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Comment & Response
January 11, 2021

Why Is Antibiotic Treatment Rarely Performed in COVID-19–Positive Children Admitted in Pediatric Intensive Care Units?

Author Affiliations
  • 1Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, Monserrato, Italy
JAMA Pediatr. 2021;175(4):431-432. doi:10.1001/jamapediatrics.2020.5348

To the Editor Shekerdemian et al1 reported 48 coronavirus disease 2019–positive children (median age, 13 years) admitted to pediatric intensive care units in the US and Canada. Overall, 83% of children were not treated with antibiotics, and 17% had been treated with azithromycin. We deeply reflected on this, especially considering that 83% were also affected by severe comorbidities.

In acute diseases affecting the lungs, such as sepsis or acute respiratory distress syndrome, the lung microbiota is enriched in intestinal bacteria, such as Bacteroidetes and Enterobacteriaceae, triggering a dangerous proinflammatory vicious circle (more gut in the lung).2 In fact, the gut becomes hyperpermeable (leaky gut) and bacteria can move through the colon wall and reach the lung (hypothesis of intestinal lymph), promoting inflammation (with an increase in inflammation markers, such as interleukins 6 and 8, associated with an increased alveolus-capillary permeability), infection, and acute lung damage.3

Recent data suggest a close correlation between the pulmonary microbiota and intensive care unit hospitalization.4 In particular, changes occurring in the lung microbiota can help to predict if and to what extent critically ill patients will respond to the treatment. In a recent study of 91 adult patients, only those colonized in the lung by Enterobacteriaceae in the gut were admitted to the intensive care unit. In addition, patients showing a high number of bacteria in the lungs, and especially a prevalence of typical (good) lung bacteria, showed a better outcome 1 day after intensive care unit hospitalization for respiratory distress syndrome (globally requiring fewer days of ventilation). Contrarily, the presence of 2 groups of bacteria normally colonizing the gut (Lachnospiraceae and Enterobacteriaceae) was common in the lung microbiota of patients with the worst outcome.4

In conclusion, it can be deduced that the bacterial species found in the lung can be predictive of the outcomes. What remains to be understood is whether it is possible to modify the lung microbiota, both to prevent and to treat lung damage. The pathways regarding the gut-lung axis are not fully clear, but it is well known that respiratory tract infections can complicate with gastrointestinal dysfunctions and the other way around: this phenomenon can be also be observed in patients with coronavirus disease 2019 infection, as shown in studies performed on cats.5

The action of angiotensin-converting enzyme 2 is influenced by the intestinal microbiota. We believe that for a better outcome, a course of antibiotics effective on intestinal bacteria could be considered, particularly in critically ill children undergoing endotracheal intubation.3

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Article Information

Corresponding Author: Flaminia Bardanzellu, MD, Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, SS 554 km 4,500, 09042 Monserrato, Italy (bardanzellu.flaminia@virgilio.it).

Published Online: January 11, 2021. doi:10.1001/jamapediatrics.2020.5348

Conflict of Interest Disclosures: None reported.

References
1.
Shekerdemian  LS, Mahmood  NR, Wolfe  KK,  et al; International COVID-19 PICU Collaborative.  Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units.   JAMA Pediatr. 2020;174(9):868-873. doi:10.1001/jamapediatrics.2020.1948PubMedGoogle ScholarCrossref
2.
Mukherjee  S, Hanidziar  D.  More of the gut in the lung: how two microbiomes meet in ARDS.   Yale J Biol Med. 2018;91(2):143-149.PubMedGoogle Scholar
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Fanos  V, Pintus  MC, Pintus  R, Marcialis  MA.  Lung microbiota in the acute respiratory disease: from coronavirus to metabolomics.   J Pediatr Neonat Individual Med. 2020;9(1):e090139. doi:10.7363/090139.Google Scholar
4.
Dickson  RP, Schultz  MJ, van der Poll  T,  et al; Biomarker Analysis in Septic ICU Patients (BASIC) Consortium.  Lung microbiota predict clinical outcomes in critically ill patients.   Am J Respir Crit Care Med. 2020;201(5):555-563. doi:10.1164/rccm.201907-1487OCPubMedGoogle ScholarCrossref
5.
Meazzi  S, Stranieri  A, Lauzi  S,  et al.  Feline gut microbiota composition in association with feline coronavirus infection: a pilot study.   Res Vet Sci. 2019;125:272-278. doi:10.1016/j.rvsc.2019.07.003PubMedGoogle ScholarCrossref
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