High Rates Of Drug Resistance Research Articles

Identification of antimicrobial resistance genes and drug resistance analysis of Escherichia coli in the animal farm environment

BackgroundAntibiotics are widely used to prevent and control diseases and infection for reducing the morbidity and mortality of animals, because of the high-density stocking in modern food-source animal production. However, the overuse of antibiotics in animal farms results in antimicrobial resistance (AMR), and causes public health issues through the food chain. Therefore, the AMR analysis of the farms and their surrounding environments is great significance to public health. MethodsTo investigate the distribution of AMR genes and analyze the antimicrobial drug resistance of Escherichia coli in feces and surrounding soil of animal farm in Zhanjiang, China. E. coli was isolated and identified through PCR, and the distribution of 21 common antimicrobial drug resistance genes were also detected by using PCR. The minimum inhibitory concentration (MIC) of the isolated E. coli strains against 22 drugs was detected using the broth double dilution method. ResultsThe results showed that the different AMR genes were detected in both feces and soil, and the detection rate of each AMR gene was higher than 50%. The detection rate of most AMR genes in feces was higher than those in soil. Besides, the isolated 88 strains of E. coli were resistant to 22 kinds of antimicrobial drugs. The highest drug resistance rate (100%) was observed for amoxicillin, colistin, doxycycline and oxytetracycline, and the drug resistance rate of cephalosporins was less than 10%. The drug resistance rate of the isolated strains of E. coli from feces was higher than those from soil, however, in both of feces and soil, most of the isolated strains of E. coli from (77.55% of isolates from feces, 79.49% of isolates from soil and total 78.41%) showed multi-drug resistance (resistant to 15−22 drugs). ConclusionOverall, the detection rate of AMR genes in feces and soil from hog farms was high, and the isolated strains of E. coli from both feces and soil showed multi-drug resistance. Also, the results showed that the AMR genes and drug resistance in the feces and soil from the hog farms are similar. These findings suggested that the AMR genes could be transmitted horizontally from the animal feces to surrounding environments of farms. Therefore, it is urgent need to strengthen the monitoring and guide the rational use of antimicrobial drugs in the hog industry of Zhanjiang, China.

ANTIMICROBIAL SUSCEPTIBILITY OF FOSFOMYCIN IN BACTERIAL ISOLATES FROM URINARY TRACT INFECTION : A STUDY FROM TERTIARY HEALTHCARE CENTER IN HIMACHAL PRADESH

BACKGROUND: Urinary tract infections (UTIs) are common with an annual global incidence of at least 250 million cases; and Escherichia coli is the most common pathogen. Many antibiotics once used to treat UTI are now ineffective due to the development of antimicrobial resistance. Fosfomycin, discovered in late 1960s, has rekindled clinical interests because of reported susceptibilities of current pathogens to the agent. This study was done with the objective to determine in vitro fosfomycin susceptibility of common uropathogens and determining the antimicrobial susceptibility pattern of these organisms. MATERIAL AND METHOD: Retrospective study was conducted in the Department of Microbiology for a duration of 2 years from October 2019 to September 2021. Urine samples were received and culture was done on MacConkey agar and AST was performed on signicant bacteriuria ≥105 CFU /ml with fosfomycin as per CLSI guidelines. Total of 9442 urine samples were collected duri RESULT: ng the duration of 2 years. Out of these 1657(17.5%) showed signicant growth. Male to female ratio was 1:1.9 in our study. Majority of the bacteria isolated were uropathogenic E.coli 960(57.9%) followed by Klebsiella spp 185(11.1%). Susceptibility to fosfomycin was seen majorly in all enterobacterales with 96.7% sensitivity to E.coli and 100% sensitivity towards Staphylococcus aureus and Enterococcus spp. In CONCLUSION: conclusion, our study indicates that fosfomycin is active in vitro against a considerable percentage of urinary isolates, which simultaneously exhibit high rates of antimicrobial drug resistance to the conventionally used antimicrobial agents.

Tumor-Derived Exosomal Non-Coding RNAs: The Emerging Mechanisms and Potential Clinical Applications in Breast Cancer.

