Risk factors for cefepime nonsusceptible Gram-negative infections in allogeneic hematopoietic cell transplant recipients

J Oncol Pharm Pract. 2019 Mar;25(2):279-288. doi: 10.1177/1078155217731507. Epub 2017 Sep 26.


Purpose: Allogeneic hematopoietic cell transplant recipients undergo myelosuppressive chemotherapy to allow engraftment of stem cells and are at particularly high risk for bacterial infections and adverse outcomes. Patients undergoing hematopoietic cell transplant are at increased risk for healthcare-associated infections, including infections with multidrug-resistant pathogens. Cefepime is a commonly prescribed antibiotic for empiric therapy in hematopoietic cell transplant patients, but there is minimal data describing cefepime resistance rates, risk factors for resistance, and clinical outcomes associated with cefepime-resistant infections.

Methods: Adult (≥18 years old) allogeneic hematopoietic cell transplant recipients with a culture positive for a gram-negative rod between January 2010 and January 2016 were spilt into two groups: cefepime susceptible and cefepime nonsusceptible . The primary objective of this study was to identify risk factors for cefepime nonsusceptible through multivariable logistic regression.

Results: A total of 107 patients were included (27 cefepime nonsusceptible, 80 cefepime-susceptible), yielding a 25.2% nonsusceptibility rate. Multivariable analysis yielded age >60 years old, Klebsiella spp. infection, Acinetobacter spp. infection, healthcare exposures within 90 days, acute gastrointestinal graft-vs-host-disease, and chronic graft-vs-host-disease at multiple locations as significant risk factors for cefepime nonsusceptible. The receiver operating characteristic area under the curve of the model was 0.851. Thirty-day all-cause mortality (29.6% versus 16.3%, p = 0.13) and length of hospitalization (19 versus 12.5 days, p = 0.0650) were numerically higher in the cefepime nonsusceptible group.

Conclusions: Hematopoietic cell transplant patients with acute gastrointestinal graft versus host disease, extensive chronic graft-vs-host-disease, advanced age, previous healthcare exposures, or infections with Klebsiella and Acinetobacter are at increased risk for cefepime nonsusceptible. Patients infected with cefepime nonsusceptible pathogens may have higher rates of mortality and length of hospitalization.

Keywords: Antimicrobial resistance; allogeneic hematopoietic cell transplantation; cefepime; gram-negative bacterial infections; risk factors.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Cefepime / therapeutic use*
  • Female
  • Graft vs Host Disease / etiology
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / etiology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Transplantation, Homologous


  • Anti-Bacterial Agents
  • Cefepime