-Alanine-D-alanine ligase (Ddl) catalyzes the biosynthesis of an essential bacterial peptidoglycan precursor D-alanyl-D-alanine and it represents an important target for development of new antibacterial drugs. A series of semicarbazides, aminocarbonyldiazenecarboxylates, diazenedicarboxamides, and hydrazinedicarboxamides was synthesized and screened for inhibition of DdlB from Escherichia coli. Compounds with good inhibitory activity were identified, enabling us to deduce initial structure-activity relationships. Thirteen diazenedicarboxamides were better inhibitors than D-cycloserine and some of them also possess antibacterial activity, which makes them a promising starting point for further development.     

Sensitivity to antibiotics and antibacterial preparations of conditionally pathogenic bacteria isolated from patients with gastrointestinal tract dysfunctions]

Sensitivity of 690 cultures of the conditionally pathogenic microbes of Enterobacteriaceae and Pseudomonadaceae to 17 drugs was studied with the agar diffusion method. It was found that 98.6 per cent of the cultures had multiple resistance to 2--10 drugs. Most of the cultures were resistant to erythromycin, carbenicillin and ampicillin. Different species of the conditionally pathogenic microorganisms were resistant to different numbers of the drugs. Thus, Ps. aeruginosa cultures were resistant to 6--10 drugs, the cultures of Citrobacter were resistant to 3--8 drugs and the cultures of Kl. pneumonia were resistant to 2--5 drugs. Levomycetin, tetracycline, streptomycin and biseptol proved to be the most active antibacterial drugs.     

Clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs: comparison with homosexual seroconverters and infected and non-infected intravenous drug misusers.

OBJECTIVE--To study the clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs. DESIGN--Case-control study in cohorts of drug misusers and homosexual men. SETTING--Outpatient clinic, Municipal Health Service, Amsterdam. SUBJECTS--Misusers of intravenous drugs from our prospective cohort who seroconverted for HIV. Controls were drug users positive for HIV, drug users negative for HIV, and homosexual men who had seroconverted. RESULTS--Five out of 18 (28%) drug users were admitted to hospital with bacterial pneumonia in the four to six months between their last visit at which they were HIV negative and their first visit when they were HIV positive. For comparison none of the 27 homosexual men who seroconverted for HIV, three out of 177 (2%) drug users negative for HIV, and 10 out of 112 (9%) drug users positive for HIV reported bacterial pneumonia. One out of the 18 drug users who seroconverted suffered from oesophageal candidiasis at the time of seroconversion. Other clinical symptoms did not differ between drug users who seroconverted and those who remained negative for HIV, probably due to the high background morbidity among the drug users. CONCLUSIONS--Seroconversion to HIV-1 among intravenous drug misusers is associated with bacterial pneumonia. Those drug users with previously negative test results for HIV who are admitted to hospital for bacterial pneumonia should be tested to detect primary infection with HIV-1.     

The synthesis of chitosan-based silver nanoparticles and their antibacterial activity

Chitosan-based silver nanoparticles were synthesized by reducing silver nitrate salts with nontoxic and biodegradable chitosan. The silver nanoparticles thus obtained showed highly potent antibacterial activity toward both Gram-positive and Gram-negative bacteria, comparable with the highly active precursor silver salts. Silver-impregnated chitosan films were formed from the starting materials composed of silver nitrate and chitosan via thermal treatment. Compared with pure chitosan films, chitosan films with silver showed both fast and long-lasting antibacterial effectiveness against Escherichia coli. The silver antibacterial materials prepared in our present system are promising candidates for a wide range of biomedical and general applications.     

Characterization of clinical strains of MSSA,MRSA and MRSE isolated from skin and soft tissue infections and the antibacterial activity of ZnO nanoparticles

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). MRSA is an important pathogen in the healthcare sector that has neither been eliminated from the hospital nor community environment. In humans, S. aureus causes superficial lesions in the skin and localized abscesses, pyogenic meningitis/encephalitis, osteomyelitis, septic arthritis, invasive endocarditis, pneumonia, urinary tract infections and septicemia. Investigations focused in the search of other alternatives for the treatment of MRSA infections are in progress. Among the range of compounds whose bactericidal activity is being investigated, ZnO nanoparticles (ZnO–NPs) appears most promising new unconventional antibacterial agent that could be helpful to confront this and other drug-resistant bacteria. The aim of present study is to investigate the antibacterial potential of ZnO–NPs against Staphylococcus species isolated from the pus and wounds swab from the patients with skin and soft tissue infections in a tertiary care hospital of north India. ZnO–NPs (≈19.82 nm) synthesized by sol–gel process were characterized using scanning electron microscopy, X-ray diffraction , and Atomic force microscopy. The antibacterial potential was assessed using time-dependent growth inhibition assay, well diffusion test, MIC and MBC test and colony forming units methods. ZnO–NPs inhibited bacterial growth of methicillin-sensitive S. aureus (MSSA), MRSA and methicillin-resistant S. epidermidis (MRSE) strains and were effective bactericidal agents that were not affected by drug-resistant mechanisms of MRSA and MRSE.     

高海拔地区慢性阻塞性肺疾病患者 病原菌分布及相关因素分析

摘要：目的 探究高海拔地区慢性阻塞性肺疾病（COPD）患者病原菌分布及相关危险因素。方法 选取2016年1月至2019年1月青海省中医院收治的274例COPD患者为研究对象,对患者痰液进行病原菌培养,分析病原菌分布情况及感染多重耐药菌（MDRO）的相关危险因素。结果 274例患者痰液中共培养出致病菌165株,阳性率为60.2%;其中革兰阴性菌占71.5%（118/165）,革兰阳性菌占17.0%（28/165）,真菌占11.5%（19/165）。单因素分析显示,COPD患者发生MDRO感染与年龄、糖尿病病史、卧床时间、呼吸机污染、机械通气史和频繁更换抗菌药有一定相关性（χ2=8.326、4.868、21.298、5.534、19.686、11.549,均P<0.05）,Logistic分析显示,呼吸机污染、机械通气史、频繁更换抗菌药和卧床时间是COPD患者发生多重耐药菌感染的危险因素（OR=1.292、2.112、1.752、1.625,均P<0.05）。结论 高海拔地区COPD患者病原菌以革兰阴性菌为主,而呼吸机及管路污染、机械通气史、频繁更换抗菌药及卧床时间长是COPD患者发生多重耐药菌感染的危险因素。应加强对相关病原菌及危险因素的监测,降低患者感染风险。