Long-Acting Antiretroviral Drug Therapy in Adolescents: Current Status and Future Prospects.

Approximately 50% of human immunodeficiency virus (HIV)-infected adolescents fail to achieve complete viral suppression, largely due to nonadherence to their antiretroviral drug regimens. Numerous personal, financial, and societal barriers contribute to nonadherence, which may lead to the development of HIV drug resistance. Long-acting antiretroviral drugs hold the promise of improved adherence because they remove the need for swallowing one or more pills daily. Cabotegravir (an integrase strand transfer inhibitor) and rilpivirine (a non-nucleoside reverse transcriptase inhibitor) can now be intramuscularly co-administered to HIV-infected adolescents every 4-8 weeks if they are virologically suppressed and without resistance mutations to cabotegravir or rilpivirine. Adverse effects are few and non-severe. Widespread use of this complete antiretroviral therapy may be limited by drug costs, need for sites and skilled personnel who can administer the injections, and ethical challenges. Other long-acting medications and new antiretroviral therapy delivery systems are under active investigation and show great promise.

Risk Factors for Acquisition of Extended-spectrum Beta-lactamase and AmpC Resistant Gram-negative Bacteria in Critically Ill Infants With Congenital Heart Disease.

In a cohort of 257 infants with congenital heart disease admitted to the pediatric intensive care unit, 22 infants had positive cultures for extended-spectrum beta-lactamase or AmpC Gram-negative bacteria. These infants had longer exposure to broad-spectrum antibiotics, greater support with invasive devices and longer intensive care and hospital lengths of stay.

A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.