Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTA

BACKGROUND: Fever and neutropenia (FN) is a common complication of chemotherapy for cancer. Prompt empiric broad-spectrum antibiotic therapy in FN is typically considered standard of care, but the definition of prompt is not clear. We seek to systematically review the available data on the association between time to antibiotics (TTA) administration and clinical outcomes in patients with FN being treated with chemotherapy. There have been several efforts to reduce TTA in patients with FN, by implementing specific interventions, presuming there will be a beneficial effect on patient-important outcomes. This systematic review will also collect data on such interventions and their effect to reduce TTA and potentially change clinical outcomes. METHODS/DESIGN: The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, CDSR, CENTRAL, and LILACS. A full-search strategy is provided. Lists of studies identified by references cited and forward citation searching of included articles will also be reviewed. Studies will be screened, and data extracted by one researcher and independently checked by a second. Confounding biases and quality of studies will be assessed with the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool. Data will be presented in narrative and tabular forms; in addition, if appropriate data is available, random effects meta-analysis will be used to examine TTA. A detailed analysis plan, including an assessment of heterogeneity and publication bias, is provided. DISCUSSION: This study aims to evaluate the association between TTA and patient-important clinical outcomes. Additionally, it will identify, critically appraise, and synthesise information on performed interventions and its effect to reduce TTA as a way of gaining insight into the potential use of these approaches. This will provide better knowledge for an adjusted treatment approach of FN. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [ CRD42018092948 ].