Is it Time to Give Inhaled Antibiotics Another Chance?

Ventilator-associated pneumonia (VAP) develops in as many as 27% of ventilated patients in US hospitals, and estimates suggest that it accounts for as much as half of all antibiotic use in the intensive care unit (ICU).

With so much attention being paid to reducing overall antibiotic use to combat infections caused by resistant strains, VAP is now in the crosshairs of efforts to improve delivery—and delivery methods for—treatment, and there is clearly a need for formulations designed to help ensure patients receive the correct amount of drug to the correct location. Enter inhaled antibiotics.

In a review published in the September 2017 issue of Infectious Disease Clinics (IDC), Lucy B. Palmer, MD, Associate Professor of Medicine in the Division of Pulmonary, Critical Care, and Sleep Medicine at Stony Brook University School of Medicine in New York argues that inhaled antibiotic therapy provides higher drug concentrations of antibiotics with fewer systemic side effects than IV therapy, and that recent data indicates that it may, in fact, reduce resistance. However, she acknowledges that additional multisite studies are needed to confirm this latter potential benefit and to assess their overall efficacy.

In general, the use of inhaled antibiotics in VAP has been frowned upon since a 1975 study published in the New England Journal of Medicine, in which all ICU patients were treated for their entire stay with atomized polymyxin B and, if intubated, the instilled form of the drug. This “universal administration,” Dr. Palmer writes, resulted in the development of polymyxin-resistant strains in the study patients, and thus pneumonia with 64% mortality.

“The investigators called the topical treatment a dangerous form of therapy and this led to what is now called the 40 years of fear of inhaled antibiotics,” she continues in the IDC paper. (Dr. Palmer did not respond to a request for comment from Contagion^® on deadline.)

According to the author, however, more recent research has identified potential benefits for inhaled formulations. In fact, she notes, multiple studies have shown that “antibiotic concentrations achieved… with targeted therapy far exceed the minimum inhibitory concentration (MIC) of pathogens with very low or nondetectable levels in the serum.” And this has yielded promising results in multiple studies.

A meta-analysis of recent studies by Zampieri et al, for example, found that inhaled antibiotics “had higher rates of clinical cure” with no differences in microbiological cure, mortality, duration of mechanical ventilation, ICU length of stay, or renal toxicity. And, a study in which 60 critically-ill intubated patients received inhaled colistin for the treatment of VAP caused by multidrug-resistant pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae) found that 83% of them achieved bacteriologic and clinical response.

Finally, in a study performed by her own team, Dr. Palmer notes that 8 of 24 participants receiving placebo inhaled antibiotic and systemic antibiotics acquired resistant organisms during treatment compared with 0 of 19 patients receiving inhaled antibiotics alone. In the placebo group receiving only systemic antibiotics, 4 participants with sensitive bacteria developed resistance, while only 1 of the 19 patients receiving inhaled antibiotics acquired a resistant organism.

In her concluding remarks, Dr. Palmer writes, “In view of the threat of increasingly resistant organisms present in the ICU… large multicenter trials targeting antimicrobial therapy to the lung are needed… Clinical trials must be designed to assess not only clinical end points such as resolution of signs and symptoms of respiratory infection, but, data should also be acquired for new primary outcomes, such as effects on the amounts and duration of systemic antibiotic used. Trials should also document antimicrobial resistance in the ICU….”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.