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.

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.

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.

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.

Multi Drug Resistance Bacterial Isolates of Surgical Site Infection

Multi drug resistance microorganism is considered to be one of the major health problems. The aim of this study was to determine antibiotic susceptibility pattern of bacterial pathogens of surgical site infection. A total 250 samples were included, out of which 62.4% showed significant bacterial growth. Gram negative bacteria were 85.25% and gram positive bacteria were 14.75%;among them 65.38% of the total isolates were multi drug resistance (MDR). The age group between 31 - 40 found the highest number of isolates 22.4%. Among gram negative bacilli, the highest production of MDR was found in Acinetobacter spp. followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. In gram positive cocci, the highest production of MDR was found in Staphylococcus aureus. Acinetobacter spp. was found highly susceptible to amikacin and gentamycin 20.1% followed by ofloxacin and ciprofloxacin 18.6% and 16.2% respectively. Staphylococcus aureus showed 100% sensitive to clindamycin whereas penicillin showed 100% resistance followed by amoxycillin (93.75%). Amikacine and clindamycin were drugs of choice for gram negative and gram positive bacteria respectively. This study showed that alarming increase of infections was caused by multi drug resistance bacterial organisms. It increases length of stay and may produce lasting sequelae and requires extra resources for investigations, management and nursing care. Surveillance of surgical site infection is a useful tool to demonstrate the magnitude of the problem and find out appropriate preventive methods.

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.

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

Effects of multidrug resistance, antisense RNA on the chemosensitivity of hepatocellular carcinoma cells

BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM. METHODS: The recombinant adenoviruses pAdEasy- GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein- producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by flow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis. RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpressionof mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96% respectively. CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.

Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019

BACKGROUND In this study,recent trends in the distribution and drug resistance of pathogenic bacteria isolated from patients treated at a burn ward between 2006 and 2019 were investigated.AIM To develop more effective clinical strategies and techniques for the prevention and treatment of bacterial infections in burn patients.METHODS Clinical samples with positive bacteria were collected from patients at the burn ward in Beijing Jishuitan Hospital in China between January 2006 and December 2019.The samples were retrospectively analyzed,the distribution of pathogenic bacteria was determined,and the trends and changes in bacterial drug resistance during different period were assessed.Drug resistance in several main pathogenic bacteria from 2006 to 2011 and from 2012 to 2019 was comparatively summarized and analyzed.RESULTS Samples from 17119 patients were collected and analyzed from 2006 to 2019.Surprisingly,a total of 7960 strains of different pathogenic bacteria were isolated at this hospital.Among these bacteria,87.98%(7003/7960)of the strains were isolated from burn wounds,and only 1.34%(107/7960)were isolated from the blood of patients.In addition,49.70%(3956/7960)were identified as Grampositive bacteria,48.13%(3831/7960)were Gram-negative bacteria,and the remaining 2.17%(173/7960)were classified as fungi or other pathogens.Importantly,Staphylococcus aureus(21.68%),Pseudomonas aeruginosa(14.23%),and Staphylococcus epidermidis (9.61%) were the top three pathogens most frequentlyisolated from patients.CONCLUSION In patients treated at the burn ward in this hospital from 2006 to 2019,Staphylococcus aureus and Pseudomonas aeruginosa were the predominant clinicalpathogens responsible for bacterial infections. The circumstantial detection anddetailed monitoring of the intensity and growth of different pathogenic bacteria inclinical patients as well as tests of drug sensitivity during burn recovery areparticularly important to provide guidelines for the application of antibiotics andother related drugs. Careful collection and correct, standard culture of bacterialspecimens are also crucial to improve the efficiency of bacterial infectiondetection. Effective monitoring and timely clinical treatment in patients may helpreduce the possibility and rate of infection as well as alleviate the effects of drugresistance among patients in burn centers.

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.

Enhanced anticancer effect of doxorubicin by TPGS-coated liposomes with Bcl-2 siRNA-corona for dual suppression of drug resistance

Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.

