Multidrug-Resistant of Escherichia coli and Salmonella spp. Strains in Chicken Feces Intended for Consumption in Open Spaces of Ouagadougou, Burkina Faso

Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains. In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp. using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria. The results showed that out of the 400 samples collected, 81.25% and 63.5% were contaminated by Escherichia coli and Salmonella spp., respectively. Among these, 86.15% of identified Escherichia coli and 50.78% of Salmonella spp. displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxime (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin clavulanic acid (AMC), 23.57% aztreoname (ATM) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp. isolates resistant to at least one tested antibiotic, 34.88% were resistant to CTX;41.08% to CAZ;35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP. Our study revealed high prevalence of resistance in bacterial strains isolated from local chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections.

JNK1,JNK2,and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells

BACKGROUND:Multidrug resistance(MDR)is extremely common in hepatocellular carcinoma(HCC)and is a major problem in cancer eradication by limiting the efficacy of chemotherapy.Modulation of c-Jun NH2-terminal kinase(JNK)activation could be a new method to reverse MDR.However,the relationship between JNK activity and MDR in HCC cells is unknown.This study aimed to explore the relationship between MDR and JNK in HCC cell lines with different degrees of MDR.METHODS:A MDR human HCC cell line,SMMC-7721/ ADM,was developed by exposing parental cells to gradually increasing concentrations of adriamycin.The MTT assay was used to determine drug sensitivity.Flow cytometry was used to analyze the cell cycle distribution and to measure the expression levels of P-glycoprotein(P-gp)and MDR-related protein(MRP)-1 in these cells.JNK1,JNK2 and JNK3 mRNA expression levels were quantified by real-time PCR.Expression and phosphorylation of JNK1,JNK2,and JNK3 were analyzed by Western blotting.RESULTS:The MDR of SMMC-7721/ADM cells resistant to 0.05 mg/L adriamycin was mainly attributed to the overexpression of P-gp but not MRP1.In addition,these cells had a significant increase in percentage in the S phase,accompanied by a decrease in percentage in the G0/G1 phase,which is likely associated with a reduced ability for cell proliferation and MDR generation.We found that JNK1,JNK2,and JNK3 activities were negatively correlated with the degree of MDR in HCC cells.CONCLUSION:This study suggests that JNK1,JNK2,and JNK3 activities are negatively correlated with the degree of MDR in HCC cells.

P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers

The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1 A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.

Reversal of P-glycoprotein-mediated Multidrug Resistance in SGC7901/VCR Cells by PPARγ Activation by Troglitazone

Over-expression of P-glycoprotein(P-gp),an ATP-dependent drug efflux pump,represents one of the major mechanisms that contribute to multidrug resistance(MDR) in cancer cells.This study examined the effects of troglitazone,a ligand of peroxisome proliferator-activated receptor gamma(PPARγ),on P-gp-mediated MDR in SGC7901/VCR cells(a vincristine-resistant human gastric cancer cell line).The expression of P-gp was detected by RT-PCR and Western blotting,respectively.The SGC7901/VCR cells were treated with 0.1 mg/L vincristine(VCR) alone or in combination with 1,5,10 μmol/L troglitazone for 24 h.PPARγ was measured by electrophoretic mobility shift assay(EMSA).The intracellular concentration of Rhodamine123(Rh123,a fluorescent P-gp substrate) was assayed to evaluate the activity of P-gp.The cell cycle and apoptosis were measured by flow cytometry.The results showed that the P-gp was increasingly expressed in SGC7901,BGC823 and SGC7901/VCR cells in turn,suggesting that MDR in the SGC7901/VCR cells was mediated by the increased expression of P-gp.In the SGC7901/VCR cells,the expression level of total PPARγ was increased,however,the protein level and activity of PPARγ in the nuclei of cells decreased significantly.Troglitazone elevated the PPARγ activity in SGC7901/VCR cells in a dose-dependent manner.Troglitazone decreased the P-gp expression and markedly enhanced the accumulation of Rh123 in SGC7901/VCR cells in a dose-dependent manner.We also found that troglitazone significantly increased the percentage of SGC7901/VCR cells in the G2/M phase and decreased the cell percentage in G1 and S phase in a dose-dependent manner.Troglitazone significantly increased the apoptotic rate of SGC7901/VCR cells treated by VCR or ADR in a dose-dependent manner.It was concluded that P-gp-overexpressed SGC7901/VCR cells have minor endogenous PPARγ activity.Elevation of the PPARγ activity by troglitazone can reverse P-gp-mediated MDR via down-regulating the expression and activity of P-gp in SGC7901/VCR cells.It was suggested that troglitazone can dramatically enhance the sensitivity of P-gp-mediated MDR cancer cells to chemotherapeutic agents.

