Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans

Background

There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died.

Methods

Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis.

Results

Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate.

Conclusions

This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.

     

Characterizing physician concerns with publicly supporting abortion at Wisconsin's largest medical school

Objective

To examine factors associated with physicians' level of concern and perceived consequences of publicly supporting abortion at Wisconsin's largest and only publicly funded medical school.

Methods

We surveyed physicians at the University of Wisconsin School of Medicine and Public Health about their knowledge, attitudes, and referral practices regarding abortion care. Among those who expressed support for abortion (N = 701), we analyzed perceived concerns about making their support public.

Results

Nearly a quarter (22%) of respondents felt very or extremely concerned that taking a strong public stance on abortion would alienate patients and 17% felt very or extremely concerned that doing so would alienate coworkers. More than a quarter (27%) felt very or extremely concerned that publicly supporting abortion would lead to harassment or harm. Those with greater concerns about expressing public support for abortion were comparatively less willing to refer for or participate in abortion care themselves.

Conclusions

Many physicians supportive of abortion reported concerns over publicizing their support for this common health care service. These concerns may render physicians less likely to refer patients for needed abortion care or weigh in on abortion policy.     

Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative

Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1–14) and age at PSOT-BL diagnosis was 8.0 years (range: 1–17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4–12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French–American–British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow-up was 6.7 years (range: 0.5–17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL.