Suppression of P-gp induced multiple drug resistance in a drug resistant gastric cancer cell line by overexpression of Fas

AIM To observe the drug sensitizing effect andrelated mechanisms of fas gene transduction onhuman drug-resistant gastric cancer cellSGC7901/VCR(resistant to Vincristine).METHODS The cell cycle alteration wasobserved by FACS.The sensitivity of gastriccancer cells to apoptosis was determined by invitro apoptosis assay.The drug sensitization ofcells to several anti-tumor drugs was observedby MTT assay.Immunochemical method wasused to show expression of P-gp and Topo Ⅱ ingastric cancer cells.RESULTS Comparing to SGC7901 and pBK-SGC7901/VCR,fas-SGC7901/VCR showeddecreasing G2 cells and increasing S cells,theG2 phase fraction of pBK-SGC7901/VCR wasabout 3.0 times that of fas-SGC7901/VCR,but Sphase fraction of fas-SGC7901/VCR was about1.9 times that of pBK-SGC7901/VCR,indicatingS phase arrest of fas-SGC7901/VCR.FACS alsosuggested apoptosis of fas-SGC7901/VCR,fas-SGC7901/VCR was more sensitive to apoptosisinducing agent VM-26 than pBK-SGC7901/VCR.MTT assay showed increased sensitization offas-SGC7901/VCR to DDP,MMC and 5-FU,butsame sensitization to VCR according to pBK-SGC7901/VCR.SGC7901,pBK-SGC7901/ VCRand fas-SGC7901/VCR had positively stainedTopo Ⅱ equally.P-gp staining in pBK- SGC7901/VCR was stronger than in SG07901,but there was little staining of P-gp in fas.SGC7901/VCR.CONCLUSION fas gene transduction couldreverse the MDR of human drug-resistant gastriccancer cell SGC7901/VCR to a degree,possiblybecause of higher sensitization to apoptosis anddecreased expression of P-gp.

Antibacterial effect of Allium sativum cloves and Zingiber officinale rhizomes against multiple-drug resistant clinical pathogens

Objective:To evaluate the antibacterial properties ot Allium sativum(garlic) cloves and Zingiber officinale(ginger) rhizomes against multi-drug resistant clinical pathogens causing nosocomial infection.Methods:The cloves of garlic and rhizomes of ginger were extracted with 95%(v/v) ethanol.The ethanolic extracts were subjected to antibacterial sensitivity test against clinical pathogens.Results:Anti-bacterial potentials of the extracts of two crude garlic cloves and ginger rhizomes were tested against five gram negative and two gram positive multi-drug resistant bacteria isolates.All the bacterial isolates were susceptible to crude extracts of both plants extracts.Except Enterobacter sp.and Klebsiella sp.,all other isolates were susceptible when subjected to ethanolic extracts of garlic and ginger.The highest inhibition zone was observed with garlic(19.4S mm) against Pseudomonas aeruginosa(P.aeruginosa).The minimal inhibitory concentration was as low as 67.00 μg/mL against P.aeruginosa.Conclusions:Natural spices of garlic and ginger possess effective anti-bacterial activity against multi-drug clinical pathogens and can be used for prevention of drug resistant microbial diseases and further evaluation is necessary.

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

MDR-Chin研究解析:耐多药肺结核全口服短程治疗方案在中国的应用前景

全球耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)的治疗研究趋势是缩短疗程。MDR-Chin研究是中国第一项探索全口服短程方案治疗MDR-TB和准广泛耐药结核病(pre-extensive drug-resistant tuberculosis,pre-XDR-TB)的队列研究,主要验证了3种不同治疗方案的有效性和安全性。结果表明,在停药后12个月的随访期内,96%的MDR-TB患者和83.3%的pre-XDR-TB患者达到了良好结局;总体良好结局率为92.9%。虽然3级或更高级别的不良事件很常见(48.1%),但大多可管可控,且严重不良事件较少(7.7%)。该研究保持了低失访率,体现了全口服短程方案的优势,并展示了在资源有限的环境中的应用潜力。本文中,笔者介绍了MDR-Chin研究的概况,分析其优点和缺点,并探讨全口服短程治疗方案在中国实施的可能性及未来的临床研究方向。

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Transduction of Fas gene or Bcl-2 antisense RNA sensitizes cultured drug resistant gastric cancer cells to chemotherapeutic drugs

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Novel mechanism of drug resistance to proteasome inhibitors in multiple myeloma

Multiple myeloma(MM) is a cancer caused by uncontrolled proliferation of antibody-secreting plasma cells in bone marrow, which represents the second most common hematological malignancy. MM is a highly heterogeneous disease and can be classified into a spectrum of subgroups based on their molecular and cytogenetic abnormalities. In the past decade, novel therapies, especially, the first-in-class proteasome inhibitor bortezomib, have been revolutionary for the treatment of MM patients. Despite these remarkable achievements, myeloma remains incurable with a high frequency of patients suffering from a relapse, due to drug resistance. Mutation in the proteasome β5-subunit(PSMB5) was found in a bortezomib-resistant cell line generated via long-term coculture with increasing concentrations of bortezomib in 2008, but their actual implication in drug resistance in the clinic has not been reported until recently. A recent study discovered four resistance-inducing PSMB5 mutations from a relapsed MM patient receiving prolonged bortezomib treatment. Analysis of the dynamic clonal evolution revealed that two subclones existed at the onset of disease, while the other two subclones were induced. Protein structural modeling and functional assays demonstrated that all four mutations impaired the binding of bortezomib to the 20 S proteasome, conferring different degrees of resistance. The authors further demonstrated two potential approaches to overcome drug resistance by using combination therapy for targeting proteolysis machinery independent of the 20 S proteasome.

Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin A in cisplatin--inducedhuman epithelial ovarian cancer resistant cell line 3Ao/cDDP

Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.

Natural Remedies against Multi-Drug Resistant <i>Mycobacterium tuberculosis</i>

Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.

Bi-Directional Regulation by Chinese Herbal Formulae to Host and Parasite for Multi-Drug Resistant <i>Staphylococcus aureus</i>in Humans and Rodents

A decline in the immunopotential of the host plays acritical factor(s) in the occurrence of infections with methicillin-resistant Staphylococcus aureus (MRSA) or microorganisms by opportunistic infection. In such an infection, no way out for therapeutic concept, therefore bi-directional trial was the final choice. So we selected aformula, Dang Gui Liu Huang Tang (dLHT), which could both augmentimmune factorsin host and exert bacteriostatic effect. We sought to break through the epidemic by MRSA especially in elderly patient, by the fundamental and clinical trial by employing minor TCM, characterizing bidirectional ability of the decoction by western methods. Animal Experiment: Mitomycin-C (MMC)-treated mice with or without the infection of MRSA were made. The experimental design was made up to examine the bacteriostatic action as well as the immunopo-tentiating bias of the promising Chinese herbal medicine, dLHT, which was first proved for its immune potentiating activities as well as their sensitivity to antibiotics, but not direct aseptic effect was clear for MRSA. Both basic and clinical data showed that this formula was effective on repelling from the infectious focus after the treatment of MRSA infection. After the administration of dLHT, the number of white blood cells in MMC-treated mice recovered to 80% of the normal level. In addition, the phagocytic activity of macrophages increased to 70% in the dLHT-treated group, while that of the non-treated group was only 20%. The bactericidal activity also recovered to the level close to the normal value by dLHT. The ratio of neutrophils in the dLHT-administered group increased to 2.2% (normal mice, 2.6%), whereas that in the non-terated group was only 0.5%. The bacterial count in the liver of MRSA-challenged mice reached the peak at six hours after the challenge in both dLHT-treated and non-treated mice. However, the number of bacteria in dLHT group was much greater than that in the non-treated group. The bacterial count in the blood showed an increase 12 and 24 hours after the challenge. Even 24 hours after the challenge, a significant number of bacteria existed in the blood of dLHT-administered group, whereas only a small number of bacteria detectable 6 hours after the challenge and the number gradually decreased thereafter in the dLHT-administered group. MRSA-challenged MMC-treated mice were treated by dLHT, vancomycin, or dLHT and vancomycin. All of non-treated mice died 8 days after the MRSA challenge, whereas the survival rates were 60% after dLHT treatment, 40% after vancomycin treatment, and 80% after dLHT and vancomycin treatment. All of MMC-treated mice, to which the phagocytic cells prepared from MMC-treated mice with dLHT administration had adoptively been transferred, survived from MRSA challenge. On the other hand, the survival rate of MMC-treated mice, to which the lymphocytes prepared from the same mice had adoptively been transferred, was 40%. Clinical Trial: All cases with dLHT treatment showed negative culture results for MRSA after the dLHT administration. The culture generally became negative less than 50 days after the initial administration, whereas one control case needed more than 100 days and the other was dead of the infection. One representative case, who was a 78-year-old woman suffering from hypertension, atrial fibrillation, and cerebral bleeding in the right occipital lobe, infected with MRSA during the antibiotic therapy for Streptococcus pneumoniae. The antibiotic therapy was halted and the dLHT administration started. Three weeks later, the culture result became negative. In addition, serum protein and albumin values also returned to the level that they had had before the infection of MRSA.

Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

Objective To explore the interaction of Anxa2 with P-Glycoprotein(P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA(shRNA) targeting P-gp was transfected into MCF-7/ADR cells,and monoclonal cell strains were screened.The expression of P-gp was detected by Western blot.Transwell chambers were used to observe the cell migration capacity and invasion ability.The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down,and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells(P<0.05).There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities.The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells.The interaction of Anxa2 with P-pg may play an important role in the enhanced invasiveness of MDR human breast cancer cells.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Liposome-mediated Functional Expression of Multiple Drug Resistance Gene in Human Bone Marrow CD34^+ Cells

Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.

A Comparative Study of Drug Susceptibility Testing Techniques for Identification of Drug Resistant TB in a Tertiary Care Centre, South India

India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative method which could be cost-effective by combining the drugs in the same tube for identification of drug resistance. Drug Susceptibility Test (DST) results of 1000 sputum samples are got from suspected TB patients against INH (isoniazid) and Rifampicin by two techniques: a) a modified technique with both drugs in the same MGIT tube and b) a standard technique with the antibiotics in separate MGIT tubes for the diagnosis of MDR-TB (Multidrug Resistant). 39 samples were contaminated and were excluded from final analysis. 198 were smear positives by the concentrated Ziehl-Neelsen’s staining method. 219 were found to be culture positive out of which 195 were identified as M. tuberculosis complex. 40 (20.5%) strains were identified as MDR-TB by the conventional method and 39 were picked up by the modified DST. INH and Rifampicin mono-resistance accounted for 32 (16.4%) and 4 (2%) respectively. 99% concordance was observed between the two tests in categorizing MDR-TB. Similarly modified technique with combination of the second line Antibiotics-Ofloxacin, Kanamycin and Capreomycin was applied on the identified MDR strains in a stepwise manner. 6 (15%) were identified as Pre-XDR strains and 2 (5%) were found to be XDR-TB strains. This study implies that combining drugs in the same tube may be an equivalent and possibly a cost-effective alternative which needs to be explored further.

THE AMPLIFICATION AND EXPRESSION OF MDR1 GENE IN ADRIAMYCINE RESISTANT CELL LINE OF COLON CANCER CELL HR8348

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2015—2022年天水市肺结核患者耐药情况及利福平耐药特征分析

