Penicillamine prevents damaging redox in vitro interactions of bilirubin and copper

Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu2+. However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu2+ to Cu1+ in 1:1 stoichiometry. Apparently, BR undergoes degradation, i.e. BR and Cu2+ do not form stable complexes. The binding of Cu2+ to inorganic phosphates, liposomal phosphate groups, or to chelating drug penicillamine, impedes redox interactions with BR. Cu1+ undergoes spontaneous oxidation by O2 resulting in hydrogen peroxide accumulation and hydroxyl radical production. In relation to this, copper and BR induced synergistic oxidative/damaging effects on erythrocytes membrane, which were alleviated by penicillamine. The production of reactive oxygen species by BR and copper represents a plausible cause of BR toxic effects and cell damage in hyperbilirubinemia. Further examination of therapeutic potentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed

Impact of Antibiotic Consumption on Antimicrobial Resistance to Invasive Hospital Pathogens

The aim of our investigation is to correlate the wholesale data on antibiotic consumption expressed in daily doses per 1000 inhabitants per day (DID) with the resistance rate of invasive pathogen bacteria from 2017 to 2021. The data on antimicrobial resistance were collected from an analysis of the primary isolates of hospitalized patients. According to the CAESAR manual, the selected pathogens isolated from blood culture and cerebrospinal fluids were tested. The consumption of antibiotics for systematic use showed a statistically significant increasing trend (β = 0.982, p = 0.003) from 21.3 DID in 2017 to 34.5 DID in 2021. The ratio of the utilization of broad-spectrum to narrow-spectrum antibiotics increased by 16% (β = 0.530, p = 0.358). The most consumed antibiotic in 2021 was azithromycin (15% of total consumption), followed by levofloxacin (13%) and cefixime (12%). A statistically positive significant correlation was discovered between the percentage of resistant isolates of K. pneumoniae and consumption of meropenem (r = 0.950; p = 0.013), ertapenem (r = 0.929; p = 0.022), ceftriaxone (r = 0.924; p = 0.025) and levofloxacin (r = 0.983; p = 0.003). Additionally, the percentage of resistant isolates of E. coli and consumption of ertapenem showed significant correlation (r = 0.955; p = 0.011). Significant correlation with consumption of the antibiotics widely used at the community level, such as levofloxacin, and resistance isolated in hospitals indicates that hospital stewardship is unlikely to be effective without a reduction in antibiotic misuse at the community level