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PCP - “Pregnancy Causes Problems”

16/10/2014

1 Comment

 
A fretful junior doctor called for advice because their pregnant patient was extremely short of breath and they didn’t know why. They thought the patient might have PCP but couldn’t understand how that could have happened. It sounded like a difficult problem sure enough but more details were required. Shortness of breath in pregnancy is not uncommon... pregnancy can impact the diaphragm... but junior doctors don’t normally jump to the diagnosis of PCP when expectant mothers become short of breath. 
Further questioning revealed that the patient was a lady from Sub-Saharan Africa with a new diagnosis of HIV infection and a CD4 count less than 200/mm3. Because of her low CD4 count she is at risk of infection with micro-organisms that do not normally cause infections in people, the so called “opportunists”. Any HIV positive patient with a low CD4 count is at risk of developing PCP and should be started on Co-Trimoxazole (Septrin). But despite being on prophylactic Co-Trimoxazole she still appeared to have developed PCP!? The junior doctor was perplexed as they thought the prophylaxis should have prevented her illness.
What is PCP?
PCP is an opportunistic lower respiratory tract infection caused by the fungus Pneumocystis jirovecii (previously known as Pneumocystis carinii, but this name is now used to only describe the species that infects rats!). P. jirovecii is everywhere in the environment, and approximately two thirds of us have acquired it through inhalation by the time we are 2 years old. The micro-organism remains in the lungs (latent) without causing any problem unless we become immunosuppressed for some reason. As the immune system becomes inadequate, e.g. the loss of CD4 lymphocytes in HIV infection (it is an AIDS defining illness) or chemotherapy induced neutropaenia, it no longer holds the organism in check so the fungus becomes active and infection occurs.
So why did this pregnant HIV positive patient develop PCP despite being given prophylaxis?
Co-Trimoxazole is normally very effective at preventing PCP but there are some problems with its use in pregnancy. Because it is an anti-folate drug it can be associated with congenital birth defects when used in the 1st trimester.

Some doctors give extra supplements of folic acid to try and prevent the development of birth defects however there is evidence that high folic acid supplementation in pregnancy increases the risk to the mother of PCP treatment failure and death. P. jirovecii uses this folic acid to bypass the action of the Co-Trimoxazole. Co-Trimoxazole normally kills bacteria by preventing the bacteria’s synthesis of folic acid but it seems that this fungus can utilise free folic acid for its DNA synthesis therefore it is not killed. 
So it’s a Catch 22...give folic acid and increase the risk to the mother of dying from PCP or don’t give folic acid and increase the risk of birth defects in the baby! The current recommendation from the Infectious Diseases Society of America is to treat PCP in all trimesters but only give folic acid supplementation in the 1st trimester when the risk of developing congenital birth defects is at its highest; the benefits of giving the antibiotic during this period outweigh the risk of harm from treatment.
How to diagnose PCP
The key to making the diagnosis is having a strong suspicion of PCP in an immunosuppressed patient. There are no definite characteristics however patients tend to have hypoxia which worsens on minimal exertion e.g. walking to the toilet. 
PCP - CXR
PCP - ground glass shadowing
The Chest X-ray classically shows ground-glass shadowing (the name comes from the changes looking like the ground glass joints of chemistry equipment). 

In the UK there are 2 commonly used diagnostic strategies for PCP. 
1.   Direct staining of Bronchoalveolar lavage (BAL) specimens either using a Silver-Grocott stain in histopathology or immunofluorescence in microbiology
2.   Molecular detection of P. jirovecii using PCR on either a BAL sample or an EDTA blood sample
PCP - Silver-Grocott stain in histopathology
PCP - immunofluorescence in microbiology
The EDTA blood PCR has improved our ability to diagnose PCP because many of these patients are too hypoxic to tolerate a BAL. The positive predictive value of blood PCR is high and confirms the diagnosis because the micro-organism has to have invaded through the lungs in order for this test to be positive. However, the negative predictive value of blood PCR is poor so it doesn’t rule out the diagnosis.

How is PCP treated?
If the diagnosis is suspected then treatment should be started before tests results are confirmed, as most laboratories in the UK don’t have the capability to diagnose PCP quickly. First line treatment of PCP is IV or PO Co-Trimoxazole (Septrin) at high doses, 30mg/kg QDS or 60mg/kg BD, although the dose does need adjusting for renal failure. Co-Trimoxazole is still used to treat even if the patient has been on prophylaxis because the doses used to treat it are much higher than those used to prevent it (typically prophylaxis is with 480mg a day whereas treatment is with 8,400mg a day!). Treatment should be continued for 21 days. The other crucial component of treatment is the use of steroids, normally PO Prednisolone 40mg BD. It is the steroids that save lives in PCP as they damp down the inflammation associated with infection and give enough time for the antibiotics to work. Second line treatment for severe PCP is with Primaquine and Clindamycin, but usually only under the guidance of a specialist in infectious diseases or genitourinary medicine.
Key points:
• PCP is a severe disease, and it should be considered in any profoundly immunosuppressed patient with a lower respiratory tract infection
• PCP in pregnancy should be treated normally as the benefit of treatment outweighs the risk of harm to the baby
• Investigation takes time and therefore treatment should be initiated as soon as possible
• Even with appropriate treatment the mortality can be as high as 20-40%

For this patient the treatment went well and so far there does not appear to be any problems for her baby.
1 Comment
Dr. Sushmita Mukherjee link
7/11/2020 04:59:24 pm

You have covered each points very precisely. The post couldn't be any better.

Reply



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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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