Impact of Empirical Antibiotic Regimens on Mortality in Neutropenic Patients with Bloodstream Infection Presenting with Septic Shock

Abstract

Objectives: We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. Methods: Multicenter retrospective study (2010-2019) of two prospective cohorts comparing BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Results: Of 1563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% vs 15%, p<0.001). Gram-negative bacilli caused 81% of episodes with septic shock; gram-positive cocci, 22%; and Candida species 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% vs 51%, p=0.002). Age >70 years (OR 2.3, 95% CI 1.2-4.7), IEAT for Candida spp. or gram-negative bacilli (OR 3.8, 1.3-11.1), acute kidney injury (OR 2.6, 1.4-4.9) and amikacin as the only active antibiotic (OR 15.2, 1.7-134.5) were independent risk factors for mortality, while combination of β-lactam and amikacin was protective (OR 0.32, 0.18-0.57). Conclusions: Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study

“…Many studies have focused on assessing the impact on mortality of an inadequate empirical antimicrobial treatment not only in specific scenarios, like the intensive care units (ICU) (Alvarez-Lerma; Ibrahim et al; Kollef et al; Luna et al; Rello et al; Kreger et al, 1980; Savage et al, 2016 ) but also it has been analysed in a broad spectrum of infections ( Mettler et al, 2007 ; Paul et al, 2010 ). Concretely in patients with bacteremia, inadequate therapy has demonstrated to negatively impact on mortality in specific populations like oncohematological patients with febrile neutropenia ( Martinez-Nadal et al, 2020 ; Chumbita et al, 2022 ) or cirrhotic patients ( Park, 2015 ). Also, results from a very recent meta-analysis indicated that i-EAT substantially had a negative impact on survival of patients with BSIs at short and long term ( Hung et al, 2022 ).…”

“…Despite of the relevance of choosing i-EAT, there is much less evidence on the risk factors associated with this practice. Some studies have focused on concrete patient-related factors ( McDonald et al, 2005 ; Retamar et al, 2013 ) while others have analysed heterogeneous clinical syndromes ( Mettler et al, 2007 ), have small sample size ( Bai et al, 2021 ) or have focused on specific populations like neonates ( Hsu et al, 2015 ) or immunosuppressed patients ( Martinez-Nadal et al, 2020 ; Chumbita et al, 2022 ), which makes their findings ungeneralizable to general adult population. More recently, some studies have focused on the impact of isolation of multidrug resistant (MDR) strains on the adequation of empirical antimicrobial treatment choice ( Girometti et al, 2014 ; Carrara et al, 2018 ) showing higher rates of i-EAT when a MDR microorganism was identified and thus, a negative impact on mortality.…”

Development and validation of nomograms for predicting the risk probability of carbapenem resistance and 28-day all-cause mortality in gram-negative bacteremia among patients with hematological diseases

“…In addition, we also found that septic shock was the predominant and significant predictor for 28-day mortality in our nomogram. Not surprisingly, septic shock, as a clinical manifestation of the severity of infections and organ dysfunction, has been detected to be associated with high mortality in several previous studies involving patients with HM and the general populations ( Andria et al., 2015 ; Chumbita et al., 2022 ; Xiao et al., 2020 ; Zhang et al, 2020 ). In the current study, we could understand that 60.3% (41/68) of non-survivors underwent septic shock, of which 50.9% (27/53) of patients were categorized as CR-GNB BSI.…”

“…Therefore, in clinical practice, the severity of the infection plays a crucial role in the prognosis. As demonstrated by Chumbita et al, (2022), when administered with inappropriate experimental antibiotic therapy, septic shock was associated with extremely high mortality in febrile neutropenic patients with BSI. Apparently, this conclusion further highlights the importance of epidemiological surveillance in different hospitals.…”

Timing in antibiotic therapy: when and how to start, de-escalate and stop antibiotic therapy. Proposals from a stablished antimicrobial stewardship program

“…As delay reduces the effectiveness of antibiotherapy, so does the prescription of antibiotics that are not active against the pathogens causing the infection [13]. Surprisingly, in our current clinical practice, the rate of prescribing empirical antibiotic therapy that is inactive or ineffective is very high (up to 20 and 30%) [13][14][15][16][17][18]. And the rate would be even worse assuming this new strategic concept that appears in recent leading publications: that in severe infections caused by multidrug-resistant bacteria, two active antibiotics improve the survival rate over that achieved with monotherapy [16, [19][20][21].…”