Bacteriophage therapy (BT) employs bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in three lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n=2) and Burkholderia dolosa (n=1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient expired. No BT-related adverse events were identified in the three cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.

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BackgroundManaging multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life.MethodsA closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice.ResultsA total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so.ConclusionSeveral important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment.

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Background: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based off of results from a clinical trial conducted prior to the Omicron variant. Its clinical effectiveness has not been well described in the Omicron era.  We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all cases. Methods: We used the electronic medical record to identify patients who received T/C at our institution.  Among these patients, we assessed for cases of symptomatic COVID-19 and associated hospitalizations before and after receiving T/C. We used chi square tests and Fishers exact p-values to examine differences between characteristics of those who got COVID before and after T/C prophylaxis.   Results: Of 1295 T/C recipients, 121 (9.3%) developed symptomatic COVID-19 before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Among those with infection prior to T/C, 36/121 (29.8%) were hospitalized, including 8 (6.6%) admitted to the ICU. Among those with COVID-19 after receiving T/C, 6/102 (5.9%) were hospitalized but none required ICU admission. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected prior to T/C treatment occurred during Omicron BA.1 surge, while the majority of cases among post-T/C recipients occurred when BA.5 was predominant.  Patients infected with COVID-19 prior to receiving T/C had received fewer vaccine doses and were less likely to receive COVID-19 therapeutics compared to those with COVID-19 after having received T/C. Conclusion: We identified COVID-19 infections after T/C prophylaxis. Among persons eligible for T/C, COVID-19 illnesses occurring after T/C were less likely to require hospitalization compared to those with COVID-19 prior to T/C. In the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

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Background: Despite increased utilization of hepatitis C virus-infected (HCV+) organs for transplantation into HCV-uninfected recipients, there is lack of standardization in HCV-related patient education/consent and limited data on financial and social impact on patients. Methods: We conducted a survey on patients with donor-derived HCV infection at our center transplanted between 4/1/2017 and 11/1/2019 to assess: why patients chose to accept HCV+ organ(s), the adequacy of their pre-transplant HCV education and informed consent process, financial issues related to copays after discharge, and social challenges they faced. Results: Among 49 patients surveyed, transplanted organs included heart (n = 19), lung (n = 9), kidney (n = 11), liver (n = 4), heart/kidney (n = 4), and liver/kidney (n = 2). Many recipients accepted an HCV-viremic (HCV-V) organ due to perceived reduction in waitlist time (n = 33) and/or trust in their physician's recommendation (n = 29). Almost all (n = 47) felt that pre-transplant education and consent was appropriate. Thirty patients had no copay for direct-acting antivirals (DAA) for HCV, including 21 with household income <$20 000; seven had copays of <$100 and one had a copay >$1000. Two patients reported feeling isolated due to HCV infection and eight reported higher than anticipated medication costs. Patients' biggest concern was potential HCV transmission to partners (n = 18) and family/friends (n = 15). Overall almost all (n = 47) patients reported a positive experience with HCV-V organ transplantation. Conclusion: We demonstrate that real-world patient experiences surrounding HCV-V organ transplantation have been favorable. Almost all patients report comprehensive HCV-related pre-transplant consent and education. Additionally, medication costs and social isolation/exclusion were not barriers to the use of these organs.

Background Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates.MethodsIn this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015.ResultsWe determined that all 26 CRAB isolates possessed multiple β-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like β-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010–2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time.ConclusionsThis study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.Electronic supplementary materialThe online version of this article (10.1186/s12941-017-0248-3) contains supplementary material, which is available to authorized users.