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.

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.

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.

Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells

Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.

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.

Multidrug-resistant bacterial infections after liver transplantation: An ever-growing challenge

Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.

Immune formulation-assisted conventional therapy on anti-infective effectness of multidrug-resistant Mycobacterium tuberculosis infection mice

Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic(PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties(e.g.,those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus,a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.

The Role of Pyridoxine in the Prevention and Treatment of Neuropathy and Neurotoxicity Associated with Rifampicin-Resistant Tuberculosis Treatment Regimens: A Topic Review

Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.

Synergistic Effect of Hyperthermia and Neferine on Reverse Multidrug Resistance in Adriamycin-resistant SGC7901/ADM Gastric Cancer Cells

Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.

Isolation and identification of multidrug-resistant Staphylococcus haemolyticus from a laboratory-breeding mouse

Objective:To analysis and identify a bacterium strain isolated from laboratory breeding mouse far away from a hospital.Methods:Phenotype of the isolate was investigated by conventional microbiological methods,including Gram-staining,colony morphology,tests for haemolysis, catalase,coagulase,and antimicrobial susceptibility test.The meek and 16S rRNA genes were amplified by the polymerase chain reaction(PCR) and sequenced.The base sequence of the PCR product was compared with known 16S rRNA gene sequences in the CenBank database by phylogenetic analysis and multiple sequence alignment.Results:The isolate in this study was a gram positive,coagulase negative,and catalase positive coccus.The isolate was resistant to oxacillin,methicillin,penicillin,ampicillin,cefazolin,cipr of loxacin erythromycin,et al.PCR results indicated that the isolate was meek gene positive and its 16S rRNA was 1465 bp.Phylogenetic analysis of the resultant 16S rRNA indicated the isolate belonged to genus Saphylococcus,and multiple sequence alignment showed that the isolate was Saphylococcus haemolyticus with only one base difference from the corresponding 16S rRNA deposited in the CenBank.Conclusions: 16S rRNA gene sequencing is a suitable technique for non-specialist researchers.Laboratory animals are possible sources of lethal pathogens,and researchers must adapt protective measures when they manipulate animals.

Severe infection with multidrug-resistant Salmonella choleraesuis in a young patient with primary sclerosing cholangitis

Massive global spread of multidrug-resistant(MDR) Salmonella spp. expressing extended-spectrum beta-lactamase(ESBL) and additional resistance to fluoroquinolones has often been attributed to high international mobility as well as excessive use of oral antibiotics in livestock farming. However, MDR Salmonella spp. have not been mentioned as a widespread pathogen in clinical settings so far. We demonstrate the case of a 25-year-old male with primary sclerosing cholangitis who tested positive for MDR Salmonella enterica serotype Choleraesuis expressing ESBL and fluoroquinolone resistance. The pathogen was supposedly acquired during a trip to Thailand, causing severe fever, cholangitis andpancreatitis. To our knowledge, this is the first report of Salmonella enterica serotype Choleraesuis in Europe expressing such a multidrug resistance pattern. ESBL resistance of Salmonella enterica spp. should be considered in patients with obstructive biliary tract pathology and travel history in endemic countries.

Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy

We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.

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.

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

The incidence of gram-negative multidrug-resistant(MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through Pub Med search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients.

REVERSAL EFFECTS OF MIFEPRISTONE ON MULTIDRUG RESISTANCE(MDR) IN DRUG-RESISTANT BREAST CANCER CELL LINE MCF7/ADR IN VITRO AND IN VIVO