Breast cancer (BC) is the most frequent malignancy and is ranking the leading cause of cancer-related death among women worldwide. At present, BC is still an intricate challenge confronted with high invasion, metastasis, drug resistance, and recurrence rate. Exosomes are membrane-enclosed extracellular vesicles with the lipid bilayer and recently have been confirmed as significant mediators of tumor cells to communicate with surrounding cells in the tumor microenvironment. As very important orchestrators, non-coding RNAs (ncRNAs) are aberrantly expressed and participate in regulating gene expression in multiple human cancers, while the most reported ncRNAs within exosomes in BC are microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Notably, ncRNAs containing exosomes are novel frontiers to shape malignant behaviors in recipient BC cells such as angiogenesis, immunoregulation, proliferation, and migration. It means that tumor-derived ncRNAs-containing exosomes are pluripotent carriers with intriguing and elaborate roles in BC progression via complex mechanisms. The ncRNAs in exosomes are usually excavated based on specific de-regulated expression verified by RNA sequencing, bioinformatic analyses, and PCR experiments. Here, this article will elucidate the recent existing research on the functions and mechanisms of tumor-derived exosomal miRNA, lncRNA, circRNA in BC, especially in BC cell proliferation, metastasis, immunoregulation, and drug resistance. Moreover, these tumor-derived exosomal ncRNAs that existed in blood samples are proved to be excellent diagnostic biomarkers for improving diagnosis and prognosis. The in-depth understanding of tumor-derived exosomal ncRNAs in BC will provide further insights for elucidating the BC oncogenesis and progress and exploring novel therapeutic strategies for combating BC.

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs.

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.

Detection of Enterotoxigenic Staphylococcus aureus in Patients with Gastroenteritis in Erbil/Iraq

Gastroenteritis is one of the words serious public health problem, and enterotoxigenic Staphylococcus aureusis one of the causes of gastroenteritis. The aim of this study was the molecular detection of enterotoxigenicgenes in Staphylococcus aureus, then detection the association of resistance patterns with the toxigenicityof strains. Microbiological analysis of fecal samples from patients with gastroenteritis was performed fordetection of S. aureus. The samples were cultured and identified by routine bacteriological methods andVITEK 2 system. Subsequently PCR amplification of enterotoxin genes (sea and seb) was carried outon all S. aureus strains. The results indicated that in total of 417 fecal samples taken from patients withacute gastroenteritis, 30 grew S. aureus (7.19%), and of 417 fecal samples 96 yielded bacterial pathogens(23.02%), S. aureus was the most common bacterial pathogen found in 30/96 cases (31.25%). In 30 isolatedof S. aureus, penicillin sensitive S. aureus were 2 (6.67%), methicillin sensitive S. aureus were 19 (63.33%),multidrug resistant S. aureus were 12 (40%), methicillin resistant S. aureus were 11 (36.67%), Extensivedrug resistance were 3 (10%), and none of them was pan drug resistant,and all isolates were sensitive tovancomycin. The PCR results showed that 7/30 (23.33%) of the S. aureus isolates possessed the sea gene,and 3/30 (10 %) had the seb gene. In total of 30 isolates Staphylococcal enterotoxin genes sea and seb weremore prevalent among methicillin resistant S. aureus were 6/11 (54.54%), 3/11 (27.27%) respectively, thenin multidrug resistant S. aureus which were 6/12 (50%), and 3/12 (25%) respectively, and in Extensivelydrug resistance S. aureus sea was1/3 (33.33%) and there is no seb genes, while in methicillin sensitive S.aureus sea was 1/19 (5.26%), and there is no seb genes, and there was no Staphylococcal enterotoxin genessea and seb in penicillin sensitive S. aureus. The result confirmed the involvement of enterotoxigenic S.aureus in the occurrence of gastroenteritis, and isolates with enterotoxin genes have a higher drug resistancerate.

In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.

