Additional anti-Gram-positive antibiotic treatment for febrile neutropenic cancer patients

Abstract

Background: The pattern of infections among neutropenic cancer patients has shifted in the last decades to a predominance of Gram-positive infections. Some of these Gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment.

Objectives: To assess the effectiveness of empirical anti-Gram-positive (antiGP) antibiotic treatment for febrile neutropenic cancer patients in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment.

Search strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004), EMBASE (January 1980 to 2004), LILACS (1982 to 2004), conference proceedings, and all references of included studies. First authors of all included and potentially relevant trials were contacted.

Selection criteria: Randomised controlled trials comparing one antibiotic regimen to the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic cancer patients.

Data collection and analysis: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Relative risks (RR) with 95% confidence intervals (CI) were calculated. A random effects model was used for all comparisons showing substantial heterogeneity (I(2 )> 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible.

Main results: Thirteen trials and 2392 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in eleven studies and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Seven studies were assessed in the overall mortality comparison and no significant difference between the comparator arms was seen, RR 0.82 (95% CI 0.56 to 1.20, 852 patients). Ten trials assessed failure including modifications as failures, while six assessed overall failure, disregarding treatment modifications. Failure with modifications was significantly reduced, RR 0.76 (95% CI 0.68 to 0.85, 1779 patients) while overall failure was equal, RR 1.00, 95% CI (0.79 to 1.27, 943 patients). Both mortality and failure did not differ significantly among patients with Gram-positive infections, but comparisons were small. Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates, and were associated with a reduction in documented Gram-positive superinfections. Resistant colonisation was not documented in the studies.

Authors' conclusions: Current evidence shows that the addition of antiGP treatment, namely glycopeptides, prior to documentation of a Gram-positive infection does not improve outcomes.