Genomic investigation of Salmonella enterica Serovar Welikade from a pediatric diarrhea case first time in Shanghai, China.

BACKGROUND: Salmonella, an important foodborne pathogen, was estimated to be responsible for 95.1 million cases and 50,771 deaths worldwide. Sixteen serovars were responsible for approximately 80% of Salmonella infections in humans in China, and infections caused by a few uncommon serovars have been reported in recent years, though not with S. Welikade. This study reports the first clinical case caused by S. Welikade in China and places Chinese S. Welikade isolates in the context of global isolates via genomic analysis. For comparison, S. Welikade isolates were also screened in the Chinese Local Surveillance System for Salmonella (CLSSS). The minimum inhibitory concentrations (MICs) of 28 antimicrobial agents were determined using the broth microdilution method. The isolates were sequenced on an Illumina platform to identify antimicrobial resistance genes, virulence genes, and phylogenetic relationships. RESULTS: The S. Welikade isolate (Sal097) was isolated from a two-year-old boy with acute gastroenteritis in 2021. Along with the other two isolates found in CLSSS, the three Chinese isolates were susceptible to all the examined antimicrobial agents, and their sequence types (STs) were ST5123 (n = 2) and ST3774 (n = 1). Single nucleotide polymorphism (SNP)-based phylogenetic analysis revealed that global S. Welikade strains can be divided into four groups, and these three Chinese isolates were assigned to B (n = 2; Sal097 and XXB1016) and C (n = 1; XXB700). In Group B, the two Chinese ST5123 isolates were closely clustered with three UK ST5123 isolates. In Group C, the Chinese isolate was closely related to the other 12 ST3774 isolates. The number of virulence genes in the S. Welikade isolates ranged from 59 to 152. The galF gene was only present in Group A, the pipB2 gene was only absent from Group A, the avrA gene was only absent from Group B, and the allB, sseK1, sspH2, STM0287, and tlde1 were found only within Group C and D isolates. There were 15 loci unique to the Sal097 isolate. CONCLUSION: This study is the first to characterize and investigate clinical S. Welikade isolates in China. Responsible for a pediatric case of gastroenteritis in 2021, the clinical isolate harbored no antimicrobial resistance and belonged to phylogenetic Group B of global S. Welikade genomes.

Transformation of Two Cases of Lung Adenocarcinoma into Pulmonary Sarcomatoid Carcinoma following Treatment.

Accumulating evidence shows that histologic transformation is involved in the drug resistance of lung cancer. Moreover, it is common for lung adenocarcinoma to transform into small-cell lung cancer or squamous cell carcinoma; however, clinical cases with sarcomatoid transformation have been rarely reported. Thus, both the diagnosis and treatment of lung adenocarcinoma with sarcomatoid transformation remain difficult. Here, we discuss two patients with lung adenocarcinoma with sarcomatoid transformation-analyzing the diagnosis, clinical features, immunohistochemical characteristics, therapy, and prognosis-with the hope that this report will be used as a reference for future treatment of these patients.

Prevalence, sequence type, and quinolone resistance of Neisseria lactamica carried in children younger than 15 years in Shanghai, China.

OBJECTIVE: Neisseria lactamica has an important influence on carriage and antimicrobial susceptibility of N. meningitidis, a major pathogen of septicemia and meningitis. In China, quinolone resistance is highly prevalent in N. meningitidis but unknown in N. lactamica. This study investigates the carriage rate, sequence type, and ciprofloxacin resistance of N. lactamica in children in China. METHODS: During 2014-2016, throat swabs were collected from 2,239 children in Shanghai. The ciprofloxacin minimum inhibitory concentrations of the isolates were determined by the agar dilution method. RESULTS: The overall carriage rate of N. lactamica was higher (8.9%) than that of N. meningitidis (0.9%) and peaked at two years (37.1%). The resistance frequency of N. lactamica to ciprofloxacin was 98.5% (197/200). There were 65 sequence types (STs). Clonal complex (cc) 640 (45.5%) dominated, while ST-14031 was predominant (37%, 74/200). All isolates possessed a GyrA mutation; 17 isolates (8.5%) harbored additionally a ParC mutation. Assigned to 39 different alleles, the gyrA sequences from these N. lactamica isolates formed an N. lactamica cluster, which also included eight alleles from N. meningitidis. CONCLUSION: The N. lactamica isolates in China showed distinct characteristics with lower genetic diversity and a much higher prevalence of quinolone resistance than in other countries.

Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China.

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ) non-susceptibility in Shanghai, China. GAS (n = 2,258) recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258), with the phenotype more prevalent in GAS isolated from adults (14.3%) than from children (1.2%). Eighty percent (24/30) of FQ-non-susceptible isolates were also resistant to both macrolides (ermB) and tetracycline (tetM) including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs) identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152) of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12) were macrolide and tetracycline resistant. Phylogenetic analysis of the parC QRDR sequences suggested the possibility that FQ resistance may be acquired through inter-species lateral gene transfer. This study reports the emergence of macrolide, tetracycline, and fluoroquinolone multidrug-resistant clones across several GAS emm types including emm1 and emm12, warranting continual surveillance given the extensive use of fluoroquinolones in clinical use.

Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA.

BACKGROUND AND OBJECTIVE: Multiple drug resistance (MDR) to chemotherapeutic agents often leads to a failure to respond to chemotherapy. We utilized an in vitro chemosensitivity test to identify sensitive and effective chemotherapeutic drugs and further elucidated the correlation between the in vivo chemosensitivity and clinical outcomes. METHODS: Here, we evaluated the in vitro chemosensitivity and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291 lung cancer patients to seven chemotherapy regimens using an ATP-based tumor chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma patients (90 cases) to these single-drug and chemotherapy regimens were compared. Furthermore, the correlations between the chemosensitivity and clinical outcomes were investigated in 16 stage III squamous cell carcinoma patients. RESULTS AND CONCLUSION: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP (54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates. Approximately 31.7% of patients developed resistance to all eight single-drug chemotherapies, and 25.8% of patients displayed resistance to all seven chemotherapy regimens. In addition, lung squamous cell carcinoma was significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma (P<0.05). Further analysis showed that patients with higher drug sensitivity tended to have longer disease-free survival (18 months vs. 8.5 months) than patients displaying drug resistance (P<0.05). These results suggest that the implementation of in vitro drug susceptibility testing before chemotherapy can effectively prevent the occurrence of primary drug resistance and inappropriate drug treatment.