PMC7334765_01
Timeline of antibiotic therapies, antibiotic susceptibility pattern of the primary pathogen (Burkholderia cepacia complex (Burkholderia multivorans)*), and colony forming units (CFU) of this pathogen relative to the initiation of high-dose inhaled nitric oxide therapy on day 1. The antibiotic susceptibility data are reported as susceptible S, intermediate I, or resistant R. *Due to limitations in commercial identification systems to reliably distinguish among species of the Burkholderia cepacia complex, Burkholderia multivorans identification was reported as the Burkholderia cepacia complex by our clinical microbiology laboratory. The patient's isolates had been confirmed as Burkholderia multivorans by the Burkholderia cepacia Research Laboratory and Repository (Ann Arbor, Michigan, USA) within the prior year.
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The patient acquired this pathogen in her sputum six years before, and over time, it developed increasing antibiotic resistance (Figure 1). Sputum was collected prior to (days 1 and 16), midcycle (days 3 and 23), and on completion (days 12 and 28) of each NO cycle (Figure 1). On days 1, 12, 23, and 28, B. multivorans grew from the patient's sputum, but the CFU count was low (Figure 1).
Relationship between therapies, vital signs, and inflammatory markers in an adolescent with CF, treated with intravenous antibiotics and high-dose inhaled nitric oxide. The first and second hospital admissions are shown on the left and right panels of the figure, respectively. Duration of therapy with either intravenous antibiotics or inhaled nitric oxide is shown at the top of the figure.
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The patient received a total of 46 intermittent inhalations of 160 ppm NO over a 28-day period during two separate hospital admissions: days 1-12 and days 16-28 (Figure 2). Fever, white blood cell count, and C-reactive protein all decreased with therapy (Figure 2).
Schematic representation of the inhaled nitric oxide delivery system. The nitric oxide gas source was a 850 ppm nitric oxide in nitrogen tank. This gas was mixed with medical air in a gas blender, and the resulting gas mixture was blended with oxygen in the mechanical ventilator. The blender and FiO2 dial were both adjusted to achieve the targeted nitric oxide and oxygen concentrations. Large and small nitrogen dioxide scavengers were placed in series along the inspiratory limb. The gas mixture was delivered to the patient via a sealed facemask. Delivered gas was sampled just proximal to the patient, and nitric oxide and nitrogen dioxide concentrations were analyzed with a portable gas analyzer.
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Oxygen, medical air, and NO were blended and introduced through a ventilator (Puritan Bennett 980 Series, Medtronic, Minneapolis, Minnesota, USA) (Figure 3).
Methemoglobin levels (mean +- standard deviation) from data recorded at 5-minute intervals during 30-minute and 60-minute inhalations of high-dose nitric oxide. Curves demonstrate a reproducible and expected rise in methemoglobin during therapy and reduction 30 minutes after cessation (note: data from 45-minute inhalations were omitted for clarity, but follow a similar rise, peak, and decrease 30 minutes post-inhalation).
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SetTM Technology, Irvine, CA) and never surpassed our safety threshold of 5%. Specifically, at the end of the 30-minute and 60-minute inhalations, the highest recorded methemoglobin levels were 3.1% and 4.1%, respectively, and returned to baseline prior to subsequent treatments (Figure 4).