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  • Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Receiving Aerosolized Antibiotics

What Are the Microbiological Implications of Aerosolized Antibiotics?
There is understandable concern that prolonged use of aerosolized antibiotics could lead to the development of significant antibiotic resistance in P aeruginosa and that intrinsically resistant bacterial and fungal pathogens could emerge during therapy.
Development of Resistance in P aeruginosa While Receiving Aerosolized Antibiotics
Several studies of antibiotic resistance following aerosolized antibiotics in CF patients have been published. In some, the use of aerosolized antibiotics has not been associated with the emergence of resistance and in others, aerosolized antibiotics were associated with the emergence of resis-tance that appeared to be transient as organisms became susceptible after antibiotic treatment was discontinued. In these latter studies, the emergence of resistance did not appear to have clinical consequences.
Treatment with preservative-free tobramycin, 300 mg bid, was associated with increased tobramycin MICs at the end of the study in 15% of treated patients as compared with 3% of placebo-treated patients. The clinical significance of increasing tobramycin MICs in patients treated with tobramycin has not been determined. P aeruginosa respiratory tract isolates from patients in this study were categorized in three ways: all isolates; highest-density isolates; and highest MIC isolates. MIC50* and MIC90* of treatment and placebo groups are presented in Table 3. In general, the highest-density isolates were not the isolates with the highest MIC. This implies that treatment with aerosolized tobramycin did not select for a large population of resistant isolates during the 6-month study. natural asthma treatment

Methodologic Issues for Determining Resistance to Aerosolized Antibiotics
Studies of the development of resistance in P aeruginosa require a standardized, validated method for susceptibility* testing. The susceptibility breakpoints used currently in clinical microbiology laboratories most likely do not apply to aerosolized antibiotics, as significantly higher concentrations of drug can be delivered directly to the CF lung. Thus, a method that determines a wide range of MICs rather than categorization of strains as susceptible or resistant is needed to monitor resistance to aerosolized antibiotics. For example, during the preservative-free aerosolized tobramycin study, a semiautomated broth microdilution technique was utilized that was able to measure MICs as high as 1,024 ^g/mL (Sensititre; Accumed; West Lake, OH).
Table 3—Summary of the P aeruginosa Tobramycin MIC (pg/mL) as Determined in the Phase III Aerosolized Tobramycin Trial of 300 mg bid

Aerosolized Tobramycin Group Placebo Group
Isolates Wk 0 Wk 20 Wk 24 Wk 0 Wk 20 Wk 24
All isolates
MIC50 1.0 1.0 1.0 1.0 1.0 1.0
MIC90^ 8.0 16.0 16.0 8.0 8.0 4.0
Highest-density isolates
MIC50 1.0 1.0 1.0 1.0 1.0 1.0
MIC90 4.0 16.0 16.0 4.0 4.0 4.0
Highest MIC isolates
MIC50 2.0 4.0 2.0 2.0 2.0 2.0
MIC90 16.0 64.0 32.0 16.0 16.0 8.0
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