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Eradication of Pseudomonas aeruginosa infection

Question
My daughter cultured Pa at the last clinic visit. She was symptom free. The doctor prescribed 28 days of inhaled Antibiotic, and I asked to add an oral antipseudomonal, but she would not.

Finished the 28 day cycle, and a week later my daughter has a raging lung infection and now pneumonia. I asked the doctor again to prescribe the oral antipseudomonal. Again she said no, and just told us to start another 28 days of inhaled antibiotic.

We were told the oral antibiotic does not make a difference by a new doctor fresh out of her fellowship and entirely too conservative with treatments.

I have read the research and early erradication of pseudomonas will give my daughter the best survival options. This is really starting to tick me off because I want a more aggressive approach, and she is being too conservative IMHO.

I've talked to hundreds of patients and most who were treated with an inhaled antibiotic alone are now colonized with PA. Although they all still speak strongly that the inhaled is the only answer. ummm ok.

I dont agree and I do not follow status quo. Research study being guidelines. We need to treat patients like individuals, but I am looking for any additional advice to back up my findings.


Answer
Dear questionner

Thank you for your question. Pseudomonas aeruginosa (PA) is, as you have indicated, a most important, and indeed frequent, infection in individuals with cystic fibrosis.[1] Chronic infection with PA is defined as regular culture of the organism from sputum or respiratory secretions on 2 or more occasions extending over at least a 6 month period.[2] Our understanding is that chronic infection with PA is associated with a more rapid decline in lung function,[3] increased morbidity, and increased mortality in the subsequent 10 years after diagnosis of chronic infection.[4] Furthermore, patients who were prevented from developing chronic PA infection with appropriate antibiotic treatment are less likely to deteriorate over a 2 year period in contrast to people who have became chronically infected.[5] Therefore, all efforts should be taken to eradicate PA infection in a timely fashion.

Early treatment of PA infection is about 80% successful after first isolation.[6] Different treatment regimens are used and the optimal method is not entirely clear. What inhaled antibiotic was used for your daughter? There is evidence that 28 days of tobramycin solution for inhalation (TOBI), 300 mg twice daily, is a safe and effective alternative to reduce PA density in young children with cystic fibrosis.[7]

Guidelines from the UK Cystic fibrosis Trust indicate that when PA is first isolated, eradication should be attempted with nebulised colistin and oral ciprofloxacin, and, failing that, intravenous anti-Pseudomonal antibiotics and nebulised colistin should follow. In general, if re-infection occurs, a similar approach should be adopted.[8]

Regards
Dr David Comer

References

1. Lyczak, JB, Cannon CL, Pier GB. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002; 15:194-222.
2. Hoiby N. Pseudomonas aeruginosa infection in cystic fibrosis. Relationship between mucoid strains of Pseudomonas aeruginosa and the humoral immune response. Acta Pathol Microbiol Scand 1974 Sect B 82:551-558.
3. Kerem E, Corey M, Gold R, Levison H. Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonization with Pseudomonas aeruginosa. J Pediatr 1990; 116:714-719.
4. Hudson VL, Wielinski CL, Regelman WE. Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years J Pediatr 1993; 122:854-860.
5. Frederiksen B, Lanng S, Koch C, Hoiby N. Improved survival in the Danish center-treated cystic fibrosis patient: results of aggressive treatment. Pediatr Pulmonol 1996; 21:153-158.
6. Littlewood JM, Miller MG, Ghonheim AT, Ramsden CH. Nebulised colomycin for early Pseudomonas colonisation in cystic fibrosis. Lancet 1985; i:865.
7. Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Resp Crit Care Med 2003; 167:841-849.

04.03.2013
3.3.13
There is a publication from Bals et al. giving an overview of antibiotic treatment of CF lung disease: Bals, Hubert and Tümmler 2010 in the Journal of Cystic Fibrosis, Voulme 10, Suppl2:S146-S151: "Antibiotic treatment of CF lung disease: From bench to beside".
In here, it is also pointed out that "the optimal therapeutic regimen and duration of early treatment [of Pseudomonas aeruginosa infection] remains unclear". Among others, results of the ELITE study are presented that compares 28 days of tobramycin inhalation twice daily versus 56 days of tobramycin inhalation: "it concluded that inhalation of tobramycin twice daily for 28 days is as effective as 56 days and well tolerated therapy for early P. aeruginosa infection in CF patients."
In the EPIC clinical trial inhaled tobramycin was associated with oral ciprofloxacin or with placebo: "no difference was observed between the treatment groups in the proportion of recurrent P. aeruginosa positive cultures, in time to pulmonary exacerbation requiring antibiotics or in other measures of clinical efficacy (change in mean weight or in mean FEV1 from baseline)."
However, there are no uniform guidelines on the best regimen, and often, oral or i.v. antibiotics are used in combination or followed by inhalative antibiotics. More studies are needed to find out the optimal regimen.
D. d'Alquen