Abstract
Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13–0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38–0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.
Highlights
Half of the deaths due to Acute Myeloid Leukemia (AML) are related to infections, being Gram negative bacteria the most prominent pathogens [1]
In order to clarify the actual role of fluoroquinolone prophylaxis (FP) and surveillance cultures (SC) in the management of infection in AML patients, we prospectively evaluated the efficacy of an active surveillance program (ASP) on the reduction of infection and mortality due to multiresistant Gram negative bacteria in an endemic MR-GNB setting
Our results show that strict compliance with fluoroquinolone prophylaxis, together with systematic surveillance cultures and contact precautions for colonized patients by MR-GNB, resulted in a reduction in the incidence of multidrug resistant Gram negative bacterial infections (MR-GNBI) and infectious mortality during the aplastic period of chemotherapy
Summary
Half of the deaths due to Acute Myeloid Leukemia (AML) are related to infections, being Gram negative bacteria the most prominent pathogens [1]. The increasing appearance of multidrug resistant Gram negative bacterial infections (MR-GNBI) constitutes one the most important medical threats of present time [2] and has a profound impact in the treatment of AML. The use of fluoroquinolone prophylaxis (FP) in endemic settings is a matter of debate, as they result in an increasing prevalence of resistant microorganisms and may reduce the efficacy of subsequent antibacterial treatment [6]. Routine active surveillance cultures (SC) from gastrointestinal tract and contact precautions in colonized patients have proven to be useful in intensive care and solid organ transplantation settings [7,8] but its cost-effectiveness in AML is to be demonstrated [9]. There is no international agreement on how to organize and implement active surveillance control measures for the detection of colonized AML [10]
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