Background: cancer patients develop neutropenia, a decrease in the subset of leukocytes responsible for protection against bacteria, as a result of chemotherapy or cancer. Neutropenia predisposes the patients to severe bacterial infections. Standard antibiotic regimens for cancer patients with neutropenia and fever are directed at most of the bacteria that can cause infections. However, a subset of resistant bacteria belonging to the the Gram-positive group (Staphylococcus aureus and Streptococci) remain untreated unless specific antibiotics are added to the treatment.
Review question: we assessed whether the addition of specific antiGram-positive antibiotics prior to identification of a causative bacteria improves survival and cure among cancer patients with fever and neutropenia.
Search dates: the evidence is current to August 2013.
Study characteristics: we included randomised controlled trials that compared a standard antibiotic regimen to the same regimen with an antibiotic directed at Gram-positive bacteria. Overall, 13 randomised controlled trials were included with 2392 patients or episodes of infection. The antibiotics were given to cancer patients with neutropenia and fever as first-line treatment (11 trials) or for recurrent fever (two trials).
Study funding sources: in 8/13 of the trials the trial received funding from the industry.
Key results: mortality did not differ significantly between patients groups. Antibiotic treatment was more frequently modified among patients who did not initially receive specific antibiotics against Gram-positive bacteria, but overall treatment failures were not significantly different. We attempted to examine the durations of fever and hospital stay, but these were not consistently reported. The addition of specific antibiotics against Gram-positive bacteria resulted in more adverse events, mainly rash. We conclude that antibiotic treatment directed against resistant Gram-positive bacteria can await identification of bacteria and need not be given routinely prior to bacterial identification.
Quality of the evidence: overall the quality of the evidence was good since it relied on randomised controlled trials, most of which were at low risk of bias. A limitation of the results for mortality was that all-cause mortality was not reported and could not be obtained in 6/13 of the studies. The trials did not examine specific circumstances that might mandate empirical use of antibiotics against Gram-positive bacteria and thus the evidence is relevant to cancer patients with fever, without low blood pressure, or a focus of infection that might be caused by Gram-positive bacteria.