Gafter-Gvili, A., Fraser, A., Paul, M., Vidal, L., Lawrie, T.A., van de Wetering, M.D., . . . Leibovici, L. (2012) Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database of Systematic Reviews, 1, CD004386.
The purpose of this meta analysis and sytematic review was to evaluate the effect of antibiotic prophylaxis on mortality and infection in neutropenic patients. In addition, subgroups of patients who may benefit the most were identified, and whether or not the effectiveness of different antibiotic regimens were similar was evaluated, as were the adverse effects of different regimens and the emergence of quinolone-resistant bacteria.
119 total references were retrieved. Cochrane Handbook for Systematic Reviews methods were used to evaluate and commend on the literature used.
Active antitumor treatment
Antibiotic prophylaxis resulted in significant reduction in risk of mortality across 46 trials analyzed (RR = 0.66, 95% confidence interval [CI] [0.55, 0.79], p < 0.00001). The greatest effect was with quinolones, although differences between regimens was not statistically significant. The effect was larger for trials in which prophylaxis was begun at the onset of neutropenia. An advantage was seen for all quinolones except for norfloxacin. Antibiotic prophylaxis significantly reduced infection-related mortality (RR = 0.61, 95% CI [0.48, 0.77], p = 0.04), decreased occurrence of fever, documented infection, and occurrence of bacteremia. Quinolones and TMP-SMZ were both associated with side effects that were mostly diarrhea and nausea. TMP-SMZ was associated with drug resistant bacteria cultures (RR = 2.42, 95% CI [1.35, 4.36]). With quinolones, no significant differences were noted between study groups compared to placebo or other interventions. Addition of gram-positive coverage did not show any apparent benefits in terms of mortality.
Findings support use of quinolones as prophylaxis of choice since they reduced risk of death compared to placebo or not intervention and were generally associated with fewer side effects and less resistant bacterial cultures in treated patients. Levofloxacin or ciprofloxacin are recommended.
Prophylactic quinolone antibiotic therapy is recommended for patients with hematologic cancers and those who are likely to develop neutropenia. Additional research is needed to better define patients with solid tumors that may benefit from antibiotic prophylaxis. In most studies, prophylaxis was begun when chemotherapy was initiated, rather than when neutropenia occurred. Prophylaxis should be accompanied by surveillance to monitor quinolone-resistant gram-negative bacteria and other resistant organisms.