Unveiling the genetic architecture and transmission dynamics of a novel multidrug-resistant plasmid harboring blaNDM-5 in E. Coli ST167: implications for antibiotic resistance management.

BACKGROUND: The emergence of multidrug-resistant (MDR) Escherichia coli strains poses significant challenges in clinical settings, particularly when these strains harbor New Delhi metallo-ß-lactamase (NDM) gene, which confer resistance to carbapenems, a critical class of last-resort antibiotics. This study investigates the genetic characteristics and implications of a novel blaNDM-5-carrying plasmid pNDM-5-0083 isolated from an E. coli strain GZ04-0083 from clinical specimen in Zhongshan, China. RESULTS: Phenotypic and genotypic evaluations confirmed that the E. coli ST167 strain GZ04-0083 is a multidrug-resistant organism, showing resistance to diverse classes of antibiotics including ß-lactams, carbapenems, fluoroquinolones, aminoglycosides, and sulfonamides, while maintaining susceptibility to monobactams. Investigations involving S1 pulsed-field gel electrophoresis, Southern blot analysis, and conjugation experiments, alongside genomic sequencing, confirmed the presence of the blaNDM-5 gene within a 146-kb IncFIB plasmid pNDM-5-0083. This evidence underscores a significant risk for the horizontal transfer of resistance genes among bacterial populations. Detailed annotations of genetic elements-such as resistance genes, transposons, and insertion sequences-and comparative BLAST analyses with other blaNDM-5-carrying plasmids, revealed a unique architectural configuration in the pNDM-5-0083. The MDR region of this plasmid shares a conserved gene arrangement (repA-IS15DIV-blaNDM-5-bleMBL-IS91-suI2-aadA2-dfrA12) with three previously reported plasmids, indicating a potential for dynamic genetic recombination and evolution within the MDR region. Additionally, the integration of virulence factors, including the iro and sit gene clusters and enolase, into its genetic architecture poses further therapeutic challenges by enhancing the strain's pathogenicity through improved host tissue colonization, immune evasion, and increased infection severity. CONCLUSIONS: The detailed identification and characterization of pNDM-5-0083 enhance our understanding of the mechanisms facilitating the spread of carbapenem resistance. This study illuminates the intricate interplay among various genetic elements within the novel blaNDM-5-carrying plasmid, which are crucial for the stability and mobility of resistance genes across bacterial populations. These insights highlight the urgent need for ongoing surveillance and the development of effective strategies to curb the proliferation of antibiotic resistance.

Predictive values of the hemoglobin, albumin, lymphocyte and platelet score (HALP) and the modified -Gustave Roussy immune score for esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy.

The hemoglobin, albumin, lymphocyte and platelet (HALP) score and the Gustave Roussy immune score (GRIm⁃Score) are prognostic markers in several types of malignant tumors. The prognostic values of HALP score and GRIm⁃Score in concurrent chemoradiotherapy for unresectable esophageal cancer remain unknown. METHODS: We enrolled 150 esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy in our institution between 2013 and 2018. The cutoff values for HALP, and GRIm⁃Score were defined by using receiver's operating characteristic curves. Survival was analyzed with the Kaplan- Meier method, with differences analyzed with the log-rank test. Multivariate Cox proportional-hazards models were used to evaluate the prognostic significance of HALP and GRIm for ESCC. RESULTS: HALP was significantly associated with the Zubrod ECOG WHO performance status, tumor location, and the clinical tumor, node, metastasis stage. Modified GRIm (mGRIm) was only significantly associated with metastasis / recurrence before radiotherapy (χ2 = 6.25). Univariate Cox regression analysis showed that higher mGRIm (HR 1.9 95%CI 1.3-2.9) and lower HALP (HR 2.4 95%CI 1.6-3.7) were all associated with worse OS. Multivariate COX analysis found that higher mGRIm score (HR 1.7 95%CI 1.1-2.6), and lower HALP score (HR 2 95%CI 1.3-3.2) were both independent risk factors of overall survival. The nomogram c-index in inside validation was 0.66. CONCLUSION: Both HALP and mGRIm are independent prognostic factors for patients with unresectable ESCC.

Prognostic value of modified-Gustave-Roussy Immunity Score in resectable proximal gastric cancer.

The prognostic evaluation of GRIm score has been confirmed in many tumor species. The purpose of this study is to clarify the value of GRIm score in the prognostic evaluation of patients with resectable proximal gastric cancer. A single center retrospective study was conducted in 174 patients with proximal gastric cancer who underwent radical total gastrectomy. An in-depth analysis was carried out to explore the prognostic differences between high and low GRIm, and the influencing factors of disease-free survival rates and overall survival rates were analyzed by Cox regression model and Kaplan-Meier method. A total of 174 patients were divided into two groups: 135 patients were marked in L-mGRIm and 39 patients in H-mGRIm groups respectively. The median OS of the H-mGRIm and L-mGRIm groups were 23.2 and 38.6 months, respectively. The median DFS of the H-mGRIm and L-mGRIm groups was 16.9 and 31.7 months, respectively. Both DFS and OS were significantly different between groups (P = .000, P = .000). In multivariate analysis, ZPS (2 vs 0-1: HR 1.99 95% CI 1.05-3.76 P = .035), LDH (≥193 vs <193:HR 0.6; 95% CI 0.38-0.95 P = .028), mGRIm score (2-3 vs 0-1: HR 2.4; 95% CI 1.09-5.23 P = .029) was independent risk factors of OS. The age (>65 vs ≤65 years HR 0.63; 95% CI 0.4-0.95 P = .003), LDH (>193 U/L vs ≤193 U/L: HR 0.55; 95% CI 0.37-0.82 P = .004) and mGRIm score (2-3 vs 0-1: HR 4.74; 95% CI 2.24-9.9 P = .000) as an independent risk factor for DFS. mGRIm score is a novel, simple and effective index for prognosis evaluation of resectable cardiac cancer and can be used as a part of the risk stratification process.

Streptococcus dysgalactiae subsp. dysgalactiae presents with progressive weakness in limbs: a case report and literature review.

BACKGROUND: Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. CASE PRESENTATION: She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. CONCLUSION: Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.