Epidemiological investigation and analysis of etiological characteristics of infection on 3 067 hospitalized pediatric patients with burns

Objective: To investigate the epidemiological characteristics and etiological distribution of infection on 3 067 hospitalized pediatric patients with burns, and explore the prevention and treatment strategy of pediatric burns. Methods: A cross-sectional survey was conducted. An analysis was performed on the data of 3 067 hospitalized pediatric patients with burns who met the inclusion criteria and were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from January 2012 to December 2020, including gender, age, causative factors, locations and severities of burns, seasons of accidents, and the type, source of tissue or body fluid, and drug resistance of pathogenic bacteria. API bacterial identification batten and automatic microbial identification system were applied for pathogen identification. Drug sensitivities of top 3 consistent ratio pathogen identifed were tested with minimum inhibitory concentration and disk diffusion method. WHONET 5.6 software was applied to analyze the data. Results: There were 3 067 hospitalized pediatric patients with burns, including 1 768 boys and 1 299 girls. The majority of pediatric burn patients were >1 and ≤4 years, accounting for 72.9% (2 236/3 067), and the minority of pediatric burn patients were >8 and ≤12 years, accounting for 4.9% (150/3 067). Moderate burns and severe burns of pediatric burn patients accounted for the majority parts, and the proportions of the two were close. The top cause of pediatric burns was scald, accounting for 81.6% (2504/3 067). Extremities were the most common burn sites in that of entire 3 254. The most pediatric burns occurred in winter, accounting for 29.4% (903/3 067). A total of 1 018 strains of pathogenic bacteria were collected from pediatric burn patients, all of which were non-repeated isolates. The pathogens with top five consistent ratio were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, and Escherichia coli, among which Staphylococcus aureus ranked the first every year. The pathogens were mainly isolated from the wound exudate, accounting for 81.34% (828/1 018). Staphylococcus aureus from 2012 to 2020 showed no resistance to vancomycin, linezolid or teicoplanin while Staphylococcus aureus isolated in 2019 was 100% resistant to macrolides, penicillin, aminoglycosides, and quinolones. Pseudomonas aeruginosa was not resistant to polymyxin B. Acinetobacter baumannii showed a high rate of drug resistance to most antibiotics. Conclusions: Among the pediatric burn patients admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from 2012 to 2020, the majority are male children aged >1 and ≤4 years with moderate burns. Scalds are the leading cause; and extremities are the common burn sites; and the most pediatric burns occurre in winter. Staphylococcus aureus from wound exudate is the primary pathogen of burn wound infections in pediatric patients.

MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress.

Ovarian cancer is a common gynecologic cancer with a high rate of recurrence, drug resistance, and mortality, thereby necessitating novel molecular target therapies. Ovarian cancer as a solid tumor has constantly been challenged by endoplasmic reticulum stress (ERS). Currently, XBP1 as a therapeutic target in solid tumors plays a key role in adaptation to ERS. Single-stranded RNAs usually modulate posttranscriptional of the gene activity. miR-30c-2-3p has been demonstrated to inhibit the expression of XBP1. Here, we evaluated the effect of miR-30c-2-3p on controlling XBP1-CHOP-BIM and its apoptotic effects on ovarian cancer cell lines during ERS. The ER stress was assessed using Thioflavin T staining in OVCAR3 and SKOV3 cells. The expression of ER stress genes was measured by QRT-PCR. The protein levels of XBP1(s), BIP/GRP78, CHOP, and BIM were evaluated using Western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were evaluated using BrdU, MTT, Annexin V-FITC/PI staining, and caspase-12 and -3 activities assays. We found that miR-30c-2-3p significantly decreased the folding capacity of ER, leading to ERS intensification (P<0.05). Additionally, the Western blot analysis showed the modest up-regulation of CHOP and BIM with pro-apoptotic activity and down-regulation of the BIP protein. Furthermore, mimic miR-30c-2-3p transfection not only decreased cell proliferation but also induced cell death in ovarian cancer cells in response to the Tm-treatment. Our results indicated that the apoptotic pathway was induced possibly through activation of caspases -12 and -3 and elevation of the Bax/Bcl-2 ratio. Overall, the present paper adds new evidence to the possible treatment of miR-30c-2-3p via impeding the XBP1 transcription in ovarian cancer cells provoking apoptotic pathways by XBP1/CHOP/BIM mediators.

