Unlucky dip: Rational diagnostic testing for infections

We see lots of children with suspected infections. Modern microbiology techniques have opened up a huge array of tests: some new and expensive, but we are often still reliant on good old fashion microscopy and culture.

With so many tests so readily available, we need to think hard about diagnostic stewardship. This means testing the right patients for the right reasons. We must be wary of over-diagnosis, preventing confusion, anxiety or unnecessary treatment, and making choices that represent good value. Many tests can be expensive and are often not necessary to make management decisions.

With that in mind, let’s take a look at some of the most common diagnostic tests for infections, and when we should (or shouldn’t!) be deploying them.

Urine dips and MC&S

Urinary tract infections (UTIs) are the most common serious bacterial infection in high-income countries. There are many departments where it is routine to set up every febrile child to get a “clean catch” urine as soon as they arrive. This is unwise, because it is VERY EASY to contaminate a urine sample from a clean catch. We have all seen children or parents putting their hands/feet/face in the bowl, and let’s be honest – if the child is sitting on the container, it’s basically directly under the body’s primary waste pipe.

Accepting a decent risk of false positives, we must aim to test only those who need the test. So when should we do it?

Fever without a source

This is the primary indication for doing a urine dip, and it is a sensible one. However, still not every child with fever and no source needs a urine dip. Older children can report urinary symptoms, and the absence of these makes a UTI much less likely. In addition, by school age, UTIs in males with normal renal tracts become very rare, so urine testing also becomes less useful.

As a framework, urine dips should be performed in the following groups with fever and no source (assuming they have no risk factors for UTIs and have no red flags):

Outside of these groups, use your clinical discretion to decide if the pre-test probability justifies the risk of a false positive – take into consideration the child’s age, gender, duration of symptoms, how unwell they appear, and obviously if they have known risk factors such as renal abnormalities or previous UTIs.

Symptoms of UTI

This seems obvious – but it’s worth stating that once urinary symptoms are present (increased frequency, dysuria) you should dip the urine to check for infection, and it may be worth sending samples for MC&S even if they are dip negative in this scenario (you can withhold treatment pending results).

It is worth taking more care for children with non-urinary symptoms, such as abdominal pain or vomiting (which is probably not predictive of UTI). Once at school age (particularly in boys) these symptoms are unlikely to be a symptom of a UTI so a higher threshold for testing should be adopted.

Some people say that all children with rigors require urine testing. Rigors are not evidenced to have any influence on the risk of UTI (or any significant risk of bacterial infection). If there is another source of the fever, urine dip is certainly not indicated on the basis of a rigor alone.

For more information on relative risks for UTIs in younger children, the supplementary materials to the UTI risk calculator study make an interesting read.

What about hot babies with bronchiolitis?

This becomes a slightly more controversial topic, and decisions require risk stratification based on the age of the child. For example, a febrile neonate with bronchiolitis might be lucky to escape the full shebang of a septic screen anyway – and a quick in/out catheter is unlikely to yield a false positive.

The literature on this topic is a bit confusing because of varying definitions of UTI and bronchiolitis (some studies including any child with RSV detected in their nose). The most recent meta-analysis with more stringent criteria for diagnosing UTI found a rate of concomitant UTI with bronchiolitis of 0.8% – low enough that testing is not advised.

Bottom line: if an infant has a fever and a clinical diagnosis of bronchiolitis, then urine dip is not necessary in most instances – however this should be given strong consideration in infants <60d and should be performed in neonates.

Blood culture

For a full myth busting exercise in blood cultures, please read the recent DFTB post on this topic. Some things to bear in mind if you’re thinking of taking a blood culture:

• You are testing for bacteraemia. If you do not suspect bacteraemia, do not send a blood culture.
• Blood cultures are extremely low yield in uncomplicated skin/soft tissue infection and pneumonia and should be avoided.
• You do not need to wait for a fever to take a blood culture – it has no influence on the likelihood of obtaining a positive result. If you suspect bacteraemia, take the culture now.
• If you are going to take a blood culture, aim to inoculate at least 1ml of blood per year of the child’s age. Less than this and you increase the risk of contamination and decrease the sensitivity.

Wound swab

When it comes to swabbing for microscopy, culture and sensitivity (MC&S), there is a golden rule*:

Do not swab any non-sterile site that you have not already clinically diagnosed as being infected.

