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

Abstract

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. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared 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. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 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% versus 51%, P = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of β-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). 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.

Keywords: bacteremia; empirical treatment; mortality; neutropenia; shock.

FIG 1

Additional value for empirical combination treatment with specific Gram-positive coverage and amikacin in patients with septic shock regarding antimicrobial susceptibility of the isolated microorganism. For specific Gram-positive coverage, (i) isolated microorganism was resistant to Gram-positive coverage in 69% of cases; (ii) isolated microorganism was susceptible to Gram-positive coverage, but another active antibiotic was also administered in 13% of cases; and (iii) Gram-positive coverage was the only active antibiotic in 18% of cases. For amikacin, (i) isolated microorganism was resistant to amikacin in 15% of cases; (ii) isolated microorganism was susceptible to amikacin, but another active antibiotic was also administered in 78% of cases; and (iii) amikacin was the only active antibiotic in 7% of cases. *, including glycopeptides (vancomycin and teicoplanin), daptomycin, and linezolid.