Neutropenic sepsis: prevention and management in people with cancer

Antibiotic prophylaxis

The use of fluoroquinolones for the prophylaxis of neutropenic sepsis is advised in recommendations 1.2.1.1 and 1.2.1.2 in the NICE guideline. One Cochrane review (Gafter-Gvili et al. 2012) is an update to a Cochrane review first published in 2005 which was included as evidence during the development of recommendations in the original guideline. The results of the updated Cochrane review found significant reductions in mortality with quinolone prophylaxis which supports the current recommendations in the guideline.

Recommendation 1.2.1.3 states that granulocyte colony-stimulating factor (G-CSF) should not be routinely offered for the prevention of neutropenic sepsis in adults receiving chemotherapy. Two Cochrane reviews (Renner et al. 2012 and Estcourt et al. 2015) found prophylactic colony-stimulating factors (CSFs) reduced febrile neutropenia in patients undergoing chemotherapy. However, the Cochrane authors assessed the included trials as very low quality. Although these reviews do not support recommendation 1.2.1.3, further evidence is required to confirm the results and there is no impact on the current recommendations.

In contrast, several new Cochrane reviews support the current recommendation 1.2.1. The review from Estcourt et al. 2016, suggests there is insufficient evidence to determine whether granulocyte transfusions affect all-cause mortality in people who are neutropenic. This finding is supported Mhaskar et al. 2014 who concluded that it is unclear whether a combination of CSF and antibiotics reduce the rate of infection-related mortality in people with chemotherapy induced febrile neutropenia. Two further reviews (Skoetz et al. 2015 and Hutzschenreuter et al. 2016) concluded that there was a lack of data to inform the use of G‑CSF in people receiving chemotherapy.

Initial antibiotic therapy

Recommendation 1.4.3.1 advises offering beta lactam monotherapy as initial empiric antibiotic therapy and recommendation 1.4.3.2 advises not to offer aminoglycoside to patients with suspected neutropenic sepsis. In support of these recommendations, 1 review (Paul et al. 2013) found significantly lower rates of mortality, adverse events and super-infections following the use of beta lactam monotherapy compared to combination therapy with aminoglycoside.

Glycopeptide antibiotics

Recommendation 1.4.3.3 advises not offering empiric glycopeptide antibiotics to patients with suspected neutropenic sepsis who have central venous access devices. This recommendation is supported by a review (Beyar-Katz et al. 2017), which found no benefit of additional antibiotic treatment with glycopeptides and a further review (van de Wetering et al. 2013), which found no benefit of antibiotics administered prior to the insertion of a catheter.

Switch to oral antibiotics

Recommendation 1.5.3.3 advises that after 48 hours and in patients whose risk of developing septic complications has been reassessed as low, antibiotic therapy can be switched from intravenous to oral administration. This is supported by 1 review (Vidal et al. 2013), which found no significant differences in mortality and treatment failure rates between intravenous and oral treatment for febrile neutropenia.

Hospital discharge

Recommendation 1.5.3.4 advises on the use of a scoring system and clinical judgement to determine low risk for discharge from hospital. One review (Loeffen et al. 2016) concluded that there is no evidence to suggest that early discharge from hospital is less safe in children with febrile neutropenia at low risk of bacterial infections. However, the review does not specify any criteria for determining low risk and children should still be carefully assessed before discharge.

Diet

One review (van Dalen et al. 2016) examined the use of low bacterial diets for the prevention of cancer chemotherapy related neutropenia. This was an update to a previous Cochrane review which concluded that there was no evidence to suggest that a low bacterial diet prevented infections. No new studies were identified in the updated review and the Cochrane authors could not make definitive conclusions. There are currently no recommendations in the NICE guideline on diet and this is unlikely to change at present as there is no new conclusive evidence in this area.

Antibiotics

One topic expert highlighted concerns about the accuracy of antibiotic guidance, however, no supporting evidence was provided and evidence found during the surveillance review generally supports current recommendations.

Age groups

One topic expert highlighted concerns about the applicability of recommendations to different age groups, specifically older age and children. However, no supporting evidence was provided and no new evidence in older children was found during the surveillance review.

Rapid diagnosis

One topic expert suggested that the surveillance review should focus on rapid diagnosis and direct access oncology pathways. However, we did not find any new evidence in these areas during the surveillance review.

Outpatient treatment

Topic experts highlighted 1 study (Taplitz et al. 2018) for consideration. This is a clinical practice guideline from the US which focuses on outpatient treatment of fever and neutropenia in adults. The clinical practice guideline includes evidence that supports recommendation 1.5.2.1 on the provision of outpatient care for this population and also suggests that the NICE guideline is generally in line with current international practice in this area.