Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy
Anat Gafter-Gvili, Abigail Fraser, Mical Paul, Liat Vidal, Theresa A Lawrie, Marianne D van de Wetering, Leontien C M Kremer, Leonard Leibovici, Anat Gafter-Gvili, Abigail Fraser, Mical Paul, Liat Vidal, Theresa A Lawrie, Marianne D van de Wetering, Leontien C M Kremer, Leonard Leibovici
Abstract
Background: Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality.
Objectives: This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention.
Search methods: We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies.
Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients.
Data collection and analysis: Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software.
Main results: One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection (53 trials, 6383 participants; RR 0.51, 95% CI 0.42 to 0.62) and other indicators of infection.There were no significant differences between quinolone prophylaxis and TMP-SMZ prophylaxis with regard to death from all causes or infection, however, quinolone prophylaxis was associated with fewer side effects leading to discontinuation (seven trials, 850 participants; RR 0.37, 95% CI 0.16 to 0.87) and less resistance to the drugs thereafter (six trials, 366 participants; RR 0.45, 95% CI 0.27 to 0.74).
Authors' conclusions: Antibiotic prophylaxis in afebrile neutropenic patients significantly reduced all-cause mortality. In our review, the most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefits of antibiotic prophylaxis outweighed the harm such as adverse effects and the development of resistance since all-cause mortality was reduced. As most trials in our review were of patients with haematologic cancer, we strongly recommend antibiotic prophylaxis for these patients, preferably with a quinolone. Prophylaxis may also be considered for patients with solid tumours or lymphoma.
Conflict of interest statement
None
Figures
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 All‐cause mortality, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 1.1 drug vs. placebo/no intervention.
Funnel plot of comparison: 1.1 drug vs. placebo/no intervention for the outcome: All‐cause mortality.
Forest plot of comparison: 2 Infection related mortality, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 2.1 drug vs. placebo/no intervention.
Funnel plot of comparison: 2 Infection related mortality, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 2.1 drug vs. placebo/no intervention.
Forest plot of comparison: 3 Febrile patients and febrile episodes, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 3.1 drug vs. placebo/ no intervention.
Forest plot of comparison: 14 Infection resistant to drug taken, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 14.1 drug vs. placebo/ no intervention.
Forest plot of comparison: 14 Infection resistant to drug taken, prophylaxis vs. placebo/no intervention or other antibiotic, outcome: 14.2 quinolone vs. TMP‐SMZ.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/no intervention.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 1 All‐cause mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/no intervention.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 2 Infection related mortality, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 3 Febrile patients and febrile episodes, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 4 Clinically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 5 Microbiologically documented infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 6 Gram‐negative infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 7 Gram‐positive infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 systemic + nonabsorbable vs systemic.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 8 Bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 quinolone+other vs. quinolone.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 9 Gram‐negative bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 10 Gram‐positive bacteraemia, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 11 Side effects, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/no intervention.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 12 Side effects requiring discontinuation, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 quinolone+other vs. quinolone.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 TMP‐SMZ vs. other.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 nonabsorbable vs. systemic.
Comparison 13 Fungal infection, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 systemic + nonabsorbable vs systemic.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 1 drug vs. placebo/ no intervention.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 2 quinolone vs. TMP‐SMZ.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 3 ciprofloxacin vs. norfloxacin.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 4 norfloxacin vs. pefloxacin.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 5 quinolone+other vs. quinolone.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 6 nonabsorbable vs. systemic.
Comparison 14 Infection resistant to drug taken, prophylaxis versus placebo or no intervention or other antibiotic, Outcome 7 TMP‐SMZ vs. other.
Comparison 15 All‐cause mortality, quinolone versus placebo or no intervention, according to different characteristics, Outcome 1 quinolone vs. placebo/no intervention according to disease status.
Comparison 15 All‐cause mortality, quinolone versus placebo or no intervention, according to different characteristics, Outcome 2 quinolone vs. placebo/no intervention according to type of quinolone.
Comparison 15 All‐cause mortality, quinolone versus placebo or no intervention, according to different characteristics, Outcome 3 quinolone vs. placebo/no intervention according to timing of chemotherapy initiation.
Comparison 15 All‐cause mortality, quinolone versus placebo or no intervention, according to different characteristics, Outcome 4 quinolone vs. placebo/no intervention according to year of publication.
Comparison 16 Sensitivity analyses by randomisation generation, drug versus placebo or no intervention, Outcome 1 Mortality.
Comparison 16 Sensitivity analyses by randomisation generation, drug versus placebo or no intervention, Outcome 2 Febrile patients.
Comparison 16 Sensitivity analyses by randomisation generation, drug versus placebo or no intervention, Outcome 3 Clinically documented infection.
Comparison 16 Sensitivity analyses by randomisation generation, drug versus placebo or no intervention, Outcome 4 Microbiologically documented infection.
Comparison 17 Sensitivity analyses by allocation concealment, drug versus placebo or no intervention, Outcome 1 Mortality.
Comparison 17 Sensitivity analyses by allocation concealment, drug versus placebo or no intervention, Outcome 2 Febrile patients.
Comparison 17 Sensitivity analyses by allocation concealment, drug versus placebo or no intervention, Outcome 3 Clinically documented infection.
Comparison 17 Sensitivity analyses by allocation concealment, drug versus placebo or no intervention, Outcome 4 Microbiologically documented infection.
Comparison 18 Sensitivity analyses by blinding, drug versus placebo or no intervention, Outcome 1 Mortality.
Comparison 18 Sensitivity analyses by blinding, drug versus placebo or no intervention, Outcome 2 Febrile patients.
Comparison 18 Sensitivity analyses by blinding, drug versus placebo or no intervention, Outcome 3 Clinically documented infection.
Comparison 18 Sensitivity analyses by blinding, drug versus placebo or no intervention, Outcome 4 Microbiologically documented infection.
Source: PubMed