Omadacycline for a Carbapenem-Resistant Enterobacter cloacae-Associated Wound Infection.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) are problematic pathogens because infections caused by these organisms are associated with significant morbidity and mortality. These organisms often harbor multiple resistance mechanisms, which makes it difficult to treat their associated infections. Treatment typically consists of intravenous antibiotics that are selected based on the specific susceptibility pattern for the pathogen. Data on the use of oral antibiotics for the treatment of infections caused by CRE are sparse. Case Presentation: In this case, a 62-year-old female presented with a chronic left leg wound infection. She previously underwent surgical debridement and skin grafting, which were unsuccessful. She was initially prescribed minocycline for the infection, but the wound got re-infected. At this time, the wound had significant surrounding erythema, drainage, and slough. A wound culture was obtained and demonstrated growth of carbapenem-resistant Enterobacter cloacae and methicillin-resistant Staphylococcus aureus. The patient was initiated on oral omadacycline, and she responded with resolution of the cellulitis and wound drainage. Conclusion: This case demonstrates that omadacycline may be beneficial as an oral medication for the treatment of complicated acute bacterial skin and skin structure infections caused by carbapenem-resistant Enterobacter cloacae.

Allogeneic Hematopoietic Cell Transplant for Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome.

Systemic juvenile idiopathic arthritis (sJIA) is characterized by arthritis, fever, rash, lymphadenopathy, hepatosplenomegaly, and serositis. Macrophage activation syndrome is the most feared complication of sJIA with a high risk of mortality. We report a 16-year-old female diagnosed with refractory systemic juvenile idiopathic arthritis (sJIA) complicated by recurrent macrophage activation syndrome (MAS), severe joint disease, and lung involvement requiring prolonged immunosuppressive therapy. She received a matched unrelated allogeneic hematopoietic cell transplant (Allo-HCT) using a reduced-intensity conditioning regimen and is now, 3 years after the transplant, with complete resolution of sJIA symptoms, off immunosuppressants, and with significant improvement in the quality of life.

Risk Factors for Noninvasive Ventilation Failure in Children Post-Hematopoietic Cell Transplant.

RATIONALE: Little is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients. OBJECTIVE: We sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement. METHODS: This is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016. RESULTS: 97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p<0.001), and higher respiratory rate at multiple hours of NIPPV use (1hr p=0.02, 2hr p=0.04, 4hr p=0.008, 8hr p=0.002). Using respiratory rate at 4 hours a multivariable model was constructed. This model demonstrated high ability to discriminate NIPPV failure (AUC=0.794) with the following results: respiratory rate >40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), p<0.001] and vasoactive use [aOR=4.9 (95% CI: 1.9, 13.1), p=0.001]. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT [14 days (IQR:4, 73) vs 54 (IQR:21,117), p<0.01] and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056). CONCLUSIONS: In this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation.

Use of belatacept as alternative graft vs host disease prophylaxis in pediatric allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T-lymphocyte-associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. METHODS: We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. RESULTS AND CONCLUSION: Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use.

Vitamin D has no impact on outcomes after HSCT in children-A retrospective study.

Vitamin D not only plays an important role in bone metabolism but is also involved in multiple immune-mediated processes in the body which may be adversely affected in those with low levels. Most pediatric studies evaluating the association of vitamin D in patients undergoing allogeneic HSCT are single-center studies. We present the results of retrospective study at 5 centers across the United States in pediatric patients undergoing allogeneic HSCT. (VDD) and (VDI) were defined by vitamin D levels of <20 ng/ml and 21-30 ng/ml, respectively. The mean vitamin D levels pre-HSCT, day +30, and +100 were suggestive of VDI, but normalized thereafter. We compared the transplant characteristics and outcomes in 233 patients with VDD and VDI and those with normal levels and found no statistical difference in neutrophil or platelet engraftment, infections (viral, bacterial, or fungal) post-HSCT, length of hospital stay during HSCT, graft failure, acute or chronic GvHD, survival at day +100 and 1 year, or relapse of primary malignancy. We conclude that VDI or deficiency does not affect any of the common transplant variables after allogeneic HSCT in children. There is a need of a large multicenter prospective study to evaluate its role further.

Disseminated Toxoplasmosis in a Child Following Allogeneic Hematopoietic Cell Transplantation.

A 23-month old female with hypoplastic myelodysplastic syndrome underwent allogenic hematopoietic cell transplantation (HCT), complicated by development of acute exotropia. Bilateral chorioretinal scars and a ring enhancing brain lesion were identified in further workup. Disseminated toxoplasmosis post-allogeneic HCT was subsequently confirmed by serologic and polymerase chain reaction testing results.

Ocular hemorrhage secondary to thioguanine-associated veno-occlusive disease in a child with acute lymphoblastic leukemia in delayed intensification.

Hepatic VOD is a potentially fatal complication during stem cell transplantation and is rarely seen in the non-transplant setting. We report the case of a five-year-old boy who presented with visual complaints during delayed intensification phase of treatment for ALL. He was found to have bilateral retinal hemorrhages associated with profound thrombocytopenia due to chemotherapy. VOD was diagnosed based on EBMT criteria and was managed with supportive care. Despite resolution of VOD, his vision progressively deteriorated and resulted in blindness. This case highlights the significance of close monitoring of ALL patients in delayed intensification when they are at risk for developing VOD, the importance of refractory thrombocytopenia as a diagnostic feature and the potential for VOD to manifest with intraocular bleeding.

Successful treatment with eculizumab for posterior reversible encephalopathy syndrome due to underlying transplant-associated thrombotic microangiopathy in patients transplanted for sickle cell disease.

