A Case of Persistent Intra-Abdominal Stenotrophomonas maltophilia Infection Despite Bacteriophage Therapy

Abstract

Multidrug resistant infections are a challenge in the health care setting and a cause of patient morbidity and mortality. Bacteriophages (phages) are viruses that target and kill bacteria and have been used in patients to treat bacterial infections. We present a case of disseminated Stenotrophomonas maltophilia infection, with pulmonary, intra-abdominal and bloodstream involvement. The patient was treated with a combination of antibiotics and personalized phage therapy, administered daily for 12 days both intravenously as well as via intra-abdominal drains. Phage therapy was well-tolerated, the patient cleared S. maltophilia from their bloodstream and their intra-abdominal abscesses were stable or decreased in size. However, the intra-abdominal fluid cultures remained positive for S. maltophilia. Unfortunately, the patient passed away 2 months after completion of phage therapy due to multiorgan failure. These data highlight the difficulty of treating critically ill patients and clearing complex, biofilm mediated infections, even with phages. More information is needed regarding the optimal treatment protocols for phage therapy in complex multifocal infections.

Keywords: Stenotrophomonas maltophilia; bacteriophage; phage therapy.

FIG. 1.

The lytic activity profile of the phage used in these studies. (a) Documentation of lytic activity: Left: Serial dilutions of the SFD1 phage cocktail spotted onto lawn of SFD1. Right: Enlarged view of individual cocktail plaques on lawn of SFD1. Each tick represents 1 mM. (b) Killing assay: average (n = 2) bacterial titer after 4 hours of incubation in the presence of the SFD1 cocktail at the indicated MOIs. Challenge with each MOI resulted in a roughly 2-log decrease in bacterial titer. (c) Synogram: Concentrations of either minocycline or phage alone can reduce bacterial growth (left column and bottom row), but combinations of phage (10³ PFU/mL or greater) and minocycline (0.5–4 μg/mL) result in less killing than phage alone (compare bottom row with the 4 rows above) indicating antagonistic interaction. (d) Serum neutralization: average SFD cocktail titer (n = 3) before (T₀) and after (T₃₀) a 30-min incubation in phage buffer or patient serum during or posttreatment. Error bars indicate standard deviation and statistics were determined by unpaired t-test or Mann–Whitney test. CT, computed tomography; MOI, multiplicity of infection.

FIG. 2.

Timeline of the patient’s treatment course. The patient grew S. maltophilia from blood and abscess fluid. Blood cultures cleared, but abscess fluid was persistently positive for S. maltophilia growth.

FIG. 3.

Imaging of the patient’s infection. CT images of abdomen and pelvis without contrast before phage therapy (a) and after phage therapy (b). There is a mild decrease in size of the intraabdominal abscess. CT, computed tomography.