Search

The preferred strategy for preventing CMV in at‐risk populations in alloHCT has undergone a significant practice shift in recent years where the pendulum has swung from a pre‐emptive approach to now offering letermovir prophylaxis to all CMV seropositive recipients. Letermovir prophylaxis has resulted in significant reductions in post‐transplant clinically significant CMV infection (csCMVi) as well as other important outcomes such as CMV disease, resistant, and refractory CMV infections and nonrelapse mortality. However, prophylactic strategies are not without some limitations, namely delayed onset CMV infections, delayed CMV‐specific T cell immune reconstitution, increased drug costs and limited data within pediatric populations. Thus, this review aims to provide an overview of prophylaxis and pre‐emptive CMV preventative strategies, and how they are applicable in the current era of letermovir prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection increases mortality and morbidity following allogeneic hematopoietic stem‐cell transplantation (alloHSCT). Universal antiviral prophylaxis with letermovir is effective but unsubsidized in Australia. Valaciclovir demonstrates anti‐CMV activity in high doses, but few current real‐world studies explore its use as primary prophylaxis in high‐risk patients post‐alloHSCT. Methods: We performed a retrospective analysis of alloHSCT recipients at high risk of clinically significant CMV infection (cs‐CMVi), defined as a plasma CMV DNA viral load of >400 IU/ml requiring preemptive therapy, or CMV disease. High‐risk recipients were CMV seropositive and underwent T‐cell depleted, haploidentical or umbilical cord stem‐cell transplants. Consecutive patients transplanted from July 2018 to January 2020, treated with valaciclovir 2 g TDS from day +7 to +100 (HD‐VALA), were compared to a historical cohort (July 2017–June 2018) who only received preemptive CMV therapy, and standard valaciclovir (SD‐VALA) for varicella/herpes prophylaxis. We compared incidence of and time to cs‐CMVi. Results: In the SD‐VALA cohort (n = 27, median CMV follow‐up duration 259 days), 23/27 (85%) developed cs‐CMVi at a median of 39 days. For the HD‐VALA cohort (n = 35, median CMV follow‐up duration 216 days), 19/35 (54%) developed cs‐CMVi, at a median of 68 days. Time to cs‐CMVi was significantly longer in HD‐VALA cohort (p <.0001). On multivariate analysis, HD VALA reduced the risk of cs‐CMVi (HR 0.32, p =.0005). Conclusions: In alloHSCT recipients at high risk for cs‐CMVi, HD‐VALA resulted in lower cumulative reactivation, and delayed reactivation, reducing requirement for preemptive CMV therapy in the early post‐engraftment period. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID‐19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological‐based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non‐culture methods employing fungal biomarkers in pre‐emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first‐line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological‐based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after solid organ transplantation. There has been a significant shift in disease epidemiology with the introduction of antiviral prophylaxis, with CMV disease occurring later and clinical presentations more atypical. We describe two cases of very late‐onset CMV disease where first disease occurred 15 and 18 years post–renal transplantation, with both cases complicated by antiviral drug resistance. We subsequently review the published cases and literature of very late‐onset CMV disease (onset > 10 years post–solid organ transplantation) as an increasingly recognized phenomenon which is emerging as an important aspect in improving long‐term patient outcomes in the current era of renal transplantation. [ABSTRACT FROM AUTHOR]

Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25%) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1%) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15% versus 7%, P  = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7; 95% CI, 1.6 to 8.5; P  = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95% CI, 1.2 to 4.1; P  = .017) and for late-onset IFD was a hazard ratio of 3.95 (95% CI, 1.7 to 9; P  = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P  = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications. [ABSTRACT FROM AUTHOR]