Emergent Fluoroquinolone Resistance in Viridans Streptococcal Species in Cancer Patients

Abstract

Objectives: Viridans group streptococci (VGS) are known to be associated with morbidity and mortality in cancer and hematopoietic cell transplant recipients (HCT), and reports have described the development of fluoroquinolone (FQ) resistant VGS in these populations. To understand recent trends, we evaluated the frequency of VGS bacteremia and prevalence of FQ-resistance at a large tertiary medical system with a dedicated cancer center. Methods: We identified patients from the University of Washington Medical Center (UW) and Seattle Cancer Care Alliance (SCCA) with any detected VGS from blood cultures between 1/2006 and 12/2012 for inclusion in the study. All patients were >18 years of age and categorized into cancer and non-cancer populations. Microbiologic data were abstracted from laboratory databases; demographic and outcome data on cancer patients were collected through electronic medical record review. Fisher's exact and Mann Whitney tests were used to compare study populations and multivariate logistic regression used to identify risk factors for FQ resistance in cancer patients with VGS. Results: We identified 261 patients that had VGS identified from blood cultures from 2006-2012, of whom 165/261 (63%) were cancer patients. Among cancer patients, most had a primary diagnosis of a hematological malignancy (142/165 [86%]), and 69/165 (42%) were HCT recipients. We identified an increase in VGS cases among cancer patients over time. Of VGS identified at a species level (n=150), <italic>S. mitis</italic> was more common in the cancer population (72/95 [75.8%] vs. 29/55 [52.7%], p=0.004). Antimicrobial sensitivities for VGS indicated no statistical differences in resistance to penicillin (9.0% vs. 8.1%), clindamycin (11.3% vs. 7.1%), erythromycin (34.0% vs. 20.2%), ceftriaxone (1.9% vs. 6.1%) and vancomycin (0% in both) when comparing cancer to non-cancer patients. Overall, 102 of 261 isolates (39%) were FQ resistant. However, nearly all resistant isolates were from cancer patients (99/165 [60%] vs. 3/96 [3%]; p<0.001). Calendar year, HCT, primary oncologic diagnosis, chemotherapeutic regimen, and levofloxacin prophylaxis were associated in univariate analyses, but the only significant risk factor in multivariate analyses was prophylactic levofloxacin use (OR 397 [95% CI 43.6-3628]). When excluding levofloxacin from the model, only calendar years 2009-2012 (OR 4.2 to 7.1) was associated with resistant VGS. Overall mortality was higher in patients with FQ resistant VGS [41.7% vs. 27.9%; p=0.018], but associated and attributable mortality were not significantly different [12% vs. 6.7%; p=0.36]) when compared to those without resistance. Conclusion: In a large tertiary healthcare system, we demonstrated that an increase in VGS bacteremia cases was almost exclusively found in cancer and HCT patients. Not surprisingly, the use of levofloxacin for neutropenic prophylaxis at the cancer center was associated with FQ resistance.