To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human breast cancer cell line MCF7/ADR and its mechanisms. Methods: Expression of MDR1 and MDR-associated protein(MRP) mRNA in MCF7/ADR cells was detected using reverse transcription- polymerase chain reaction(RT-PCR). Western blotting was used to assay the protein levels of P-glycoprotein (P-gp) and MRP. Intracellular rhodamine 123 retention and [3H]vincristine (VCR) accumulation were measured by flow cytometry and liquid scintillation counter, respectively. MTT reduction assay was used to determine the sensitivity of cells to the anticancer agent, adriamycin (ADR). Additionally, a MCF7/ADR cell xenograft model was established to assess the reversal effect of mifeprisone on MDR in MCF7/ADR cells in vivo. Results: Miferpristone dose-dependently down- regulated the expression of MDR1 and MRP mRNA in MCF7/ADR cells, accompanied by a significant decrease in the protein levels of P-gp and MRP. After exposure to 5, 10, and 20 mmol/L mifepristone, MCF7/ADR cells showed a 3.87-, 5.81-, and 7.40-fold increase in the accumulation of intracellular VCR(a known substrate of MRP), and a 2.14-, 4.39-, and 5.53-fold increase in the retention of intracellular rhodamine 123(an indicator of P-gp function), respectively. MTT analysis showed that the sensitivity of MCF7/ADR cells to ADR was enhanced by 7.23-, 13.62-, and 20.96-fold after incubation with mifepristone as above-mentioned doses for 96 h. In vivo, mifepristone effectively restored the chemosensitivity of MCF7/ADR cells to ADR. After 8 weeks of administration with ADR(2 mg穔g-1穌-1) alone or in combination with mifepristone(50 mg穔g-1穌-1), the growth inhibitory rate of xenografted tumors in nude mice was 8.08% and 37.25%, respectively. Conclusion: Mifepristone exerts potent reversal effects on MDR in MCF7/ADR cells in vitro and in vivo through down- regulation of MDR1/P-gp and MRP expression and inhibition of P-gp- and MRP-dependent drug efflux, thus increasing the sensitivity to anticancer drug.

Drug-Induced Hypothyroidism during Anti-Tuberculosis Treatment of Multidrug-Resistant Tuberculosis: Notes from the Field

We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R

AIM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrugresistant (MDR) cell of HCC bothin vitro and in vivo. METHODS: A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2 000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhIFN-γ, monoclonal anti-CD3 antibody, rhIL-1α as well as rhIL-2, which were added into the culture. To detect the cytotoxicityof the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. Asto in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT PCR; the P-glycoprotein expression increased from 1.32%of parent cells to 54%. CIK cells expanded vigorously bymore than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P＜0.01),the same as that of CIK from normal individuals. Each of the 17 patients received 1-5×1010 of CIK celltransfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry.CONCLUSION: A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.

Postoperative multidrug-resistant Acinetobacter baumannii meningitis successfully treated with intravenous doxycycline and intraventricular gentamicin: A case report

BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.

Antibacterial Activity of Exogenous Glutathione and Its Synergism on Antibiotics in Methicillin-Associated Multidrug Resistant Clinical Isolates of Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most problematic human pathogens. Antibiotic treatment of MRSA often associated with resistance to multiple classes of antibiotics is extremely challenging and urgently demands action to treat MRSA. Glutathione (GSH) is a biogenic thiol-compound that maintains an optimal intracellular redox-potential required for various normal cellular processes. Antibacterial activity of exogenous GSH has been reported in some bacterial pathogens but is largely unknown in MRSA. Aim: This study aimed to understand antibacterial activity of GSH, its role in antibiotic susceptibility, and a potential antibacterial mechanism in clinical isolates of S. aureus. Materials and Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), checkerboard, time-killing, and bacterial killing assays were performed for 14 clinical isolates of S. aureus including 10 MRSA and two type strains (ATCC 700699 and 35556). Results: MIC and MBC levels for the clinical and type strains were 15 - 20 mM and 25 - 40 mM of GSH, respectively. Subinhibitory concentrations of GSH synergistically enhanced susceptibility of all tested-antibiotics, resulting in sensitizing all-tested S. aureus. Bacterial-killing produced by GSH-mediated acidity was significantly higher than that by hydrochloric acid-mediated acidity. Conclusion: Overall results concluded that GSH exhibited antibacterial activity on S. aureus regardless of antibiotic susceptibility and synergistically enhanced antibiotic susceptibility. Additionally, GSH-mediated acidity was one of the antibacterial mechanisms. These findings suggest that GSH may be a potential antimicrobial agent or adjuvant for the conventional anti-MRSA regimens.