Evaluate the distribution of virulence genes and to investigate antibiotic resistance pattern among Shigella species isolated from children with shigellosis in Iran

The present study was performed to evaluate the frequency of virulence genes, including ipaH, ial, set1A, set1B, sen, virF, invE, sat, sigA, pic and sepA and assess antibiotic resistance pattern among Shigella isolates acquired from pediatric patients in Shiraz, Iran. Three hundred and nine isolates were isolated, from October 2018 to March 2019 from the feces of children with diarrhea; we used standard microbiological and serological tests for Shigella species. Overall, 73 (23.6%) isolates were positive for Shigella spp. The highest rate species of Shigella was S. sonnei (61.64%), followed by S. flexneri (37%) and S. boydii (1.36%). All the isolates were positive for ipaH gene, followed by ial (95.8%), virF (85%), InvE (75.3%), sen (28.7%), set1A (10.9%) and set1B (10.9%). The presence of sigA, sepA, sat and pic genes as SPATE genes was confirmed among 80.8%, 32.8%, 24.6% and 6.8% of Shigella isolates, respectively. Our investigations also indicated a high resistance percentage against trimethoprim-sulfamethoxazole and ampicillin in Shigella isolates. Our results displayed that S. sonnei was the predominant serogroup detected from children with shigellosis in Shiraz, Iran. As demonstrated in this study, most of the isolates showed a high prevalence rate of drug-resistance. S. flexneri carried a higher number of virulence genes. Our results indicated that certain symptoms were found to be related to the presence of specific different virulence factors. In addition, this study provided information that can increase our knowledge of the contribution of virulence genes in disease severity.

The bacteriological characteristics and drug resistance of the nasopharyngeal region in 311 cases of adenoid hypertrophy with secretory otitis media

Objective:To analyze the bacteriological distribution and drug resistance of nasopharynx in patients with adenoid hypertrophy complicated with secretory otitis media, and to clarify the distribution of pathogenic bacteria, so as to provide guidance and basis for antibiotic use in clinical treatment. Methods:A retrospective analysis was performed on 311 patients with adenoid hypertrophy and secretory otitis media who underwent surgical treatment in the department of otolaryngology head and neck surgery, Affiliated Hospital of Qingdao University from February 2013 to January 2020. They were divided into 3 groups by age: Group A（0-5 years old）, Group B（6-10 years old）, and Group C（11-16 years old）. The secretions from deep adenoid near the eustachian tube of the affected ear were collected during the surgery for bacterial culture and drug resistance analysis. Results:One hundred and forty-two strains of pathogenic bacteria were isolated and cultured, with a detection rate of 45.66%. Staphylococcus aureus （63 strains）, streptococcus pneumoniae （15 strains） ,streptococcus pyogenes （13 strains） and moraxella cachinella（28 strains）was the main strain.Staphylococcus aureus had high drug resistance rate to penicillin, erythromycin and clindamycin.Streptococcus pneumoniae and Streptococcus pyogenic had high resistance rates to erythromycin,clindamycin and tetracycline. The resistance rate of Moraxella catarrhalis to ampicillin and co-trimoxazole was higher. Conclusion:The main pathogens detected in patients with adenoid hypertrophy complicated with secretory otitis media are staphylococcus aureus, streptococcus pneumoniae, streptococcus pyogenes and moraxella catarrhalis. Drug resistance of different pathogens is quite different. So it is recommended to carry out extensive bacteriological detection, and select antibiotics according to the principle of rational drug use and the results of drug resistance test, so as to achieve good therapeutic effect.

Prevalence, Clinical Characteristics and Changes of Antibiotic Resistance in Children with Nontyphoidal Salmonella Infections from 2009-2018 in Chongqing, China.

PurposeNontyphoidal Salmonella (NTS) is a leading bacterial cause for acute gastroenteritis in children. With the increasing use of antibiotics worldwide, antibiotic resistance has become a global problem. However, data on NTS infections and changes in antibiotic resistance among children remain limited in China. We aimed to characterize the prevalence, clinical feature, serotype and the changes of antibiotic resistance of NTS in children in Chongqing.Methods501 hospitalized children with NTS infections (confirmed by positive NTS culture) in Children’s Hospital of Chongqing Medical University from January 2009 to December 2018 were included. The clinical data and drug sensitivity test results were retrospectively reviewed and analyzed. Antibiotic resistance in NTS infections was compared between 2009–2013 and 2014–2018.ResultsA total of 501 isolates were detected. Most NTS infections occurred in children under three years old, which mainly occurred between July and October. The numbers of patients with diarrhea, fever, and vomiting were 472 (94.2%), 422 (84.2%) and 146 (29.1%), respectively. Serogroup B (67.5%) was the predominant serogroup isolates. And Salmonella Typhimurium was the most common serotype (79.2%). The study compared the drug resistance of NTS from 2009 to 2013 with that from 2014 to 2018. We found the drug resistance rates of NTS to cefazolin, cefotaxime, ciprofloxacin, levofloxacin and imipenem showed an upward trend. The drug resistance rates of NTS to chloramphenicol, ampicillin, ceftriaxone, cefepime and compound sulfamethoxazole decreased slightly, but still showed high drug resistance rates. And drug resistance rates of NTS to piperacillin/tazobactam and ceftazidime decreased significantly in the last ten years. Multi-drug resistance (MDR) isolates, were detected among 69 cases (13.7%) of 501 children with NTS infections.ConclusionThe overall antibiotic resistance rates remained at a high level in Chongqing. Continuous surveillance of antibiotic resistance in NTS and control measures such as avoiding unnecessary antibiotic therapy in general NTS gastroenteritis are important. For severe or invasive infections caused by NTS infection in Southwest China, the use of ceftazidime is recommended until antibiotic sensitivity test results are available. And the choice of antibiotics should be based on the curative effect and the antibiotics sensitivity results.

Microtubule-Targeted Self-Assembly Triggers Prometaphase-Metaphase Oscillations Suppressing Tumor Growth.

Microtubules are highly strategic targets of cancer therapies. Small molecule antimitotic agents are so far the best chemotherapeutic medication in cancer treatment. However, the high rate of neuropathy and drug resistance limit their clinical usage. Inspired by the multicomponent-targeting feature of molecular self-assembly (MSA) overcoming drug resistance, we synthesized peptide-based rotor molecules that self-assemble in response to the surrounding environment to target the microtubule array. The MSAs self-adjust morphologically in response to the pH change and viscosity variations during Golgi-endosome trafficking, escape trafficking cargos, and eventually bind to the microtubule array physically in a nonspecific manner. Such unrefined nano-bio interactions suppress regional tubulin polymerization triggering atypical prometaphase--metaphase oscillations to inhibit various cancer cells proliferating without inducing obvious neurotoxicity. The MSA also exerts potent antiproliferative effects in the subcutaneous cervix cancer xenograft tumor model equivalent to Cisplatin, better than the classic antimitotic drug Taxol.

Keratin nanoparticles and photodynamic therapy enhance the anticancer stem cells activity of salinomycin

The high rates of aggressiveness, drug resistance and relapse of breast cancer (BC) are mainly attributed to the inability of conventional therapies to equally eradicate bulk differentiated cells and cancer stem cells (CSCs). To improve the effectiveness of BC treatments, we report the in-water synthesis of novel keratin-based nanoformulations, loaded with the CSC-specific drug salinomycin (SAL), the photosensitizer chlorin e6 (Ce6) and vitamin E acetate (SAL/Ce6@kVEs), which combine the capability of releasing SAL with the production of singlet oxygen upon light irradiation. In vitro experiments on BC cell lines and CSC-enriched mammospheres exposed to single or combined therapies showed that SAL/Ce6@kVEs determine synergistic cell killing, limit their self-renewal capacity and decrease the stemness potential by eradication of CSCs. In vivo experiments on zebrafish embryos confirmed the capacity of SAL nanoformulations to interfere with the Wnt/β-catenin signaling pathway, which is dysregulated in BC, thus identifying a target for further translation into pre-clinical models.

Monitoring and Analysis of Drug Resistance of Yersinia in Fresh Meat

Objective To monitor the drug resistance status of yersinia isolates from fresh meat, grasp the drug resistance spectrum and trend of Yersinia isolates in Our province, and provide important reference data for guiding the rational application of antibiotics in human clinical practice and controlling the spread of drug resistant strains. Methods A total of 600 pieces of fresh pork, beef and chicken were collected from several farmers' markets and supermarkets in Changchun every month for 15 months from August 18th to October 19th. 80 strains of Yersinia strains were detected, and MIC concentrations of drug resistance were detected by microbroth dilution with 15 antibiotic sensitive plates. Results 80 strains of Yersinia strains were counted. The total drug resistance rate of Yersinia pestis was 98.8%, and cefazolin (CFZ) had the highest drug resistance rate of 92.5.% (74/80). Erythromycin (ERY) was followed by 58.8% (47/80). Ampicillin (AMP) 57.5% (46/80); Naproxil acid (NAL) and cefoxitin (CFX) were 28.8 (23/80) and were somewhat resistant to other antibiotics. But all strains were sensitive to imipenem (IMP) and gentamicin (GEN). There were 28 strains with multiple drug resistance, accounting for 35.4% (28/79). Conclusion There are multiple antibiotic resistance in Yersinia strains in this monitoring, and the multiple drug resistance is serious and the resistance spectrum is diverse. In order to ensure food safety and human health, great attention should be paid to and enhanced drug resistance monitoring of Yersinia.

