ABSTRACT Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant Klebsiella pneumoniae (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical K. pneumoniae isolates during 2017–2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially phoPQ, contributed more to colistin resistance. mgrB mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of phoPQ system. This study also identified three novel point mutations in pmrAB system, in which D313N mutation in pmrB was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene mrkA. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR K. pneumoniae, which is a noticeable superbug and could cause a severe challenge to public health.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2022.2036078?needAccess=true

Emergence of colistin-resistant hypervirulent Klebsiella pneumoniae (CoR-HvKp) in China

Drug resistance characteristics and molecular typing of Escherichia coli isolates from neonates in class A tertiary hospitals: A multicentre study across China.

Droplet digital PCR (ddPCR) recently has been shown to be a potential diagnostic tool for adults with bloodstream infections (BSIs); however, its application in children remains obscure. In this study, 76 blood samples of children with suspected BSIs were synchronously detected by traditional blood cultures (BCs) and ddPCRs. Our team validated the diagnostic performance of ddPCR including sensitivity, specificity, and positive and negative predictive values. The 76 pediatric patients from the hematology department (67.1%), the pediatric intensive care unit (PICU, 27.6%), and other departments (5.2%) were enrolled. The positive rate of ddPCR results was 47.9%, whereas that for BC was 6.6%. In addition, the time consumption of ddPCR was shorter, only for 4.7 ± 0.9 h, in comparison with the detection timing of BC (76.7 ± 10.4 h, p < 0.01). The levels of agreement and disagreement between BC and ddPCR were 96.1% and 4.2%, and the negative agreement reached 95.6%. The sensitivity of ddPCR was 100%, with corresponding specificities ranging from 95.3 to 100.0%. In addition, a total of nine viruses were identified by ddPCR. In China, the multiplexed ddPCR first could be a tool for the rapid and accurate diagnosis of children with suspected BSIs and can be an early indicator of the possibility of viraemia in children with immunosuppression.

/pdf/clinical-application-of-a-multiplex-droplet-digital-pcr-in-iid3e3jo.pdf

Clinical Application of a Multiplex Droplet Digital PCR in the Rapid Diagnosis of Children with Suspected Bloodstream Infections

An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics.All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis.ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184-199.326, P<0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009-10.055, P<0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis.E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility. 

Risk Factors Associated with Multi-Drug Resistance in Neonatal Sepsis Caused by Escherichia coli

The diagnosis of neonatal sepsis in lower-income countries is mainly based on clinical presentation. The practice necessitates empirical treatment with limited aetiology and antibiotic susceptibility profile knowledge, prompting the emergence and spread of antimicrobial resistance. We conducted a cross-sectional study to determine the aetiology of neonatal sepsis and antimicrobial resistance patterns. We recruited 658 neonates admitted to the neonatal ward with signs and symptoms of sepsis and performed 639 automated blood cultures and antimicrobial susceptibility testing. Around 72% of the samples were culture positive; Gram-positive bacteria were predominantly isolated, contributing to 81%. Coagulase-negative Staphylococci were the most isolates, followed by Streptococcus agalactiae. Overall, antibiotic resistance among Gram-positive pathogens ranged from 23% (Chloramphenicol) to 93% (Penicillin) and from 24.7% (amikacin) to 91% (ampicillin) for Gram-negative bacteria. Moreover, about 69% of Gram-positive and 75% of Gram-negative bacteria were multidrug-resistant (MDR). We observed about 70% overall proportion of MDR strains, non-significantly more in Gram-negative than Gram-positive pathogens (p = 0.334). In conclusion, the pathogen causing neonatal sepsis in our setting exhibited a high resistance rate to commonly used antibiotics. The high rate of MDR pathogens calls for strengthening antibiotic stewardship programs.

/pdf/bacterial-aetiology-of-neonatal-sepsis-and-antimicrobial-c15qg077.pdf

Bacterial Aetiology of Neonatal Sepsis and Antimicrobial Resistance Pattern at the Regional Referral Hospital, Dar es Salam, Tanzania; A Call to Strengthening Antibiotic Stewardship Program

