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Meta-Analysis
. 2013 Oct 9;2013(10):CD003992.
doi: 10.1002/14651858.CD003992.pub3.

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients

Liat Vidal  1 , Itsik Ben Dor, Mical Paul, Noa Eliakim-Raz, Ellisheva Pokroy, Karla Soares-Weiser, Leonard Leibovici
Affiliations
Meta-Analysis

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients

Liat Vidal et al. Cochrane Database Syst Rev. .

Abstract

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.

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 another antibiotic were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics.

Authors' conclusions: Based on the present data, oral treatment is an acceptable alternative to intravenous antibiotic treatment in febrile neutropenic cancer patients (excluding patients with acute leukaemia) who are haemodynamically stable, without organ failure, and do not have pneumonia, infection of a central line or a severe soft-tissue infection. The wide CI for mortality allows the present use of oral treatment in groups of patients with an expected low risk for mortality, and further research should be aimed at clarifying the definition of low risk patients.

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Conflict of interest statement

None known

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 Oral versus intravenous antibiotic therapy, outcome: 1.1 Mortality.
4
4
Funnel plot of comparison: 1 Oral versus intravenous antibiotic therapy, outcome: 1.3 Treatment failure ‐ per protocol analysis.
1.1
1.1. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 2 Treatment failure.
1.3
1.3. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 3 Treatment failure ‐ per protocol analysis.
1.4
1.4. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 4 Adverse events requiring discontinuation of antibiotics.
1.5
1.5. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 5 Gastrointestinal adverse events ('post‐protocol' analysis).
1.6
1.6. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 6 Lost to follow‐up.
1.7
1.7. Analysis
Comparison 1 Oral versus intravenous antibiotic therapy, Outcome 7 Treatment failure not dt modification in update.
2.1
2.1. Analysis
Comparison 2 Oral versus intravenous antibiotic therapy ‐ subgroup analysis, Outcome 1 Treatment failure ‐ age.
2.2
2.2. Analysis
Comparison 2 Oral versus intravenous antibiotic therapy ‐ subgroup analysis, Outcome 2 Treatment failure ‐ source of infection.
2.3
2.3. Analysis
Comparison 2 Oral versus intravenous antibiotic therapy ‐ subgroup analysis, Outcome 3 Treatment failure ‐ severity of neutropenia.
2.4
2.4. Analysis
Comparison 2 Oral versus intravenous antibiotic therapy ‐ subgroup analysis, Outcome 4 Treatment failure ‐ type of malignancy.
3.1
3.1. Analysis
Comparison 3 Methodological quality of studies, Outcome 1 Allocation concealment.
4.1
4.1. Analysis
Comparison 4 Post hoc subgroup analyses, Outcome 1 Setting.
4.2
4.2. Analysis
Comparison 4 Post hoc subgroup analyses, Outcome 2 Type of oral antibiotics.
See this image and copyright information in PMC

Update of

References

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References to other published versions of this review

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