A 2023 commentary critically evaluates the longstanding recommendation endorsing the combined use of intravenous cephalosporins and oral macrolide antibiotics, specifically azithromycin, for the treatment of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). The commentary highlights that this recommendation, stemming from the 2014 NHLBI Expert Panel Report, is based on low-quality evidence and emphasizes the paucity of randomized controlled trials examining antibiotic efficacy and safety in ACS. Earlier investigations by the National Acute Chest Syndrome Study Group identified infections with Chlamydia pneumoniae and Mycoplasma pneumoniae as common causes of ACS in children, supporting macrolide use. However, more recent data indicate that these pathogens may be less prevalent than previously thought, and asymptomatic carriage is well-documented, raising concerns about empirical macrolide therapy’s justification. The widespread implementation of multiplex polymerase chain reaction (PCR) assays in clinical practice has enabled near-perfect negative predictive value for detecting these organisms, allowing clinicians to identify when macrolide treatment may be unnecessary. The commentary further discusses that despite this improved microbial diagnostic capacity, the entrenched practice of routinely administering macrolides to all ACS patients remains largely unchallenged, driven by historical precedent and potential immunomodulatory benefits observed in chronic pulmonary conditions. Nonetheless, robust evidence supporting immunomodulatory roles of macrolides in acute respiratory illnesses such as ACS is lacking, and corticosteroid use in ACS is regarded as controversial and generally not recommended. The author underscores the importance of antibiotic stewardship given the risk of macrolide resistance and cautions against continued use of macrolides in cases where multiplex PCR testing excludes C. pneumoniae and M. pneumoniae infections. Although macrolides have a favorable safety profile, their use without supportive data constitutes unnecessary exposure and contradicts principles of evidence-based medicine. Ultimately, the 2023 commentary calls for reevaluation of entrenched treatment paradigms based on low-quality evidence, advocating more selective and diagnostic-guided antibiotic use in ACS management. [1]
A 2024 clinical review provides a detailed overview and expert guidance on the management of acute pain in children and adolescents with SCD, emphasizing rapid assessment and early initiation of multimodal pain management. A comprehensive evaluation, including history, physical examination, and laboratory studies, is recommended to identify alternative diagnoses and SCD-related complications such as acute chest syndrome, stroke, and infection. Children with SCD are at increased risk for infections caused by encapsulated organisms, with Streptococcus pneumoniae, Salmonella, Escherichia coli, and Staphylococcus aureus among the most commonly isolated bacteria in the United States. Most institutions recommend ceftriaxone for empiric antibiotic therapy because of its long half-life and coverage of encapsulated organisms. However, repeated ceftriaxone exposure has rarely been associated with potentially fatal hemolysis; because of this risk, the authors’ institution uses ampicillin as first-line empiric antibiotic therapy. Notably, the review does not discuss the addition of a macrolide or otherwise provide recommendations regarding atypical antimicrobial coverage. [2]
The 2019 Cochrane systematic review was an update of the 2015 review evaluating the efficacy and safety of empiric antibiotic therapy for ACS in individuals with SCD. Because infectious and noninfectious causes of ACS may present similarly and numerous pathogens, including bacteria, have been implicated, antibiotics are commonly prescribed empirically for ACS; however, there is no standardized antibiotic approach, and treatment practices may vary geographically. The review sought randomized controlled trials (RCTs) evaluating antibiotics, either alone or in combination, compared with placebo, standard treatment, or alternative antibiotic regimens, with additional interest in differences according to treatment regimen, patient age, and geographic location. Consistent with the findings of the 2015 review, the updated literature search through July 2019 identified no eligible RCTs evaluating antibiotic treatment approaches for ACS in patients with SCD. Consequently, no quantitative synthesis or assessment of the comparative efficacy or safety of specific antibiotic regimens could be performed. The authors concluded that RCT evidence remains unavailable to establish an optimal antibiotic regimen for ACS, despite the routine empiric use of antibiotics in clinical practice, and noted that further trials were unlikely to be conducted; therefore, the Cochrane review would no longer be regularly updated. [3], [4]