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

AIM:To study the expression and phosphorylation of extracellular signal-regulated kinase(ERK)1 and ERK2 in multidrug resistant(MDR)hepatocellular carcinoma(HCC)cells.METHODS:MDR HCC cell lines,HepG2/adriamycin(ADM)and SMMC7721/ADM,were developed by exposing parental cells to stepwise increasing concentrations of ADM.MTT assay was used to determine drug sensitivity.Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein(P-gp)and multidrug resistant protein 1(MRP1)expression levels.ERK1 and ERK2 mRNA expression levels were measured by quantitative real-time PCR(QRTPCR).Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.SMMC7721/ADM were resistant not only to ADM,but also to multiple anticancer drugs.The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells(8.92%±0.22%vs 0.88%±0.05%,P<0.001)and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells(7.37%±0.26%vs 1.74%±0.25%,P<0.001).However,the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells.In addition,the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase.QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells.Compared with the expression of parental cells,ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells.However,ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells.Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION:ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells.ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells.

REGULATION OF EXPRESSION OF P-GLYCOPROTEIN AND GST BY MULTIDRUG-RESISTANT REVERSORS IN ADM-SENSITIVE AND ADM-RESISTANT HUMAN TUMOR CELL LINES

Objective: To investigate the regulation of p-glycoprotein (PgP) and GST expression from three reversors in ADM-sensitive and ADM-resistant human leukemic cell lines and KB cell lines. Methods: Immunocytochemical(ICC) technique was applied to detect the multidrug-resistant gene products, PgP and GST in K562 cells, K562/ADM cells and KB cells before or after treatment with three resistant reversors, i.e., verapamil(VER), dipyriamole(DPM) and cyclosporin A(CsA). Results: PgP expression was observed in K562/ADM cells but not in K562 cells or KB cells, and GSTPI expression, in KB cells but not in K562 cells or K562/ADM cells. Overexpressions of PgP were induced after treatment with VER, or DPM or CsA for 24 h in K562 cells but not KB cells. DPM-treated K562/ADM cells expressed PgP much lower than DPM-ree of K562/ADM cells with CsA for 24 h. Induced GSTPI expression was found after treatment with DPM, but not VER or CsA in K562 cells. No significant difference was observed for GSTPI expresion in KB cells before and after treatment with VER, or DPM, or CsA. Conclusion: The findings suggested that reversal activity of some drug resistant reversors, such as VER, DPM, CsA, may be declined by themselves through induction of PgP, perhaps GST.

Multidrug Resistance P-glycoprotein Function of Bone Marrow Hematopoietic Cells and the ReversalAgent Effect

The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells.The expression of P-gp on the surface of CD cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking o fCD hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-2O9. The results showed that the P-gp expression rate of bone marrow CDL cells was 13. 3 %. MS-209 obviously increased the Rhodamin-123 uptake of CD positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29. 6 %, but it was increased to 43. 3 % in the presence of MS-209 with the difference being significant (P< 0. 05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function- MS-209could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoeitic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.

Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

The relationship among amyloid-βdeposition,sphingomyelin level,and the expression and function of P-glycoprotein in Alzheimer’s disease pathological process

In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-βas the central cause of Alzheimer’s disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-βand their potential association in the pathological process of Alzheimer’s disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer’s disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Together,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer’s disease drugs.

Effect of Cyclooxygenase Inhibition on P-Glycoprotein Expression and Phenytoin Level in Brain Tissue of Pilocarpine Induced Epilepsy in Rats

Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/kg) or celecoxib (20 mg/kg), either alone or combined with phenytoin (50 mg/kg). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. Phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Linked Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: Phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptake of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.

Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing

Objective To explore the genotyping characteristics of human fecal Escherichia coli(E. coli) and the relationships between antibiotic resistance genes(ARGs) and multidrug resistance(MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.Methods Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs,multilocus sequence typing(MLST), and polymorphism trees were analyzed using whole-genome sequencing data(WGS).Results This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal(49/70) and healthy groups(15/24).Conclusion We developed a random forest(RF) prediction model of TEM.1 + baeR + mphA + mphB +QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.

