Results Of Drug Sensitivity Test Research Articles

Analysis of Differences in Neonatal Sepsis Caused by Streptococcus Agalactiae and Escherichia Coli.

Streptococcus agalactiae (GBS) and Escherichia coli (E. coli) are the main pathogenic bacteria in neonatal sepsis. Therefore, the clinical characteristics, nonspecific indicators, and drug susceptibilities of these two bacteria were studied. In total, 81 and 80 children with sepsis caused by GBS and E. coli infection, respectively, admitted to the neonatal department of our hospital between May 2012 and July 2023, were selected, and the clinical characteris-tics of the two groups were analyzed. Nonspecific indicators and drug sensitivity test results were analyzed retrospectively. Birth weight, tachypnea, groan, tachycardia or bradycardia, and the incidence of complications, such as pneumonia, respiratory failure, and purulent meningitis, were higher in the GBS group than in the E. coli group. The children were born prematurely, and the mother had a premature rupture of membranes. The incidence of jaundice, abdominal distension, atypical clinical manifestations, and complications of necrotizing enterocolitis was lower than of the E. coli group, and the differences were statistically significant (p < 0.05). The WBC, NE#, NE#/LY#, hs-CRP, and PCT of the GBS group were higher than those of the E. coli group, whereas the MPV, D-D, and FDP levels were lower than those in the E. coli group. The differences were all statistically significant (p < 0.05). The 81-bead GBS had high resistance rates against tetracycline (95%), erythromycin (48.8%), and clindamycin (40%), and no strains resistant to vancomycin, linezolid, penicillin, or ampicillin appeared, whereas 80 strains of E. coli were more resistant to penicillin and third-generation cephalosporins, with the higher resistance rates to ampicillin (68.30%), trimethoprim/sulfamethoxazole (53.6%), and ciprofloxacin (42.90%). Resistance rates to carbapenems and aminoglycosides were extremely low. Both GBS and E. coli neonatal sepsis have specific clinical characteristics, especially in terms of clinical manifestations, complications, non-specific indicators, and drug resistance. Early identification is important for clinical diagnosis and treatment.

Treatment modalities for advanced solid pseudopapillary tumor of the pancreas.

e16327 Background: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. However, a minority of SPT patients present aggressive behavior and develop recurrent or metastatic diseases. The treatment strategies of advanced SPTs remain unclear. Our study aimed to explore the treatment modalities of aggressive SPTs and the role of endocrine therapy. Methods: The data on clinicopathologic characteristics and treatment of advanced SPT patients from Sun Yat-Sen University Cancer Center and Shen Zhen People's Hospital were collected. The treatment modalities were explored by co-analyzing our local cohort and published literatures. Single sample gene set enrichment analysis (ssGSEA) was used to explore the functional enrichment pathway (GSE43795). Fresh surgical specimens from 10 SPT patients were collected for endocrine drugs sensitive test in vitro by performing tumor histoculture end-point staining computer image analysis (TECIA). Results: A total of 77 advanced SPT patients including 14 cases in our local cohort and 63 cases from published literatures were enrolled. 60 patients received local treatment including cytoreductive surgery, interventional therapy or radiation therapy. 55 patients who had undergone cytoreductive surgery have better outcome compared with others (P = 0.046, HR = 4.12). 31 patients received systemic chemotherapy and 6 patients received targeted therapy. There were 2 patients achieved partial response after chemotherapy. In our local cohort, 5 patients received endocrine therapy with tamoxifen plus megestrol. One patient achieved partial response with duration of response (DOR) of 89 months. 4 patients showed stable disease. ssGSEA for GSE43795 showed that Wnt signaling pathway and its inhibitory pathway-progesterone receptor signaling pathway were simultaneously enriched in SPTs. The results of endocrine drug sensitive test in vitro by TECIA showed response rate of 50% (5/10) in megestrol group, 40% (4/10) in tamoxifen group, and 30% (3/10) in testosterone propionate group. Conclusions: Advanced SPTs did not appear chemosensitive. Cytoreductive surgery may improve survival. Simultaneously enriching Wnt and progesterone receptor signaling pathway may partially explain the low aggressive ability of SPT and their unbalance may lead to the aggressive behavior of SPT. Endocrine therapy with tamoxifen plus megestrol, by enhancing the progesterone signaling pathway, seems to be a promising regimen for advanced SPTs, which is worth to be noted and further studied.

Performance of the BD MAX MDR-TB assay in a clinical setting and its impact on the clinical course of patients with pulmonary tuberculosis: a retrospective before-after study.

Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

Abstract 6895: Application of MiniPDX® in clinical indication identification and anti-tumor drug development

Abstract MiniPDX® (Mini-patient-derived xenograft) is a novel, rapid (7~10days), and accurate method for drug sensitivity testing in vivo. It was referred as in vivo version of organoid assy. The testing material can be fresh patient tumor samples or tissues from established PDX models. We have systematically evaluated and compared the response rates of MiniPDX® assays and PDX assays pairwise in 26 PDX models across 3 types of cancers to 12 clinically relevant regimens for chemical and targeting drugs. The results demonstrate a high correlation between drug responses of the two assays, with sensitivity of 80% and specificity of 93%. More and more studies showed that MiniPDX® drug sensitivity test results were consistent with clinical responses in most patients, which indicated MiniPDX® models have great potential in guiding personalized medicine. LIDE has successfully conducted over 3,000 MiniPDX® tests for clinical precision medicine, covering more than 50 indications. The application of MiniPDX® extends beyond therapeutic selection, facilitating the prioritization of approved pharmacological interventions and informing the discovery pipeline for novel agents. Importantly, the MiniPDX® Mouse Trial using fresh tumor samples generated from the clinic is beneficial for determination of potential clinical indications. Only thousands of fresh cells leftover from MiniPDX® preparation are sufficient to get genomic and transcription data by OncoVee ® K-cell technology. The combination of MiniPDX® assay and omics data would be very useful for determination of potential biomarkers to distinguish responders and non-responders in population with certain indication(s) and leveraged for patient stratification and selection criteria in clinical trial design. In addition, we have developed a new version of MiniPDX® assay for immunotherapy (IO-FIVE, Immuno-Oncology Fast In Vivo Efficacy test) by using fresh patient cancer cells with autologous immune cells to maximally mimic human tumor microenvironment before seeding in immune-deficient mice. This assay allows for the tracking of cellular viability and phenotype pre- and post-treatment, thus providing a robust metric of in vivo immunotherapeutic efficacy within a fortnight. Citation Format: Bin Xie, Hongkui Chen, Shizhu Zhao, Le Li, Song Xi, Yu Di, Yang Liu, Xinlei Chen, Xiaorong Gu, Zhenle Bi, Kaimeng Hu, Loc Van, Josh Caggiula, Candice Tang, Danyi Wen. Application of MiniPDX® in clinical indication identification and anti-tumor drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6895.

Abstract 6890: 2D Tumor cell culture based Ex vivo drug sensitivity screening platform for South African patient samples (leukemia, multiple myeloma, ovarian and uterine cancer) demonstrate potential for targeted cancer therapies

Abstract Resistance to standard chemotherapy is a major challenge with Leukemia (Leuk), Multiple Myeloma (MM), Ovarian Cancer (OvCa) and Uterine Cancer (UtCa) treatments, which ultimately leads to relapse. Our study objective is to establish a robust drug sensitivity screening platform that can identify drugs and drug combinations that are effective in precision medicine for individual South African patient samples (Leuk, MM, OvCa and UtCa). Given that resistance to chemotherapy treatment accounts for high mortality and morbidity, we focus on the hypothesis that several drug combinations will be required for patients to achieve better response for drug regimens beyond first line of chemotherapy. Therefore, our defined objectives were to 1) establish 2D ex vivo tumour cell culturing using South African patient samples; 2) develop a drug sensitivity screening platform through which selected single and drug combinations will be identified; 3) to provide South African cancer (OvCa, Ut Ca, CLL, MM) patients with individualized treatment options with effective drug combinations for targeted therapies. Through collaboration with, Steve Biko Hospital Pretoria, Chris Hani Baragwanath Hospital and Wits Donald Gordon Medical Centre, Johannesburg, South Africa, we performed 100 patient sample collections including Acute myeloid leukaemia (AML) (n=7), Chronic lymphocytic leukaemia (CLL) (n=4), Chronic myeloid leukaemia (CML) (n= 30), MM (n=40), OvCa (n=10), UtCa (n=4) and healthy donors (n=5). Culture setting for all patient-derived tumor cells were established through the 2D cancer cell culturing in 96 well plates. This was followed by functional drug sensitivity testing using a panel of FDA approved chemotherapy drugs. The average turnaround time from biopsy to drug sensitivity test results is currently at 14 days. We have completed ex vivo drug sensitivity screening to perform analysis on patient samples (n=80) using 30 drugs with a concentration range of 1-1000 nm. Our preliminary drug sensitivity screening studies show good response to proteosome inhibitors, melphalan, doxorubicin and kinase inhibitors. We have established a wound healing assay for OvCa and UtCa samples and demonstrated sustained cell growth for the period of 2 weeks with tumor cells growing faster than twin normal tissue. We are now at stage of performing drug sensitivity screening for OvCa and UtCa patient samples for both twin normal and tumor tissues. We have established a drug sensitivity screening platform and wound healing assay with primary patient derived cells that utilizes South African Patient samples to select effective drugs for monotherapy and also drug combinations. Citation Format: Mutsa Takundwa, Vanelle Kenmogne, Thudzelani Malise, Bernice Monchusi, Phumuzile Dube, Ekene Nweke, June Fabian, Heather Maher, Justin du Toit, Vinitha Philip-Cherian, Pascaline Fru, Adekunle Sajo, Arnold (Arrie) Mouton, Matthys C. van Aardt, Cathy Visser, Greta Dreyer, Deepak Govindaraj. 2D Tumor cell culture based Ex vivo drug sensitivity screening platform for South African patient samples (leukemia, multiple myeloma, ovarian and uterine cancer) demonstrate potential for targeted cancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6890.

