Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis

Harvard University, Cambridge, Massachusetts, United States
Pediatric Pulmonology (Impact Factor: 2.7). 07/2007; 42(7):610-23. DOI: 10.1002/ppul.20625
Source: PubMed


Among young children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality. Early intervention strategies include tobramycin solution for inhalation (TSI), which can eradicate lower airway Pa from cultures obtained at the end of 28 days of treatment in young children.
We conducted an open label, sequential cohort study of TSI in young children with CF to investigate duration of antimicrobial treatment effect. The primary outcome was lower airway Pa eradication per bronchoalveolar lavage (BAL) fluid culture. Sequential treatment cohorts varied by duration of treatment (28 or 56 days) and timing of follow-up BAL (at Days 56, 84, or 112). Subjects (N = 36) were treated with TSI, 300 mg twice daily, for 28 days or 56 days per cohort assignment.
Among 31 evaluable subjects, culture based, lower airway Pa eradication was observed in the majority of subjects for up to 1-3 months following TSI treatment: 75% in Cohort 28/56 (days of treatment/day of follow-up BAL), 63% in Cohort 28/84, 82% in Cohort 56/112, and 75% in Cohort 28/112. Non-mucoid Pa at baseline and/or exotoxin A seronegativity were associated with higher rates of eradication. There was a less pronounced effect of TSI treatment on Pa eradication from oropharyngeal cultures in all cohorts. TSI treatment was associated with reduced neutrophilic airway inflammation and was not related to any serious adverse events.
TSI monotherapy is safe and can eradicate lower airway Pa for up to 3 months after treatment in young children with CF.

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    • "There was an improvement in lung function noted before the intervention. In another cohort study [41], 36 young children treated with TSI (tobramycin solution for inhalation) 300 mg BID for 28 days or 56 days eradicated P. aeruginosa for up to 3 months after treatment. There are three new trials [42] [43] [44] that were not included in the above CR. "
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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).
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    • "The most commonly used aerosolised antibiotics are tobramycin and colistimethate sodium, which can be delivered twice daily for prolonged periods of time [3]. A preservative-free and stable formulation of tobramycin solution (TOBI®, 300 mg in 5 mL of 1/4 normal saline) is available for the long-term management of P. aeruginosa infection in patients with CF [5] [6]. It has been studied extensively [7] and is recommended to be administered using the LC Plus jet nebuliser (PARI GmbH, Stranberg, Germany) powered by a suitable compressor, which delivers a flow rate of 4–6 L/min and/or a back pressure of 110– 217 kPa. "
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    • "Intrinsic properties of biofilms can lead to an increase in antibiotic resistance through the expression of certain genes in a biofilm-specific manner (Mah et al. 2003; Zhang and Mah 2008). In addition to the contribution of biofilm-specific antibiotic resistance mechanisms, clinical isolates of P. aeruginosa from CF patients often display an increased level of expression of antibiotic efflux pumps, leading to an increasing resistance to common antibiotics used for the treatment and prevention of this infection, including tobramycin (an aminoglycoside) and ciprofloxacin (a fluoroquinolone) (Westbrock-Wadman et al. 1999; Döring et al. 2000; Pumbwe and Piddock 2000; Sobel et al. 2003; Llanes et al. 2004; Poole 2005; Gibson et al. 2007). Pseudomonas aeruginosa contains numerous antibiotic efflux pumps, such as MexAB–OprM and MexXY–OprM, which are able to pump tobramycin and ciprofloxacin across Table 1. "
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