Multidrug-resistant Pseudomonas aeruginosa has become one of global threat pathogens for human health due to insensitivity to antibiotics. Recently developed reprogramming metabolomics can identify biomarkers, and then, the biomarkers were used to revert the insensitivity and elevate antibiotic-mediated killing. Here, the methodology was used to study cefoperazone/sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF) and identified reduced glycolysis and pyruvate cycle, a recent clarified cycle providing respiratory energy in bacteria, as the most key enriched pathways and the depressed glucose as one of the most crucial biomarkers. Further experiments showed that the depression of glucose was attributed to reduction of glucose transport. However, exogenous glucose reverted the reduction to elevate intracellular glucose via activating glucose transport. The elevated glucose fluxed to the glycolysis, pyruvate cycle, and electron transport chain to promote downstream proton motive force (PMF). Consistently, exogenous glucose did not promote SCF-mediated elimination but potentiated aminoglycosides-mediated killing since aminoglycosides uptake is PMF-dependent, where amikacin was the best one. The glucose-potentiated amikacin-mediated killing was effective to both lab-evolved PA-RSCF and clinical multidrug-resistant P. aeruginosa. These results reveal the depressed glucose uptake causes the reduced intracellular glucose and expand the application of metabolome-reprogramming on selecting conventional antibiotics to achieve the best killing efficacy.
IntroductionSince December 2012, the prophylactic use of caffeine to treat AOP in preterm infants has been approved in China. This study aimed to investigate the relationship between early caffeine treatment initiation and the incidence of oxygen radical diseases in neonatology (ORDIN) in Chinese preterm infants.MethodsA retrospective study was conducted at two hospitals in South China, involving 452 preterm infants with gestational ages less than 37 weeks. The infants were divided into early (227 cases, initiating within 48 h after birth) and late (225 cases, initiating over 48 h after birth) caffeine treatment group. Logistic regression analysis and Receiver Operating Characteristic (ROC) curves were used to evaluate the association between early caffeine treatment and the incidence of ORDIN.ResultsThe results showed that extremely preterm infants in early treatment group had a lower incidence of PIVH and ROP compared to those in the late treatment group (PIVH, 20.1% versus 47.8%, P = 0.02; ROP, 70.8% versus 89.9%, P = 0.025). Very preterm infants in the early treatment group had a lower incidence of BPD and PIVH compared to those in the late treatment group (BPD, 43.8% versus 63.1%, P = 0.002; PIVH, 9.0% versus 22.3%, P = 0.001). Moreover, VLBW infants who received early caffeine treatment exhibited a decreased incidence of BPD (55.9% versus 80.9%, P = 0.000), PIVH (11.8% versus 33.1%, P = 0.000), and ROP (69.9% versus 79.8%, P = 0.043) compared to those in the late treatment group. Infants in the early caffeine treatment showed a reduced likelihood of PIVH (adjusted odds ratio, 0.407; 95%CI, 0.188–0.846) but did not exhibit a significant association with other terms of ORDIN. ROC analysis revealed that early initiation of caffeine treatment was associated with lower risk of BPD, PIVH, and ROP in preterm infants.DiscussionIn conclusion, this study demonstrates that early initiation of caffeine treatment is associated with a decreased incidence of PIVH in Chinese preterm infants. Further prospective investigations are necessary to verify and elucidate the precise effects of early caffeine treatment on complications in preterm Chinese infants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.