Distribution and antimicrobial resistance patterns of urinary pathogens in preoperative midstream urine cultures from Chinese patients with urinary calculi: a meta-analysis.

This study comprehensively evaluates the distribution patterns and antimicrobial resistance profiles of urinary pathogens in Preoperative midstream urine cultures collected from patients with urinary calculi in China over the last two decades. A cross-sectional analysis of 41 studies was conducted. A systematic search across various databases, including Wanfang Data, CNKI, SinoMed, Embase, PubMed, and Web of Science, was carried out, covering the time period from 2002 to 2022. Using R 4.2.1 software, a meta-analysis was performed to assess heterogeneity using Cochran's Q test and the I2 statistic. In the analysis of preoperative midstream urine cultures from Chinese patients with urinary calculi, gram-negative bacteria dominated at 69%, with Escherichia coli (43%), Klebsiella pneumoniae (8%), Proteus mirabilis (6%), Pseudomonas aeruginosa (5%), Acinetobacter baumannii (3%), and Enterobacter cloacae (4%) being prominent. Gram-positive organisms included Enterococcus faecalis (9%), Enterococcus faecium (5%), and Staphylococcus aureus (4%). Over time, proportions of Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus decreased, while Klebsiella pneumoniae and Pseudomonas aeruginosa increased. Notably, Escherichia coli proportion reduced from 37 to 33% within the last two decades. Antimicrobial resistance analysis indicated declining resistance in E. coli (e.g., co-trimoxazole from 73 to 55%, gentamicin from 64 to 40%), but rising resistance in piperacillin and cefotaxime (34-60%). Enterococcus faecalis exhibited increasing resistance to ampicillin (5-69%), gentamicin (59-94%), and tetracycline (77-89%) over time, while resistance to levofloxacin and ciprofloxacin notably decreased (72-16% and 49-8%, respectively). Over the past two decades, the proportion of gram-negative bacteria was declined, while the proportion of gram-positive bacteria increased. Escherichia coli remained the most common pathogen in the urine culture of patients with urinary calculi in China and the resistance of Escherichia coli to commonly used antibiotics increased. Clinicians should select appropriate antibiotics according to the results of urine culture and drug sensitivity test to reduce the occurrence of antibiotic resistance.

Establishment and characterization of DPC-X4: a novel mixed-type ampullary cancer cell line.

