Prompt initiation of empiric antimicrobial therapy in FN is critical.
A variety of empiric antibiotic regimens may be used. While published guidelines are useful, they cannot replace a good knowledge of local resistance patterns.
Regular surveillance of the local microbiological data is necessary to aim for the best choice of first line empiric therapy 5.
Mechanisms of invasion of bacteria into the bloodstream:
Blood cultures are positive in 20-30% of paediatric or adult patients with febrile neutropaenia 1,2. This is a conservative estimate in view of:
- Frequently an inadequate blood volume is drawn for blood cultures in paediatric patients 6.
- Difficulty in recovering some organisms, which can be fastidious to culture (e.g. yeast).
Most patients will be colonized by the infecting organisms, usually after initial admission to the hospital, before invasive disease becomes apparent 7. This is important because knowledge of local bacterial flora on a particular unit can inform empiric antibiotic choices.
Organisms will then either:
a) Invade an injured mucosal barrier secondary to chemotherapy (translocation from the oral mucosa or gut) or
b) Access the blood stream via the skin, through central venous catheters or skin breakdown.
Gut translocation represents a major route of infection, and some authors have advocated the use of non-absorbable antibiotics in order to eradicate the carriage of potential pathogen in the gut 8. However, there is ongoing debate in the literature about the usefulness of this approach and its impact on the potential emergence of multi-resistant organisms.
The microbiology of FN is a constantly changing picture. In the last decade, the focus has shifted toward an increased prevalence of Gram positive organisms which now represent about 60-70% of blood cultures of patients with FN 4.
Figure 1: Distribution of Organisms in Blood Cultures (n=261) at the BC Children’s Hospital 10/2003- 4/2008
Gram positive organisms:
In order of frequency organisms recovered are:
- Coagulase negative Staphylococcus
- Viridans Group Streptococcus (VGS)
- Staphylococcus aureus
- Enterococcus faecalis
Resistance in gram positive organism is important to consider, and due to organisms such as penicillin resistant VGS, Methicillin Resistant Staphylococcus Aureus and Vancomycin Resistant Enterococcus.
Gram negative organisms:
Responsible for most of the mortality associated with sepsis in oncology patients. They are present in 25-30% of blood cultures. Most commonly isolated are:
- E. coli
- Klebsiella pneumoniae
- Enterobacter spp.
- Acinetobacter baumanii
- Serretia marcessens
- Pseudomonas aeruginosa: Although usually described as a classical pathogen in the context of FN, its prevalence is highly variable from institution to institution.
Mechanisms of resistance in Gram negative organisms, mostly due to the production of ß-lactamases, are important to understand. This will be discussed in a later section.
Anaerobic organisms (<5%) are more commonly associated with intra-abdominal sepsis and typhlitis (inflammation of the caecum seen post chemotherapy).
Infections with fungal pathogens (<5%), such as Candida spp. and Aspergillus spp., are playing an important role in high risk patients (HSCT, AML) with persistent severe FN.