Preventing Infections in Cancer Patients: Antibiotics, Hematopoetic Growth Factors or Both? a Network Analysis

Background: Infectious complications such as febrile neutropenia belong to the most serious complications of chemotherapy including stem cell transplantation for cancer. The mortality rate associated with febrile neutropenia is approximately 10%. Meta-analyses have shown that both hematological growth factors (CSFs) and antibiotics prevent infections. A comparison of these two agents or their combination has not been examined in systematic reviews. We therefore conducted a network analysis to determine the role of antibiotics and CSFs for the prophylaxis of infections in cancer patients receiving myelosuppressive chemotherapy or hematopoetic stem cell transplantation (SCT).

Methods: The network analysis included all randomized controlled trials that compared two or more of the following prophylaxis options: no prophylaxis, prophylaxis with antibiotics alone, prophylaxis using CSFs alone or prophylaxis using combinations of both, CSFs and antibiotics. Trails that did report overall survival, on study mortality, infection-related mortality, clinically documented infections, microbiologically documented infections or fever/febrile neutropenia were excluded. A Bayesian network analysis with four treatment options was performed; results are presented as odds ratios (OR) with 95% credibility intervals (CI).

Results: The best prophylaxis in the network with regard to preventing infections and infection-related mortality is the combination of antibiotics and CSFs. Comparing antibiotics alone to CSFs alone yields an OR of 1.00 (95% CI 0.69–1.52) for clinically documented infections. For the combination of both antibiotics and CSFs compared to only antibiotics or only CSFs, the incidence of clinically documented infections was also reduced (OR=0.61, 95% CI (0.46–0.77)). This is also true for the subgroup of patients receiving SCT or patients with acute leukemia.

Conclusions: For patients receiving myelosuppressive chemotherapy, antibiotics and CSFs are similarly efficient in reducing infections. The choice of agent can therefore be based on preferences of the treating physician and the adverse events expected. The best prophylactic regimen however is the prophylaxis using both, antibiotics and CSFs. The combination should be considered for patients at high risk of developing infections such as those receiving SCT or patients with acute leukemia.