Mixed-type ampullary cancer is a distinct subtype of ampullary cancer that manifests a merging of the biological characteristics of both intestinal and pancreaticobiliary subtypes. The absence of established cell lines specific to this subtype has resulted in a concomitant scarcity of research on its tumorigenic mechanisms and the development of novel therapeutic modalities. The present study achieved the successful establishment of a novel mixed-type ampullary cancer cell line, designated DPC-X4 through primary culture techniques. Subsequent analyses pertaining to phenotypic characteristics, molecular profiling, biomarker identification, and histological features validated the DPC-X4 cell line as a potent model for delineating the pathogenesis of mixed-type ampullary cancer and facilitating the development of new pharmacological agents. This newly established cell line was subjected to continuous cultivation for 1year, with stable passaging for over 50 generations. Notably, the DPC-X4 cell line manifested typical morphological features associated with epithelial tumors. Furthermore, the population doubling time for the DPC-X4 cell line was determined at 70h. Short tandem repeat (STR) analysis confirmed that the DPC-X4 cell line exhibited a high genetic concordance with the primary tumor from the patient. Karyotypic profiling indicated an abnormal sub-triploid karyotype, with representative karyotypes of 57, XXY inv (9), 14p + , 15p + , der (17), + mar. The DPC-X4 cell line demonstrated a high capacity for efficient organoid formation under suspension culture conditions. In addition, the subcutaneous inoculation of DPC-X4 cells into NXG mice led to the formation of xenografted tumors. The results of drug sensitivity testing indicated that DPC-X4 cells were sensitive to paclitaxel and resistant to oxaliplatin, 5-fluorouracil, and gemcitabine. Immunohistochemistry revealed positive expression of CK7, CK19, and CK20 in DPC-X4 cells, while CDX2 demonstrated negative expression. In addition, positive expression of E-cadherin and vimentin was identified in DPC-X4 cells, with a proliferation index indicated by Ki-67 at 70%. The findings of our study establish DPC-X4 as a novel mixed-type ampullary cancer cell line, which can serve as a potential experimental model for exploring the pathogenesis of ampullary cancer and the development of therapeutic drugs.

Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil.

The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries. We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results. Binomial logistic regression models were employed to evaluate whether Hr was associated with an unfavorable ATT outcome: death or failure, compared to cure or treatment completion. Among 60 804 TB cases reported in SINAN, 21 197 (34.9%) were included in the study. In this database, the frequency of unfavorable outcomes was significantly higher in those with Hr in contrast to isoniazid-sensitive persons with pulmonary TB (9.1% vs 3.05%; P < .001). Using a binomial logistic regression model, Hr was independently associated with unfavorable outcomes (odds ratio, 3.34 [95% confidence interval, 2.06-5.40]; P < .001). Hr detected prior to ATT was predictive of unfavorable outcomes at the national level in Brazil. Our data reinforce the need for high-TB-burden countries to prioritize DST to detect Hr. Effective treatment regimens for Hr-TB are needed to improve outcomes.

Drug-resistant Tuberculosis in Pediatric

Introduction: Drug-resistant tuberculosis (DR TB) is a condition where Mycobacterium tuberculosis is resistant to isoniazid, rifampicin or resistant to isoniazid and rifampin as well as other first-line anti-tuberculosis drugs (OAT). Tuberculosis (TB) is a contagious infectious disease, caused by Mycobacterium tuberculosis germs where the source of transmission is through droplets containing TB germs. Case Report: A 10 years 7 months girl, came to the MDR Polyclinic at the Haji Adam Malik Medan Central General Hospital (RSUP HAM Medan) on March 21 2023 bringing the results of the TB Molecular Rapid Test (TCM-TB) examination from the Teladan Barat Health Center with Rifampicin results were resistant and on March 24 2023 the patient was hospitalized. Currently, the patient is complaining of a cough that has been experiencing for ± 3 weeks. Cough with the impression of a dry cough and is continuous so that it interferes with daily activities. The cough does not improve even though the patient has taken cough medicine. There is no fever, there is also no history of previous fever. According to the anamnesis from the patient's parents, there has been a weight loss in the last 2 months, around ± 4 kg. There is no family history of long-term cough, but according to parents, there is a neighbor of the patient who suffers from pulmonary TB and is undergoing treatment. Discussion: After the diagnosis of drug-resistant tuberculosis is confirmed, an evaluation is carried out whether the patient meets the criteria for drug-resistant TB treatment guided by short-term or long-term oral drug-resistant tuberculosis. Patients who meet the evaluation criteria for treatment can immediately be given short-term oral drug-resistant tuberculosis therapy. If the patient does not meet the criteria for short-term treatment, long-term drug-resistant tuberculosis treatment is given. Routine evaluations are carried out during treatment and when the results of drug sensitivity tests are available, treatment is adjusted according to the examination results. Conclusion: A case of drug-resistant tuberculosis in a girl aged 10 years 7 months has been reported which was diagnosed based on anamnesis, physical examination, and supporting examinations, there was also a history of close contact with TB sufferers, and the results of TCM examination of sputum fluid showed rifampicin resistant MTB growth. Patients are treated as drug-resistant TB cases with a short-term regimen with regular monitoring of treatment response and side effects.