目的:分析2015—2022年甘肃省天水市肺结核患者耐药情况及利福平耐药特征,为优化耐药结核病卫生政策提供科学依据。方法:采用回顾性研究方法,从“中国疾病预防控制信息系统”子系统“结核病管理信息系统”中收集2015—2022年天水市肺结核患者实验室检测结果、耐药筛查和耐药结核病诊断信息等资料,分析患者病原学阳性率、药物敏感性试验结果和耐药诊断时间等。结果:2015—2022年,天水市共登记活动性肺结核患者8458例,除外结核性胸膜炎的肺结核患者为7895例,病原学阳性率为28.32%(2236/7895),且从2015年的11.33%(177/1562)上升至2022年的61.30%(236/385),呈明显上升趋势(χ_(趋势)^(2)=1014.480,P=0.000);天水市应耐药筛查肺结核患者2360例,实际耐药筛查率为85.00%(2006/2360),从2015年的54.80%(97/177)上升至2022年的93.39%(240/257),呈明显上升趋势(χ_(趋势)^(2)=397.292,P=0.000);天水市耐药检出率为98.90%(1984/2006),利福平耐药检出率为15.73%(312/1984),从2015年的10.42%(10/96)上升至2017年的28.57%(62/217),再下降至2022年的11.34%(27/238),呈先上升后下降趋势(χ_(趋势)^(2)=27.248,P=0.000)。312例利福平耐药患者中,男性[198例(63.46%)]多于女性[114例(36.54%)];年龄相对集中在20~29岁[85例(27.24%)]和40~49岁[66例(21.15%)],且老年患者(60~83岁)比例从2016年的9.52%(2/21)上升至2022年的25.93%(7/27),呈明显上升趋势(χ_(趋势)^(2)=4.801,P=0.028);职业以农民为主[213例(68.27%)];痰涂片结果以涂阳患者居多[215例(68.91%)],但痰涂片阳性率从2015年的100.00%(10/10)下降至2022年的59.26%(16/27),呈下降趋势(χ_(趋势)^(2)=17.664,P=0.000)。耐药谱前3位依次为利福平+异烟肼+乙胺丁醇[26.92%(84/312)]、利福平[26.28%(82/312)]和利福平+异烟肼[23.40%(73/312)]。耐药患者诊断时间中位数(四分位数)从2016年的145(91,196)d逐年下降至2019年的21(12,39)d。结论:2015—2022年天水市肺结核患者病原学阳性率和耐药筛查率均呈逐年上升趋势,利福平耐药检出率波动较大,耐药诊断时间明显缩短,建议加大老年肺结核患者利福平耐药筛查力度,以减少耐药肺结核的传播。

2020—2022年某医院主要细菌耐药情况分析

目的通过分析福建中医药大学附属第二人民医院2020年1月—2022年12月常见细菌的耐药性,了解医院的细菌耐药情况,为临床提供合理使用抗菌药物的参考依据。方法通过回顾性分析方法对2020年1月—2022年12月福建中医药大学附属第二人民医院患者标本分离的病原菌株进行统计,从病原菌标本分布、病原菌种类及耐药等方面进行分析。结果2020—2022年分离的菌株共计12009株,呼吸道标本(包括痰、肺泡灌洗液)最多。前5位为大肠埃希菌2139株(17.81%)、肺炎克雷伯菌1342株(11.17%)、铜绿假单胞菌1094株(9.11%)、金黄色葡萄球菌为主793株(6.60%)、鲍曼不动杆菌541株(4.50%)。耐碳青霉烯类肺炎克雷伯菌(Carbapenemresistant K.pneumoniae,CR-KP)和耐碳青霉烯类铜绿假单胞菌(Carbapenemresistant Pseudomonas aeruginosa,CR-PA)2022年比2020年明显升高,差异有统计学意义(P<0.01)。其余3种耐甲氧西林金黄色葡萄球菌(Methicillin-resistant S.aureus,MRSA)、耐碳青霉烯类大肠埃希菌(Carbapenemresistant Escherichia coli,CR-EC)、耐碳青霉烯类鲍曼不动杆菌(Carbapenemresistant Acinetobacter baumannii,CRAB)3年间检出率差异无统计学意义(P>0.05)。鲍曼不动杆菌对大多数常用抗菌药物耐药率>50%。结论福建中医药大学附属第二人民医院主要以革兰阴性杆菌为主,鲍曼不动杆菌对大多数常用抗菌药物耐药率>50%,CR-KP(耐碳青霉烯类肺炎克雷伯菌)和CR-PA(耐碳青霉烯类铜绿假单胞菌)的耐药率呈增高趋势,建议临床密切关注病原菌耐药情况的变化,减少多重耐药菌的产生。