Meta‑analysis of influencing factors associating with treatment outcome of multidrug resistant tuberculosis

Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary tuberculosis.Method:Case control studies on the factors influencing the treatment outcome of multidrug-resistant pulmonary tuberculosis in Chinese databases(CNKI,VIP,Wanfang,Sinomed)and English databases(Pubmed,Web of science,Medline,Embase,Scopus)were searched and collected by computer.The search period was from the establishment of the database to January 2023.After screening and quality evaluation,RevMan5.4 was used for meta-analysis.Result:Totally 18 articles were ultimately included,with a sample size of 7328 people.The results showed that retreatment,complications,adverse reactions,and gender were related to the treatment outcome of multidrug-resistant pulmonary tuberculosis.The OR values and 95%CI of each factor were 0.22(0.17-0.29),0.38(0.32-0.46),0.27(0.17-0.44),and 0.43(0.33-0.56),respectively.Conclusion:Complications,retreatment,adverse reactions,and male gender are effective risk factors for the treatment outcome of multidrug-resistant pulmonary tuberculosis.In clinical practice,more targeted measures are needed for different types of patients.Due to the limitations of the number of studies,the above conclusions require more research to support them.

REVERSION OF MULTIDRUG RESISTANCE IN THE P-GLYCOPROTEIN POSITIVE BREAST CANCER CELL LINE(MCF-7/ADR) BY INTRODUCTION OF HAMMERHEAD RIBOZYME

A hammerhead ribozyme which site-specifically cleaved the GUC position in canon 880 of the mdr1 mRNA was designed. The target site was chosen between the two ATP binding sites, which may be important for the function of the P-Gp as an ATP-dependent pump. A DNA sequence encoding the ribozyme gene was then incorporated into a eukaryotic expression vector (pH Apr-1 neo) and transfected into the breast cancer cell line MCF-7/Adr, which is resistant to adriamycin and expresses the MDR phenotype. The ribozyme was stably expressed in the cell line by the RNA dot blotting assay. The result of Northern blot assay showed that the expressed ribozyme could decrease the level of mdrl mRNA expression by 83. 5 %; and the expressed ribozyme could inhibite the formation of p-glycoprotein detected by immuno- cy-tochemistry assay and could reduce the cell’s resistance to adrimycin; this means that the resistant cells were 1 000-fold more resistant than the parental cell line(MCF-7), whereas those cell clones that showed ribozyme expression were only 6-fold more resistant than the parental cell line. These results show that a potentially useful tool is at hand which may inactivate MDR1 mRNA and revert the multidrug resistance phenotype.

Sensorineural Hearing Loss in Multidrug-Resistant Tuberculosis Patients in Kinshasa (Democratic Republic of Congo): Prospective Cohort Study of Therapeutic Regimen with Aminoglycoside versus Bedaquiline

Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.

肠杆菌科细菌mcr-1流行病学研究

目的探讨临床常见肠杆菌科细菌携带质粒介导多黏菌素耐药基因(mcr-1)的情况,为医院感染防控提供依据。方法收集2018年1月至2022年3月浙江省台州医院临床分离得到的菌株共1980株,包括大肠埃希菌1400株,肺炎克雷伯菌580株。采用PCR检测mcr-1基因;利用微量肉汤稀释法和E-test法检测抗生素对mcr-1阳性菌株的最低抑菌浓度;采用接合试验检测mcr-1基因在可转移质粒上的位置;通过提取细菌DNA基因组进行全基因组测序,并对测序结果进行多位点序列分型、质粒Inc分型和耐药基因识别等分析。结果在1400株大肠埃希菌中,共检测出6株携带mcr-1,阳性率为0.43%;580株肺炎克雷伯菌,仅1株检出mcr-1,阳性率为0.17%。其中5株菌株接合试验成功。6株大肠埃希菌的ST型分别是ST648、ST95、ST359、ST602、ST453、ST156,肺炎克雷伯菌是ST25。质粒Inc分型结果显示不同菌株携带相同类型质粒,提示该类质粒可以在菌株间水平传播。耐药基因分析发现7株细菌均携带大量的耐药基因,其中1株大肠埃希菌和肺炎克雷伯菌同时携带mcr-1和碳青霉烯耐药基因。结论mcr-1在大肠埃希菌和肺炎克雷伯菌中的分离率相对较低,然而考虑到含有mcr-1的质粒在不同细菌之间水平传播的潜力,以及mcr-1与同一质粒内的多个耐药基因整合的能力,在临床环境中要加强对多重耐药菌的管理。

Determinants of the Sensorineural Hearing Loss in Patients with Multidrug-Resistant Tuberculosis in Kinshasa (Democratic Republic of the Congo): A Prospective Cohort Study

Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.