A skin swab, throat swab, eye swab etc. will grow bacteria 100% of the time, because these places are non-sterile. They will often grow pathogens, because many pathogens are quite happy just being colonisers a lot of the time, and actually some of them are more often found as bystanders than as trouble-makers (Pseudomonas aeruginosa is a prime example – it is very rarely pathogenic in non-sterile sites). A positive swab does not diagnose infection.

YOU have to diagnose infection; a swab will just tell you what bacteria is causing it.

I would like to give a special shout out to gastrostomies at this point – just because they are “mucky” is not a good reason to swab. If you do swab it, you will find good old Pseudomonas (it loves playing in wet stuff). Skin and soft tissue infections are red, hot and inflamed +/- a bit of pus. Yellowish clearish greenish stuff is normally just serous fluid, so don’t worry about it and don’t swab it!

The same goes for babies sticky eyes. If you swab it, it will grow bacteria, but this tells you nothing about whether they are infected. Look for inflammation, if you find it then diagnose infection, treat empirically and send a swab if you are concerned about resistant bacteria.

*there are some exceptions to the golden rule, including burns and chronic wounds in immunosuppressed patients.

Throat swabs

Before starting – let’s remember that you cannot diagnose a bacterial throat infection with a swab alone. If you are considering swabbing a throat for MC&S, you must have already clinically diagnosed infection.

Guidelines vary quite widely in their recommendations to swab or not swab when diagnosing tonsillitis. It is worth considering that a throat swab has a reasonable sensitivity for group A Strep, if performed correctly. Sadly – we are all dreadful at performing throat swabs in children (who are usually very good at not wanting a throat swab), and often get a good dose of tongue and palate. Not good.

A further thing to consider is that approximately half of all throat swabs positive for group A Strep just indicate carriage – you’ve found the bug, but it’s just a bystander.

This means that if you swab and haven’t found the bacteria, it might be there but you’ve missed it, and if you have found it, there’s a 50% chance it’s not causing the illness anyway…

If it’s extremely important you detect the presence of group A Strep (for example in populations high risk for rheumatic fever) then I would definitely do a swab. If it’s not (and it usually is not), then make your decision to treat or not on clinical grounds alone.

Also, remember that in children <4yrs group A Strep tonsillitis is rare and almost never causes complications, so if you’re thinking of doing a throat swab for a child in this age group you need to have a very good reason.

Respiratory virus testing

Respiratory tract infections are extremely common in children. There is a fair amount of controversy and disagreement about the role for respiratory virus testing. It can have several roles:

1. Local epidemiology. Some big/university hospitals like to keep track of what’s circulating, and will often have guidelines on who and when they want these tests performed.
2. Cohorting. In bronchiolitis season, some hospitals might fill one bay with RSV and another with Rhinovirus. This is an evidence free zone.
3. Fever without a source. Influenza in particular can cause horrible febrile illnesses in children without the classic respiratory prodrome. The idea is to detect the flu to prevent unnecessary antibiotics.

A group of children you should not test for respiratory viruses is anyone with cough and coryza. They do not need a test – they can be safely diagnosed clinically, and the presence or absence of a virus on testing does not change anything.

What about in lower respiratory tract infections? We can imagine that the discovery of a virus would prevent unnecessary antibiotics. However, respiratory viruses are common (even among non-hospitalised populations) and co-infection with bacteria is also common in viral infections. The presence of a virus does not preclude a bacterial infection. As such, their use in this context is contentious, and they do not appear to reduce antibiotic use.

For a thorough look at the principles and evidence of respiratory virus testing in children, I would recommend this excellent review paper.

Conclusions

• Not every child with fever and no source needs a urine dip. Do it in infants, young girls and children with fever persisting >48hrs. Otherwise, use clinical discretion.
• You probably don’t need to urine dip febrile children with clinical bronchiolitis.
• Only do blood cultures if you suspect bacteraemia, and take lots of blood if you do.
• Only send a swab for MC&S from a non-sterile site if you’ve already diagnosed infection.
• Throat swabs are usually not useful. Only do them for high risk groups.
• Respiratory virus testing is not useful in most circumstances. Only do it if you have a definite plan for how it will change your management.
• When in doubt – if you can’t explain how the test will change your management, don’t do the test.