Genomic Characteristics of a Carbapenem-Resistant Klebsiella pneumoniae Co-Carrying bla NDM-5 and bla KPC-2 Capsular Type KL25 Recovered from a County Level Hospital in China.

Background: Hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP) has been spreading rapidly worldwide. Here, we investigated the genomic characteristics of ST11 K. pneumoniae isolate SM117 with capsular serotype KL25, co-carrying bla NDM-5, two copies of bla KPC-2 and multiple plasmid-borne virulence genes from a county level hospital in China. Methods: Antimicrobial susceptibility of K. pneumoniae SM117 was evaluated. The Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms were applied to sequence the genome and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, antibiotic resistance genes, plasmid replicon types and virulence genes. The phylogenetic analysis was performed based on the core genome single nucleotide polymorphisms (cgSNPs) using CSI Phylogeny 1.4, and further visualized by Interactive Tree of Life (iTOL) V5 web server. Results: The whole-genome sequence of K. pneumoniae SM117 is made up of eight contigs totaling 6,104,486 bp, contain a 5,612,620 bp single chromosome and seven plasmids. The isolate was assigned to ST11 with capsular serotype KL25, co-carrying including bla NDM-5, bla KPC-2 and multiple plasmid-borne virulence genes including rmpA2 and aerobactin genes iucABCD-iutA. The coexistence of bla KPC and bla NDM in K. pneumoniae strains exhibit a high degree of resistance to ß-lactam antibiotics. The strain SM117 also carries multiple antibiotic resistance genes, making it resistant to all antibiotics except polymyxin. The closest relative of K. pneumoniae C793 was identified in 2023 from a hospital surface sample in Zhejiang, China, with just 52 SNPs difference. Conclusion: This study reported the genomic characteristics of a multidrug-resistant ST11 K. pneumoniae with capsular serotype KL25, co-carrying bla NDM-5, two copies of bla KPC-2 genes and multiple plasmid-borne virulence genes in China. These findings will provide important knowledge of the antibiotic resistance mechanisms, genomic epidemiological characteristics and transmission dynamics of multidrug-resistant K. pneumoniae.

Predicting Hypertensive Disease in the First Trimester of Pregnancy: Risk Models and Analysis of Serum D-dimer Levels Combined with Plasma Pregnancy-Associated Protein A, Free ß-Subunit of Human Chorionic Gonadotropin, and Fetal Nuchal Translucency.

We aimed to investigate the predictive ability of serum levels of D-dimer (DD) in the first trimester for the occurrence of hypertensive disorders of pregnancy (HDP). In this retrospective, case-cohort study, we measured the levels of DD, plasma pregnancy-associated protein A (PAPP-A), and free ß-subunit of human chorionic gonadotropin (free ß-hCG) and analyzed fetal nuchal translucency (NT) in 150 healthy gravidas, 126 cases of gestational hypertension (GH), 53 cases of preeclampsia (PE), and 41 cases with severe preeclampsia (SPE). Likelihood ratio models and risk models were built using single markers (DD, PAPP-A, free ß-hCG, and NT) and combinations of those markers. Analyses showed that the levels of DD multiple of the median (MoM) in the GH, PE, and SPE groups were all significantly higher than those in the control group, with significant differences between groups (χ 2 = 70.325, P < 0.001). The area under curve (AUCs) for DD in the GH, PE, and SPE groups was 0.699, 0.784, and 0.893, respectively; the positive likelihood ratio (+LR) was 1.534, 1.804, and 2.941, respectively; and the negative likelihood ratio (-LR) was 0.022, 0.081, and 0, respectively. When the cut-off values of DD for the GH, PE, and SPE groups were 0.725, 0.815, and 0.945 MoM, respectively, the corresponding sensitivities were 0.992, 0.962, and 1.000, respectively. As gestational hypertension progressed, the levels of DD tended to increase gradually. The maternal serum level of DD in the first trimester had correlative and diagnostic value for HDP. The sensitivity and specificity of maternal serum levels of DD level in the first trimester for different types of HDP were significantly different; the best sensitivity and specificity were detected in the SPE group. First trimester DD level, combined with other biochemical markers, may improve our ability to diagnose HDP.

Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free ß-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case-control study.

BACKGROUND: This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free ß-subunit of human chorionic gonadotropin (free ß-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP). MATERIALS AND METHODS: In this retrospective case-control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free ß-hCG levels for HDP. RESULTS: DD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free ß-hCG > DD > DD + AFP > DD + free ß-hCG > AFP + free ß-hCG > AFP > free ß-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free ß-hCG alone and AFP + free ß-hCG could reduce false positive rate and improve + LR. CONCLUSION: DD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free ß-hCG + AFP had the greatest diagnostic value for SPE.

[Maternal serum alpha fetoprotein and free ß-hCG of second trimester for screening of fetal gastroschisis and omphalocele].

OBJECTIVE: To assess the detection of maternal serum alpha fetoprotein (MSAFP) and free beta-HCG levels of second trimester for screening of fetal gastroschisis and omphalocele. METHODS: Clinical data of 622 639 pregnant women from 5 prenatal screening centers in Hangzhou during October 2007 and September 2016 were analyzed retrospectively. Thirty cases of gastroschisis and 30 cases of omphalocele diagnosed by ultrasonography and postmortem findings were enrolled in the study and 116 cases of pregnant women with normal fetal development during the same period were selected as control group. The cut-off value and area under ROC curve (AUC) of MSAFP and free ß-hCG for diagnosis of fetal gastroschisis and omphalocel were analyzed. RESULTS: MSAFP levels of women with fetal gastroschisis and omphalocele were 4.41 (0.88-11.69) MOM and 2.31 (0.72-23.20) MOM, which were significantly higher than that of control group[0.98 (0.41-2.26) MOM, all P<0.01]. Free ß-hCG level of women with fetal gastroschisis was 1.25 (0.35-19.94) MOM, which was significantly higher than that of control group[0.86 (0.17-6.11) MOM, P<0.05). But there were no significant difference in free ß-hCG between fetal omphalocele group[1.03(0.21-8.95)]and control group (P>0.05). The AUCs of MSAFP for diagnosis of gastroschisis and omphalocele were 0.897 (95% CI:0.822-0.972) and 0.852(95% CI:0.762-0.942), respectively (all P<0.01). Taking 1.655 MOM as the cut-off value of MSAFP for abdominal wall defects (gastroschisis and omphalocele), the sensitivity was 68.30%, specificity was 99.60% and Youden index was 0.649. CONCLUSIONS: MSAFP of second trimester is a better biomarker than free ß-hCG in screening abdominal wall defects.