Th1/Th2细胞表达对耐多药肺结核患者治疗转归的影响

目的探讨辅助T细胞1(Th1)/辅助T细胞2(Th2)细胞表达对耐多药肺结核(MDR-TB)患者治疗转归的影响。方法回顾性纳入南阳市中心医院2019年1月至2022年9月收治的92例MDR-TB患者临床资料。所有患者均接受左氧氟沙星、贝达喹啉、利奈唑胺、氯法齐明、环丝氨酸联合治疗,强化治疗周期为6个月。根据强化治疗结束后患者治疗转归情况将患者分为转归良好组(74例)和转归不良组(18例)。对比两组一般资料和治疗前所测的Th1、Th2细胞表达情况及其他实验室指标,分析Th1/Th2细胞表达对患者治疗转归的影响。结果转归不良组有既往吸烟史占比、Th2高于转归良好组,Th1、Th1/Th2低于转归良好组(P<0.05)。经点二列相关性分析显示,Th1、Th2、Th1/Th2细胞表达与MDR-TB患者治疗转归情况有关。绘制受试者工作特征(ROC)曲线,结果显示,Th1、Th2、Th1/Th2细胞表达预测MDR-TB患者治疗转归的曲线下面积(AUC)分别为0.827、0.813、0.883,Th1/Th2预测价值最高。结论Th1/Th2细胞表达可对MDR-TB患者治疗转归的产生影响,其值越高,治疗转归不良发生率越高。

耐多药肺结核合并2型糖尿病1例并文献复习

耐多药肺结核的诊治是全球结核病控制的重难点问题,若合并糖尿病将进一步加大治疗难度,影响疾病的转归。本例患者自2015年开始,先后经历2次抗结核治疗失败,经过痰培养及药敏检查确诊耐多药肺结核,调整抗结核治疗方案的同时加强血糖的管理,最终治愈停药。本病例为耐多药肺结核与糖尿病共病患者的诊治提供了参考。

百里香酚对犊牛源生物被膜阳性金黄色葡萄球菌耐药性的消除作用

为了了解内蒙古地区犊牛病料中生物被膜阳性金黄色葡萄球菌的流行情况、耐药情况及百里香酚对生物被膜阳性金黄色葡萄球菌耐药性的消除作用。本试验采用生化鉴定和PCR方法,对采集到的104份犊牛病料进行金黄色葡萄球菌的分离鉴定;采用K-B法检测了金黄色葡萄球菌分离株对18种抗菌药物的敏感性;采用改良结晶紫染色法测定分离株的生物被膜形成能力;选取2株生物被膜强阳性菌株,采用微量肉汤稀释法测定百里香酚对分离株的最小抑菌浓度,并进行百里香酚耐药性消除试验。结果显示,在104份犊牛病料中共分离鉴定获得43株金黄色葡萄球菌。药敏试验结果显示,金黄色葡萄球菌分离株对氨苄西林、头孢西丁、卡那霉素、复方新诺明和红霉素5种抗菌药物的耐药率达到50.0%以上;74.4%(32/43)的分离株为多重耐药株。生物被膜形成能力强、中、弱和无生物被膜形成能力的分离株分别占比23.3%(10/43)、16.3%(7/43)、32.6%(14/43)和27.9%(12/43);生物被膜阳性株中83.9%(26/31)为多重耐药株。百里香酚对2株生物被膜强阳性株的最小抑菌浓度均为256 mg/mL,经百里香酚处理后均恢复了对头孢噻肟的敏感性。结果表明,百里香酚对生物被膜阳性金黄色葡萄球菌具有一定的耐药消除作用。

多药耐药相关蛋白转运体在药物性肝损伤中的作用研究进展

肝脏是人体新陈代谢最旺盛的器官,也是体内多种药物的解毒器官。当长期或过量使用药物时会增加药物性肝损伤(DILI)的风险。多药耐药相关蛋白(MRPs)是位于细胞膜上的功能蛋白,可转运多种药物,在DILI中发挥重要作用。MRPs功能的抑制、缺失是药物肝毒性产生的重要原因。本文对MRPs的结构、表达部位及功能进行归纳,并对MRPs与DILI的关系及其改善DILI的机制进行总结,期望更好地了解MRPs转运体与DILI的关系,为后续防治DILI提供参考。