Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges.

Advancement in solid organ transplantation and hematopoietic stem cell transplant continues to improve the health outcomes of patients and widens the number of eligible patients who can benefit from the medical progress. Preserving the effectiveness of antimicrobials remains crucial, as otherwise transplant surgeries would be unsafe due to surgical site infections, and the risk of sepsis with neutropenia would preclude stem cell transplant. In this review, we provide updates on three previously discussed stewardship challenges: febrile neutropenia, Clostridioides difficile infection, and asymptomatic bacteriuria. We also offer insight into four new stewardship challenges: the applicability of the "shorter is better" paradigm shift to antimicrobial duration; antibiotic allergy delabeling and desensitization; colonization with multidrug-resistant gram-negative organisms; and management of cytomegalovirus infections. Specifically, data are accumulating for "shorter is better" and antibiotic allergy delabeling in transplant patients, following successes in the general population. Unique to transplant patients are the impact of multidrug-resistant organism colonization on clinical decision-making of antibiotic prophylaxis in transplant procedure and the need for antiviral stewardship in cytomegalovirus. We highlighted the expansion of antimicrobial stewardship interventions as potential solutions for these challenges, as well as gaps in knowledge and opportunities for further research.

Transplantid.net: A Pilot Crowdsourced, Living, Online Library of Resources for the Teaching and Practice of Transplant Infectious Diseases.

The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them.

Antimicrobial therapies are essential tools for transplant recipients who are at high risk for infectious complications. However, judicious use of antimicrobials is critical to preventing the development of antimicrobial resistance. Treatment of multidrug-resistant organisms is challenging and potentially leads to therapies with higher toxicities, intravenous access, and intensive drug monitoring for interactions. Antimicrobial stewardship programs are crucial in the prevention of antimicrobial resistance, though balancing these strategies with the need for early and frequent antibiotic therapy in these immunocompromised patients can be challenging. In this review, we summarize 5 frequently encountered transplant infectious disease stewardship challenges, and we suggest strategies to improve practices for each clinical syndrome. These 5 challenging areas are: asymptomatic bacteriuria in kidney transplant recipients, febrile neutropenia in hematopoietic stem cell transplantation, antifungal prophylaxis in liver and lung transplantation, treatment of left-ventricular assist device infections, and Clostridioides difficile infection in solid-organ and hematopoietic stem-cell transplant recipients. Common themes contributing to these challenges include limited data specific to transplant patients, shortcomings in diagnostic testing, and uncertainties in pharmacotherapy.

Candida glabrata Empyema Thoracis-A Post-COVID-19 Complication.

The COVID-19 pandemic is associated with a significant increase in the incidence of invasive mycosis, including pulmonary aspergillosis, mucormycosis, and candidiasis. Fungal empyema thoracis (FET) is an uncommon clinical presentation of invasive fungal disease (IFD) associated with significant mortality. Here, we describe the first report of a patient with post-COVID-19 multifocal necrotizing pneumonia complicated by a polymicrobial empyema that included Candida glabrata. Candida empyemas represent another manifestation of a COVID-19-associated fungal opportunistic infection, and this infrequently encountered entity requires a high degree of clinical suspicion for timely identification and management. Therapy for empyemas and other non-bloodstream Candida infections may differ from candidemia due to several pharmacokinetic parameters impacting bioavailability of the antifungal in the affected tissue (e.g., pleural space) and is an area that needs more investigation.

Reproductive Tract Bleeding in Adolescent and Young Adult Females with Inherited Bleeding Disorders: An Underappreciated Problem.

Reproductive tract bleeding is an underappreciated health care problem among adolescent and young adult (AYA) females with inherited bleeding disorders (IBDs) comprising von Willebrand disease, platelet disorders, hemophilia carriership, and rare factor deficiencies. IBDs are prevalent in women of all ages and have been detected in about 50% of women with menorrhagia or heavy menstrual bleeding (HMB) and about 20% of women with postpartum hemorrhage (PPH). The clinical spectrum of gynecologic and obstetric bleeding in AYA with IBDs ranges from HMB, ovulation bleeding, and surgical bleeding to miscarriages and life-threatening PPH. Reproductive tract bleeding adversely affects the quality of life of this patient population, in addition to causing substantial morbidity and mortality. Early diagnosis of IBDs offers the opportunity for timely intervention with hormones, hemostatic agents, and prophylaxis with factor concentrates, thereby improving outcomes. This review summarizes the epidemiology, pathophysiology, clinical manifestations, diagnostic approach, management, and prophylaxis for reproductive tract bleeding in AYA with IBDs. This review provides a multidisciplinary approach to the problem, which is critical to improve the outcomes of this patient population.

Prevention of Mycobacterium tuberculosis Transmission in Health Care Settings.

Patients with tuberculosis (TB) pose a risk to other patients and health care workers, and outbreaks in health care settings occur when appropriate infection control measures are not used. This article discusses strategies to prevent transmission of Mycobacterium tuberculosis within health care settings. All health care facilities should have an operational TB infection control plan that emphasizes the use of a hierarchy of controls (administrative, environmental, and personal respiratory protection). Resources available to clinicians who work in the prevention and investigation of nosocomial transmission of M tuberculosis also are discussed.

Post-partum occurrence of Wunderlich syndrome and microangiopathic haemolytic anaemia (MAHA): a case report.

