Systematic Anti-Mold Prophylaxis Results in Very Low Incidence of Invasive Fungal Infections in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Abstract

Background: Herpes simplex virus (HSV) reactivation is a common problem for patients after allogeneic hematopoietic stem cell transplant (HCT). Acyclovir (ACV) or valacyclovir are commonly used to prevent HSV reactivation. The prolonged administration of antiviral prophylaxis as well as the severity and/or the long-term immunosuppression, among other factors, creates favorable conditions for the development of ACV-resistant HSV infections after HCT. We aim to describe the clinical presentation, course, management, and effects on survival of ACV-resistant HSV after HCT. Methods: From January 2002 to December 2013, the medical records of HCT recipients with a microbiological diagnosis of ACV-resistant HSV were reviewed. We collected data on patient demographics, the infection episode, its treatment, relationship with graft versus host disease (GVHD) and outcomes. Results: We identified 18 patients diagnosed with ACVresistant HSV infection. Median age at diagnosis was 47 years (range: 17-73). Most patients (14/18) had a matched related (n¼5) or unrelated HCT (n¼9), three had a cord blood and one a haploidentical HCT, and 14 (78%) received antithymocyte globulin (ATG) as part of the conditioning regimen. All but one patient received antiviral prophylaxis. Twelve patients had oral HSV, and 6 perineal. HSV reactivation was diagnosed at a median of 25 days (IQR¼ 9-85) post HCT with half of the cases occurring before engraftment. GVHD requiring systemic corticosteroids within 2 months of diagnosis occurred in 10/18 patients. ACV resistance was suspected, and susceptibilities ordered, at a median of 64 days after initial HSV clinical diagnosis. Treatment strategies were complex, requiring combination therapy in 8/18 patients, including intravenous foscarnet (n¼14), cidofovir (n¼4) and/ or topical cidofovir (n¼8) or imiquimod (n¼3). The median treatment for ACV-resistant HSV was 83 days. One-third of the patients were classified as non-responders, and 39% (7/ 18) had a very slow response. Morbidity included hospitalization and acute kidney injury secondary to antivirals in 50%, with 22% of the patients requiring dialysis. Three deaths could be attributed to HSV including one case of HSV hepatitis and two of pneumonitis. Conclusions: Persistent HSV lesions not responding to ACV therapy or the appearance of satellite lesions, especially during the pre-engraftment period and on patients receiving systemic corticosteroids for GVHD should prompt antiviral resistance testing and change of therapy should be considered. ACV-resistant HSV causes significant morbidity and mortality in HCT recipients, including prolonged treatment, complications including renal failure, hospitalization, and end-organ disease.Background: Recipients of Cord blood (CBT) T-cell depleted (TCD) and mismatched unrelated (URD) donors allografts are at high risk for invasive mold infections (IMI). The impact of mold-active prophylaxis (PPX) on the incidence and outcomes of mold infections is not well defined. Methods: Retrospective review of 988 consecutive a...