Journal Club 2017

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial

Santolaya ME, Alvarez AM, Acuña M, et al. Clin Microbiol Infect. 2016 Nov 14. pii: S1198-743X(16)30556-0. doi: 10.1016/j.cmi.2016.11.001.

Background:

Respiratory viral infections are important causes of morbidity in children, including those with febrile neutropaenia (FN). Early detection of respiratory viral infections in children with cancer and FN may help optimise management by reducing hospitalisation and antimicrobial use. This prospective, multicentre randomised, open-label study examined safety and efficacy of ceasing antimicrobial treatment 48 hours after admission in children with cancer and FN, with a demonstrated respiratory viral infection, absence of positive bacterial culture, and favourable clinical course (temperature ≤ 38C, absence of an identifiable new clinical focus, and CRP <90 mg/L).

Main findings:

Respiratory viruses were detected by multiplex PCR from nasopharyngeal aspirates in one third (319/951, 33%) of oncology patients admitted with FN from July 2012 to December 2015 in 5 participating hospitals in Santiago, Chile. 176/319 (55%) patients with favourable clinical course were randomised at 48 hours. Approximately half each were randomised to either maintain (92/176) antimicrobials or to cease (84/176). Median duration of antimicrobial use was 7 days vs 3 days (P<0.0001), with similar frequency of uneventful resolution; 89/92 (97%) and 80/84 (95%) respectively, OR 1.48 (95% C.I. 0.32-6.83), P=0.61. Days of fever (2 vs 1), days of hospitalization (6 vs 6) and bacterial infections throughout the episode (2% vs 1%) were also similar, with one case of sepsis requiring PICU admission in the group that maintained antimicrobials, but no deaths.

Take home messages:

This study demonstrated uneventful resolution in 95% of episodes of febrile neutropenia with documented respiratory viral infection in which antimicrobials were withdrawn 48hours after admission. Antimicrobial use was safely reduced, based on stringent clinical and microbiological diagnostic criteria. The results favour incorporating molecular respiratory viral studies in initial evaluation of all children with cancer presenting with febrile neutropenia, and using this information to consider withdrawing antibiotics in stable children at 48hours. This study is an important advance in evidence-based management in children with febrile neutropenia.

Submitted by Laila Al Yazidi, Brendan McMullan and Pamela Palasanthiran, Sydney Children’s Hospital.