Literature Spotlight: Azithromycin for Neonatal Neuroprotection

Wait, did I read that correctly??… Using Z-pak for neonatal neuroprotection!

That was my initial reaction when I first saw the headline “Repurposing azithromycin for neonatal neuroprotection.” (1) 

Azithromycin (aka Zithromax Z-Pak, Zithromax TRI-PAK, Zmax, and Zithromax) is a macrolide antibiotic commonly used in the treatment of bacterial infections caused by a wide variety of organisms such as Haemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, Staphylococcus aureus, mycobacterium avium, and many others. 

However, researchers from the University of Michigan recently discovered that azithromycin may also have neuroprotective effects following hypoxic-ischemic brain injury (HIE). 

Aside from its use in treating bacterial infections, azithromycin has also been shown to have anti-inflammatory properties. And as you know, inflammation is a contributing factor to the pathogenesis of neonatal hypoxic-ischemic brain injury. 

Inflammation pathogenesis in HIE

In neonates, cerebral ischemia initiates an immediate innate immune response.  Within minutes of the insult, microglia (support cells that provide immune surveillance in the brain) are activated producing inflammatory and anti-inflammatory cytokines, and other substances which break down the blood-brain barrier. Peripheral leukocytes flood the compromised brain tissue, exposing it to systemic responses that further exacerbate inflammation and brain damage. (2)

 

 

Azithromycin Treatment Protocol

Researchers tested multiple treatment protocols in which azithromycin was administered in doses ranging from 15 to 45 mg/kg within 15 min to 4 hours following hypoxic insult in seven-day-old rat pups. 

 

 

Results & Conclusion

The results? All doses of azithromycin resulted in some improvement in function and reduction in brain injury.  As we’ve heard before time is brain, and this notion held true for the timing of azithromycin treatment post-injury.  The degree of efficacy was dose-dependent and decreased with increasing treatment delay. Additionally, a multiple-dose series administered over a 48 hour period following the ischemic injury was found to be more effective than a single dose.

Researchers concluded that azithromycin “could be an attractive candidate drug for repurposing and evaluation for neonatal neuroprotection in clinical trials.”

This is not the first time that researchers are turning to substances commonly used for other conditions, to investigate if they can potentially save damaged neurons.   

In premature infants, melatonin, that is commonly used as a sleep aid, is being studied for its anti-inflammatory properties to support neuronal repair after an intraventricular bleed. Erythropoietin (commonly used in the NICU to prevent red blood cell transfusion in preterm infants) is also being investigated as adjunctive therapy to therapeutic hypothermia in infants with HIE and this trial will complete enrollment later this year. Now, azithromycin is getting some attention for its potential with the term-infant HIE population! Time will tell whether or not azithromycin will be trialed an agent to support infants with hypoxic-ischemic injuries too.

 

REFERENCES

  1. Repurposing azithromycin for neonatal neuroprotection. https://www.ncbi.nlm.nih.gov/pubmed/31100754
  2. Inflammatory responses in hypoxic-ischemic encephalopathy. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764334/?tool=pmcentrez&report=abstract

 

 

 

 

 

Sharing is caring!