1439. High Rates of Drug Resistance in Escherichia coli from a Pilot Antimicrobial Resistance Surveillance System in Cambodia

BackgroundAntimicrobial resistance (AMR) is a major and growing global public health problem. The Cambodia Ministry of Health established a pilot laboratory-based AMR surveillance system for blood specimens in 2017. The objective of this study is to characterize AMR among pathogenic isolates from blood samples.MethodsA retrospective analysis was performed using one year of data from a pilot AMR Surveillance system in Cambodia. Four blood culture isolate pathogens were included: Escherichia coli, Klebsiella pneumoniae, Salmonella Typhi /Salmonella Paratyphi A and Staphylococcus aureus. Blood culture isolates that were referred from eleven sentinel sites were analyzed at the National Public Health Laboratory for identification. Antibiotic susceptibility testing (AST) was done using disk diffusion, minimum inhibitory concentration method following Clinical Laboratory Standard Institute (CLSI) guidelines.ResultsAmong 214 pathogenic isolates from blood samples, E.coli was the most common (56.1%), followed by Salmonella Typhi/Salmonella Paratyphi A (18.7%), Staphylococcus aureus (13.5%), and Klebsiella pneumoniae (11.7%). Methicillin Resistance Staphylococcus aureus (MRSA) was detected in half of the isolates. E.coli was resistant to ampicillin (94.4%), trimethoprim-sulfamethoxazole (84.5%), and ceftriaxone (79.2%). Salmonella Typhi was resistant to ampicillin (73.3%) and trimethoprim-sulfamethoxazole (60.0%) and Salmonella Paratyphi A were resistant to fluoroquinolones (91.7%). For last resort antibiotics, E.coli was resistant to carbapenem groups (3.2% for imipenem, 4.9% for meropenem, and 5.0% for ertapenem). Klebsiella pneumoniae was not resistant to any groups.Conclusion E.coli was found at high rates in blood samples and was resistant to common antibiotics used in Cambodia. These pilot data show the importance of establishing a national AMR surveillance system in Cambodia to monitor AMR trends following GLASS guidelines.Disclosures All Authors: No reported disclosures

High rate of virological failure and HIV drug resistance in semi-rural Gabon and implications for dolutegravir-based regimen efficacy.

The projected UNAIDS goal of ending AIDS by 2030 requires significant global efforts to improve current and future ART strategies. In this study, we assessed viral load (VL) suppression and acquired drug resistance, as well as future efficacy of dolutegravir-based combinations for patients living in semi-rural regions of Gabon. Eligible study participants were adults receiving ART and recruited between 2018 and 2019 in Franceville, Gabon. VL testing was conducted to assess VL suppression and HIV drug resistance (HIVDR) testing was performed to identify resistance mutations and assess their impact on ongoing and future ART regimens. We recruited 219 participants overall. The median time on ART was 27 months and 216/219 participants were on first-line ART. VL suppression (VL < 1000 copies/mL) was 57.1% (95% CI 50.5-63.8) overall; 59.4% (51.4-67.5) and 52.2% (40.3-64.2) for women and men, respectively. The overall prevalence of HIVDR was 21.9% among the study population and 67.2% among those who failed ART. Presence of both NRTI and NNRTI mutations was found in 84.6% of sequences with drug resistance mutations, and full activity of a dolutegravir-based first-line regimen including tenofovir disoproxil fumarate/lamivudine/dolutegravir was expected only for 5/39 patients with a resistant virus. This study shows a very low rate of VL suppression in a semi-rural context in Africa. Moreover, the high burden of HIVDR has affected both current and newly recommended ART strategies. Better management of ART in resource-limited settings is still a challenging ambition.

