Empirical antibiotic therapy in the treatment of patients with cancer and neutropenic fever
The systematic empirical addition of antibacterial drugs active against gram-positive microorganisms does not improve outcomes in patients with cancer and febrile neutropenia.
If we turn to the problem of infection in patients with oncopathology and neutropenia, it should be noted that in recent decades, Gram positive microorganisms have prevailed among pathogens. Some of these Gram-positive pathogens show an increase in resistance to beta-lactams, for which it is necessary to prescribe a more specific antibacterial treatment.
In order to assess the effectiveness of empirical antibacterial therapy directed against Gram-positive pathogens in patients with oncopathology and febrile neutropenia, a systematic review and meta-analysis were performed, during which mortality and treatment ineffectiveness were considered the main parameters evaluated. To assess the frequency of development of resistance, cases of other infections and adverse events associated with the appointment of additional antibacterial therapy, active against Gram-positive pathogens, have been revealed.
Searches were performed in the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, number 7), the MEDLINE databases (from 1966 to 2013), EMBASE (from 1982 to 2013), LILACS (from 1982 to 2013), data presented at conferences, as well as in article references on relevant topics.
A meta-analysis included randomized controlled trials comparing an antibiotic regimen to the same regimen, but with the addition of an antibiotic active against gram-positive microorganisms in the treatment of patients with oncology and neutropenic fever.
Two experts independently assessed the relevance of the studies to be included in the meta-analysis. A total of 13 studies were selected for systematic review, with a total of nearly 2,400 patients or episodes of neutropenic fever (n = 2,392).
Empirical antibacterial therapy, active against Gram-positive pathogens, was used as initial therapy in 11 studies and in 2 studies with persistent neutropenic fever. In 9 studies, glycopeptides were prescribed. In 7 studies, overall mortality was estimated, and there was no statistically significant difference between the groups compared (relative risk 0.82, 95% confidence interval 0.56-1.2, 852 patients).
10 studies evaluated treatment failure, including modification of treatment as a criterion for failure, while 6 studies evaluated overall treatment failure regardless of modification of treatment.
Ineffectiveness with modification was significantly lower (relative risk 0.76, 95% CI 0.68-0.85, 1779 patients), while without modification, the overall treatment failure was the same (relative risk 1, 0, 95% CI 0.79-1.27, 943 patients).
Mortality and treatment failure did not differ statistically significantly between patients with Gram-positive infections, however, the number of studies in this comparison was small. The use of glycopeptides did not increase the incidence of fungal superinfection and resulted in a decrease in documented cases of superinfection caused by Gram-positive pathogens. Colonization by resistant mutants has not been studied in the studies analyzed.
Thus, current evidence suggests that routine empirical supplementation of drugs active against Gram-positive strains (especially glycopeptides) does not improve outcomes in patients with cancer and neutropenic fever.