Patients with acute leukaemia or certain types of cancers are being treated with intensive chemotherapy which can make them neutropenic. This means that the patient has too few white blood cells and is therefore not as well protected against infection. The smallest infection can even quickly turn into a life-threatening one.
A fever is usually the first symptom of a serious infection. In case of neutropenic fever, treatment with a powerful and broad-spectrum antibiotics is started as quickly as possible. Currently, the antibiotics is administered for a long time: at least 7 days, or longer until the white blood cells have recovered completely. However, only 20 to 30 per cent of neutropenic fever cases are caused by an infection. The other patients are therefore unduly treated with antibiotics: it is meant to protect them but also causes adverse effects. What's more, long use of antibiotics can have serious consequences.
The past years, UZ Leuven and the Erasmus Medisch Centrum in Rotterdam have taken a different approach to neutropenic fever. In Leuven the patients are given a broad-spectrum antibiotics until all blood cells have recovered again; in Rotterdam the patient is re-assessed after 72 hours and antibiotics treatment is stopped if no infection focus has been found. The researchers wanted to analyse both methods and check whether they were equally safe.
The trial showed that a shortened antibiotics treatment had the same effect as the longer approach. In both patient groups, there was no significant difference in the number of patients that developed a blood infection, needed intensive care or died.
The trial showed the it can be safe to stop the broad-working antibiotics treatment faster, even if the patient still has a fever.Dr. Toine Mercier, haematology assistant
Dr. Toine Mercier, haematology assistant at UZ Leuven: “This trial shows that, in certain cases, it can be safe to stop a broad-spectrum antibiotics treatment quicker, even if the patient still has a fever. This is an argument to reliably start comparing the two treatment options in larger trials. Large randomised trials are very time and labour intensive, but crucial to gather sufficient proof.”
Follow-up trial in Flemish university hospitals
In a first next step UZ Leuven will set up a multicentre trial together with UZ Gent, UZ Antwerpen, UZ Brussel and a number smaller hospitals, to map the effect of a shortened antibiotics treatment. Patients that develop neutropenic fever, but that do not have an infection, will be split up in two groups. One group will be given a broad-spectrum antibiotic for three days, the other group is treated with antibiotics until they are fever-free.
If a shorter antibiotics treatment in correctly selected patient groups turns out to be just as safe, it could be a signal to review the European and American guidelines. If the approach can be changed internationally, it will lead in a decrease in the worldwide use of antibiotics.Prof. dr. Johan Maertens, haematologist
With these trials, the researchers hope to gather additional proof and provide an important contribution to the worldwide problem of excessive use of antibiotics. Prof. dr. Johan Maertens, haematologist at UZ Leuven: “If a shorter antibiotics treatment in correctly selected patient groups turns out to be just as safe, it could be a signal to review the European and American guidelines. If the approach can be changed internationally, it will lead in a decrease in the worldwide use of antibiotics and we can take a new step in the fight against the advance of multiresistant bacteria. Only by looking in the same direction will be able to tackle this worldwide threat.”
Worldwide threat of antibiotic resistance
Why is the excessive worldwide use of antibiotics such a big problem? “Long use of broad-spectrum antibiotics can increase the risk of dangerous intestinal infections as well as affecting the microbiome of the intestines”, says dr. Alexander Schauwvlieghe, who worked on the trial as UZ Leuven researchers and who is involved in the follow-up trial at UZ Gent as a member of staff. “In addition, frequent use of antibiotics can also make certain bacteria less susceptible for the benefits of one or more types of antibiotics. This means that bacteria have taught themselves to protect themselves against our antibiotics. The consequence of antibiotic resistance is also that infections that could normally be easily treated, can now lead to serious diseases. This has to be avoided as much as possible in the future.”