Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a PropensityMatched Cohort Study (AMINOLACTAM Study)

Albasanz-Puig A., Gudiol C., Puerta-Alcalde P., Ayaz C. M., Machado M., Herrera F., ...More

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol.65, no.8, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 65 Issue: 8
  • Publication Date: 2021
  • Doi Number: 10.1128/aac.00045-21
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database, DIALNET
  • Keywords: febrile neutropenia, hematological patients, aminoglycosides, combination empirical treatment, Gram-negative bloodstream infection, BETA-LACTAM, PSEUDOMONAS-AERUGINOSA, SEPTIC SHOCK, BACTEREMIA, MONOTHERAPY, GUIDELINES, RESISTANCE, MORTALITY, AGENTS, CARE
  • Hacettepe University Affiliated: Yes


To test the hypothesis that the addition of an aminoglycoside to a beta-lactam antibiotic could provide better outcomes than beta-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (beta-lactam plus aminoglycoside) was compared to beta-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.