Colorectal cancer tissue-originated spheroids reveal tumor intrinsic signaling pathways and mimic patient clinical chemotherapeutic response as a rapid and valid model

Locally advanced colorectal cancer requires preoperative chemotherapy to reduce local recurrence and metastasis rates, but it remains difficult to predict the tumor will be sensitive to which treatments. The patient-derived organoids (PDOs) are considered an effective platform for predicting tumor drug responses in precision oncology. However, it has the limitation of being time-consuming in practical applications, especially in neoadjuvant treatment. Here we used cancer tissue-originated spheroids (CTOS) method to establish organoids from a heterogeneous population of colorectal cancer specimens, and evaluated the capacity of CTOS to predict clinical drug responses. By analyzing the relationship of the activities of drug-treated CTOS, drug targets and target-related pathways, tumor intrinsic effective-target-related pathways can be identified. These pathways were highly matched to the abnormal pathways indicated by whole-exome sequencing. Based on this, we used half effective concentration gradients to classify CTOS as sensitive or resistant to chemotherapy regimens within a week, for predicting neoadjuvant treatment outcomes for colorectal cancer patients. The drug sensitivity test results are highly matched to the clinical responses to treatment in individual patients. Thus, our data suggested that CTOS models can be effectively screened ex vivo to identify pathways sensitive to chemotherapies. These data also supported organoid research for personalized clinical medication guidance immediately after diagnosis in patients with advanced colorectal cancer.

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India.

Whole-genome sequencing has created a revolution in tuberculosis management by providing a comprehensive picture of the various genetic polymorphisms with unprecedented accuracy. Studies mapping genomic heterogeneity in clinical isolates of Mycobacterium tuberculosis using a whole-genome sequencing approach from high tuberculosis burden countries are underrepresented. We report whole-genome sequencing results of 242 clinical isolates of culture-confirmed M. tuberculosis isolates from tuberculosis patients referred to a tertiary care hospital in Southern India. Phylogenetic analysis revealed that the isolates in our study belonged to five different lineages, with Indo-Oceanic (lineage 1, n = 122) and East-African Indian (lineage 3, n = 80) being the most prevalent. We report several mutations in genes conferring resistance to first and second line antitubercular drugs including the genes rpoB, katG, ahpC, inhA, fabG1, embB, pncA, rpsL, rrs, and gyrA. The majority of these mutations were identified in relatively high proportions in lineage 1. Our study highlights the utility of whole-genome sequencing as a potential supplemental tool to the existing genotypic and phenotypic methods, in providing expedited comprehensive surveillance of mutations that may be associated with antitubercular drug resistance as well as lineage characterization of M. tuberculosis isolates. Further larger-scale whole-genome datasets with linked minimum inhibition concentration testing are imperative for resolving the discrepancies between whole-genome sequencing and phenotypic drug sensitivity testing results and quantifying the level of the resistance associated with the mutations for optimization of antitubercular drug and precise dose selection in clinics. IMPORTANCE Studies mapping genetic heterogeneity of clinical isolates of M. tuberculosis for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 M. tuberculosis isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of M. tuberculosis in Southern India. We report several genetic variations in M. tuberculosis that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize M. tuberculosis genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.

Retracted: Correlation between Sputum Bacterial Culture Positive Rate and Drug Sensitivity Test Results and Disease Severity in Inpatients and Its Clinical Significance: A Systematic Review and Meta-Analysis.

[This retracts the article DOI: 10.1155/2022/5102100.].

Evaluation of pathogen distribution and antimicrobial resistance in breast plastic surgery infection.

The demand for mammaplasty has increased in recent years, and infection remains one of the common and serious post-operative complications. In this study, we analyzed the pathogen distribution and antibiotic susceptibility of breast plastic surgery infections, and compared the differences in pathogenic species between surgical procedures. The number of each species was counted in the microbial samples of breast plastic surgery infections in Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2021. The in vitro antibiotic sensitivity testing data were analyzed using WHONET 5.6 software. The surgical techniques, the period of infection, and other details were gathered in accordance with the clinical data. There were a total of 42 cases included, and 43 different types of pathogenic bacteria, mostly gram-positive bacteria, were found. CoNS (13/43) and Staphylococcus aureus (22/43) made up the majority. The most prevalent of the five Gram-negative bacteria was Pseudomonas aeruginosa. Results of drug sensitivity tests indicate that S. aureus is highly sensitive to vancomycin, cotrimoxazole, and linezolid, whereas CoNS is highly sensitive to vancomycin, linezolid, and chloramphenicol. Both of these bacteria show high resistance to erythromycin and penicillin. Breast augmentation, breast reconstruction, and breast reduction surgery were the most frequently associated breast surgery procedures in this study with infections, with the highest number of infections occurring following breast augmentation with fat grafting, breast reduction surgery, and breast reconstruction with autologous tissue. Various breast plastic surgery procedures have different common pathogens of infection, but the most prevalent are CoNS and S. aureus. Additionally, the majority of the infections in this study were in the early stages. Gram-positive bacteria were the predominant cause of breast plastic surgery infections, and the types of infection strains, the period of infection onset, and the antibiotic susceptibility of prevalent strains varied between breast plastic procedures.

