Early aggressive eradication therapy for intermittent Pseudomonas Aeruginosa airway colonisation in cystic fibrosis patients: 15 years experience

Department of Pediatrics, 5003, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Journal of Cystic Fibrosis (Impact Factor: 3.48). 08/2008; 7(6):523-30. DOI: 10.1016/j.jcf.2008.06.009
Source: PubMed


Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment.
All isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype.
146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p<0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3-4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates.
Treatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.

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    • "The study was carried out over 44 months as only 16% of the treated patients developed chronic P. aeruginosa infection after 3(1/2) years compared with 72% of the control patients. Hansen et al. [48] included 146 patients and used oral ciprofloxacin (25–50 mg/kg/d) and inhalations of colistin (2 million units TID) for 3 months. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. "
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    ABSTRACT: The optimal antibiotic regimen is unclear in management of pulmonary infections due to pseudomonas and staphylococcus in cystic fibrosis (CF). We systematically searched all the published literature that has considered the evidence for antimicrobial therapies in CF till June 2013. The key findings were as follows: inhaled antipseudomonal antibiotic improves lung function, and probably the safest/most effective therapy; antistaphylococcal antibiotic prophylaxis increases the risk of acquiring P. aeruginosa; azithromycin significantly improves respiratory function after 6 months of treatment; a 28-day treatment with aztreonam or tobramycin significantly improves respiratory symptoms and pulmonary function; aztreonam lysine might be superior to tobramycin inhaled solution in chronic P. aeruginosa infection; oral ciprofloxacin does not produce additional benefit in those with chronic persistent pseudomonas infection but may have a role in early or first infection. As it is difficult to establish a firm recommendation based on the available evidence, the following factors must be considered for the choice of treatment for each patient: antibiotic related (e.g., safety and efficacy and ease of administration/delivery) and patient related (e.g., age, clinical status, prior use of antibiotics, coinfection by other organisms, and associated comorbidities ones).
    The Scientific World Journal 12/2013; 2013:645653. DOI:10.1155/2013/645653 · 1.73 Impact Factor
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    • "The cytokine concentration and increased influx by neutrophils are inversely correlated with lung function in CF patients, suggestive of the destructive neutrophil-induced inflammatory response (Sagel et al. 2002; Picinin et al. 2010). Prophylactic aggressive antibiotic regimens, usually consisting of 2 different antibiotic classes (e.g., colistin, aminoglycosides [tobramycin], and fluoroquinolones) are highly recommended for CF patients to delay P. aeruginosa lung colonization (Doring and Hoiby 2004; Hansen et al. 2008). Once the infections are confirmed, maintenance antibiotics are administered to reduce morbidity and increase pulmonary function (Ramsey et al. 1999; Equi et al. 2002). "
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    ABSTRACT: North American ginseng is known to have immunomodulatory and antipseudomonal properties in vitro. In this study we investigated the effects of aqueous ginseng extract, either alone or in a combination with the antibiotic tobramycin, in an animal model of chronic Pseudomonas aeruginosa lung infection. The lungs of male rats (n = 5) were infected with P. aeruginosa (2 × 10(8) cfu/mL) in agar-beads by intratracheal instillation. Starting on day 7 post-infection, animals were treated daily for 3 consecutive days with saline, tobramycin (300 μg/kg body mass, intratracheal), and (or) ginseng (100 mg/kg body mass, subcutaneous); animals were sacrificed 24 h after the third drug treatment. Lung bacteria counts, cytokine levels in sera, and lung histopathology were examined. The treatment of infected animals with tobramycin [6.6 × 10(4) colony forming units (cfu)], ginseng (5.3 × 10(4) cfu), or tobramycin plus ginseng (2.0 × 10(3) cfu) lessened the lung infection compared with the control group (saline treated) (6.0 × 10(6) cfu). The levels of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-12p70, IFN-γ, GM-CSF, TNF-α) in infected animals were significantly increased with co-treatment of ginseng plus tobramycin. These data suggest that co-administration of aqueous ginseng extract and tobramycin stimulated the pro-inflammatory response and promoted the killing of P. aeruginosa.
    Canadian Journal of Physiology and Pharmacology 11/2013; 91(11):935-940. DOI:10.1139/cjpp-2013-0073 · 1.77 Impact Factor
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    • "It has been previously observed that aerosol antibiotic treatment is also efficient when lower antibiotic drug concentration is administered.22–26 Several aerosol antibiotics are currently approved, including tobramycin,26–33 aztreonam lysine,34–40 and colistimethate sodium,41–46 and other new formulations are under development, including polymyxins,47 aminoglycosides,48–53 fluoroquinolones,54,55 and fosfomycin.56 Several respiratory diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis, show changes in parameters of the respiratory system, eg, sputum viscosity. "
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    ABSTRACT: Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed.
    Drug Design, Development and Therapy 10/2013; 7:1115-1134. DOI:10.2147/DDDT.S51303 · 3.03 Impact Factor
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