Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Emergence of Intrinsically Resistant Pathogens
To define a breakpoint for resistance to aerosolized tobramycin, efforts to correlate the MIC of P aeruginosa isolates and clinical efficacy were made in the preservative-free tobramycin study. There was no significant difference in clinical response among patients with isolates with MICs < vs > 64 ^g/mL. Unfortunately, too few patients had high-level resistance (defined as MIC > 128 ^g/mL) to correlate a breakpoint with clinical efficacy. Ongoing studies of this group of patients may enable definition of a new breakpoint for resistance when using aerosolized tobramycin.
Emergence of Intrinsically Resistant Pathogens
Organisms such as B cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans are virtually always resistant to aminoglycosides and many are resistant to colistin as well. B cepacia is recognized as an important pathogen in patients with CF, but the role of S maltophilia and A xylosoxidans in CF lung disease is less clear. To date, only a limited number of studies have examined the emergence of these organisms during treatment with aerosolized antibiotics. During continuous administration of aerosolized colistin for 3 months, no resistant pathogens or fungal colonization occurred. MacLusky et al identified five patients harboring B cepacia prior to treatment in both the control and treatment groups and subsequently identified four additional patients with this pathogen during treatment (three control patients and one patient in the treatment group). Ramsey et al found two patients at entry and three patients who acquired B cepacia and 10 who acquired S maltophilia while enrolled in the aerosolized tobramycin, 600 mg tid, treatment trial. natural asthma inhaler
In the preservative-free 300-mg tobramycin study, colonization with B cepacia was an exclusion criterion at entry. Only one patient in the placebo group acquired B cepacia. Six patients in the treatment group and 10 patients in the placebo group acquired S maltophilia and A xylosoxidans was acquired by one patient in the treatment group and three patients in the placebo group. In this same study, 24 patients in the treatment group and only one patient in the placebo group became colonized with Candida albicans. The number of patients with Aspergillus species detected in sputum increased from 52 to 70 in the treatment group but decreased from 62 to 47 in the placebo group. The clinical significance of this colonization is unclear, but it bears further observation. Thus, it did not appear that patients receiving aerosolized tobramycin were at higher risk of acquiring intrinsically resistant bacterial pathogens than patients receiving placebo during the 6 months of the trial.