Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem cell transplant patients: intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group
Background: This intercontinental study aimed to study Gram-negative rods (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during six months post-HSCT (February/2014-May/2015) were prospectively collected, and analysed for rates and risk factors for resistance to fluoroquinolones, non-carbapenem anti-Pseudomonas beta-lactams (non-carbapenems), carbapenems and multidrug-resistance (MDR). Results: Sixty-five HSCT centers from 25 countries (Europe, Australia, Asia) reported data
on 655 GNR episodes/704 pathogens in 591 patients (Enterobacteriaceae, 73%; non-fermentatives, 24% and 3% others). Half GNR were fluoroquinolone- and non-carbapenems-resistant; 18.5% carbapenem-resistant; 35.2% MDR. The total resistance rates were higher in allo-HSCT vs. auto-HSCT patients (p<0.001); but similar in community-acquired infections. Non-carbapenems-resistance and MDR were higher in auto-HSCT patients in centers providing vs. non-providing fluoroquinolone prophylaxis (p<0.01). Resistance rates were higher in southeast vs. north-west Europe; similar in children and adults; excluding higher fluoroquinolone- and beta-lactam beta-lactamase inhibitors-resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem-resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone-resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; non-carbapenems-resistance: hospital-acquired infection, breakthrough on non-carbapenems or other antibiotics (excluding fluoroquinolones, non-carbapenems, carbapenems), donor type; carbapenem-resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; MDR: longer hospitalization, breakthrough on beta-lactam beta-lactamase inhibitors and carbapenems. Inappropriate empirical therapy and mortality were significantly more common in infections caused by resistant bacteria. Conclusion: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empirical antibiotic protocols. Knowledge of pathogen-specific resistances enable early appropriate empirical therapy. Monitoring of resistance is crucial.