Efficacy and mortality of ceftazidime/avibactam-based regimens in carbapenem-resistant Gram-negative bacteria infections: A retrospective multicenter observational study

ObjectivesLimited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. MethodsThis multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. ResultsA total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. ConclusionCAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients’ different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.

Abstract LB358: Efficacy of a functional precision medicine approach in relapsed/refractory pediatric cancer patients: results from a prospective clinical study

Abstract Personalized medicine often serves as the first salvage therapy strategy when standard oncology treatments fail. However, most precision oncology approaches rely on molecular profiling which, unfortunately, provides therapeutic options for less than 10% of cancer patients. Functional precision medicine (FPM) complements molecular profiling by combining it with rapid, high-throughput drug testing on live patient cells to identify promising treatment options. In this study, we investigated the efficacy of FPM in the management of pediatric patients with recurrent and/or refractory cancers. We enrolled 25 pediatric/young adult patients with refractory solid or liquid cancers in this clinical trial (number NCT03860376). Enrolled patients represented the breadth of cancer indications generally presenting in pediatric patients: acute lymphoblastic leukemia (3 patients), acute myeloid leukemia (3 patients), astrocytoma (1 patient), ependymoma (1 patient), Ewing’s sarcoma (4 patients), glioblastoma (1 patient), malignant rhabdoid tumor (1 patient), medulloblastoma (1 patient), neuroblastoma (1 patient), osteosarcoma (4 patients), rhabdomyosarcoma (4 patients) and Wilms’ tumor (1 patient). We used a functional ex vivo drug sensitivity test (DST) panel encompassing 40 formulary drugs frequently used at Nicklaus Children’s Hospital and 47 non-formulary drugs approved by FDA for cancer treatment, as well as drugs from phase III and IV clinical trials. Drug sensitivity scores (DSS) were calculated for each drug based on cancer cells’ responses. DST results were then combined with results from targeted mutation profiles to match actionable mutations with selective targeted therapies. FPM and molecular data were prospectively generated and treatment recommendations were provided to an FPM Molecular Tumor Board (MTB) of clinicians. In total, 19 of 25 patients (76%) had complete functional and molecular profiling data provided to the MTB to support clinical decision-making. Six patients had their subsequent treatment guided by FPM recommendations, of which 83% (five of six patients) demonstrated greater than 1.3x increased progression-free survival compared to their previous therapy. Interestingly, hierarchical clustering analysis of DST results shows that patients with the same subtype of cancer do not cluster together, and no cancer subtype is differentially represented in either high-level cluster, suggesting the importance of functional profiling to provide deeper insight into individual patient pharmacological response. This FPM study is the first pediatric cancer study to enroll both solid and hematologic cancers regardless of tumor type, and the first FPM study in the United States to generate prospective treatment data on pediatric oncology patients. We illustrate the feasibility and efficacy of FPM to meet the needs of cancer patients with both liquid and solid tumors, especially for high-risk populations such as pediatric cancer patients. Citation Format: Arlet Maria Acanda de la Rocha, Maggie Fader, Ebony R. Coats, Joseph Dunn, Leat Perez, Carolina Velasquez, Jeanette Galano, Cima Saghira, Ileana Sotto, Yana Vorontsova, Ziad Khatib, Haneen Abdella, Cristina M. Andrade-Feraud, Alexa Jacome, Victoria Reis, Lilliam Rimblas, Nicole Tomas, Paula S. Espinal, Noah Berlow, Tomás R. Guilarte, Jennifer McCafferty-Fernandez, Daria Salyakina, Diana J. Azzam. Efficacy of a functional precision medicine approach in relapsed/refractory pediatric cancer patients: results from a prospective clinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB358.

