What is the optimal anti-pseudomonal treatment when Pa is first isolated?

Pseudomonas aeruginosa causes lung infection and chronic lung infection is still the leading cause of lung infection and morbidity in CF. So as a CF community we must be vigilant about:

  1. Infection control
  2. Surveillance
  3. Early diagnosis
  4. Early treatment

Whereas the median age for chronic infection used to be 5 years, its now around 25 years in the top US centres.

Of course the million dollar question (there are many withn pseudomonas but the one we’re most concerned with) is which is the most effective course of treatment for eradication?

While inhaled Tobramycin has been shown to transiently clear the pseudomonas from  the lower airways – it doesn’t clear the lungs of the inflammation which is a key factor in the disease progression and continues the cycle of damage.

Study # 1

In a study cited in this preso, patients were randomised to receive one of two aggressive approaches of 4 weeks inhaled Tobi vs 2 weeks of IV Tobi and Ceftazadine (which is what we do at our clinic) and then they had did a bronch wash of the lower airways (the gold standard to see what’s kicking about down there).

The results showed that there was a difference in the inflammatory markers but it appears that the conclusions drawn were that the results were not significant enough to balance out the feasability, costs and side effects of the systemic IV antibiotic treatment.

Study # 2

The next study compared the two different treatment methods in the US and the UK amongst asymptomatic children (ie. not sick but just positive culture)

Inhaled Tobramycin for 28 days (USA)

VS

Inhaled colistithemate + oral ciprofloxin for 3 months (UK)

After one year the groups had no significant differences in BMI, FEV1, pseudomonal-specific igg – none of the markers that we care about.

After 2 years, 10% of the patients had chronic pseudomonal infection in both groups.

You can watch it online here: http://www.ustream.tv/recorded/75462435

Study # 3

Comparing two more treatment protocols:

Inhaled Tobramycin + oral ciprofloxin

VS

Inhaled colistithemate + oral ciprofloxin

Again this study resulted in no major difference in the eradication profile.

Study # 4

The Standford University team also looked at the timing approach for pseudomonal eradication protocols over a 5-10 year period with their own clinic.

Group # 1 – After a positive Pa culture, they received the initial 28 days inhaled Tobramycin followed by a cycle of treatment for the next 5-6 months (presumably month on, month off).

Group # 2 – Group # 1 – After a positive Pa culture, they received the initial 28 days inhaled Tobramycin followed by a second cycle of treatment if they continued to culture Pa in their swabs.

That group that received the “cycle of treatment” irrespective of whether they continued to test positive or negative for Pa following the initial infection.

Patients on the “cycle therapy” got their 5 rounds of antibiotic therapy post infection regardless of whether the sputum was clear or positive Pa after the initial treatment did not seem to be protected from exacerbations.

So what is the gold standard of care when it comes to Pa?

  1. Inhaled antibiotic therapy – Tobramycin twice daily for 28 days
  2. Against the use of an anti-pseudomonal drug to avoid infection
  3. Routine surveillance sputum cultures to test for pseudomonas before symptoms set in
  4. Positive pseudomonas cultures should be treated quickly (inside of 4 weeks)
  5. There is robust evidence that pseudomonas eradication treatment is effective but there is no definitive result to suggest that one method is superior to another.

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