ABSTRACT
Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.
ABSTRACT
Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred after 9 months prompting the transition of therapy to oral gentamicin with subsequent remission. Malakoplakia should be considered in the differential of solid organ transplant recipients with recurrent gastrointestinal infections.
ABSTRACT
Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients.
Subject(s)
Acetates , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Quinazolines , Adult , Humans , Child , Cytomegalovirus , Antiviral Agents/therapeutic use , Transplant Recipients , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.
Subject(s)
Cytomegalovirus Infections , Lymphopenia , Neutropenia , Organ Transplantation , Child , Humans , Valganciclovir/therapeutic use , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Body Surface Area , Retrospective Studies , Cytomegalovirus , Neutropenia/etiology , Neutropenia/drug therapy , Organ Transplantation/adverse effects , Body Weight , Ganciclovir/therapeutic useABSTRACT
Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.
Subject(s)
Adenovirus Infections, Human , Gastroenteritis , Liver Failure, Acute , Liver Transplantation , Child , Humans , Liver Transplantation/adverse effects , Adenoviridae , Liver Failure, Acute/etiology , Liver Failure, Acute/surgeryABSTRACT
Perinatal human immunodeficiency virus transmission, while rare in the United States, should be considered in children with a history of recurrent infections, chronic respiratory symptoms and developmental delay. A delayed diagnosis of human immunodeficiency virus in children can lead to significant morbidity and mortality. We present a 6-year-old male who presented for evaluation and management of antibiotic refractory chronic cough and purulent nasal secretions, with a history of recurrent bacterial pneumonias and sinus infections, disseminated varicella zoster, and global developmental delay. He likely had perinatally acquired human immunodeficiency virus. At the time of his human immunodeficiency virus diagnosis, he met the criteria for acquired immunodeficiency syndrome and was ultimately diagnosed with lymphocytic interstitial pneumonia (LIP). Our case illustrates the importance of universal human immunodeficiency virus screening of pregnant women, consideration of human immunodeficiency virus, and the prompt initiation of treatment. We believe this case serves as an important reminder for all medical providers who care for pregnant women and children.
ABSTRACT
BACKGROUND: Enteroviruses can cause severe infections, including viral myocarditis, meningitis, acute flaccid myelitis, and viral myositis. METHODS/RESULTS: We report a 3-year-old female renal transplant recipient who presented to a tertiary care hospital with elevated serum liver aminotransferases and subsequently developed proximal muscle pain, weakness, and respiratory distress during the first week of hospitalization. Imaging of the lower extremities revealed diffuse myositis of the proximal thigh and pelvic muscles. A muscle biopsy was obtained and revealed necrotizing myositis with immunostaining positive for enterovirus, consistent with a diagnosis of enterovirus necrotizing myositis. She had complete resolution of symptoms with steroids, intravenous immune globulin, reduced tacrolimus dose, and physical therapy. CONCLUSIONS: Enterovirus myositis should be included in the differential diagnosis for necrotizing myositis following renal transplantation in children.
Subject(s)
Enterovirus Infections , Enterovirus , Fasciitis, Necrotizing , Kidney Transplantation , Myelitis , Myositis , Child , Child, Preschool , Enterovirus Infections/diagnosis , Enterovirus Infections/pathology , Female , Humans , Kidney Transplantation/adverse effects , Myelitis/complications , Myositis/diagnosis , Myositis/drug therapy , Myositis/etiologyABSTRACT
Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.