New Insight on Epidemiology and Management of Bacterial Bloodstream Infection in Patients With Hematological Malignacies

Abstract

Bloodstream infections (BSI) are a significant cause of morbidity and mortality in onco-hematologic patients. The Gram-negative bacteria were the main responsible for the febrile neutropenia in the sixties; their impact declined due to the use of fluoroquinolone prophylaxis. This situation was followed by the gradual emergence of Gram-positive bacteria also following the increased use of intravascular devices and the introduction of new chemotherapeutic strategies. In the last decade, the Gram-negative etiology is raising again because of the emergence of resistant strains that make questionable the usefulness of current strategies for prophylaxis and empirical treatment. Gram-negative BSI attributable mortality is relevant, and the appropriate empirical treatment significantly improves the prognosis; on the other hand the adequate delayed treatment of Gram-positive BSI does not seem to have a high impact on survival. The clinician has to be aware of the epidemiology of his institution and colonizations of his patients to choose the most appropriate empiric therapy. In a setting of high endemicity of multidrug-resistant infections also the choice of targeted therapy can be a challenge, often requiring strategies based on off-label prescriptions and low grade evidence.In this review, we summarize the current evidence for the best targeted therapies for difficult to treat bacteria BSIs and future perspectives in this topic. We also provide a flow chart for a rational approach to the empirical treatment of febrile neutropenia in a multidrug resistant, high prevalence setting.

Bloodstream infections caused by Klebsiella pneumoniae in onco‐hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey

“…In a univariate analysis conducted on these 149 patients, variables associated with 21-day mortality were: severe (62, 86.1% vs. 49, 63.6%; P 5 0.001) and/or prolonged neutropenia (53, 73.6% vs. 39, 50.6%; P 5 0.004), acute myeloid leukemia (59, 81.9% vs. 52, 67.5%; P 5 0.04), respiratory tract as primary site of BSI(13,18.1% vs. 5, 6.5%; P 5 0.03), septic shock (41, 56.9% vs. 4, 5.2%; P < 0.001), altered state of consciousness (32, 44.4% vs. 5, 6.5%; P < 0.001), acute renal(20,27.8% vs. 5, 6.5%; P < 0.001) and/or respiratory (50, 69.4% vs. 9, 11.7%; P < 0.001) and/or hepatic failure(11,15.3% vs. 1, 1.3%; P < 0.001), and inadequate initial antimicrobial therapy (64, 88.9% vs. 51, 66.2%; P 5 0.001). On the contrary, the complete remission stage of HM disease(3,4.2% vs. 18, 23.4%; P < 0.001) and/or treatment with a combination of antibiotics (40, 55.5% vs. 69, 89.6%; P < 0.001) were significantly associated with survival.In the Cox regression analysis (model B) the variable combination therapy was retained as independently associated with survival (HR…”

“…In recent years, a clear trend has been reported in the epidemiology of severe infections, in particular BSIs; a shift has been shown from Gram-positive to Gram-negative bacteria in HM patients, with mortality rates significantly higher in patients with BSI caused by Gram-negative bacteria compared to those with BSI caused by Gram-positive bacteria [1,2]. Furthermore, a worrisome and extensive emergence of antimicrobial-resistance in Gram-negatives has been recently reported in HM patients [1][2][3][4]. In particular, resistance to carbapenems caused by Klebsiella pneumoniae (KP) has become a significant problem in several countries [5,6], and has recently been reported as one of the major emerging causes of severe and fatal infections in HM patients in Italy [2,7,8].…”

New insight on antimicrobial therapy adjustment strategies for gram-negative bacterial infection

“…This strategy is based on a fact that inappropriate or delayed treatment significantly worsens patients’ outcomes, and how to choose proper initial antimicrobial therapy based on patients’ characteristics and community or hospital's antibiotic resistance data has extensively been discussed in previous studies. [2,5,7,10,11,18] However, the value of different adjustment strategies has not been discussed but in some circumstances clinicians have to decide whether to adjust therapy before culture results are available. Thus, in our study, apart from confirmation of importance of appropriate initial therapy, we discuss this question and found that for patients needing therapy adjustment, a strategy based on MST had no significant effect on mortality, accompanied with longer hospitalization time, delayed therapy adjustment, and unobvious clinical outcome improvement, compared with strategy based on clinicians’ experience.…”

“…In terms of critical role of appropriate initial therapy, lots of studies have verified it in patients with blood stream infections or pneumonia, [4,12,14,18,19] and many strategies aimed at early appropriate therapy have been explored. [11,20–24] In our study, we also confirmed it in patients with gram-negative bacterial infection.…”

Epidemiology, resistant pathogens and main causes of early death of bloodstream infection in patients with hematological malignancies from 2012 to 2019 in a Chinese tertiary hospital

“…However, the incidence of Gram-negative bacterial infections has risen in recent years [6] . Gram-negative pathogens have higher antimicrobial resistance profiles worldwide, especially in China (carbapenem-resistant Klebsiella pneumoniae [CRKP] 20.9% and carbapenem-resistant Acinetobacter baumannii [CRAB] 70.7% in 2017) [7] .…”