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CHILDREN with cancer receive potent chemotherapy and supportive care, which together have revolutionised survival from childhood cancer. A child with acute lymphoblastic leukaemia diagnosed in Australia in 1970 had approximately a 40% chance of survival. Today, that figure is above 90%. Unfortunately, that same chemotherapy which has improved survival by killing cancer cells also makes children vulnerable to life-threatening infections.
Antibiotics are commonly prescribed for children with fever and neutropenia while undergoing treatment for cancer. These antibiotics usually include a broad-spectrum β-lactam antibiotic with activity against Pseudomonas aeruginosa. Antibiotics from the aminoglycoside class (such as gentamicin) are often prescribed as an additional measure. This is done for a theoretical benefit of treating any bacteria that might be causing an infection and happen to be resistant to the β-lactam antibiotic prescribed, as well as for a potential synergistic effect, on the theory that two drugs are better than one.
Aminoglycosides – more harm than good?
Unfortunately, this common (although not universal) approach may be doing more harm than good. In a recent report, we examined antibiotic prescribing in 858 episodes of fever and neutropenia among 462 children treated in cancer centres across Australia.
In 30% of these episodes (255 in total), an aminoglycoside antibiotic was prescribed. Surprisingly, we found that children prescribed one of these aminoglycosides were almost four times more likely to suffer harm from this approach – measured as one or more of relapse of infection, admission to an intensive care unit, late-onset severe sepsis, or death. Although a possible explanation for this was that children who received an aminoglycoside were more unwell to begin with, we could not find evidence for this in our analysis.
We also found that guidelines for aminoglycoside prescribing in these children varied substantially by state. Some recommend aminoglycosides routinely and others only under certain conditions. In our study, we could not find any circumstances where aminoglycosides appeared to provide benefit.
In addition, Australia has national consensus guidelines for adults, which recommend aminoglycosides only for adults with fever and neutropenia who have signs of systemic compromise. There are, however, only local guidelines for children and no national guideline exists.
An international guideline for children with fever and neutropenia recommends against routinely prescribing aminoglycosides.
Infections in children with cancer in 2020 – it’s no PICNICC
Fortunately, there has never been a better time to confront this issue. Children with cancer in Australia have access to world-class services, the latest clinical trials, and a network of dedicated multidisciplinary specialists providing care.
In recent years, there has been increasing attention to improving and standardising care beyond anticancer drugs, with a focus on improving optimising supportive care of all kinds, including infection management. Research in Australia has shown it is possible to improve the timing of antibiotic administration for children with fever and neutropenia but discrepancies remain in the type and appropriateness of prescribing.
Collaborative research, such as the Australian PICNICC study, has involved clinicians from haematology/oncology, emergency medicine and infectious diseases from around the country. It has generated important findings to better understand the burden of fever and neutropenia among Australian children with cancer, to better characterise the types of infections seen as well as potential for home-based care.
Time for a national approach
There is now an opportunity to revisit guidelines for antibiotic therapy for children with fever and neutropenia in cancer at a national level. Recent Australian research and international guidelines suggest that aminoglycosides should not be routinely prescribed in this setting.
Using the clinical and research networks developed during these paediatric fever and neutropenia studies, health care providers are in a unique position to forge a consensus and take the next steps to improve outcomes for children.
Dr Brendan McMullan is a paediatric infectious diseases physician and microbiologist at Sydney Children’s Hospital, Randwick, Sydney, and is undertaking a PhD at the University of Melbourne.
Dr Gabrielle Haeusler is a paediatric infectious diseases physician and clinician scientist working at Royal Children’s Hospital and the Peter MacCallum Cancer Centre, Melbourne.
Professor Karin Thursky is an infectious Diseases physician and health services researcher, and is the Implementation Stream lead for the National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne.
Professor Tracey O’Brien is a paediatric oncologist and transplant physician and Director of Kids Cancer Centre, Sydney Children’s Hospital, Randwick, Sydney.
The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.