Role of Intravenous Azithromycin as Adjunctive Therapy in Children With Acute Encephalitis Syndrome (AES): An...

Acute encephalitis syndrome (AES) has high morbidity and mortality in children. Empirical treatment of AES often consists of third-generation cephalosporins, with vancomycin and acyclovir, and frequently excludes the use of azithromycin, targeted at scrub typhus. In a resource-constrained setting, testing for scrub typhus becomes challenging. Considering the lacunae in the existing literature, there is a need for robust evidence to determine the role of additional azithromycin use in children with AES.  Objective: To evaluate the efficacy and safety of adjunctive intravenous azithromycin treatment in children with AES compared to standard therapy alone.

An open-label, two-arm randomized controlled trial was conducted at a tertiary care teaching hospital with a level III pediatric intensive care unit. Children aged one to 14 years with AES were enrolled. Intravenous azithromycin in addition to conventional treatment (n=30) and conventional treatment (third-generation cephalosporin, vancomycin, and acyclovir) were compared. The primary outcome measure was all-cause mortality. Secondary outcome measures included the total length of hospital stay, the proportion of children with significant disability as determined by the Liverpool Outcome Score (LOS) at discharge, and the proportion of children who experienced at least one serious adverse event.

The two groups were comparable in terms of all-cause mortality (23.3% vs. 20%; p=0.75), duration of hospital stay (12.57 days vs. 13.67 days; P=0.28), and significant disability at the time of discharge (52.40 vs. 53.47 days; P=0.79). None developed serious life-threatening adverse events.

Additional treatment with intravenous azithromycin does not impact all-cause mortality among children with AES. Further evaluation is suggested with an adequately powered study and long-term follow-up.