Resistance Concerns

The use of antimicrobial therapies through aerosolization avoids many of the toxicities associated with systemic therapy with aminoglycosides or polypeptide agents. However, the risk for promoting antibiotic resistance is a concern. The emergence of highly resistant organisms has been reported with repeated courses of systemic antimicrobial agents for pulmonary infection [33-35].

To date, data on the potential for this problem have been equivocal, with some studies showing no increase in risk and others showing an association, although the resistance pattern did not persist when aerosol therapy was discontinued.

Resistant Pseudomonas species have been reported with prolonged use or repetitive courses of inhaled tobramycin. After three months of treatment with aerosolized tobramycin 600 mg three times daily, the percentage of patients growing a pseudomonal isolate with a tobramycin MIC of 8 or more increased from 29% to 73% [32]. In studies with the commercially available product where cyclic therapy was administered, the tobramycin MIC S 16 against Pseudomonas aeruginosa was higher in the treatment group compared to placebo (23% vs. 8%) [36].

With the commercially available tobramycin product, an increase in the MIC for Pseudomonas was increased in 15% of subjects receiving treatment compared to 3% with placebo. The importance of this finding is unclear, since the pseudomonal isolates with the highest density were not the ones with the highest MIC.

Additionally, there is a question about the relevance of the MICs used in the clinical laboratory, since much higher concentrations of the antibiotic are present in bronchial and alveolar fluids when aerosol therapy is administered. Additional research is needed to clarify the relationship between the MIC of pseudomonal isolates and the clinical response when aerosol therapy is administered.

In addition to the impact on P. aeruginosa MICs, the use of inhaled tobramycin is also associated with an increased rate of isolation of fungus in the sputum, including Candida albicans and Aspergillus species [32]. The increased presence of these fungi did not appear to be associated with deterioration in clinical status. The chronic use of inhaled tobramycin has not been associated with an increased risk of colonization or infection with other bacteria, including Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans.

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