A study published in the Journal of Antimicrobial Chemotherapy expounds the clinical benefits of early target attainment of azithromycin therapy when treating children with lower respiratory tract infections (LRTIs).
Azithromycin is the most widely used macrolide (antibiotics that prevent growth of bacteria by binding to the 50S subunit of the bacterial ribosome to interfere with the translation of mRNA) in children for the therapy of LRTIs. Early target attainment is the key factor influencing the outcome of antimicrobial therapy. The relationship between appropriate early treatment and enhanced survival has been well demonstrated. Once an infection is highly suspected or confirmed, the first 24 to 48 hours is paramount for the success of antimicrobial therapy. Failure to combat the causative pathogen adequately within this critical period increases the risk for mortality. This study evaluated the relationship between azithromycin concentrations during the first 24 to 48 hours of therapy and the clinical outcome to optimize antimicrobial therapy.
Children hospitalized at the Beijing Children’s Hospital for LRTIs (n=44) from 2014 to 2017 were included. The mean age and weight of the 44 children at the time of study were 5.25 years and 20.98 kg. To evaluate target attainment, azithromycin trough concentrations were collected within the first 2 days of hospitalization. Given the pharmacokinetic/pharmacodynamic characteristics of azithromycin for effective bacterial eradication, a target trough concentration of 0.25 mg/L was selected to maintain the minimum inhibitory concentration that is required to inhibit 90% of suspected pathogenic bacteria. The assessment of response to azithromycin therapy, partial or complete, was based on clinical (signs and symptoms of infection and inflammatory markers) and radiologic (radiograph or computed tomography findings) improvement or resolution, as well as on proven or presumed eradication of the pathogen. Lack of response to azithromycin therapy was defined as unchanged or worsened clinical signs and symptoms, inflammatory markers, and radiologic findings after 5 to 7 days of treatment. The median dosage of azithromycin was 10 mg/kg/day in the enrolled patients. The median duration of therapy was 5.0 days. The median trough level was .16 mg/L (range, .01-.34 mg/L).
Azithromycin trough concentrations were ≤.25 mg/L in 36 cases (82%) and >.25 mg/L in 8 cases (18%). Antibacterial efficacy as measured by decreased C-reactive protein (P=.006) and percentage of neutrophils (P=.043) was significantly higher in children with trough concentrations >.25 mg/L compared with children with trough concentrations ≤.25 mg/L. No significant differences were observed for other effectiveness parameters. Although large interindividual variability in trough concentrations was demonstrated, the standard treatment was well tolerated and no liver injury or cardiovascular risk was detected. No drug-related adverse events were shown to have a casual association with azithromycin therapy.
Overall, the investigators concluded that, “To the best of our knowledge, our study shows, for the first time, the clinical benefits of early target attainment for azithromycin therapy in children.”
Liu S, Zheng Y, Wu X, et al. Early target attainment of azithromycin therapy in children with lower respiratory tract infections [published online July 27, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky273.