Melendez, Dante P.

AbstractIntroductionCytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell‐mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment.MethodsWe serially assessed CMV CMI using the QuantiFERON‐CMV assay (QF‐CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post‐prophylaxis CMV infection and post‐treatment relapse, respectively.ResultsOnly one (4.2%) of 24 CMV D+/R‐ patients demonstrated positive QF‐CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post‐prophylaxis CMV infection; all four had undetectable QF‐CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF‐CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p = .0036).ConclusionSince CMV D+/R‐ SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment.

Abstract Background Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). As a lack of immunity predisposes to infection, a laboratory test that measures CMV-specific cell-mediated immunity (CMV CMI) may help guide antiviral prophylaxis, predict relapses and correlate with outcomes. We assessed CMV CMI in CMV D+/R- patients during valganciclovir primary prophylaxis and in CMV viremic SOTRs during antiviral treatment, and correlated the results with post-prophylaxis CMV infection and post-treatment relapse, respectively. Methods CMV CMI was assessed in two groups of SOTRs using the QuantiFERON© CMV interferon-gamma release assay (IGRA), with level &gt;0.2 IU/mL suggestive of immunity. The first group included CMV D+/R- SOTRs who underwent monthly CMV CMI testing during 6 months of valganciclovir prophylaxis. These patients were prospectively followed for CMV episodes for 1 year post transplant. The second group included SOTRs with CMV viremia or disease, who underwent CMV CMI testing at time of CMV diagnosis and at various time points during antiviral treatment. These patients were prospectively followed for CMV relapse for 1 year post-primary CMV episode. Standard definitions were used to define CMV infection and disease. Results In the primary prophylaxis cohort, 24 CMV mismatched (D+/R-) SOTRs were enrolled. Only 1 patient (4.2%) demonstrated a CMV CMI &gt;0.2 IU/mL by the end of prophylaxis; this patient did not develop CMV disease. Four (16.6%) patients developed post-prophylaxis CMV infection, none of which had CMV CMI &gt;0.2 IU/ml. In the post-treatment cohort, 20 CMV viremic SOTRs were enrolled, including 12 D+/R- (60%). Eighteen (90%) had CMV CMI levels &gt;0.2 IU/mL by end of treatment and none developed CMV relapse. In contrast, the single patient who relapsed after treatment had a CMV CMI response &lt; 0.2 IU/ml (p=0.05). Conclusion CMV D+/R- SOTRs are unlikely to develop CMV CMI during valganciclovir prophylaxis. Thus, the utility of CMV CMI for risk stratification of post-prophylaxis CMV infection in CMV D+/R- SOTRs is questionable. Conversely, CMV CMI testing may potentially be a useful marker of CMV relapse risk after treatment and guide the role of secondary antiviral prophylaxis. Disclosures Elitza Theel, PhD, D(ABMM), Euroimmun US: Advisor/Consultant|Oxford Immunotech: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant|Serimmune Inc: Advisor/Consultant Raymund R. Razonable, MD, American Society of Transplantation: Board Member|gilead: Grant/Research Support|novartis: DSMB|regeneron: Grant/Research Support|Roche: Grant/Research Support.

Abstract Background The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. Methods This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. Results Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). Conclusions Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

ABSTRACT We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% ( P ≤ 0.001), respectively, and specificities were 91.8% and 97.4% ( P = 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively ( P < 0.0001). In this group, the PCR panel detected Staphylococcus aureus in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid.

ABSTRACT PCR coupled with electrospray ionization mass spectrometry applied to synovial fluid specimens had an 81% sensitivity and a 95% specificity for the diagnosis of prosthetic joint infection.