Oral regimen for high dose methotrexate urine alkalinization: a systematic review and meta-analysis.

OBJECTIVE: Urine alkalinization prevents nephrotoxicity in patients receiving high-dose methotrexate (HDMTX). While the standard approach involves IV sodium bicarbonate, alternative oral bicarbonate regimens are crucial in drug shortages and outpatient settings. This study aims to review the efficacy and safety of such regimens. METHODS: PubMed, WOS, and Scopus were systematically searched using the PRISMA protocol for relevant studies involving human subjects, including randomized clinical trials, retrospective, prospective, cohort, case reports, and case series studies. There were no restrictions on language, time, or age group. Qualified and eligible papers were used to extract data on efficacy and safety indicators, and the final relevant records were assessed for quality using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) assessment tool. RESULTS: 12 studies with 1212 participants were included in the systematic review, with pooled data from 8 studies used for meta-analysis. No significant differences in mean differences (MDs) or odds ratio (OR) were found after the oral bicarbonate regimen, except for when urine pH fell to < 7 (MD: 0.91, 95% CI: 0.32, 1.5, P < 0.05) and the incidence of diarrhea (OR: 2.92, 95% CI: 1.69, 5.05, P < 0.05). CONCLUSION: An oral bicarbonate regimen is a safe and effective way to alkalize HDMTX urine, providing a viable and cost-effective alternative to IV protocols. Further prospective multicenter studies are necessary. Systematic review registration identifier: CRD42023379666.

Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection.

PURPOSE: Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections. METHODS: 29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200 mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24 h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model. RESULTS: The mean area under the curve over the last 24-h (AUC0-24) value and accuracy (mean ± standard deviation) in the fasting and fed states were 220.24 ± 119.15 and 290.55 ± 276.20 µg × h/mL, respectively. There was no significant difference among AUCs following fasting and non-fasting conditions (P > 0.05). The probability of reaching the therapeutic goals at the minimum inhibitory concentration (MIC) of 4 mg/L, was only 1.6%. CONCLUSION: In critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels.

LipoxinA4 as a Potential Prognostic Marker of COVID-19.

This pilot study aimed to determine early changes of LXA4 levels among the hospitalized patients confirmed as COVID-19 cases following the clinical management and its correlation with commonly used inflammatory markers, including erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. Thirty-one adult hospitalized patients infected with the non-severe COVID-19 were included. LXA4 levels were measured at the baseline and 48-72 hours after hospitalization. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were determined during the five days. LXA4 levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA4 levels. LXA4 may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA4 could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA4 role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.