Widespread multidrug-resistant (MDR) and multi-virulent diarrheagenic E. coli create several crises among human and animal populations worldwide. For this reason, we looked forward to a breakthrough with this issue and tried to highlight these emerging threats. A total of 140 diarrheagenic E. coli isolates were recovered from animal and human sources. The O26 serotype, alongside the ampicillin/cefoxitin resistance phenotype, was predominant among both human and animal isolates. Of note, imipenem represented the most effective antibiotic against all the investigated isolates. Unfortunately, 90% and 57.9% of the tested isolates showed MDR and multi-virulent patterns, respectively. The animal isolates were more virulent and showed higher sensitivity to antimicrobial agents. Both animal and human isolates could not be arranged into related clusters. A strong negative correlation between the existence of virulence genes and antimicrobial resistance was clearly detected. A significant correlation between serotypes and antimicrobial resistance was not detected; meanwhile, a significant positive correlation between some serotypes and the presence of certain virulence genes was announced. Finally, our results confirmed the urgent need for restricted guidelines, in addition to new alternative therapies, due to the genetic diversity and wide spreading of MDR side by side with multi-virulent E. coli isolates.

Urinary tract infections (UTIs) can be caused by multiple drug-resistant bacteria. Empirical broad-spectrum antibiotics help minimize the risk of disease progression. Although antibiotic de-escalation is important to reduce resistance, adverse drug effects, and costs, few studies have evaluated the impact of antibiotic de-escalation on complicated UTIs in hospitalized patients. In this retrospective cohort single center observational study conducted over a period of 1 year at Prince Sultan Military Medical City (PSMMC), the rate of antibiotic de-escalation following reporting culture and sensitivity results, hospital length of stay (LOS), and factors associated with antibiotic de-escalation failure were determined. Ninety-one patients were enrolled in this study. Baseline characteristics were comparable between groups. The rate of successful de-escalation was 29.7% (27 patients) while 70.3% (64 patients) failed to experience de-escalation. The median hospital LOS was significantly lower in successfully de-escalated patients, at 3 days interquartile range (IQR) (2-6), while in the failed group it was 10 days IQR (6-21) (p<0.001). However, the identified factor associated with failure was a multidrug-resistant (MDR) pathogen that was significantly higher in the failed group than in the successful group: 38 patients (59.4%) versus 6 patients (22.2%; p<0.001), respectively. Antibiotic de-escalation is an essential antimicrobial stewardship strategy. The findings of this study showed that de-escalation was associated with better patient outcomes (i.e., reduced hospital LOS) in patients admitted due to UTIs. In this study's site hospital, there is a potential for improving the current de-escalation rate. MDR pathogens were the only significant reason identified for de-escalation failure. Further data are needed on the large scale to evaluate reasons for de-escalation failure.

This is a single-center, retrospective, cohort study aimed to evaluate the clinical outcomes of multi-drug resistance in Acinetobacter baumannii infections (MDR-AB) in intensive care unit (ICU) patients with or without a COVID-19 infection and risk factors for blood stream infection. A total of 170 patients with MDR-AB were enrolled in the study. Of these, 118 (70%) patients were admitted to the ICU due to a COVID-19 infection. Comparing the COVID-19 and non-COVID-19 groups, the use of mechanical ventilation (98.31% vs. 76.92%, p = 0.000), the presence of septic shock (96.61% vs. 82.69%, p = 0.002), and the use of steroid (99.15% vs. 71.15%, p = 0.000) and tocilizumab therapies (33.05% vs. 0%, p = 0.000) were more prevalent and statistically more significant in patients with COVID-19 infections. The average length of the ICU stay (21.2 vs. 28.33, p = 0.0042) was significantly lower in patients with COVID-19 infections. Survival rate was 21.19% for the COVID-19 group and 28.85% for non-COVID-19 group with a p-value = 0.0361. COVID-19 status was associated with significantly higher hazards of death (HR 1.79, CI 95% 1.02–3.15, p = 0.043). Higher SOFAB (15.07 vs. 12.07, p = 0.0032) and the placement of an intravascular device (97.06% vs. 89.71%, p = 0.046) were significantly associated with the development of a bloodstream infection. Our study has shown that critically ill patients with an MDR-AB infection, who were admitted due to a COVID-19 infection, had a higher hazard for death compared to non-COVID-19 infected patients.

Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)―a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals’ behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1β), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (−) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of −0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.