On examination she had widespread crackles throughout her chest consistent with a pneumonitis and bronchial breathing at her right lung base consistent with consolidation. She was started on antibiotics for her CAP and transferred to the high dependency unit for closer monitoring and respiratory support with non-invasive ventilation. After a couple of hours it was clear she was getting worse and she was transferred to critical care for intubation and ventilation.
At this point she was discussed with the Microbiologist with a view to changing her antibiotics because “she wasn’t responding”. The Microbiologist recommended an urgent Influenza test as well as a sputum or bronchoalveolar lavage sample. The clinical team were told to continue with the current antibacterials but to empirically start anti-influenza treatment with Oseltamivir. The team looked puzzled that they should consider adding Oseltamivir to their empirical treatment of CAP, the Microbiologists just said “you did get the alert that we have entered Flu Season, didn’t you?” The Influenza test confirmed that the patient did have Influenza A. The following day the sputum sample had grown a Group A beta-haemolytic streptococcus; the bacterial pneumonia is a secondary complication of the Influenza. The patient was changed to IV Benzylpenicillin PLUS IV Clindamycin to specifically target the Group A beta-haemolytic streptococcus. The most common complication of Influenza is pneumonia.
The Influenza virus itself can cause pneumonia. This type of pneumonia is often very severe and is said to have a high mortality, however I have been unable to find a figure for the mortality rate despite the high mortality being widely quoted in various academic papers and even on the CDC website. The patient’s chest x-ray tends to show bilateral hazy shadowing and specific areas of consolidation are uncommon.
Secondary bacterial pneumonia (occurring in 2.5% of cases of Influenza in over 65 year olds) is probably more common than primary viral pneumonia in Influenza. Secondary bacterial pneumonia is the main cause of death “from pneumonia” in the over 65 year olds; the mortality in the over 65 year olds and those with pre-existing lung disease, cardiac disease or immunosuppression is said to be up to 15%.
So how does this occur? The virus damages the lung epithelial cells as well as causing a loss of cilia allowing bacteria to invade the lung tissue more easily. The most common bacteria causing secondary infection in Influenza are Streptococcus pneumoniae (50%), Staphylococcus aureus (20%), Haemophilus influenzae, the clue is in its name (7%) and Group A beta-haemolytic streptococcus, S. pyogenes (4%). This rate of S. aureus is significantly higher than the normal 5-6% in community acquired pneumonia.
Group A beta-haemolytic streptococcus is less common but tends to cause very severe secondary pneumonia, as occurred in our patient. Over the last 3 years I have noticed that if flu season coincides with a high background rate of Group A beta-haemolytic streptococcus you will see more Group A beta-haemolytic streptococcus causing the secondary pneumonias. We have had high rates of Group A beta-haemolytic streptococcus in the community in the UK for the past 3 years (see scarlet fever blog) fortunately we have not had much Influenza until now.
The main clue to spotting the difference between primary Influenza pneumonia and secondary bacterial pneumonia is that in primary Influenza pneumonia the symptoms progress steadily from the onset of illness whereas in secondary bacterial pneumonia the patient initially improves before worsening again within a few days (even up to 2 weeks later). Another marker is the neutrophil count which tends to be normal in Influenza, where lymphocytosis or lymphopaenia is the main white cell picture, whereas in bacterial infections the neutrophil count will either go up or down. Some unfortunate patients get both primary pneumonia from Influenza and a secondary bacterial pneumonia. In these mixed infections there are usually changes in both the lymphocyte and neutrophil counts.
If the patient is thought to have a secondary bacterial pneumonia then community acquired pneumonia antibiotics should be given as they cover S. pneumoniae, S. aureus and H. influenzae. However consideration should be given to the “apparently” less common invasive Group A beta-haemolytic streptococcus and all its associated public health implications as well. Common combinations for severe CAP include Co-amoxiclav PLUS Clarithromycin and Teicoplanin PLUS Levofloxacin which also cover the possibility of Group A beta-haemolytic streptococcus.
