Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease

Abstract

An elderly man with refractory Mycobacterium abscessus lung disease previously developed anti-phage neutralizing antibodies while receiving intravenous phage therapy. Subsequent phage nebulization resulted in transient weight gain, decreased C-reactive protein, and reduced Mycobacterium burden. Weak sputum neutralization may have limited the outcomes, but phage resistance was not a contributing factor.

Keywords: Mycobacterium abscessus; bacteriophage; mycobacteriophage; phage therapy.

Figure 1.

Clinical response to intravenous and nebulized mycobacteriophage therapy for refractory Mycobacterium abscessus lung disease. A, Patient weight. B, Serum C-reactive protein level. C, Mycobacterial burden as measured in M abscessus log colony-forming units (CFUs)/ mL⁻¹ in sputum. D and E, Serum immunoglobulin G (IgG) (D) and sputum immunoglobulin A (panel E) log half-maximal antibody levels against phages Muddy, BPsΔ33HTH_HRM10, and ZoeJΔ45 (blue, aqua, and red, respectively) determined by enzyme-linked immunosorbent assay. F and G, Serum (F) and sputum (G) phage neutralization after 24 hours of incubation with phage in vitro expressed as efficiency of plating (EOP) relative to a control with no addition. An EOP of 1 reflects no neutralization; reduction in EOP reflects phage neutralization. H, Timeline of companion antibiotic exposure. Details provided in Supplementary Materials. Sputum CFU⁻¹ counts, serum IgG, and serum neutralization during intravenous administration are as reported previously [8]. *Samples not available or not tested. Abbreviations: CFU, colony-forming units; CRP, C-reactive protein; EOP, efficiency of plating; IgA, immunoglobulin A; IgG, immunoglobulin G; IV, intravenous; Neutⁿ, neautralization.