Is C-reactive protein sufficient to guide antimicrobial therapy for lower respiratory tract infections among children? Results from a stepped-wedge cluster randomized trial in Uganda

Résumé

The accurate identification of young children with non-severe lower respiratory tract infections who may benefit from antimicrobial therapy is crucial both for individual patient management but also to curb crowing rates of antimicrobial resistance that pose a public health threat.Research by Ciccone and colleagues suggests that using a C-reactive protein guided approach to the evaluation of young children with lower respiratory tract infections may help reduce antimicrobial prescription without increasing rates of treatment failure.Despite more than a 75% global reduction in fatal cases of lower respiratory tract infections (LRTI) from the 1990s to the 2020s, LRTIs continue to be the leading individual cause of morbidity and mortality for children aged 2 to 59 months [1].Despite such significant burden, there is no clinically feasible reference standard for the diagnosis of LRTI.A definitive diagnosis of LRTI can only be made through lung biopsy, which is neither feasible nor necessary in routine clinical practice.Due to the assumption that a high proportion of fatal LRTIs are bacterial in nature, the World Health Organization (WHO) recommends that the diagnosis and treatment of LRTI in low-and middle-income countries be driven by severity and clinical presentation, with more severe cases requiring referral to the hospital.Specifically, the WHO recommends that children aged between 2 and 59 months with a cough and age-adjusted tachypnea be treated with antibiotics either in the community for non-severe cases or in the hospital for severe cases [2].WHO-defined LRTI does not require radiographic confirmation.However, prior studies have questioned the accuracy of clinical signs and symptoms for WHO-defined LRTI compared to radiographic pneumonia [3].It should be noted, however, that chest radiographic findings cannot be used to accurately distinguish between viral and bacterial etiologies [4].To add further complexity, findings from a multi-center study involving extensive etiological testing suggest that as many as 60% of young children with LRTIs had viruses (and not bacterial infections), and thus may not directly benefit from antimicrobial therapy [5].This may explain why findings from randomized controlled trials suggest that children with non-severe WHO-defined LRTI treated with shorter courses of antimicrobial therapy (i.e., 3 days) [6] and even with placebo [7] had no

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