A case report of drug interaction between co-packaged nirmatrelvir-ritonavir and tacrolimus causing hyponatremia in a lung transplant recipient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination. CASE PRESENTATION: In this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination. CONCLUSION: Although the nirmatrelvir-ritonavir and tacrolimus combination is not contraindicated, other treatment strategies should be considered first, if available, and the dose of tacrolimus should be reduced when using the nirmatrelvir-ritonavir combination. In cases where combination therapy is necessary, serum tacrolimus levels should be closely monitored in lung transplant recipients. Documentation of more such reports is important to identify drug interactions between nirmatrelvir-ritonavir and other agents, with the aim of preventing severe adverse effects.

Association of Hypernatremia with Immune Profiles and Clinical Outcomes in Adult Intensive Care Unit Patients with Sepsis.

Both hypernatremia and an abnormal immune response may increase hospital mortality in patients with sepsis. This study examined the association of hypernatremia with abnormal immune response and mortality in 520 adult patients with sepsis in an intensive care unit (ICU). We compared the mortality and ex vivo lipopolysaccharide (LPS)-induced inflammatory response differences among patients with hyponatremia, eunatremia, and hypernatremia, as well as between patients with acquired hypernatremia on ICU day 3 and those with sustained eunatremia over first three ICU days. Compared with eunatremia or hyponatremia, hypernatremia led to higher 7 day, 14 day, 28 day, and hospital mortality rates (p = 0.030, 0.009, 0.010, and 0.033, respectively). Compared with sustained eunatremia, acquired hypernatremia led to higher 7, 14, and 28 day mortality rates (p = 0.019, 0.042, and 0.028, respectively). The acquired hypernatremia group nonsignificantly trended toward increased hospital mortality (p = 0.056). Day 1 granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor (TNF) α levels were relatively low in patients with hypernatremia (p = 0.020 and 0.010, respectively) but relatively high in patients with acquired hypernatremia (p = 0.049 and 0.009, respectively). Thus, in ICU-admitted septic patients, hypernatremia on admission and in ICU-acquired hypernatremia were both associated with higher mortality. The higher mortality in patients with hypernatremia on admission was possibly related to the downregulation of G-CSF and TNF-α secretion after endotoxin stimulation. Compared to sustained eunatremia, acquired hypernatremia showed immunoparalysis at first and then hyperinflammation on day 3.

Clinical characteristics and risk factors for mortality in cefepime-resistant Pseudomonas aeruginosa bacteremia.

BACKGROUND: To identify the clinical characteristics and risk factors for mortality of patients with cefepime-resistant Pseudomonas aeruginosa (FRPa) bacteremia. METHODS: This retrospective study analyzed adult patients with FRPa bacteremia hospitalized between January 2006 and December 2011. RESULTS: Seventy eight patients (46 male, 32 female; mean age: 72.2 ± 14.1 years) were included. Of them, 46 (59.0%) had ventilator use and 45 (57.7%) had intensive care unit stay. All the bacteremia episodes were health-care associated or hospital acquired, and 55.1% of FRPa blood isolates were multidrug resistant. The sources of bacteremia were identified in 42 patients (53.8%), with pneumonia being the most common one (28/42; 66.7%). The mean interval between admission and the sample date of the first FRPa-positive blood culture was 45.8 ± 52.6 days. The mean Pittsburgh bacteremia score was 5.0 ± 3.4. The 15-day and 30-day mortality rates were 50.0% and 65.4%, respectively. Patients (41; 52.6%) on appropriate antibiotic therapy within 72 hours of the first FRPa-positive blood culture had a higher 30-day survival rate than those without (48.8% vs. 18.9%, p = 0.011 by log-rank test). Multivariate analyses revealed that a higher Pittsburgh bacteremia score was an independent risk factor for either 15-day (p = 0.002) or 30-day mortality (p = 0.010), and appropriate antibiotic therapy within 72 hours was an independent protecting factor for either 15-day (p = 0.049) or 30-day mortality (p = 0.017). CONCLUSION: FRPa bacteremia had a high mortality rate. The disease severity and appropriate antimicrobial therapy within 72 hours of positive blood culture were related to the patients' outcome.