Okay, so it may come as no surprise to know that pneumonia is the most common complication of infection with the Influenza virus but neurological, cardiac and muscle complications can also occur in adults and children, whilst children commonly get otitis media as well.
A number of different clinical manifestations of Influenza have been described including:
- Transverse myelitis
- Guillain-Barre syndrome
It is unclear how Influenza causes these neurological conditions. An autoimmune reaction is thought to be most likely however it is possible that the cause is direct invasion of the brain and associated nerve tissue by the virus.
It is also not known whether treatment with anti-influenza drugs such as Oseltamivir or Zanamivir make any difference to the outcome of these associated neurological diseases. In these situations I take the approach that if there is evidence of current Influenza infection by PCR on either respiratory or CNS samples from a patient then I’ll treat them with an anti-Influenza drug, as I feel any potential benefit outweighs the risk of harm caused by these drugs.
Electrical conduction disturbances (on ECG) commonly occur in previously fit young adults with Influenza (50% on day 1 declining to 20% at 4 weeks). Alarming maybe, but this is not usually associated with heart damage leading to elevated heart enzymes or changes on echocardiogram.
Other cardiac manifestations of Influenza are hard to separate out from underlying ischaemic heart disease (IHD) that pre-existed in the patient, however mortality from IHD during Influenza season increases by about 40% in most studies.
Myocarditis and pericarditis have also been described as complications from Influenza infection however the mechanism by which Influenza causes these conditions is uncertain as in these patients there is no evidence of direct cardiac infection with the virus. It might be that Influenza triggers autoimmune damage to the heart in some patients. Whatever the cause, there is no specific treatment for the cardiac conditions however the patient should be treated for their Influenza with anti-Influenza drugs.
Myositis and rhabdomyolysis can occur in adults and children but are more common in children. This is more than just the aches flu gives everyone! The Influenza virus appears to directly invade and damage the muscle cells. Patients have extremely tender muscles, especially the lower leg muscles, and the creatine kinase is usually very high. Muscle breakdown can result in muscle proteins being passed through the kidneys into the urine (myoglobinuria) and even renal failure in severe cases. It is unclear if anti-influenza drugs make any difference to myositis or rhabdomyolysis but I would apply the same argument as for neurological disease above and treat (I feel any potential benefit outweighs the risk of harm caused by these drugs).
Between 10% and 50% of children develop otitis media 3-4 days after the onset of Influenza. This is approximately 3-5% of all children every year. Whilst this has a large socioeconomic impact in terms of missed school days and parents being off work to care for their children, it is usually self-limiting and the children get better without any specific treatment or antibiotics.
So whilst it is important to diagnose Influenza early so that anti-influenza drugs can be started as soon as possible it is also important to spot complications when they occur.
People at higher risk of developing flu complications include:
- Young children under 5, and especially those under 2 years
- Adults older than 65
- Residents of nursing homes and other long-term care facilities
- Pregnant women
- People with weakened immune systems
- People who have chronic illnesses, such as asthma, heart disease, kidney disease and diabetes
- People who are morbidly obese, with a body mass index (BMI) of 40 or higher
For many complications treatment is either for the influenza itself or there is no specific treatment. Normally Oseltamivir should be started within 24 hours to gain most benefit but in very unwell patients with ongoing replication of the virus there may be benefit to giving it even after this time. The complication that can be specifically treated is secondary bacterial pneumonia which has a mortality up to 15%. Treatment is with antibiotics targeted at the common causes of community acquired pneumonia especially S. pneumoniae, S. aureus, H. influenzae and the Group A beta-haemolytic streptococcus. Our patient with Group A beta-haemolytic streptococcus pneumonia did eventually recover but it took a couple of weeks for her to be well enough to go home, and a few weeks more before she felt like her old self again.