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Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children—a systematic review of prospective trials

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Abstract

Background

There is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population.

Methods

We performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure.

Results

From 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality.

Conclusion

Based on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.

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Acknowledgements

We would like to thank Elizabeth Uleryk for her gracious assistance and expertise in conduct of the literature search. We also would like to acknowledge Rhonda Adams for her administrative assistance.

LS is supported by a New Investigator Award with the Canadian Institutes of Health Research.

Conflict of interest

There are no conflicts of interest to declare.

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Authors

Corresponding author

Correspondence to L. Sung.

Appendix 1

Appendix 1

Search strategies used to identify eligible studies

Ovid MEDLINE(R)

  1. 1

    agranulocytosis/or neutropenia/or leukopenia/

  2. 2

    fever/ or “fever of unknown origin”/

  3. 3

    1 and 2

  4. 4

    (febrile adj5 (neutropen* or granulocytop* or agranulocyto* or leukocytop??ni*)).ti,ab.

  5. 5

    3 or 4

  6. 6

    (“clinical trial, all” or clinical trial).pt. or clinical trials as topic/

  7. 7

    clinical trial, phase i.pt. or clinical trials, phase i as topic/

  8. 8

    clinical trial, phase ii.pt. or clinical trials, phase ii as topic/

  9. 9

    clinical trial, phase iii.pt. or clinical trials, phase iii as topic/

  10. 10

    clinical trial, phase iv.pt. or clinical trials, phase iv as topic/

  11. 11

    controlled clinical trial.pt. or controlled clinical trials as topic/

  12. 12

    meta-analysis.pt. or meta-analysis as topic/

  13. 13

    multicenter study.pt. or multicenter studies as topic/

  14. 14

    randomized controlled trial.pt. or randomized controlled trials as topic/

  15. 15

    or/6–14

  16. 16

    cohort studies/ or longitudinal studies/or follow-up studies/or prospective studies/

  17. 17

    case–control studies/or retrospective studies/or cross-sectional studies/

  18. 18

    prognosis/ or disease-free survival/or medical futility/or pregnancy outcome/or treatment outcome/or treatment failure/

  19. 19

    disease progression/

  20. 20

    morbidity/or incidence/or prevalence/

  21. 21

    mortality/or cause of death/or fatal outcome/or hospital mortality/or infant mortality/or maternal mortality/or survival rate/

  22. 22

    survival analysis/or disease-free survival/

  23. 23

    natural histor???.tw.

  24. 24

    predictive value of tests/

  25. 25

    or/16–24

  26. 26

    15 or 25

  27. 27

    5 and 26

  28. 28

    limit 27 to yr = “1980–Current”

  29. 29

    limit 28 to English language

EMBASE

  1. 1

    leukopenia/or agranulocytosis/or neutropenia/

  2. 2

    pyrexia idiopathica/or fever/or (fever* adj5 unknown adj5 origin*).ti,ab.

  3. 3

    1 and 2

  4. 4

    febrile neutropenia/

  5. 5

    3 or 4

  6. 6

    ct.fs. or clinical trial/or phase 1 clinical trial/or phase 2 clinical trial/or phase 3 clinical trial/or phase 4 clinical trial/or controlled clinical trial/or randomized controlled trial/or multicenter study/or meta analysis/or double-blind procedure/or single blind procedure/or triple blind procedure/or (random* or rct or rcts or ((singl: or doubl: or tripl: or trebl:) and (mask: or blind:))).mp.

  7. 7

    5 and 6

  8. 8

    cohort analysis/or longitudinal study/or prospective study/or case–control study/or hospital based case–control study/or population based case–control study/or retrospective study/or cancer recurrence/or cancer regression/or cancer relapse/or disease duration/or disease exacerbation/or prognosis/or recurrent disease/or reinfection/or relapse/or remission/or tumor recurrence/or tumor regression/or survival/or cancer survival/or disease free survival/or overall survival/or survival rate/or survival time/or incidence/or cancer incidence/or familial incidence/or morbidity/or maternal morbidity/or perinatal morbidity/or newborn morbidity/or mortality/or cancer mortality/or childhood mortality/or embryo mortality/or fetus mortality/or infant mortality/or maternal mortality/or prenatal mortality/or surgical mortality/or perinatal mortality/or newborn mortality/or death/or “cause of death”/or dying/or heart death/or sudden death/or child death/or newborn death/or prevalence/or treatment outcome/or disease free interval/or treatment failure/or drug treatment failure/or (natural adj2 history).mp. (2419301)

  9. 9

    5 and 8

  10. 10

    7 or 9

  11. 11

    4 and 6

  12. 12

    4 and 8

  13. 13

    11 or 12

  14. 14

    limit 13 to English language

Cochrane Central Register of Controlled Trials

  1. 1

    agranulocytosis/ or neutropenia/ or leukopenia/

  2. 2

    fever/ or "fever of unknown origin"/

  3. 3

    1 and 2

  4. 4

    (febrile adj5 (neutropen* or granulocytop* or agranulocyto* or leukocytop??ni*)).ti,ab.

  5. 5

    3 or 4 (1020)

  6. 6

    limit 5 to yr = “1980–Current”

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Manji, A., Beyene, J., Dupuis, L.L. et al. Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children—a systematic review of prospective trials. Support Care Cancer 20, 1135–1145 (2012). https://doi.org/10.1007/s00520-012-1425-8

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