Introduction: AML survival in low- and medium-income countries (LMIC) is still dismal, with median overall survival of less than a year, mainly related to high treatment-related mortality (TRM) rates associated with infectious complications. In recent years, this scenario has been aggravated by the increasing rates of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infections (BSI), with mortality rates of up to 50% per episode. Objectives: To describe the positive impact of a bundle of simple and readily available measures on both infectious complications and AML TRM. Methods: Eligible AML patients were treated with standard chemotherapy induction (7+3) and high-dose cytarabine consolidation in non-HEPA filtered double-occupancy rooms. Antimicrobial prophylaxis included fluconazole and levofloxacin. Beginning March 2016, patients were given voriconazole as prophylaxis during neutropenia, after induction and in all consolidation cycles. In addition, after an outbreak of CRE colonization/BSI in late 2016, we also adopted, beginning March 2017, two additional interventions: (1) selective digestive tract decontamination (SDD) with PO gentamycin (60 mg qid) in those with a positive routine surveillance rectal swab for CRE (performed weekly), and (2) AML treatment in single-bed rooms. We retrospectively analyzed the outcomes of 133 consecutive newly diagnosed de novo AML patients undergoing intensive treatment between January 2011 and March 2020. Patients were analyzed according to whether they received or not the combination of voriconazole, gentamycin (if colonization by CRE was documented in rectal swabs) and treatment in single-bed rooms (VGSB - voriconazole/gentamycin/single-bed rooms). Results: During the study period, seventy-eight (58.6%) patients received standard supportive care, while 39 (29.4%) were treated under VGSB measures;16 (12%) received only voriconazole prophylaxis and were grouped with the supportive care patients for the survival analysis. Voriconazole prophylaxis was associated with lower 1-year rates of IFI (16.6%, 95% CI: 11-22% vs. 49.5%, 95%CI: 41.5-57.5, p = 0.04). Likewise, SDD with gentamycin in CRE colonized patients effectively reduced the 1-year rate of CRE BSI episodes (22.2%, 95% CI: 8.3-36.1% vs. 73.9%, 95% CI: 63.1-84.7%). Consistent with these findings and with a multivariate survival analysis which established CRE BSI as an independent prognostic variable for 1-year overall survival (HR = 10.152 (95% CI: 1.165-4.212), p = 0.015), VGSB patients had improved 60-day (61.7%, 95% CI: 56.7-66.7 vs. 87.2%, 95% CI: 81.8-92.6, p = 0.006) and 1-year overall survival (35.8%, 95% CI: 30.8-40.8, vs. 56.3, 95% CI: 47.6-65) compared with patients in the standard of care group. Discussion: Here we have showed a consistent reduction in mortality, incidence of CRE BSI and IFI after implementation of a set of supportive measures readily available in most settings. Additional studies are warranted to evaluate the relative impact of each component of this bundle, particularly AML treatment in single-bed rooms and SDD with gentamycin, on these results. Conclusions: The addition of Voriconazole prophylaxis, SDD with gentamycin and single-bed rooms to standard AML treatment results in a clinically meaningful increase in AML survival. This finding should impact practice in LIMC and settings with an elevated incidence of CRE BSI.
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