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

• Published in: Journal of oncology pharmacy practice 2019-03, Vol.25 (2), p.279-288
• Main Authors: Boyd, AM, Perissinotti, AJ, Nagel, JL, Frame, DG, Marini, BL
• Format: Article
• Language: English
• Subjects: Acinetobacter; Antibiotics; Antimicrobial agents; Bacterial infections; Cefepime; Cell culture; Chemotherapy; Chronic infection; Exposure; Graft-versus-host reaction; Grafting; Health risk assessment; Health risks; Infections; Klebsiella; Mortality; Multidrug resistance; Pathogens; Resistance factors; Risk factors; Stem cell transplantation; Stem cells
• ISSN: 1078-1552; 1477-092X
• DOI: 10.1177/1078155217731507

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.