多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染的疗效观察

目的:评估多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染的疗效,并探讨其影响多黏菌素B疗效的可能因素。方法:选取某院重症监护室2020年2月~2022年6月诊治的26例危重症多重耐药革兰阴性菌感染患儿,根据患者的疗效分为临床有效组(n=14)和临床无效组(n=12)。比较两组患者的性别、年龄、小儿危重病例评分、合并疾病、病原菌、治疗时间、机械通气情况以及与其他抗菌药物联用情况。对其中有意义的变量进行多因素Logistic回归分析,探讨影响多黏菌素B疗效的可能因素。结果:临床有效组与无效组的性别、年龄、小儿危重病例评分、合并疾病、病原菌以及与其他抗菌药物联用情况比较均无统计学差异(P>0.05)。临床有效组的多黏菌素B使用时间较无效组更长(P=0.000),临床无效组有更多的患儿应用机械通气(P=0.034)。Logistic回归分析果结提示治疗时间(OR:2.606,95%CI:1.346~5.046,P=0.004)是影响多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染临床疗效的可能因素。结论:多黏菌素B治疗危重症儿童多重耐药革兰阴性菌感染具有较好的治疗效果,治疗时间是影响多黏菌素临床疗效的可能因素。

急诊重症监护室血流感染患者临床结局的风险因子探讨

目的探讨急诊重症监护室(emergency intensive care unit,EICU)血流感染患者临床结局的风险因子,为临床决策提供依据。方法回顾性收集2019年1月至2023年4月我院就诊的141例EICU血流感染患者的病历资料及血培养记录,采用Logistic回归分析患者死亡的危险因素,运用Cox回归分析上述因素与患者生存时间和临床结局的关系。结果在141例EICU血流感染患者中,两种及以上细菌混合血流感染[比值比(OR)=5.68,95%置信区间(CI):1.20~26.98,P<0.05]及多重耐药菌血流感染(OR=6.39,95%CI:2.78~14.67,P<0.01)与患者死亡具有显著相关性;是否根据药敏结果及时调整用药[风险比(HR)=0.47,95%CI:0.30~0.74]和多重耐药菌血流感染(HR=2.02,95%CI:1.28~3.20)是EICU血流感染患者死亡的风险因子(P<0.01)。结论尽早采集血培养,明确感染病原菌,精准用药控制感染,可以有效降低患者的死亡率。

亚抑菌浓度美罗培南对多重耐药鲍曼不动杆菌生物膜作用的研究

目的:探讨亚抑菌浓度美罗培南对多重耐药鲍曼不动杆菌(MDR-Ab)生物膜作用的影响。方法:采用微量肉汤稀释法测定某三甲医院从临床血液标本中分离的6株碳青霉烯类耐药的多重耐药鲍曼不动杆菌(MDR-AB)对美罗培南的最低抑菌浓度(MIC),结晶紫半定量法测定菌株生物膜形成能力。A组实验用96孔聚苯乙烯板体外构建MDR-AB生物膜的模型,用亚抑菌浓度美罗培南作用于成熟生物膜;B组实验用96孔聚苯乙烯板将MDR-AB浮游菌液与亚抑菌浓度美罗培南共培养。通过结晶紫半定量染色法对生物膜进行染色,再用多功能酶标仪测生物膜在560 nm波长处的OD值。结果:A组a、b、c中所形成生物膜OD值与对照组d组比较,48 h结果有统计学意义(P<0.05),而96h无统计学意义(P>0.05);B组X、Y、Z的生物膜形成过程中,48 h和96 h后OD值与对照组W有统计学意义(P<0.05)。结论:MDR-Ab有形成生物膜的能力;亚抑菌浓度美罗培南具有破坏成熟生物膜的能力,且其破坏能力随着浓度的升高而增强;1/2 MIC、MIC浓度的美罗培南可能抑制MDR-Ab生物膜形成,而1/4 MIC浓度的美罗培南则可能诱导MDR-Ab生物膜形成。