Morris, Michele I.

AbstractBackgroundIsavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side‐effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported.MethodsIn this single‐center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs.ResultsWe evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21–91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%).Nineteen patients (17.9%) developed bIFIs–nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8–253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry‐sponsored clinical trials.All‐cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co‐infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups.ConclusionISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side‐effect and drug‐interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs. image

Abstract Background Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. Methods We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration–approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. Results Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. Conclusions Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

AbstractBackgroundData on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS‐CoV‐2‐specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab–imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID‐19) in HM/HCT patients.MethodsThis was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID‐19 who received casirivimab–imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS‐CoV‐2‐specific mAbs.ResultsWe identified 59 HM/HCT patients with mild to moderate COVID‐19 who received casirivimab–imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45–65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T‐cell therapy. The median time from COVID‐19 symptom onset to SARS‐CoV‐2‐specific mAb administration was 4 (IQR: 3–6) days. Forty‐six (78%) patients received SARS‐CoV‐2‐specific mAbs as outpatients and 13 (22%) patients received SARS‐CoV‐2‐specific mAbs during hospitalization. Among patients who received SARS‐CoV‐2‐specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS‐CoV‐2‐specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID‐19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS‐CoV‐2‐specific mAb administration; two of these three deaths were attributed to COVID‐19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab–imdevimab use.ConclusionDuring the alpha and delta variant surges, early administration of bamlanivimab or casirivimab–imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID‐19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID‐19 in this population are needed. image