Correlation between Cyclin A Gene Expression in Adult Patients with Acute Leukemia and Drug Resistance

In order to investigate the relationship between the expression of cyclin A and drug resistance in adult patients with acute leukemia (AL), the mRNA expression of cyclin A, mdr1, TopⅡ α , bcl-2 was detected in 64 adult patients with AL and 20 normal controls by semi-reverse transcription polymerse chain reaction (semi-RT-PCR). It was found that the cyclin A and TopⅡ α mRNA expression levels in drug resistant group were significantly lower than in sensitive group ( P <0.01). Under the same experimental condition no cyclin A mRNA expression was detectable in all normal controls. The mdr1 and bcl-2 mRNA expression levels in resistant group were significantly higher than in sensitive group ( P <0.01). cyclin A and TopⅡ α gene expression levels were closely correlated ( r s =+0.794, P=0.000, n =64) in all AL patients, but cyclin A was not correlated with mdr1 and bcl-2 gene expression levels. In drug resistant group there was a negative correlation between the gene expression levels of cyclin A and mdr1 ( r s =-0.337, P=0.029 ). The 10 AL patients with positive lower expression of both cyclin A and TopⅡ α were all resistant to drugs. Logistic regression of Binary analysis showed the correlation between the lower expression of cyclin A and drug resistance. It was concluded that lower expression of cyclin A gene might be an unfavorable prognostic factor for patients with AL, and detection of both cyclin A and TopⅡ α gene expression would predict drug resistance in AL patients.

Microbial spectrum and drug resistance of pathogens cultured from gallbladder bile specimens of patients with cholelithiasis:A singlecenter retrospective study

BACKGROUND Bacterial infection is an important cause of cholelithiasis or gallstones and interferes with its treatment.There is no consensus on bile microbial culture profiles in previous studies,and identified microbial spectrum and drug resistance is helpful for targeted preventive and therapeutic drugs in the perioperative period.AIM To analyze the bile microbial spectrum of patients with cholelithiasis and the drug susceptibility patterns in order to establish an empirical antibiotic treatment for cholelithiasis-associated infection.METHODS A retrospective single-center study was conducted on patients diagnosed with cholelithiasis between May 2013 and December 2018.RESULTS This study included 185 patients,of whom 163(88.1%)were diagnosed with gallstones and 22(11.9%)were diagnosed with gallstones and common bile duct stones(CBDSs).Bile culture in 38 cases(20.5%)was positive.The presence of CBDSs(OR=5.4,95%CI:1.3-21.9,P=0.03)and longer operation time(>80 min)(OR=4.3,95%CI:1.4-13.1,P=0.01)were identified as independent risk factors for positive bile culture.Gram-negative bacteria were detected in 28 positive bile specimens,and Escherichia coli(E.coli)(19/28)and Klebsiella pneumoniae(5/28)were the most frequently identified species.Gram-positive bacteria were present in 10 specimens.The resistance rate to cephalosporin in E.coli was above 42%and varied across generations.All the isolated E.coli strains were sensitive to carbapenems,with the exception of one imipenem-resistant strain.K.pneumoniae showed a similar resistance spectrum to E.coli.Enterococcus spp.was largely sensitive to glycopeptides and penicillin,except for a few strains of E.faecium.CONCLUSION The presence of common bile duct stones and longer operation time were identified as independent risk factors for positive bile culture in patients with cholelithiasis.The most commonly detected bacterium was E.coli.The combination ofβ-lactam antibiotics andβ-lactamase inhibitors prescribed perioperatively appears to be effective against bile pathogens and is recommended.Additionally,regular monitoring of emerging resistance patterns is required in the future.

Drug resistance and minimal residual disease in multiple myeloma

Great progress has been made in improving survival in multiple myeloma(MM)patients over the last 30 years.New drugs have been introduced and complete responses are frequently seen.However,the majority of MM patients do experience a relapse at a variable time after treatment,and ultimately the disease becomes drug-resistant following therapies.Recently,minimal residual disease(MRD)detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response.MRD can be considered as a surrogate for both progression-free and overall survival.In this perspective,the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals.The present review gives an overview of drug resistance in MM,i.e.,mutation ofβ5 subunit of the proteasome;upregulation of pumps of efflux;heat shock protein induction for proteasome inhibitors;downregulation of CRBN expression;deregulation of IRF4 expression;mutation of CRBN,IKZF1,and IKZF3 for immunomodulatory drugs and decreased target expression;complement protein increase;sBCMA increase;and BCMA down expression for monoclonal antibodies.Multicolor flow cytometry,or next-generation flow,and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5.Sustained MRD negativity is related to prolonged survival,and it is evaluated in all recent clinical trials as a surrogate of drug efficacy.

