0
Articles |

Microbiological and Immunologic Considerations With Aerosolized Drug Delivery*

John J. LiPuma, MD
Author and Funding Information

*From the Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI.

Correspondence to: John J. LiPuma, MD, University of Michigan, 1150 W Medical Center Dr, 8323 MSRB III, Box 0646, Ann Arbor, MI 48109; e-mail: jlipuma@umich.edu



Chest. 2001;120(3_suppl):118S-123S. doi:10.1378/chest.120.3_suppl.118S
Text Size: A A A
Published online

The development of drug resistance is a major theoretical concern with the long-term delivery of aerosolized antibiotics via inhalation. A randomized, placebo-controlled, double-blind study, which compared inhaled tobramycin plus standard cystic fibrosis (CF) care to placebo plus standard CF care, examined the following microbiological parameters: percentage of patients with at least one Pseudomonas aeruginosa (PA) strain with a minimal inhibitory concentration (MIC) > 16 μg/mL (ie, the breakpoint for tobramycin resistance delivered by the parenteral route); changes in the levels of the lowest concentration required to inhibit the growth of 50% of strains tested (MIC50) and 90% of strains tested (MIC90); the percentage of patients with an increase, decrease, or change in the MIC of the most resistant and most prevalent PA strains; and the percentage of patients in whom the PA strain with the highest MIC also was the most prevalent. During the first 6 months, which included three on-drug and off-drug cycles of 4 weeks’ duration each, the percentage of tobramycin-treated patients with at least one PA isolate and with an MIC > 16 μg/mL was 13% at baseline, 26% at 20 weeks, and 23% at 24 weeks vs 10%, 17%, and 8%, respectively, for placebo-treated patients. No significant change was observed in MIC50 at 20 and 24 weeks. The increase in MIC90 was not statistically significant. At 24 weeks, there was no increase in the percentage of patients in either group in whom the PA strain with the highest MIC became most the prevalent strain. After the third on-drug cycle, 33% of the tobramycin group showed an increase in the MIC of the strain with the highest MIC. This decreased to 26% after 1 month off drug therapy. A preliminary analysis of the 12-month and 18-month data showed a decrease in the proportion of resistant PA isolates after each off-drug cycle. This return to susceptibility following an off-drug cycle was not observed at 24 months. The mechanism of resistance in this setting is believed to be increased impermeability to drug. At all time points, pulmonary function improved even in patients with MICs of ≥ 128 μg/mL. At 6 months, no increase was seen in the rates of superinfection with tobramycin-resistant, Gram-negative pathogens. Increases in Stenotrophomonas maltophilia were detected in patients after 18 and 24 months of tobramycin therapy and were similar to those rates in patients receiving placebo. These rates may be independent of inhalation therapy.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543