Multidrug-resistant (MDR) pathogens are responsible for a substantial burden of morbidity and mortality from neonatal sepsis; however, data on these sepsis-related pathogens among hospitalized neonates in China are not well characterized. In this study, a total of 240 strains were isolated from four Women and Children's hospitals in Southwest China between 2014 and 2019. Of these included pathogens, 104 (43.33%) were gram-positive bacteria, 129 (53.75%) were gram-negative bacteria, and 7 (2.92%) were fungi. Escherichia coli (E. coli, 34.01%) and Klebsiella pneumoniae (K. pneumoniae, 15.35%) were the main pathogen of neonate bacteremia. ST167 were the most prevalent STs in E. coli and ST11 in K. pneumoniae. Our study found that E. coli (62.71%) was the predominate pathogen of early-onset sepsis, among which 64.86% were MDR. Late-onset sepsis was mainly caused by K. pneumoniae (28.31%) and E. coli (24.78%), with showing that 78.33% of these pathogens were MDR. Notably, the prevalence of EO/LO pathogens were quite different from Indian and south of China. Moreover, we found that bla CTX-M (42.06%) was most dominant resistant genes with about a third isolates (31.09%) were positive for bla CTX-M-15. All the carbapenem-resistant K. pneumoniae were positive for NDM-1. Moreover, late-onset sepsis and antibiotic exposure were significantly associated with MDR infection. Emerging multi-resistant pathogens of sepsis posts a serious threat to neonatal outcomes and emphasizes an urgent need to control their further spread.

/pdf/emerging-threat-of-multidrug-resistant-pathogens-from-2ueidw2nfe.pdf

Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis

Background Neonatal sepsis is one of the major causes of morbidity and mortality in newborns. However, atypical clinical manifestations and symptoms make the early diagnosis of neonatal sepsis a challenge. Relatively high-serum soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated as a diagnostic biomarker for adult sepsis. Therefore, the meta-analysis is intended to explore the diagnostic value of suPAR for neonatal sepsis. Methods The PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Biological Medicine Disk, and Wanfang databases were retrieved from inception to 31 December 2022 to collect diagnostic accuracy studies about suPAR for neonatal sepsis. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool. Then, a meta-analysis was performed using Stata 15.0 software. Results A total of six articles involving eight studies were included. The results of the meta-analysis showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.89 [95%CI (0.83–0.93)], 0.94 [95%CI (0.77–0.98)], 14 [95%CI (3.5–55.2)], 0.12 [95%CI (0.08–0.18)], and 117 [95%CI (24–567)], respectively. The area under the curve (AUC) of summary receiver operator characteristic (SROC) curves was 0.92 [95%CI (0.90–0.94)]. Sensitivity analysis confirmed the stability of the results, and publication bias was not observed. Fagan’s nomogram results demonstrated the clinical availability of the findings. Conclusion Current evidence suggests that suPAR has potential diagnostic value for neonatal sepsis. Owing to the limited quality of the included studies, more high-quality studies are needed to verify the above conclusion.

The accuracy of soluble urokinase-type plasminogen activator receptor for the diagnosis of neonatal sepsis: a meta-analysis

Background Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, and its most common pathological types include embryonal RMS and alveolar RMS. In contrast, spindle cell RMS (SRMS) is a rare type. Moreover, the tongue is a rare primary site of RMS, and infancy is a rare age at onset. Case presentation Two infants were diagnosed with lingual RMS at 3 and 5 months after birth, respectively, and were admitted to Beijing Children’s Hospital. The pathological type in both cases was SRMS. Both were classified as low-risk and were treated with surgery and chemotherapy. Case 1 was in complete remission at the latest follow-up, and Case 2 had a relapse 10 months after stopping chemotherapy, achieving complete remission after the multimodal treatment of chemotherapy, surgery, and radiotherapy. The venous blood gene test of the two infants did not indicate a pathogenic mutation or a possible pathogenic mutation related to RMS. In Case 1, variants of the CDK4 and BRCA1 genes, both with unknown significance and a possible relation to RMS, were detected. In Case 2, three gene variants of unknown significance that were possibly associated with RMS—TRIP13, APC, and RAD54L—were identified. Conclusion Lingual RMS in infants is rare. Its clinical manifestations lack specificity, and early recognition is complex. The success and timing of local treatment are important prognostic factors. Genetic testing may be helpful for the early detection of tumor susceptibility and the estimation of prognosis.

/pdf/case-report-clinical-features-and-prognosis-of-two-infants-2rznfc7r.pdf

Case report: Clinical features and prognosis of two Infants with rhabdomyosarcoma of the tongue

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Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis

The accuracy of soluble urokinase-type plasminogen activator receptor for the diagnosis of neonatal sepsis: a meta-analysis

Case report: Clinical features and prognosis of two Infants with rhabdomyosarcoma of the tongue