Tackling antibiotic resistance in febrile neutropenia: current challenges with and recommendations for managing infections with resistant Gram-negative organisms

Abstract

Multidrug resistant (MDR) Gram-negative bacteria (GNB) have emerged as important pathogens and a serious challenge in the management of neutropenic patients worldwide. The great majority of infections are caused by the Enterobacteriaceae (especially Escherichia coli and Klebsiella spp.) and Pseudomonas aeruginosa, and less frequently Acinetobacter spp. and Stenotrophomonas maltophilia. A broader-spectrum empiric antibiotic regimen is usually recommended in patients with a history of prior bloodstream infection caused by a MDR GNB, in those colonized by a MDR GNB, and if MDR GNBs are frequently isolated in the initial blood cultures. In any situation, de-escalation to standard empiric regimen is advised if infection with MDR GNB is not documented.

Keywords:

• antibiotic
• epidemiology
• febrile neutropenia
• resistance
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Multidrug resistant (MDR) Gram-negative bacteria (GNB) have emerged as important pathogens causing infection in neutropenic patients with hematological malignancies.

• Antibiotic resistance in neutropenic patients may develop either by horizontal transmission of resistant bacteria or most typically by selective pressure exerted by broad-spectrum antimicrobial agents given as prophylaxis or therapy.

• The majority of Gram-negative bacterial infections are caused by Enterobacteriaceae (especially E. coli and Klebsiella spp.) and Pseudomonas aeruginosa.

• Patients more likely to develop MDR Gram-negative BSI are those expected to have profound and prolonged neutropenia, especially if they are in ICU and are submitted to multiple invasive procedures.

• Surveillance cultures may be of help for their negative predictive value and are more likely to be cost-effective in centers with higher incidences of Gram-negative BSI.

• Patients with previous bloodstream infection due to MDR GNB or known to be colonized by MDR GNB should receive an empiric antibiotic regimen with in vitro activity against the MDR Gram-negative pathogen.

• The antibiotic regimen should be changed to a standard empiric regimen within 48–72 h if the patient is stable and blood cultures are negative for MDR GNB.

• Preventive strategies include hand hygiene, active screening, contact precautions, geographic and personnel cohorting and the judicious use of antibiotics by the implementation of stewardship programs.