Abstract 43: Application of MiniPDX® in clinical indication identification and anti-tumor drug development

Abstract MiniPDX® represents a novel in vivo drug sensitivity test with fast turnaround (7-10 days), using either fresh patient tumor samples or tissues from established PDX models. We systematically evaluated and compared the response rates of MiniPDX® assays and PDX assays pair-wise in 26 PDX models across 3 types of cancers to 12 clinically relevant regimens for chemical and targeting drugs. The results showed a high correlation between drug responses of the two assays, with sensitivity and specificity of 80% and 93%, respectively. More studies of different tumor types showed that MiniPDX drug sensitivity test results were consistent with clinical responses in most patients, which indicated that MiniPDX® models have great potential in guiding personalized cancer therapy. LIDE has completed over 3,000 MiniPDX® tests for clinical precision medicine, covering more than 50 indications. MiniPDX® was used to rank clinically approved drugs or drug regimens to guide the selection of the best individualized treatment strategy. At the same time, screening other compounds facilitates selection of the best drug candidates for further R&amp;D. Importantly, performing MiniPDX® Mouse Trial using fresh tumor samples generated from clinic is beneficial for determination of potential clinical indications. Only thousands of fresh cells leftover from MiniPDX® preparation are sufficient to get genomic and transcription data by OncoVee™ K-cell technology. The combination of MiniPDX® assay and omics data would be very useful for determination of potential bio-markers in order to distinguish responders and non-responders in population with certain indication(s) and leveraged for patient stratification and selection criteria in clinical trial design. Currently, we are developing a new version of MiniPDX® assay for immunotherapy (IO-FIVE, Immuno-Oncology Fast In Vivo Efficacy test) by using fresh patient cancer cells with autologous immune cells to maximally mimic human tumor microenvironment before seeding in immune-deficient mice. Total cell viability and cell phenotyping are tracked before and after drug treatment to evaluate its in vivo efficacy within two weeks. More than 60 samples have been tested and the IO-FIVE functional assay can effectively distinguish the non-responder from responders for immunotherapeutic drugs. Several Investigator Initiated Trials (II-T) are on-going to further validate the correlation of IO-FIVE result to clinic endpoint. Citation Format: Yuan Long, Bin Xie, Hongkui Chen, Shizhu Zhao, Le Li, Song Xi, Danyi Wen. Application of MiniPDX® in clinical indication identification and anti-tumor drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 43.

Epidemiological Characteristics and Drug Resistance of Microbial Pathogens of Patients With Silicosis Combined With Pulmonary Infection

To investigate the epidemiological characteristics of patients with silicosis combined with pulmonary infection in recent years, to study the distribution and the drug susceptibility of fungal and bacterial pathogens in their sputum samples, and to provide references for the prevention and treatment of silicosis and the appropriate drug use. The clinical data and drug sensitivity test results of patients with silicosis combined with pulmonary infection diagnosed at the Department of Occupational Diseases, West China Fourth Hospital, Sichuan University were retrospectively analyzed. A total of 318 patients with silicosis combined with pulmonary infection who received treatment between January 2017 and December 2020 were enrolled. All the patients had positive microorganism test results. All participants were male. Their median age at the time of onset was 51.00 years and the median time of exposure to silica dust at work was 12.40 years. They worked mostly in construction, non-ferrous metal mining, and coal mining. The main types of work they did were pneumatic drilling, coal digging, and mining. The positive detection rates for the first, second and third phases of silicosis were 27.54%, 28.32%, and 32.97%, respectively. A total of 341 strains of fungal and bacterial pathogens were isolated, of which, 54.1% were fungi, including 114 strains (35.8%) of Candida albicans, and 53.1% were bacteria, including 168 strains (52.8%) of gram-negative bacteria, most of which being Klebsiella pneumoniae (30.2%). There was only 1 strain (0.3%) of gram-positive bacteria, namely Staphylococcus hemolyticus. Gram-negative bacilli were most resistant to ampicillin and highly sensitive to penicillin G and ofloxacin. Among patients with silicosis combined with pulmonary infection, the incidence of pulmonary infection increases along with the progress of silicosis. Microorganism analysis reveals high detection rates for fungi and the bacteria detected are predominantly gram-negative bacteria. The overall prospect for drug resistance rate was not optimistic.

Study on the Effect of Shuanghuanglian Powder Needle Combined with Cefoperazone and Sulbactam Sodium on &amp;lt;i&amp;gt;Pseudomonas aeruginosa in Vitro&amp;lt;/i&amp;gt;

Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively; The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups; The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains.

