High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis Targeting Burkholderia multivorans

Abstract

Background. Individuals with cystic fibrosis (CF) have persistent lung infections, necessitating the frequent use of antibiotics for pulmonary exacerbations. Some respiratory pathogens have intrinsic resistance to the currently available antibiotics, and any pathogen may acquire resistance over time, posing a challenge to CF care. Gaseous nitric oxide has been shown to have antimicrobial activity against a wide variety of microorganisms, including common CF pathogens, and offers a potential inhaled antimicrobial therapy. Case Presentation. Here, we present the case of a 16-year-old female with CF who experienced a precipitous decline in lung function over the prior year in conjunction with worsening antibiotic resistance of her primary pathogen, Burkholderia multivorans. She received 46 intermittent inhalations of 160 parts-per-million nitric oxide over a 28-day period. The gas was administered via a mechanical ventilator fitted with nitrogen dioxide scavenging chambers. Conclusions. High-dose inhaled nitric oxide was safe, well tolerated, and showed clinical benefit in an adolescent with cystic fibrosis and pulmonary colonization with Burkholderia multivorans.

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)

“…More recently, nitric oxide at a high dose (160–200 ppm) has demonstrated broad antimicrobial activity on bacteria and viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV-1), the virus that caused severe acute respiratory syndrome in 2003. 1 – 3 …”

Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects

“…Over the past two years, at Massachusetts General Hospital (Boston, MA), we have treated a teenage patient with 46-intermittent inhalation of 160 ppm NO for antibiotic resistant Burkholderia multivorans lung infection in the setting of cystic fibrosis. No adverse events or delivery system failures were observed, respiratory symptoms of the patient improved and the antibiotic pattern of the Burkholderia multivorans changed to allow common antibiotic coverage (i.e., Bactrim and Levofloxacin) [ 16 ]. Additionally, inhaled NO therapy has also shown to be a potent anti-inflammatory agent, reducing lung thrombosis after lung transplant [ 17 ].…”

NO donors and NO delivery methods for controlling biofilms in chronic lung infections

“…In K. pneumoniae infected mice, inhaling NO at lower oxygen concentration also resulted in a 5 to 10-fold reduction of CFU in BALF and lung tissues (Sun et al 2006 ). Similar bactericidal effects were also observed in CF patients, where case studies showed that intermittent administrations of 160 ppm NO significantly reduced CFU of P. aeruginosa , S. aureus , and B. multivorans in CF patients that are resistant to multiple antibiotics (Deppisch et al 2016 ; Bartley et al 2020 ). As such, inhalation of NO may improve the therapy of chronic lung infections in CF patients, particularly for those suffering from MDR pathogens.…”