Inpatient Insights
APhA Staff
Ceftaroline may be an alternative to vancomycin for MRSA bacteremia
Vancomycin remains the standard antibiotic for treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, vancomycin can cause nephrotoxicity and has other limitations related to dosing. Researchers from the Technion-Israeli Institute of Technology and Rambam Health Care Campus in Haifa, Israel, conducted a retrospective matched cohort study to compare the effectiveness of ceftaroline and vancomycin monotherapy as the initial targeted therapy for MRSA bacteremia.
The study, published in the March 2025 issue of the Journal of Antimicrobial Chemotherapy, matched adult patients treated with ceftaroline from 2019–2021 in a 1:2 ratio with patients who received vancomycin. Forty-five patients treated with ceftaroline for MRSA were matched with 83 patients who received vancomycin. Controls were matched for performance of trans-esophageal echocardiography, Charlson comorbidity index, and age.
The primary out-come was a composite of treatment failure, defined as 90-day mortality or microbiological failure.
The primary outcome of treatment failure occurred at a similar rate in patients treated with ceftaroline or vancomycin, and acute kidney injury was more common among patients treated with ceftaroline than vancomycin. The researchers concluded that although ceftaroline was not associated with improved outcomes compared with vancomycin when given as initial treatment for MRSA bacteremia, it appears to be a viable alternative to vancomycin. They noted that larger studies are needed to provide definitive results and to elucidate the risk of nephrotoxicity. ■
Coprescribing gabapentinoids with other psychoactive medications may increase risk of AMS and falls for adults receiving dialysis
Patients with chronic kidney disease are often prescribed medications, including psychoactive medications, to treat disease-associated comorbidities, to slow down progression of the disease, and to minimize morbidity and mortality rates. For patients receiving dialysis, however, some medications may be inappropriate. A group of researchers from Duke University and the University of Virginia conducted an observational cohort study to evaluate the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (e.g., sedatives or opioids) with altered mental status (AMS) and falls.
The study included adults receiving dialysis represented in the U.S. Renal Data System who had an active gabapentinoid prescription and no other psychoactive medication prescriptions in the prior 6 months who were subsequently prescribed at least one psychoactive potentially inappropriate medication. The primary outcome was acute care visits for AMS and falls. Prentice-Williams-Petersen Gap Time models estimated the association between coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty, as assessed by a validated frailty index.
Results of the study, published in the February 2025 issue of the American Journal of Kidney Diseases, indicated that coprescribing psychoactive potentially inappropriate medications was associated with increased risk for AMS and falls. Frailty significantly modified the effect of coprescribing on risk of AMS. Individuals with severe frailty had the highest risk of AMS (3.22) and falls (2.77) compared with nonfrail individuals who were not coprescribed a psychoactive potentially inappropriate medication. The authors suggested that clinicians should consider these risks when coprescribing psychoactive potentially inappropriate medications with gabapentinoids to patients receiving dialysis. ■
New oral regimens show promise for rifampin-resistant, fluoroquinolone-susceptible tuberculosis
Treatment for rifampin-resistant tuberculosis has historically been 18- to 24-month regimens that include injectable aminoglycosides or polypeptides. However, response to these common regimens is often poor, and substantial toxic effects can occur. Members of the endTB Clinical Trial Team conducted a phase three, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens using newer drugs.
A total of 754 participants were randomly assigned to receive standard therapy or one of the five combinations of bedaquiline, delamanid, linezolid, levofloxacin, or moxifloxacin, clofazimine, and pyrazinamide. The primary efficacy end point was a favorable outcome at week 73, defined by two consecutive negative sputum cultures or by favorable evolution of bacteriologic, radiologic, and clinical findings.
Results of the study, published in the January 30, 2025, issue of NEJM, indicated that at week 73, three of the new regimens produced favorable outcomes in more than 85% of participants, representing an improvement over global averages. The proportion of participants with grade three or higher adverse events was similar across the regimens, while grade three or higher hepatotoxic events occurred in 11.7% of participants overall and in 7.1% of those receiving standard therapy. The authors concluded that the consistent results support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant tuberculosis. ■
Reduced-dose vs. full-dose DOACs for extended treatment of venous thromboembolism in patients at high risk of recurrence
Once venous thromboembolism has been diagnosed, patients should take anticoagulation medication for at least 3 months to reduce the risk of recurrence, though anticoagulation medication is often extended for up to 12 or 24 months, which reduces the risk of recurrence by at least 80%. Such continuous anticoagulation, however, increases the risk of bleeding, which can exceed the risk of recurrent venous thromboembolism after stopping anticoagulation.
The RENOVE researchers conducted a noninferiority, randomized, open-label, blinded endpoint trial in 47 hospitals in France to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants (DOAC) in patients for whom extended anticoagulation was indicated. The study was published in the March 1, 2025, issue of The Lancet.
Almost 3,000 ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6 to 24 uninter-
rupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were included in the study. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily). The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent pulmonary embolism or isolated proximal deep vein thrombosis
Recurrent venous thromboembolism occurred in 19 of 1,383 patients in the reduced-dose group and in 15 of 1,385 patients in the full-dose group. Major or clinically relevant bleeding occurred in 96 patientsa in the reduced-dose group and 154 patients in the full-dose group. Adverse event occurrence was similar in the two groups.
The authors concluded that although reduction of the DOAC dose did not meet the noninferiority criteria in patients with venous thromboembolism requiring ex-
tended anticoagulation, the low recurrence rates in both groups and the substantial reduction of clinically relevant bleeding with the reduced dose could support this regimen as an option. ■