Fever under 60 days of age

Prompted by Tessa’s Top 5.5 Papers in PEM presentation at RCEM, Alasdair Munro kicked off an exciting twitter debate with the question…Would you do a full septic screen on a baby under 60 days with a fever?

Many of us will be familiar with the mantra that all children under 3 months get a full septic screen and antibiotics. It feels like we are over-treating, but this is a high risk group so is there any other way?

Does it make a difference if they are over 28 days?

Yes, and this is for several reasons. In some studies the rate of bacterial meningitis in well appearing children >28 days was 0% – meaning this could potentially be ruled out on clinical grounds alone. This is not so for children <28 days, who can appear well and still have bacterial meningitis. It is also well established that biomarkers (which are imperfect at the best of times) perform worst in this age group. As yet we have no way of differentiating a low risk group in the neonatal cohort.

Bottom line: infants <28 days of age with fever should be managed with a full septic screen and empirical antibiotics regardless of clinical appearance or biomarkers. There is more uncertainty when it comes to those over 28 days.

Does it matter if the fever was at home only?

It is a relatively common practice to treat children with a fever in the ED differently to those with just a history of fever, and some previous evidence from outpatient departments in the US seemed to suggest that children who were afebrile on presentation were at lower risk of bacteraemia or meningitis. Sadly, this has not been born out in more recent studies, therefore it appears infants <60 days with a history of documented fever are at equal risk for bacteraemia or meningitis as those with fever in the department.

The key thing here is the term ‘history’. A mother’s report that their neonate’s forehead is hot is not the same as a recorded axillary temperature (although parents are better than you would expect at detecting fever by palpation alone). This creates a trust dilemma for health care professionals who don’t want to unnecessarily treat neither do they wish to disregard a families viewpoint.

Bottom line: take a history of documented fever with the same seriousness as you would a fever in the department.

Aren’t you allowed a fever after immunisations?

Yes, but we aren’t all brave enough to confidently put a fever down to immunisations in a 2 month old, which is particularly common following the MenB vaccination. In the community, fever after immunisation is commonly seen and the c hild discharged if they look well. In hospitals, we are more reluctant to reassure and discharge. The mere act of arrival in hospital is probably a risk factor. The pre-test probability of disease is exceptionally low, but the action of attending an Emergency Department is a ‘test’ which increases the post-test probability dramatically. This probably explains why both groups of clinicians (primary and emergency care) are right in the actions they take when managing a febrile neonate. The issue is compounded by the potential for bacterial meningitis to be present in the 24 hours after vaccination, although in this particular case the child was unwell appearing.

Bottom line: if the child is well, post-immunisation, and the fever resolves, then home with appropriate safety-netting may be fine.

What does NICE say?

NICE guideline in fever and sepsis categorises one to three month olds differently from under one month olds. Some people feel less likely to do this in an unimmunised baby.

NICE Guidance (NG51)  1.6.38 Give parenteral antibiotics to infants aged under 3 months as follows:

Bottom line: NICE classifies <1 month old babies differently from 1-3 month old babies, with regards to the need for a full septic screen.

Where does procalcitonin fit into this?

Procalcitonin is a biomarker used in a similar manner to CRP. The benefits include a more rapid response to infectious insult, and equally a much quicker decline following resolution.

The reliability of PCT depends on the age group tested, and whether you’re trying to diagnose an Invasive Bacterial Infection (IBI – commonly defined as bacteraemia or meningitis), or a non-invasive Serious Bacterial Infection (SBI – commonly including UTI, bacterial gastroenteritis or bacterial pneumonia).

The evidence for infants <60 days old suggests it performs similarly to CRP for diagnosing SBI (AUC 0.81 v 0.80), but importantly is superior for diagnosis of IBI (AUC 0.91 v 0.77), which ultimately we are more concerned about. Different thresholds have been suggested, with more conservative recommendations of 0.3ng/mL up to 1ng/mL

If you are lucky enough to be able to run a procalcitonin, or even better a point-of-care (POC) one, this may affect your management of children in the 1-3 month age group.

In practice, the way it has been used is if the baby has a normal POC procalcitonin, then some people would wait for the blood and urine results, and observe the baby. No antibiotics are started at that point as long as the baby seems well.

Bottom line: if you have a POC procalcitonin available, it may be able to help you in the 1-3 month old group.

If they have a positive urine result can I stop looking there?

There is often discussion about babies with urinary tract infections having concomitant meningitis. Some people therefore would continue with the septic screen and do a lumbar puncture even where the baby has been found to have a urinary tract infection.

A study of 236 neonates with a urinary tract infection found that no babies had a definite meningitis (although two with a bloody tap had probable meningitis). A more recent study of nearly over 1700 infants <60 days with UTI found rates of concomitant meningitis of 0.9% in neonates and 0.2% in infants 29–60 days old. This is similar to the baseline risk of meningitis in this population (~0.5%).

Bottom line: the decision to perform an LP should be made clinically, and independent of the presence or absence of a UTI.

How do we assess risk?

We have all seen or heard of cases where a child presented with late onset GBS sepsis and meningitis with poor outcomes. These are traumatising cases which leave significant cortical scars and can heavily influence our practice.

We accept risk in paediatrics every day. A 1% risk of missing a diagnosis might be fine on a child with a cough ?pneumonia, but many will see 1% as an unacceptable risk with a febrile neonate. We can never eliminate risk completely, and the threshold of acceptability varies between practitioners.

The most important factor in assessing risk is understanding the incidence of disease in your population. For infants <60 days with fever, this is;

• 9–20% have a serious bacterial infection (>95% UTI)
• 1-4% have a bacteraemia
• 0.5% have a bacterial meningitis (2/3 of these present in first 4 weeks)

It is worthwhile knowing your local incidence rates of disease; while the figures above have been validated over time, understanding the demographics of your local population ensures you understand the risks of your decision making and can explain outcomes more clearly to parents.

Also it is very important to differentiate between rates of SBI and IBI, as what we are ultimately concerned about is the safety of the child if we choose not to admit and treat.

For example, if a well but febrile child presents with a UTI but an initial urine dip is negative, and the sample is sent for MC&S and the child is discharged without treatment, we will not miss the UTI entirely and the child will still receive appropriate treatment within 24–48hrs.

Conclusion

The management of the febrile infant is a common but challenging area in which research continues to inform practice. However a tension remains between acting on probabilities of disease and acting on the child in front of you. The ability of invasive bacterial illness to rapidly overwhelm an immature immune system pushes many secondary clinicians to be over cautious. It is likely both the widespread availability of valid POC tests and clear national guidance will be needed to ultimately alter time honoured approaches to these cases.