Oral antibiotics for treating febrile neutropenia in cancer patients at low risk for complications

Neutropenia (low white blood cell count) is a complication of cancer chemotherapy that exposes patients to life-threatening infections. Current practice for neutropenic patients with fever is hospital admission and treatment with intravenous antibiotics. Febrile neutropenia encompasses a spectrum of disease severity and low risk patients may be treated less aggressively. This review of randomised controlled trials showed comparable death and failure rates for oral and intravenous antibiotics for low risk patients, those with solid tumours or chronic leukaemia or lymphoma, and independent of age, source of infection and severity of the neutropenia.

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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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 strategy: 

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.

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