Aerosolized Antibiotics for the Treatment of Nosocomial Pneumonia

An Expert Interview With Michael E. Klepser, PharmD

Steven Fox

November 09, 2012

Editor's note: Nosocomial pneumonia is a common and potentially lethal complication for patients being treated in intensive care units (ICUs). Studies indicate that up to 27% of patients admitted to ICUs will develop pneumonia during their stay.

One approach clinicians are using to manage that problem — adjunctive therapy with aerosolized antibiotics — was the focus of a session at the American College of Clinical Pharmacy (ACCP) 2012 Annual Meeting, held in Hollywood, Florida.

The presentation was delivered by Michael E. Klepser, PharmD, FCCP, professor of pharmacy practice at the Ferris State University College of Pharmacy, in Big Rapids, Michigan.

In an email interview with Medscape Medical News, Dr. Klepser discussed the advantages and drawbacks of this treatment strategy.

Medscape: Is it true that more than a quarter of patients who enter ICUs develop nosocomial pneumonia?

Dr. Klepser: That's true. And the attributable mortality among ventilated patients who develop pneumonia approaches 50%.

Besides that, patients with ventilator-associated pneumonia have been reported to have stays 7 to 9 days longer than those without pneumonia.

Furthermore, owing to the severity of illness of patients in ICUs and the poor susceptibility profiles of several prominent pathogens, clinical cure rates for ventilator-associated pneumonia are typically below 60%.

Medscape: What are the primary advantages of aerosolized antibiotics?

Dr. Klepser: The advantages of delivering aerosolized antimicrobials to patients with ventilator-associated pneumonia include the attainment of high localized antibiotic concentrations at the site of infection and the avoidance of systemic antimicrobial exposure. The latter is important because some agents that we are forced to use in this setting, such as colistin, are poorly tolerated by patients when administered intravenously.

Medscape: Are there any significant drawbacks to the aerosolized approach?

Dr. Klepser: The main problems are that large well-controlled clinical trials are few and that most of the antibiotics that have been employed for inhalation have not been formulated for this means of delivery.

Additionally, because this route of delivery limits systemic exposure, patients could be at risk for bacteremia. There's also considerable variation in the ability of different nebulizers to deliver a drug to the patient. As a result, each nebulizer–antibiotic combination may need to be evaluated to determine the stability and delivery characteristics.

Last, delivery of antibiotics by inhalation may be associated with uneven distribution of the drug throughout the lungs. Inflammation, mucus, and fluids can all hinder the distribution of inhaled antibiotics to the infected sites in the lung.

Medscape: What other factors are related to the effectiveness of aerosolized delivery?

Dr. Klepser: Several factors need to be considered regarding the activity of antibiotics following inhalation. First, how much drug actually reaches the site of infection (pulmonary pharmacogenetics). Second, how long (particle size) does the antibiotic stay in the lung, and is it active in infected lung tissue (stability and binding).

Medscape: What are the major advantages and disadvantages of the available nebulizers?

Dr. Klepser: There are currently 3 general types of nebulizers available: jet, ultrasonic, and vibrating mesh. Vibrating mesh nebulizers are the most efficient and consistent in their ability to generate consistent particle size. Unfortunately, these are also the most expensive and least studied.

Ultrasonic nebulizers are able to generate consistent particle sizes and deliver medication over a relative short period of time. However, these types of nebulizers generate heat, and that can cause degradation in some medications. Ultrasonic nebulizers are also expensive.

The most common type of nebulizer is the jet nebulizer. These are inexpensive and disposable. Unfortunately, they are somewhat inconsistent with respect to particle-size generation. They also take the longest time to deliver the medication, and their delivery characteristics are influenced by factors such as humidity, viscosity of fluid, and flow rate.

Medscape: What drugs are most amenable to being aerosolized?

Dr. Klepser: Currently, only tobramycin inhalation solution and aztreonam for inhalation solution are formulated for inhalation. Unfortunately, these agents are not reliably active against the multidrug-resistant pathogens that we are concerned about in patients with ventilator-associated pneumonia. Therefore, nebulized colistin has been widely studied for this indication.

Medscape: What have studies of colistin found?

Dr. Klepser: Several studies have evaluated aerosolized colistin for the treatment of patients with ventilator-associated pneumonia. These studies used nebulized colistin as adjunctive therapy along with intravenous administration of other agents. Key pathogens that were included in these studies were multidrug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa.

These studies generally demonstrated improved patient outcomes associated with the adjunctive administration of aerosolized colistin.

However, in a study that compared the administration of intravenous (IV) colistin with IV colistin plus aerosolized colistin, no difference in outcomes was noted (Clin Infect Dis. 2010;51:1238-1244).

I do not believe that that study indicates that aerosolized colistin was ineffective; rather, it highlights the need to use a drug that is active against the expected pathogens. In this case, the IV colistin was active against the respiratory pathogens; however, one may be concerned about the ability of patients to tolerate a long course of IV colistin therapy.

Medscape: Do aerosolized antibiotics have a prophylactic role?

Dr. Klepser: Aerosolized antibiotics have been used for decades to eradicate pseudomonas colonization in patients with cystic fibrosis. Additionally, the use of aerosolized amphotericin B has been studied to prevent pulmonary fungal infections in high-risk patients. Recently, there's been a lot of interest in this means of drug delivery. However, we currently lack enough data to routinely use aerosolized antibiotics in many other settings.

Medscape: What recommendations do you have for clinicians managing patients with nosocomial pneumonia?

Dr. Klepser: Before making a decision to use aerosolized delivery of antibiotics, do your homework. This is not something you just decide to try. Detailed policies and procedures should be in place to guide clinicians on the appropriate selection of agents, nebulizers, and patient populations. Aerosolized agents should only be administered by appropriately trained personnel. Also, the use of bronchodilators prior to the nebulized delivery of medication should be considered.

In some cases, such as ventilator-associated pneumonia caused by multidrug-resistant pathogens, your back is against the wall and you have nothing to lose and everything to gain by trying adjunctive delivery of an agent such as colistin.

Dr. Klepser reports serving on the speaker's bureau for Forest Pharmaceuticals and Cubist Pharmaceuticals.