- Although Smaller than First Reported, Association Between Dolutegravir and Neural Tube Defects Persists
- Assessing Post-Discharge and Total Durations of Antimicrobial Therapy for Hospital Stays: Challenging but Important
Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.
Reviewed by Lauren Richey, MD, MPH, FIDSA
In May 2018, a preliminary report from Botswana indicated a potential association between dolutegravir exposure during conception and neural tube defects (NTDs) in newborn infants. This resulted in recommendations to limit use of dolutegravir among women planning pregnancy. The full study results are now available in the New England Journal of Medicine. In addition to the eight public hospital sites being monitored from 2014, 10 additional sites were added in 2018 with outcomes recorded. Midwives were trained to perform surface exams of newborn infants with photos for abnormalities to identify NTDs. Other major abnormalities were also identified using chart abstraction.
Nearly 120,000 live births were captured by surveillance and 99.6 percent had surface exams. Overall, 98 NTDs were found (0.08 percent). Among the 1,683 deliveries where the mother was taking dolutegravir at conception, five NTDs were found (0.3 percent). For mothers on non-dolutegravir antiretroviral therapy (ART) at conception, there were 15 NTDs out of 14,792 deliveries (0.1 percent). Major structural abnormalities were seen in 719 (0.6 percent) overall births, but 16 (0.95 percent) newborns of mothers on dolutegravir during conception.
This study confirms a potential association between dolutegravir during conception and NTDs. While the risk is small (3 out of a 1,000), it is significantly higher than the 1 out of 1,000 seen for women on non-dolutegravir ART at conception. Prior to this study, multiple other small studies had not shown this association, and only one other case had been reported to the Antiviral Pregnancy Registry. The mechanism is unclear, and ongoing studies are assessing whether dolutegravir impacts the folate pathway and whether dietary fortification or supplementation could mitigate this. It is important to note that most antiretroviral medicines, other than efavirenz, do not have any large-scale studies of exposure during conception and that large studies are necessary to ascertain the risk of rare events such as NTDs. Further assessment of birth outcomes of woman on ART during conception and pregnancy are needed.
Reviewed by Jennifer Brown, MD
The U.S. Centers for Disease Control and Prevention recommends that hospitals optimize their antimicrobial stewardship programs and reduce unnecessary antimicrobial use. Programs that track only inpatient use may not accurately capture total use attributable to hospitalizations since a significant proportion of antimicrobial use may occur in the post-discharge setting. Yet, collecting post-discharge use data can be time consuming and logistically challenging.
In the August issue of Infection Control and Hospital Epidemiology, Dyer et al. reported the results of their study that evaluated the feasibility of obtaining electronic discharge antimicrobial prescription data and determining total durations of antimicrobial exposure for hospital stays. Overall, 45,693 inpatient hospitalizations at one academic medical center and two community teaching hospitals were retrospectively reviewed; electronic medication administration records were used to determine inpatient antimicrobial days, and electronic discharge prescriptions were used to assess intended post-discharge antimicrobial days (compliance with outpatient antimicrobials was not verified). About 51 percent of admitted patients received inpatient antimicrobials, and 16 percent received electronic antimicrobial prescriptions at discharge. Another 5 percent did not receive inpatient antimicrobials, but were given electronic prescriptions for antimicrobials at discharge. Outpatient antimicrobial days accounted for 38 percent of the total days of antimicrobial therapy for hospital stays, and 78 percent of patients had antimicrobial durations of therapy that exceeded recommended durations for common diagnoses such as pneumonia, urinary tract infection, and skin/soft tissue infection.
This study underscores that assessing transitions of care and discharge antimicrobial prescribing is needed to reduce overuse and to more accurately calculate total durations of therapy for hospital stays. The challenges of electronic data extraction and analysis strategies, including the risk of missing data bias, are discussed by the investigators; however, they also provide guidance for institutions that aim to optimize discharge antimicrobial tracking and stewardship.