Incidence Rate of Fluoroquinolone-Resistant Gram-Negative Rod Bacteremia among Allogeneic Hematopoietic Cell Transplantation Patients during an Era of Levofloxacin Prophylaxis

Abstract

Background There are concerns that emerging resistance to fluoroquinolones (FQ) may be leading to increasing rates of gram-negative rod (GNR) bacteremia in hematopoietic cell transplant (HCT) recipients. We set out to describe time trends in the incidence rates (IR) of GNR bacteremia and FQ-resistant GNR bacteremia in HCT recipients during an era of levofloxacin prophylaxis. Methods We conducted a longitudinal retrospective study of adults undergoing allogeneic HCT between 2003 and 2012 at the Seattle Cancer Care Alliance (SCCA). Annual trends in the IRs of GNR bacteremia and FQ-resistant GNR bacteremia through 100 days post-transplant were assessed using Poisson regression. Cox proportional hazards regression was used to compare 30-day mortality between patients with FQ-resistant and those with FQ-sensitive GNR bacteremia. Results Of the 2306 patients included in this cohort, 280 (12.1%) had GNR bacteremia. The IRs of GNR bacteremia and FQ-resistant GNR bacteremia increased from 2003 to 2009 and decreased afterwards; however, the overall annual trends were not significant (Incidence rate ratio [IRR] =1.01; 95% confidence interval [CI]: 0.98, 1.05 and IRR=1.01; 95% CI: 0.95, 1.08, respectively). FQ-resistant GNR bacteremia was associated with increased mortality compared to FQ-sensitive GNR bacteremia, even after adjustment for underlying disease severity, conditioning regimen, and age at transplant (Hazard ratio=2.11, 95% CI: 1.06, 4.23). Conclusions On average, rates of FQ-resistant GNR bacteremia have not significantly changed at the SCCA over 10 years of FQ prophylaxis, although FQ-resistant GNR bacteremia is associated with increased mortality compared to FQ-sensitive GNR bacteremia.

Secular trends of bloodstream infections during neutropenia in 15 181 haematopoietic stem cell transplants: 13-year results from a European multicentre surveillance study (ONKO-KISS)

“…The design of the ONKO-KISS surveillance did not permit a more detailed analysis of the association of the trends of Gram-negative BSI and risk factors. Other studies, however, have reported an association between increased BSI due to Gram-negative bacteria and the emergence of fluoroquinolone resistance in E. coli [10,12,16], while others have reported inconsistent effects [24]. Furthermore, an increase of broad-spectrum b-lactamases has been reported in Gram-negative pathogens from many cancer centres [25,26].…”

Causative Organisms and Associated Antimicrobial Resistance in Healthcare-Associated, Central Line–Associated Bloodstream Infections From Oncology Settings, 2009–2012

“…Furthermore, fluoroquinolone resistance in E. coli has increased significantly during recent years in oncology settings. These findings are of concern given that fluoroquinolone-resistant E. coli infections are associated with increased mortality in oncology patients [23]. Indeed, the impact of growing antimicrobial resistance in oncology has been highlighted recently [24].…”

Decline in the Use of Surgical Biopsy for Diagnosis of Pulmonary Disease in Hematopoietic Cell Transplantation Recipients in an Era of Improved Diagnostics and Empirical Therapy

“…After transplant, all patients received immunosuppressive agents as prophylaxis against graft-versushost disease in the post-transplant period. Standard infectious prophylaxis included acyclovir for herpes simplex virus and or varicella zoster virus; trimethoprim-sulfamethoxazole, atavoquone, or dapsone for Pneumocystis jirovecii; and fungal prophylaxis with fluconazole [9]. All patients received either ceftazidime or levofloxacin for neutropenic prophylaxis [10].…”