Overcoming drug resistance by targeting protein homeostasis in multiple myeloma

Multiple myeloma(MM)is a plasma cell disorder typically characterized by abundant synthesis of clonal immunoglobulin or free light chains.Although incurable,a deeper understanding of MM pathobiology has fueled major therapeutical advances over the past two decades,significantly improving patient outcomes.Proteasome inhibitors,immunomodulatory drugs,and monoclonal antibodies are among the most effective anti-MM drugs,targeting not only the cancerous cells,but also the bone marrow microenvironment.However,de novo resistance has been reported,and acquired resistance is inevitable for most patients over time,leading to relapsed/refractory disease and poor outcomes.Sustained protein synthesis coupled with impaired/insufficient proteolytic mechanisms makes MM cells exquisitely sensitive to perturbations in protein homeostasis,offering us the opportunity to target this intrinsic vulnerability for therapeutic purposes.This review highlights the scientific rationale for the clinical use of FDA-approved and investigational agents targeting protein homeostasis in MM.

Bacterial contamination of orally-consumed crude herbal remedies:A potential source for multi-drug resistant pathogens in man

Objective:The acceptability of herbal remedies for alleviating discomforts and ill-health has become very popular, on the account of the increasing cost of allopathic medicine for personal health maintenance.The observable non-adherence of herbalists to the established World Health Organization(WHO) / National Agency for Food and Drug Administration Control(NAFDAC) regulations for the quality control of herbal medicines is an issue for concern.In view of this,34 popular and widely consumed crude herbal remedies in southwestern,Nigeria were screened for compliance with standard limits for bacterial contamination,bacteria flora and their antibiotic susceptibility pattern.Methods:Isolates recovered from samples were identified using the cultural, morphological and biochemical characteristics.They were also tested for drug sensitivity using standard procedures. Results:A heavy bacteria load ranging from 3.00×10~3-9.58×10~5 CFU/ML and 1.20×10~5- 5.41×10~5 CFU/ML was observed for water and spirit extracted preparations respectively.The bacteria flora cum contaminants were:Staphylococcus aureus,Bacillus cereus,Bacillus subtilis,Pseudomonas aeruginosa, Micrococcus luteus,Lactobacillus plantarum,Klebsiella pneumoniae,Escherichia coli,streptococcus,Shigella, Neisseria,Arthrobacter,Kurthia and Clostridium species.All the isolates were multi-drug resistant(MDR) strains.Conclusion:The crude herbal preparations consumed in Nigeria failed to comply with the internationally recognized standards regarding bacteria load and flora.The presence of MDR pathogens is of greatest concern. It poses a great risk to consumers health and could be a source of introducing MDR organisms into the human population.There is the need for the enforcement of established guidelines to ensure the safety of these preparations.

Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital

BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection.

New determinants of prognosis in bacterial infections in cirrhosis

Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of the main causes of decompensation.It is very important for clinical management to be aware of the population with the highest risk of poor outcome.This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently.Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines.Moreover,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of sepsis.It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and death.We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.

Prediction of multiple drug resistance phenotype in cancer cell lines using gene expression profiles and phylogenetic trees

When microarray gene expression data are used to predict multiple drug resistance(MDR)phenotypes for anticancer drugs,the normalization strategy and the quality of the selected signature genes are usually the main causes of inconsistency among different experiments.A stable statistical drug response prediction model is urgently required in oncology.In this study,the microarray gene expression data of multiple cancer cell lines with MDR was analyzed.For each probe-set,the expression value was defined as present/absent(1/0)and was classified into a gene set defined with protein domain organization(PDO).After employing the gene content method of phylogenetic analysis,a phylogenetic model(cell tree)for MDR phenotype prediction was built at the PDO gene set level.The results indicate that classification of cancer cell lines is predominantly affected by both the histopa-thological features and the MDR phenotype(paclitaxel and vinblastine).When applying this model to predict the MDR phenotype of independent samples,the phylogenetic model performs better than signature gene models.Although the utility of our procedure is limited due to sample heterogeneity,it still has potential application in MDR research,especially for hematological tumors or established cell lines.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A singlecenter study

AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.