Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy
Abstract
Background
Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections, but not in reducing mortality rates.
Objectives
This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention.
Search methods
Electronic searches on The Cochrane Cancer Network Register of Trials (2005), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to 2005) and EMBASE (1980 to 2005) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted.
Selection criteria
RCTs or quasi‐RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients.
Data collection and analysis
Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated.
Main results
One‐hundred and one trials (12,599 patients) performed between the years 1973 to 2005 met the inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR 0.66 [95% CI 0.55 to 0.79]) (comparison 1.1). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 50 (95% CI 34 to 268).
Prophylaxis resulted in a significant decrease in the risk of infection‐related death, RR 0.59 (95% CI 0.47 to 0.75) (comparison 2.1) and in the occurrence of fever, RR 0.77 (95% CI 0.74 to 0.81) (comparison 3.1). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all‐cause mortality, RR 0.52 (95% CI, 0.37 to 0.74) (comparison 1.101).
Authors' conclusions
Our review demonstrated that prophylaxis significantly reduced all‐cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all‐cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.
PICO
Plain language summary
To review prophylactic (preventive) antibiotic therapy given to cancer patients after chemotherapy, and before development of fever, in order to prevent infections and reduce mortality (the number of deaths)
For patients receiving chemotherapy, there is an increased risk of infection mediated through neutropenia (low white blood cell count). This is a toxic reaction of chemotherapy on the bone marrow and causes a dangerous decrease in the protective white blood cells.
The first sign of infection may be fever with the accompanying risks of morbidity (illness) and mortality. Without preventive measures, 48% to 60% of cancer patients who become feverish have an established infection. Antibiotic prophylaxis (prevention) has previously been shown to reduce fever and infections. The authors question was ‐ Does antibiotic prophylaxis save lives?
The study included 101 randomised controlled trials (RCTs) (12,599 patients) performed between the years 1973 to 2005. Antibiotic prophylaxis significantly decreased the risk of death from all causes by 34% when compared to no intervention. The authors estimate that the number of patients needed to be treated with antibiotics in order to prevent one death from all causes was 50. It also decreased the rate of death from infection, and the rate of development of fever. However, this antibiotic prophylaxis may be associated with unfavourable effects and may encourage new and more resistant infection.
Several limitations of the authors' analysis should be noted:
Most studies were limited to haematological cancer patients (mostly leukaemia). Most were conducted on hospitalized patients. Information on all cause mortality could not be obtained for all the studies. Many studies were dated.
The authors' conclusion is that following chemotherapy, patients with a low white blood count who receive preventive antibiotic treatment for bacterial infections show a decrease in mortality. They believe that prophylaxis, preferably with a quinolone antibiotic where resistance permits, should be recommended for routine use in these patients.
