Bacterial Codetection in Infants With Lower Respiratory Tract Infections

Lower respiratory tract infections (LRTIs) are common causes of acute respiratory failure (ARF) in children younger than two years. Mostly attributed to viral infections, LRTIs are commonly referred to as bronchiolitis regardless of the clinical presentation. Bacterial coinfection in children with LRTIs related to respiratory syncytial virus (RSV) has historically been reported to be low. However, recent studies have reported the presence of bacteria in the airways of intubated children with RSV infections that are often associated with longer pediatric intensive care unit (PICU) stays and ventilator days.^1-3 Still, the utility of checking tracheal cultures and the role of these bacteria in instrumented airways is not clear.^4,5 Complicating matters is that noninvasive positive pressure ventilation (NIPPV) has been increasingly used to forgo (although not completely prevent) intubation in young children with LRTIs.
 
To determine the prevalence of bacterial codetection (a surrogate for coinfection) and its significance in critically ill children with ARF, Karsies et al designed the multinational observational cohort study Bronchiolitis and Codetection (BACON).⁶ Their hypothesis was that the presence of bacteria in the airways of children younger than two years with an LRTI who were intubated was more common than has been reported because of the more widespread use of NIPPV and that this coinfection is associated with longer ventilator duration.
 
For this study, 47 participating PICUs contributed data between December 2019 and November 2020.⁶ The study group prospectively enrolled children younger than two years with either any clinical finding suggestive of an LRTI or an admission diagnosis of bronchiolitis, pneumonia, or LRTI, and the need for endotracheal intubation for ARF. Exclusion criteria included intubation for surgery, history of cardiac arrest, and the presence of a tracheostomy.
 
Data collected included demographics, the presence of acute respiratory distress syndrome (ARDS), presenting clinical symptoms, microbiologic laboratory results, the use of antibiotics, and outcomes including ventilation duration (the primary outcome of interest), PICU length of stay, and mortality. Codetection of bacteria was defined by the requirement for 1) the identification of moderate or heavy growth of bacteria (defined as ≤ 10⁴ colony-forming units/mL) and 2) the presence of moderate or many polymorphonuclear neutrophils (PMNs) (≥ 10/high-power field on Gram stain). Intubation duration was defined by the number of hours from intubation to successful extubation. Pediatric ARDS was defined using the Second Pediatric Acute Lung Injury Consensus Conference guidelines.⁷ Karsies et al did not adjust for multiple comparisons, so results of analyses were considered exploratory outside of the primary outcome.
 
A total of 556 children from 12 countries were enrolled, for a final total of 472 patients used for the primary analysis. The median age was approximately four months, with male sex predominant. Approximately 75% of the subjects had positive viral testing, with 50% demonstrating RSV. Of the cohort, 60% had moderate or many PMNs and 42% had moderate or heavy growth of pathogenic bacteria; 29% of the cohort had a codetection as defined by the study (37% of children with an admitting diagnosis of bronchiolitis, 13% with a pneumonia, and 15% with an LRTI).
 
Codetection was associated with younger age, an admitting diagnosis of bronchiolitis, and a positive viral test. Surprisingly, an admitting diagnosis of pneumonia was associated with lower odds of codetection. A total of 89% of the cohort received antibiotics, although there was no association between usage and codetection. Most importantly, codetection was not associated with a longer ventilator duration and in fact may have been associated with a shorter duration, although this finding was not statistically significant.
 
The authors demonstrated that codetection of bacteria occurred in slightly less than 30% of children younger than two years who were intubated secondary to an LRTA, which is consistent with other studies’ findings. This codetection did not result in worse outcomes, defined by this study as longer ventilation duration. Most children received antibiotics early in the course of their illness, which may have affected this result. Interestingly, the children who presented with a diagnosis of bronchiolitis had a higher incidence of codetection, compared with those who were diagnosed with pneumonia or LRTI, which indicates the difficulties in diagnosing an intubated child with a pathogenic bacterial infection. Some limitations of this study are its observational format, which did not allow for statements of causality, and the absence of data regarding the use of NIPPV prior to intubation.
 
 
References

1. Levine DA, Platt SL, Dayan PS, et al; Multicenter RSV-SBI Study Group of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. 2004 Jun;113(6):1728-1734.
2. Randolph AG, Reder L, Englund JA. Risk of bacterial infection in previously healthy respiratory syncytial virus-infected young children admitted to the intensive care unit. Pediatr Infect Dis J. 2004 Nov;23(11):990-994.
3. Wiegers HMG, van Nijen L, van Woensel JBM, Bem RA, de Jong MD, Calis JCJ. Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study. BMC Infect Dis. 2019 Nov 6;19(1):938.
4. Willson DF, Conaway M, Kelly R, Hendley JO. The lack of specificity of tracheal aspirates in the diagnosis of pulmonary infection in intubated children. Pediatr Crit Care Med. 2014 May;15(4):299-305.
5. Feldman E, Shah SS, Ahn D. Low diagnostic utility of frequent serial tracheal aspirate cultures in the PICU. Pediatr Crit Care Med. 2023 Aug 1;24(8):681-689.
6. Karsies T, Shein SL, Diaz F, et al; Bronchiolitis And COdetectioN (BACON) Study Investigators; for the Bronchiolitis Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network and the Red Colaborativa Pediátrica de Latinoamérica Network. Prevalence of bacterial codetection and outcomes for infants intubated for respiratory infections. Pediatr Crit Care Med. 2024 Mar 26. Online ahead of print.
7. Emeriaud G, López-Fernández YM, Iyer NP, et al; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2). Pediatr Crit Care Med. 2023 Feb 1;24(2):143-168.