Horita, N., Shibata, Y., Watanabe, H., Namkoong, H., & Kaneko, T. (2017). Comparison of antipseudomonal beta-lactams for febrile neutropenia empiric therapy: Systematic review and network meta-analysis. Clinical Microbiology and Infection, 23, 723–729.

STUDY PURPOSE: To compare the effectiveness and safety of antipseudomonal b-lactam empiric monotherapy for febrile neutropenia by network meta-analysis

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed, Cochrane CENTRAL, EMBASE, and Web of Science Core Collection

YEARS INCLUDED: No year limitation

INCLUSION CRITERIA: Definition of febrile neutropenia was ANC less 500 mcl or less than 1,000 mcl and temperature greater than 38 C for more than one hour or temperature greater than 38.3 C. Patients in both arms had to be treated with IV antipseudomonal beta-lactam antibiotic for initial empiric therapy of febrile neutropenia. GCSF use was allowed.

EXCLUSION CRITERIA: Granulocyte transfusion was excluded. Antibiotics not evaluated in a RCT in the past 10 years (since 2006) were excluded.

TOTAL REFERENCES RETRIEVED: 1,275

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Evaluated quality of each study using 6 domains of the Cochrane risk of bias tool

FINAL NUMBER STUDIES INCLUDED: 50 studies

TOTAL PATIENTS INCLUDED IN REVIEW: 10,872 patients

KEY SAMPLE CHARACTERISTICS: Adult and pediatric febrile neutropenia patients undergoing chemotherapy for either solid tumors or hematologic malignancies.

PHASE OF CARE: Active anti-tumor treatment     

APPLICATIONS: Elder care

Treatment success without antibiotic modification was most likely with Cefoperazone/sulbactam followed by imipenem/cilastatin, piperacillin/tazobactam, meropenem, cefepime, cefozopran, ceftazidime and panipenem/betamipron. The risk for all-cause death was lowest in all-cause death were lowest in the imipenem/cilastatin arm and highest in the cefepime arm.

Imipenem/cilastatin followed by piperacillin/tazobactam and meropenem had the best performance in the treatment success without modification and all-cause death.

• Low sample sizes
• Inconsistent definitions of neutropenic fever and treatment success; only included studies of adult patients

Antipseudomonal antibiotics are effective for empiric treatment of febrile neutropenia and imipenem/cilastatin, piperacillin/tazobactam, and meropenem had the best performance in the treatment success without modification and all-cause death. This may be due to increasing incidence of extended spectrum beta lactamase-producing bacteria that are resistant to cefepime. However, cefepime is still recommended by major guidelines for initial use and remains a reasonable choice, particularly given the concern of antibiotic resistance using carbapenems as initial empiric therapy for febrile neutropenia.