title: Infusional β-lactam antibiotics in febrile neutropenia:  has the time come?
abstract: OBJECTIVE
  Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia.
  
  
  RESULTS
  There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings.
  
  
  CONCLUSIONS
  Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.
authors.affiliation: Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Abbott
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005335:Fever of Unknown Origin / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D009503:Neutropenia / Q000150:complications*; D016896:Treatment Outcome; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams