Impact of β-lactam + Aminoglycoside Combination Regimen As Empirical Therapy For the Treatment of Bacteraemia Due to Gram-Negative Bacilli in Neutropenic Haematological Patients In An Era Of Antimicrobial Resistance (AMINOLACTAM Study)

Ulldemolins M¹, Gudiol C*^1,8, Pomares H², Akova M³, Puerta Alcalde P^, Herrera F⁵, Martín Dávila P⁶, Albasanz -Puig A^1,8, Royo Cebrecos C^1,8, Mercadal S², Ayaz MC³, Cardozo C^, Torres D⁵, Fortún J⁶, Bergas A¹, Laporte J¹, Garcia Vidal C⁴, Mancho N⁷ and Carratalà J^1,8

Received: September 19, 2018;   Published: October 05, 2018

DOI: 10.26717/BJSTR.2018.09.001836

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Abstract

Background: Current guidelines for the management of patients with febrile neutropenia don’t recommend the use of empirical combination antibiotic therapy. The addition of an aminoglycoside to the recommended broad-spectrum ß-lactam could be beneficial because of the pharmacological properties of these drugs, and because it broadens the antibacterial spectrum. However, the risk-benefit of adding an aminoglycoside to the ß-lactam is far from clear, especially considering adverse events and the current situation of widespread antimicrobial resistance. We hypothesize that combination therapy may be more effective than monotherapy in this scenario; therefore, we aim to compare the effectiveness of these two strategies for the treatment of bacteraemia due to Gram-negative bacilli (GNB) in neutropenic haematological patients.

Methods: Multinational, multicentre, retrospective, observational cohort study. Adult haematological patients with neutropenia and GNB bacteraemia receiving adequate empirical ß-lactam monotherapy, or combination therapy with a ß-lactam + aminoglycoside (January 2010 - June 2017), will be analysed. The primary endpoint will be 30-day case-fatality rate. Secondary endpoints will be 7- and 14-day case-fatality rates, nephrotoxicity, persistent bacteraemia, relapse of bacteraemia, infection by resistant bacteria, and intensive care unit admission.

Discussion: Early and appropriate empirical antibiotic therapy is the cornerstone in the treatment of patients with severe infections. In patients with impaired immunity such as those with haematological diseases and neutropenia, the role of the antibiotic in the course of infection is even more crucial. Prescribing the optimal antibiotic therapy for neutropenic patients with bacteraemia due to GNB is a daily challenge for clinicians, and the impact of monotherapy with a broad-spectrum ß-lactam versus combination therapy with a broad-spectrum ß-lactam + an aminoglycoside on clinical and microbiological outcomes remains a controversial issue. A meta-analysis published in 2013, found that ß-lactam monotherapy performed better than ß-lactam-aminoglycoside combination therapy for the treatment of bacteraemia in patients with febrile neutropenia with regard to mortality, fungal super-infections, and nephrotoxicity. However, this meta-analysis was performed with data from studies performed between 1983 and 2012, when the burden of bacterial resistance was increasing but had not yet reached the levels we are facing at the moment.

Keywords: Empirical Combination Antibiotic Therapy; Gram-Negative Bacteraemia; Bloodstream Infection; Neutropenia; Haematological Patients; Aminoglycosides

Abbreviations: AKI: Acute kidney injury; ICO Hospitalet: Institut Català d’Oncologia L’Hospitalet; IDSA: Infectious Diseases Society of America; Centro de Educación Médica e Investigaciones Clínicas (CEMIC); ECIL: European Conference on Infections in Leukaemia; ICMJE: International Committee of Medical Journal Editors; GNB: Gram-negative bacilli; IDIBELL: Institute of Biomedical Research of Bellvitge; HSCT: Haematopoietic stem cell transplantation; ICU: Intensive care unit; EUCAST: European Society of Clinical Microbiology and Infectious Diseases; MASCC: Multinational Association of Supportive Care in Cancer; MDRGNB: Multidrug-resistant Gram-negative bacilli; REIPI: Spanish Network for Research in Infectious Diseases

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