Does the Microflora of Surgery Site Infection Change After Prophylactic Use of Vancomycin Powder in the Spine Surgery

Retrospective cohort study. This study aimed to investigate the characteristics of microflora in patients with deep spinal surgical site infection (SSI) after prophylactic use of vancomycin powder (VP). A retrospective analysis was performed on patients after spinal surgery. Patients were grouped according to whether VP use and only patients with deep SSI were included in this study. General information of the patients, the dose of vancomycin, bacterial culture results, drug sensitivity test results, and SSI treatment methods were recorded. The differences of microflora between the two groups were analyzed, and the sensitivity of bacteria in the +VP group to antibiotics was analyzed. The infection rate in the +VP group was 4.9% (56/1124) vs 6.3% (93/1476) in the No-VP group (P < 0.05). The proportion of Gram-positive bacteria (GPB) in the +VP SSIs was 55.4% vs.74.1% in the No-VP group (P < 0.05). The percentage of Gram-negative bacteria (GNB) in the +VP SSIs was 46.4% vs.30.1% in the No-VP group (P < 0.05). More dose of VP cannot decrease the SSI, but the proportion of GNB in VP >1g SSIs was higher (59.0% vs 32.4%, P < 0.05). In the +VP SSIs, all of the GNB cultured were sensitive to meropenem, and linezolid covered most of the GPB cultured. Local use of vancomycin powder can reduce the incidence of SSI, but this may lead to changes in the bacterial flora. Once the SSI occurs, the case of GNB infection may be increased. The more dose of VP cannot decrease SSI but may increase the rate of GNB in the +VP SSIs. Once infections still occur after VP use, antibiotics covering GNB may be added. These findings may help guide choice of empiric antibiotics while awaiting culture data.

Screening and Drug Resistance Analysis of Non-Tuberculous Mycobacteria in Patients with Suspected Pulmonary Tuberculosis on the Hainan Island, China

China has seen a drastic increase in the incidence of non-tuberculous mycobacteria (NTM) infection, which is a notable public health issue. Due to a lack of reliable epidemiological surveillance information, there is a need to gather accurate epidemiological and surveillance data, which can help clinicians effectively treat NTM patients. Moreover, drug susceptibility testing for NTM is not frequently performed in China. This retrospective study, therefore, determined the prevalence and resistance characteristics of NTM to provide a reference to control the NTM epidemic. Sputum, alveolar lavage fluid, and other respiratory specimens were collected from 3025 patients with suspected pulmonary tuberculosis attending The Second Affiliated Hospital of Hainan Medical University from January 2014 to December 2021. Strain identification and species distribution of NTM were performed by DNA chip technology and gene sequencing, and the drug resistance of NTM isolates was evaluated by calculating the minimum inhibitory concentration through antimicrobial susceptibility testing for NTM. From 2014 to 2021, 373 strains of NTM were isolated and identified from respiratory specimens of 3025 suspected tuberculosis patients. Except in 2014, NTM-infected patients accounted for more than 10% of suspected tuberculosis patients in other years. The median age of patients with NTM infection was 62.0 years (53.0, 71.0), and the male-to-female ratio among these patients was 0.79:1. Among culture-positive strains, 12.3% (373/3040; 95% CI 11.1-13.4%) were identified as NTM comprising forty species of NTM. The forty species of NTM included 23 slow-growing mycobacteria (SGM) and 17 rapidly-growing mycobacteria (RGM). Among the NTM isolates, 58.7% (219/373; 95% CI 53.7-63.7%) were SGM and 41.3% (154/373; 95% CI 36.3-46.3%) were RGM. M.avium complex(MAC)(41.3%; 95% CI 36.3-46.3%) and M.abscessus complex (MABC)(33.2%; 95% CI 28.4-38.0%) were the most frequently detected species, followed by M.simiae Complex (11.8%; 95% CI 8.5-15.1%), M.fortuitum group (5.1%; 95% CI 2.9-7.3%), and others. Drug sensitivity test results showed that most of the NTM isolates were susceptible to amikacin and clarithromycin with a drug resistance rate of less than 10%. However, clarithromycin could induce drug resistance, followed by linezolid and moxifloxacin, and their drug resistance rate was less than 50%. During 2014-2021, the number of NTM isolates detected in the respiratory specimens of the study patients in The Second Affiliated Hospital of Hainan Medical University increased year by year. M. intracellulare is the most common pathogenic NTM species, and there is a high incidence of NTM infection on Hainan Island. Our findings might be of great importance for diagnosing and treating this patient population in Hainan.