Preexisting endothelial dysfunction and vascular injury sustained during allogeneic hematopoietic cell transplantation (HCT) increases risk for endothelial injury-related complications such as posterior reversible encephalopathy syndrome (PRES) and transplant-associated thrombotic microangiopathy (TA-TMA) in patients with sickle cell disease (SCD). We report two patients with SCD who developed PRES following allogeneic HCT. In both patients, PRES-related symptoms resolved only after a diagnosis of TA-TMA was established and eculizumab therapy was initiated. Renal manifestations at diagnosis included non-nephrotic range proteinuria and hypertension. This report highlights the importance of screening PRES-affected SCD HCT recipients for TA-TMA as usual treatment strategies may be inadequate.

A novel SAMD9 variant identified in patient with MIRAGE syndrome: Further defining syndromic phenotype and review of previous cases.

We present here a case of MIRAGE syndrome due to novel variant (c.2318T>C) in the sterile α motif domain-containing protein 9 (SAMD9) gene. Previous reports have described the clinical phenotype, which includes myelodysplasia, recurrent infections, restriction of growth and development, adrenal insufficiency, genitourinary abnormalities, and enteropathies, often resulting in fatality within the first few years of life. This report illustrates the variability in phenotype by describing an 11-year-old male, diagnosed with MIRAGE at age 9 years when his novel variant was identified through whole exome sequencing. A brief review of previously published cases of MIRAGE syndrome and the genotypic and phenotypic spectrum are presented.

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia.

AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.

A multicenter investigation of respiratory syncytial viral infection in children with hematopoietic cell transplantation.

BACKGROUND: Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States. METHODS: A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014. RESULTS: Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005). CONCLUSIONS: In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.

Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study.

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 3: Focus on Cardiorespiratory Dysfunction, Infections, Liver Dysfunction, and Delirium.

Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees.

Efficacy of Prompt Initiation of Antiretroviral Therapy in the Treatment of Hemophagocytic Lymphohistiocytosis Triggered by Uncontrolled Human Immunodeficiency Virus.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV) infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART) was initiated with darunavir, ritonavir, tenofovir, and emtricitabine. Within one week of initiation of ART, the patient began to improve clinically and hematologically and was stable enough for discharge from the hospital three weeks after starting therapy. This case suggests that treatment with ART in patients with HIV-associated HLH should be considered even in critically ill patients with low CD4 counts.

Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplant.

Acanthamoeba encephalitis is a rare, often fatal condition, particularly after HSCT, with 9 reported cases to date in the world literature. Our case was originally diagnosed with ALL at age 3 years, and after several relapses underwent HSCT at age 9 years. At 17 years of age, he was diagnosed with secondary AML for which he underwent a second allogeneic HSCT. He presented with acute-onset worsening neurological deficits on day +226 after the second transplant and a post-mortem diagnosis of Acanthamoeba encephalitis was established, with the aid of the CDC.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2-Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues.

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

Consensus Report by Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees: Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 1: Focus on Investigations, Prophylaxis, and Specific Treatment.

Veno-occlusive disease (VOD) is a common and potentially fatal complication in children undergoing hematopoietic cell transplantation (HCT). It occurs in about one-third of all patients undergoing transplantation and is fatal in 50% of patients with severe disease. Early intervention and specific treatment with defibrotide are associated with improved outcomes. However, there is a lack of supportive care guidelines for management of the multiorgan dysfunction seen in most cases. There is high variability in the management of VOD, which may contribute to the increased morbidity and mortality. Although there is ample research in the specific treatment of VOD, there is paucity of literature regarding the management of ascites, transfusions requirements, fluids and electrolyte dysfunction, delirium, and investigations in children with VOD. The joint working committees of the Pediatric Acute Lung Injury and Sepsis Investigators and the Pediatric Blood and Marrow Transplantation Consortium collaborated to develop a series of evidence-based supportive care guidelines for management of VOD. The quality of evidence was rated and recommendations were made using Grading of Recommendations, Assessment, Development and Evaluation criteria. This manuscript is part 1 of the series and focuses on the need to develop these guidelines; methodology used to establish the guidelines; and investigations needed for diagnosis, prophylaxis, and treatment of VOD in children.

Urinary tract infection with Pasteurella multocida in a patient with cat exposure and abnormal urinary tract physiology: Case report and literature review.

Pasteurella multocida is a gram-negative organism that commonly colonizes the mouth of cats and dogs, and is known to cause infection in humans associated with animal bites or scratches. Sites of infection other than skin and soft tissue are rare, but have been reported in patients with specific risk factors including anatomical abnormalities or immunosuppression. Herein, we report a case of a symptomatic urinary tract infection caused by P. multocida in a 59 year old female who presented to the hospital with complaints of systemic symptoms including malaise, rigors, and chills, as well as thick, malodorous urine. The patient self-catheterized multiple times daily due to urostomy with Kock pouch. Treatment with piperacillin/tazobactam followed by amoxicillin resulted in resolution of the infection.

Severe transplant-associated thrombotic microangiopathy in patients with hemoglobinopathies.

Incidence and severity of transplant-associated thrombotic microangiopathy (TA-TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TA-TMA who received eculizumab. A 2.5-year-old male with sickle cell disease developed TA-TMA-associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7-year-old female with ß-thalassemia major developed TA-TMA-related acute kidney injury, severe hypertension, and seizures at 6 months after transplant. Both patients progressed to chronic kidney disease (CKD). In patients with hemoglobinopathies, preexisting endothelial dysfunction may place them at a greater risk for TA-TMA and subsequent CKD.