Progress in the treatment of intra-abdominal anaerobic infection

Most abdominal infections are mixed infections caused by aerobic and anaerobic bacteria. Anaerobic infections are characterized by rancid secretions or abscess formation. Early implementation of source control is the key in the treatment of abdominal anaerobic infections. Damage control should be followed as one of the principles of surgical treatment. As the in vitro isolation and culture of anaerobic bacteria as well as its drug sensitivity test are time-consuming and sometimes inaccurate, the treatment of anaerobic bacteria infection is mostly empirical. Anti-infective therapy should be employed once anaerobic bacteria infection is confirmed. Ertapenem, Mosifloxacin, and Cefoperazone-sulbactam can be used for first-line monotherapy, while combination therapy can use second- or third-generation Cephalosporin, Quinolones plus Nitroimidazoles. Nutritional support and anti-shock treatment should not be neglected when implementing surgical control of infection source and antimicrobial therapy. Considering the increasing drug resistance of anaerobic bacteria, and the higher drug resistance rate in China as compared to western countries, the choice of antibiotics should be made rationally and based on epidemiological characteristics of anaerobic bacteria in different regions.

Electrochemical Characterization of Carboplatin at Unmodified Platinum Electrodes and Its Application to Drug Uptake Studies in Ovarian Cancer Cells

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological cancers and affects patients on all continents. Primary treatments involve surgery and the administration of chemotherapeutics, such as carboplatin, which is listed by the World Health Organization as an essential medication for the treatment of human cancers. Unfortunately, due to high rates of drug resistance of EOC towards carboplatin, cancer relapse rates are devastating, and the mechanisms of chemoresistance to carboplatin have not been adequately identified. Consequently, there is a dire need for innovative strategies that are able to detect carboplatin resistance in cancer and to further our understanding of the fundamental nature of chemoresistance towards carboplatin.The presented work describes the thorough electrochemical characterization of carboplatin. We quantify the uptake of carboplatin by ovarian cancer cells by electrochemistry to better understand mechanisms of carboplatin chemoresistance. Results emerging from this research will be important for future medical research developing novel agents to combat chemoresistance.

Bacterial Isolates from CSF Samples and Their Antimicrobial Resistance Patterns Among Children Under Five Suspected to Have Meningitis in Dilla University Referral Hospital.

IntroductionBacterial meningitis is a medical emergency that requires immediate medical attention. It causes an estimated 288,649 deaths worldwide per year, of which 94,883 death occur among children under 5 years old. Up to 24% of survivors suffer from long-term sequelae such as epilepsy, mental disability, or sensorineural deafness, especially when the disease is contracted during early childhood.ObjectiveThis study aimed to assess bacterial isolates of cerebrospinal fluid (CSF) samples and their antimicrobial resistance patterns among children under 5 years old in Dilla University Referral Hospital.Material and MethodsHospital-based cross-sectional study design was used to collect clinical data and CSF sample from children under 5 years old who were suspected for meningitis. Sediment of CSF samples was inoculated to blood agar plate, chocolate agar plate, and MacConkey agar for bacterial isolation and identification. Chemical analysis and cytological analysis were also conducted based on standard operating procedures.ResultsFrom a total of 287 CSF samples cultured, causative bacteria were detected in 38 (13.2%). From culture positive cases, the most frequent isolate was Streptococcus pneumoniae (13 (34.2%)) followed by Staphylococcus aureas (7 (18.4%)), Neisseria meningitidis (6 (16%)) and Escherichia coli (6 (16%)). Haemophilus influenzae type b was isolated in 4 (10.5%) children with meningitis. Another cause of meningitis was Streptococcus agalactiae which accounted for 10.5%. Cryptococcus neoformans was detected in 4 (1.9%) cases of meningitis. Of all bacterial isolates, about 42.1% (16/38) were multi-drug resistant. About 38.5% of S. pneumoniae had multi-drug resistance, while about 33.3% of N. meningitidis, 50% of H. influenzae, 57.1% of S. aureas and 40% of E. coli showed multi-drug resistance.ConclusionA high prevalence of bacterial meningitis and high rate of drug resistance were observed. Streptococcus pneumoniae was the leading cause of bacterial meningitis among children under 5 years old.

DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment.

Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.