Oral versus intravenous antibiotic treatment for febrile

neutropenia in cancer patients (Review)

Vidal L, Ben dor I, Paul M, Eliakim-Raz N, Pokroy E, Soares-Weiser K, Leibovici L

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2013, Issue 10

http://www.thecochranelibrary.com

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients (Review)

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .

6BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

15DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

49DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 1 Mortality. . . . . . . . . 51

Analysis 1.2. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 2 Treatment failure. . . . . . 52

Analysis 1.3. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 3 Treatment failure - per protocol

analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

Analysis 1.4. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 4 Adverse events requiring discontinuation

of antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Analysis 1.5. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 5 Gastrointestinal adverse events (post-

protocol analysis). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Analysis 1.6. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 6 Lost to follow-up. . . . . . 57

Analysis 1.7. Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 7 Treatment failure not dt modification

in update. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Analysis 2.1. Comparison 2 Oral versus intravenous antibiotic therapy - subgroup analysis, Outcome 1 Treatment failure -

age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Analysis 2.2. Comparison 2 Oral versus intravenous antibiotic therapy - subgroup analysis, Outcome 2 Treatment failure -

source of infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

Analysis 2.3. Comparison 2 Oral versus intravenous antibiotic therapy - subgroup analysis, Outcome 3 Treatment failure -

severity of neutropenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Analysis 2.4. Comparison 2 Oral versus intravenous antibiotic therapy - subgroup analysis, Outcome 4 Treatment failure -

type of malignancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

Analysis 3.1. Comparison 3 Methodological quality of studies, Outcome 1 Allocation concealment. . . . . . . 65

Analysis 4.1. Comparison 4 Post hoc subgroup analyses, Outcome 1 Setting. . . . . . . . . . . . . . . 66

Analysis 4.2. Comparison 4 Post hoc subgroup analyses, Outcome 2 Type of oral antibiotics. . . . . . . . . . 68

69ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

73APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

76WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

76HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

76CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

77DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

77SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

77NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

77INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iOral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients (Review)

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

[Intervention Review]

Oral versus intravenous antibiotic treatment for febrileneutropenia in cancer patients

Liat Vidal1, Itsik Ben dor1, Mical Paul2, Noa Eliakim-Raz1 , Ellisheva Pokroy3, Karla Soares-Weiser4, Leonard Leibovici1

1Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel. 2Unit of Infectious Diseases, Rambam

Health Care Center. Haifa, Israel and Sackler Faculty of Medicine, Tel Aviv, Israel. 3Department of Medicine A, Beilinson Hospital,

Rabin Medical Center, Petah Tikva, Israel. 4Enhance Reviews Ltd, Wantage, UK

Contact address: Liat Vidal, Department of Medicine E, Beilinson Hospital, Rabin Medical Center, 39 Jabotinski Street, Petah Tikva,

49100, Israel. vidallit@yahoo.com. VidalL2@clalit.org.il.

Editorial group: Cochrane Gynaecological Cancer Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 10, 2013.

Review content assessed as up-to-date: 31 January 2013.

Citation: Vidal L, Ben dor I, Paul M, Eliakim-Raz N, Pokroy E, Soares-Weiser K, Leibovici L. Oral versus intravenous antibiotic

treatment for febrile neutropenia in cancer patients. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD003992.DOI: 10.1002/14651858.CD003992.pub3.

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

A B S T R A C T

Background

Fever occurring in a neutropenic patient remains a common life-threatening complication of cancer chemotherapy. The common

practice is to admit the patient to hospital and treat him or her empirically with intravenous broad-spectrum antibiotics. Oral therapy

could be an alternative approach for selected patients.

Objectives

To compare the efficacy of oral antibiotics versus intravenous (IV) antibiotic therapy in febrile neutropenic cancer patients.

Search methods

The Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, MEDLINE (1966 to

January week 4, 2013), EMBASE (1980 to 2013 week 4) and LILACS (1982 to 2007). We searched several databases for ongoing

trials. We checked the conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC)

(1995 to 2007), and all references of included studies and major reviews were scanned.

Selection criteria

Randomised controlled trials (RCTs) comparing oral antibiotic(s) to intravenous antibiotic(s) for the treatment of neutropenic cancer

patients with fever. The comparison between the two could be started initially (initial oral) or following an initial course of intravenous

antibiotic treatment (sequential).

Data collection and analysis

Two review authors independently assessed trial eligibility and methodological quality and extracted data. Data concerning mortality,

treatment failures and adverse events were extracted from the included studies assuming an intention-to-treat basis for the outcome

measures whenever possible. Risk ratios (RR) with 95% confidence intervals (CI) were estimated for dichotomous data. Risk of bias

assessment was also made in line with methodology of The Cochrane Collaboration.

1Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients (Review)

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

mailto:vidallit@yahoo.commailto:VidalL2@clalit.org.il

Main results

Twenty-two trials (3142 episodes in 2372 patients) were included in the analyses. The mortality rate was similar when comparing

oral to intravenous antibiotic treatment (RR 0.95, 95% CI 0.54 to 1.68, 9 trials, 1392 patients, median mortality 0, range 0% to

8.8%). Treatment failure rates were also similar (RR 0.96, 95% CI 0.86 to 1.06, all trials). No significant heterogeneity was shown

for all comparisons but adverse events. The effect was stable in a wide range of patients. Quinolones alone or combined with an