Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial
Read article: Submitted by: Dr Rachel Heenan, Dr Shu Ki Tsoi, Dr Nelson Wang, Prof Nigel Curtis; The Royal Children’s Hospital, Melbourne, June 2024.Background:Children with cancer and febrile neutropenia (FN) caused by viral respiratory tract infections (RTIs) generally have more favourable outcomes than those with bacterial infections. This prospective non-inferiority study in Chile (2021-2023) explored whether FN patients with PCR-proven viral RTIs can have antimicrobial therapy safely withdrawn rather than continued until the end of the FN episode. Following an initial (48-72 hour) period, antimicrobial treatment was stopped only if the patient also had negative bacterial cultures and a ‘favourable clinical evolution’ (‘good clinical status’, temperature ≤38°C, no new clinical focus, and CRP <90 mg/L). The primary endpoint was the proportion of episodes with an uneventful resolution. Secondary endpoints included days of fever, days of hospitalisation, need to restart antimicrobials, sepsis, ICU admission and death.Findings:Of 301 children with FN who had a respiratory virus as the sole identified microorganism, 139 (46%) had a ‘favourable clinical evolution’ at 48-72 hours and were randomised to either continue (n=70) or withdraw (n=69) antimicrobial therapy. Median days of antimicrobial therapy were 5 versus 3 days (p<0.001), respectively. Both groups had similarly high rates of uneventful resolution (66/70 (94%) vs. 66/69 (96%); RR 1.0 95% CI 0.9-1.1). Days of hospitalisation (5 vs. 5), days with ANC <500/mm3 (4 vs. 4), and the proportion of patients with oxygen requirement (3% vs. 2%) were also similar between the groups. No cases of PICU admission, sepsis, mechanical ventilation requirement, or death were reported. The most common viruses identified were rhinovirus/enterovirus (53%) and SARS-CoV-2 (18%). Take home message:This study is consistent with previous studies finding that withdrawing antibiotics in paediatric cancer patients with FN who have a respiratory virus alone and a favourable clinical evolution is not inferior to continuing antimicrobials until the end of the FN episode.
