Inhaled amikacin
“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.
The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.
The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.
Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.
“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”
There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.
“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.
The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.
It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
Tempting strategy
“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.
Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.
No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.