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 methods
We searched The Cochrane Central Register of Controlled Tirals (CENTRAL), (The Cochrane Library Issue 3, 2007), PUBMED (1966 to 2007), LILACS (1982 to 2007), conference proceedings, and all references of included studies. First authors of all included and potentially relevant trials were contacted.
Selection criteria
Randomised controlled trials (RCTs) 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 review authors 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 (I2 >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.
PICOs
Plain language summary
Specific antibiotic treatment directed against resistant Gram‐positive bacteria can await identification of these pathogens and need not be given empirically
Resistant Gram‐positive bacteria, originating from the skin and breaks in skin integrity such as intravenous lines, have emerged as causes for infection in cancer patients. Specific antibiotics must be added to the 'standard' antibiotic regimen to cover these bacteria. The review authors identified 13 randomised controlled trials using antibiotic treatments administered prior to identifying a causative pathogen, which compared those including or excluding specific anti‐Gram positive antibiotics. Mortality and several morbidity measures following infection did not differ significantly. These specific antibiotics are 'last resort' antibiotics against infections due to Gram‐positive bacteria and their use in general should be restricted to proven infections.
