Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae bacteraemia in children: a retrospective study.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly being identified in children, but data on the clinical outcomes in this population are limited. This study aimed to characterise the risk factors for 30-day mortality with CRKP bloodstream infection (BSI) in children. METHODS: A retrospective study was performed from January 2018 to December 2021 at the First Affiliated Hospital of Zhengzhou University. Patients aged < 18 years and with CRKP BSI were included. Multivariable Cox and logistic regression were performed to determine risk factors for death and the development of septic shock following CRKP infection, respectively. RESULTS: This study identified 33 neonates aged 0-4 weeks and 37 older children. The 30-day mortality rate was 39.4% in neonates and 43.2% in older children. In the neonatal population, a higher Pitt bacteremia score (HR 1.694; 95% CI 1.313-2.186; P < 0.001) was an independent risk factor for 30-day mortality. In the non-neonatal population, higher platelet count (HR 0.990; 95% CI 0.982-0.998; P = 0.010), the use of carbapenems (HR 0.212; 95% CI 0.064-0.702; P = 0.011) and appropriately targeted antimicrobial treatment (HR 0.327; 95% CI 0.111-0.969; P = 0.044) were associated with decreased 30-day mortality. Monocyte count < 0.1 × 109 cells/L (OR 3.615; 95% CI 1.165-11.444; P = 0.026) and a higher Pitt bacteremia score (OR 1.330; 95% CI 1.048-1.688; P = 0.019) were identified as risk factors for the development of septic shock. CONCLUSIONS: Carbapenem-resistant Klebsiella pneumoniae BSI was associated with high mortality in children. Appropriate antimicrobial treatment is important to improve survival, but more work is needed to assess the efficacy of specific treatment regimens in children.

Epilepsy gene prickle ensures neuropil glial ensheathment through regulating cell adhesion molecules.

Human PRICKLE1 gene has been associated with epilepsy. However, the underlying pathogenetic mechanisms remain elusive. Here we report a Drosophila prickle mutant pk IG1-1 exhibiting strong epileptic seizures and, intriguingly, abnormal glial wrapping. We found that pk is required in both neurons and glia, particularly neuropil ensheathing glia (EGN), the fly analog of oligodendrocyte, for protecting the animal from seizures. We further revealed that Pk directly binds to the membrane skeleton binding protein Ankyrin 2 (Ank2), thereby regulating the cell adhesion molecule Neuroglian (Nrg). Such protein interactions also apply to their human homologues. Moreover, nrg and ank2 mutant flies also display seizure phenotypes, and expression of either Nrg or Ank2 rescues the seizures of pk IG1-1 flies. Therefore, our findings indicate that Prickle ensures neuron-glial interaction within neuropils through regulating cell adhesion between neurons and ensheathing glia. Dysregulation of this process may represent a conserved pathogenic mechanism underlying PRICKLE1-associated epilepsy.

Risk Factors for Mortality and Outcomes in Hematological Malignancy Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Background: This study aimed to identify risk factors for mortality and outcomes in hematological malignancy (HM) patients with bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A retrospective study was conducted at a tertiary teaching hospital in Henan Province, China, between January 2018 and December 2021. All BSIs caused by CRKP in hospitalized HM patients were identified. Data on patient demographics, disease, laboratory tests, treatment regimens, outcomes of infection, and the antimicrobial susceptibility of each isolate were collected from medical records. Results: A total of 129 patients with CRKP BSI were included in the study, and the 28-day mortality rate was 80.6% (104/129). In Cox analysis an absolute neutrophil count < 500 at discharge (hazard ratio [HR] 6.386, 95% confidence interval [CI] 3.074-13.266, p < 0.001), intensive care unit admission (HR 1.834, 95% CI 1.065-3.157, p = 0.029), and higher Pitt bacteremia score (HR 1.185, 95% CI 1.118-1.255, p < 0.001) were independent risk factors associated with 28-day mortality. Survival curve analysis indicated that compared with ceftazidime-avibactam-based therapy, both polymyxin b (HR 8.175, 95% CI 1.099-60.804, p = 0.040) and tigecycline (HR 14.527, 95% CI 2.000-105.541, p =0.008) were associated with a higher risk of mortality. Conclusion: In HM patients CRKP BSI resulted in high mortality. Intensive care unit admission, higher Pitt bacteremia score, and absolute neutrophil count < 500 at discharge were independently associated with higher mortality. Early initiation of new agents such as ceftazidime-avibactam may improve outcomes.

dFRAME: A Video Recording-Based Analytical Method for Studying Feeding Rhythm in Drosophila.

Animals, from insects to humans, exhibit obvious diurnal rhythmicity of feeding behavior. Serving as a genetic animal model, Drosophila has been reported to display feeding rhythms; however, related investigations are limited due to the lack of suitable and practical methods. Here, we present a video recording-based analytical method, namely, Drosophila Feeding Rhythm Analysis Method (dFRAME). Using our newly developed computer program, FlyFeeding, we extracted the movement track of individual flies and characterized their food-approaching behavior. To distinguish feeding and no-feeding events, we utilized high-magnification video recording to optimize our method by setting cut-off thresholds to eliminate the interference of no-feeding events. Furthermore, we verified that this method is applicable to both female and male flies and for all periods of the day. Using this method, we analyzed long-term feeding status of wild-type and period mutant flies. The results recaptured previously reported feeding rhythms and revealed detailed profiles of feeding patterns in these flies under either light/dark cycles or constant dark environments. Together, our dFRAME method enables a long-term, stable, reliable, and subtle analysis of feeding behavior in Drosophila. High-throughput studies in this powerful genetic animal model will gain great insights into the molecular and neural mechanisms of feeding rhythms.