Surveillance decision

Surveillance decision

We will not update the NICE guideline on neutropenic sepsis.

We will amend recommendation about fluoroquinolones for prophylaxis of neutropenic sepsis to add a link to the Medicines and Healthcare products Regulatory Agency (MHRA) Drug Safety Update on fluoroquinolone antibiotics.

Reasons for the decision

The NICE guideline on neutropenic sepsis recommends offering fluoroquinolones for primary prophylaxis. The guideline committee came to this conclusion after examining over 200 randomised controlled trials of primary prophylaxis, basing their decision on clinical evidence that fluoroquinolones are more effective than placebo for reducing mortality and neutropenic sepsis. Additionally, an economic model built for the guideline showed that primary prophylaxis with fluoroquinolones in solid tumours is more cost effective than other strategies, which was robust to sensitivity analysis. Risks of fluoroquinolones were noted by the committee, such as side effects and bacterial resistance, but it was agreed that the benefit of saving lives outweighed potential harms.

Routine surveillance of the guideline published in February 2019 identified a Cochrane review, which concluded that among all antibiotics examined, the most significant reduction in mortality was with quinolones. The new evidence was consistent with the recommendation to offer fluoroquinolones for prophylaxis.

In March 2019, the MHRA published a Drug Safety Update (DSU) announcing restrictions and precautions for the use of fluoroquinolone antibiotics because of rare reports of disabling and potentially long-lasting or irreversible side effects. However, the DSU also notes that restrictions should not prevent use of a fluoroquinolone for serious or severe infections if this is consistent with UK national guidance, and where the benefit is thought to outweigh the risk. Fluoroquinolone prophylaxis of serious infections, including neutropenic sepsis, is not specifically discussed. An alert about the DSU was added to the landing page of the neutropenic sepsis guideline, but the impact of the DSU on the management of this potentially fatal infection needed to be further explored in an exceptional surveillance review.

The review indicated that fluoroquinolones remain the most effective preventive measure for neutropenic sepsis. A topic expert noted that even with the safety issues highlighted in the DSU, the benefits of fluoroquinolones in terms of reduction in potentially life-threatening infections outweigh the risks.

Although the DSU has highlighted rare but serious side effects of fluoroquinolones, the restrictions announced by the DSU are aimed at treatment of mild to moderate infections, whereas fluoroquinolone use in the neutropenic sepsis guideline relates to prevention of potentially fatal infections (though the DSU does not specifically discuss prophylaxis of serious infections).

After considering the evidence originally examined by the guideline, the content of the DSU, new evidence identified since the guideline was published, and the limited response from topic experts (a haematological oncology specialist), we judged that the conclusion of the original guideline committee – that the benefits of fluoroquinolones in saving lives outweigh potential harms – remains valid.

There is therefore no impact of the DSU on recommendation to offer prophylaxis with a fluoroquinolone, but a link to the DSU will be added to the recommendation. A footnote will also be added to explain that fluoroquinolone antibiotics currently available in the UK are not licensed for prophylaxis of neutropenic sepsis and the recommendation is for off‑label use.

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