This is a case of a 27-year-old primigravida with monochorionic diamniotic twin gestation who was admitted to the hospital for induction of labour. Her postpartum course was complicated by microangiopathic haemolytic anemia (MAHA). The etiology for the MAHA was initially thought to be secondary to pre-eclampsia and vitamin B12/folate deficiency. However, she had persistent anemia and further workup demonstrated that she had a left renal cell carcinoma (RCC) with perinephric haemorrhage consistent with Wunderlich syndrome. This case was intriguing because of its unusual presentation and the several diagnostic and therapeutic challenges along the way. Abbreviations: MAHA: microangiopathic haemolytic anaemia; RCC: renal cell carcinoma; BP: blood pressure; WS: Wunderlich syndrome; CT: computed tomography; LFTs: liver function tests; LDH: lactate dehydrogenase; HELLP: haemolysis elevated liver enzymes, low platelets; DIC: disseminated intravascular coagulation; PLASMIC: score for TTP - includes platelet count <30 x 109/L, evidence of haemolysis (reticulocyte count >2.5%, haptoglobin undetectable, or indirect bilirubin >2mg/dL), active cancer, history of solid organ transplant, mean corpuscular volume (MCV) <90fL, INR <1.5, creatinine <2mg/dL. Each item is sored as being present (YES) or not (NO). Absence of active cancer and solid organ transplant gets scored with a point each. The total points are added up to categorize the severity and risk of TTP. Low risk <4, Intermediate 5, high risk >6; TTP: thrombotic thrombocytopenic purpura; APLA- anti-phophospholipid antibody; BMI: body mass index; TMAs: thrombotic microangiopathies; HUS: haemolytic uremic syndrome; vWF: von Willebrand factor.

COVID-19 in HIV-infected patients: A case series and literature review.

During the current COVID pandemic, there is growing interest to identify subsets of the population that may be at a higher than average risk of infection. One such group includes people living with HIV.

Case Report: IgG multiple myeloma and chronic myeloid leukemia in a single patient.

A 58-year-old man presented with recurrence of chronic myeloid leukemia (CML) after complete molecular remission in the setting of non-compliance with imatinib. He was restarted on imatinib and was also noted to have IgG kappa monoclonal gammopathy of undetermined significance (MGUS). The patient re-achieved molecular remission after resumption of imatinib, but his MGUS progressed to smoldering myeloma and he was eventually diagnosed with multiple myeloma (MM) and initiated on treatment for MM with thalidomide, bortezomib and dexamethasone. He has responded well to treatment of the myeloma and continues concurrent maintenance imatinib treatment for CML and is being evaluated for bone marrow transplant. The association of two concurrent hematological malignancies, CML and MM, is very rare and has been infrequently reported in literature. The pathophysiology of this has not yet been fully understood. This case report reviews the various theories to explain this and discusses the potential challenges of simultaneous treatment of MM and CML.

Cryptogenic Pyogenic Liver Abscess Due to Fusobacterium nucleatum in an Immunocompetent Patient.

In this case, a 76-year-old female presented with 3-4 days of fever with no other localizing signs. Notably, she had had an untreated Fusobacterium bacteraemia approximately 8 weeks prior to admission. She underwent abdominal imaging which demonstrated a liver abscess and had percutaneous drainage of the same. Blood and pus cultures both grew Fusobacterium nucleatum, which is an unusual organism to be associated with a liver abscess, especially in an immunocompetent host with no risk factors for this condition. Interestingly, this patient did not have any history of dental work, instrumentation, liver function test (LFT) abnormalities and no extrahepatic source for the abscess. This case highlights the importance of having a high index of clinical suspicion for an occult source of infection and emphasizes the importance of following up on cultures even after discharge of a patient, since anaerobic infections such as those caused by Fusobacterium can have a largely indolent course. LEARNING POINTS: Fever of unknown aetiology with prior bacteraemia merits a thorough work-up for occult sources such as a localized abscess or malignancy, which can cause bacterial translocation.Fusobacterium and other anaerobic infectious agents should be considered in the context of an indolent disease course since they are slow-growing in cultures, and also, if the patient has risk factors such as immunosuppression, diabetes, poor oral hygiene and so on.It is important to have systems in place in hospitals to ensure follow-up for patients who may have a positive culture after discharge from hospital to confirm that the infection is adequately addressed.

Hemophagocytic Lymphohistiocytosis (HLH) in a Patient with Disseminated Histoplasmosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by an overwhelming inflammatory cascade activation which is often associated with rapid progression and high mortality. It may be familial with an underlying genetic mutation or triggered by infection, malignancy, and autoimmune disease. Disseminated histoplasmosis caused by histoplasma capsulatum is a granulomatous fungal disease seen typically in immunocompromised patients with varied clinical manifestations and requires long-term antifungal therapy. We present the case of a 61-year-old immunocompromised female with significant travel history who came with fever, pancytopenia, and liver failure raising suspicion for HLH that prompted a bone marrow biopsy procedure. Hemophagocytic figures consistent with HLH and numerous encapsulated fungi resembling histoplasma were visualized. She was treated with intravenous (IV) liposomal amphotericin B. Etoposide chemotherapy and interleukin-1 (IL-1) antagonist anakinra were deferred in order to limit her immunosuppression, and treatment was focused on antifungal therapy.

Haemostatic efficacy of single-dose factor administration in neonates with severe haemophilia undergoing circumcision.

INTRODUCTION: Perioperative management of children with haemophilia undergoing surgery is a complex and understudied topic. Circumcision is the most common procedure performed in the neonatal period, and guidelines to prevent bleeding complications from circumcision are lacking. Treatment protocols vary widely, and many centres treat patients with factor products for up to two weeks after circumcision. There is an unmet need for studies evaluating optimal factor replacement therapy around the time of circumcision in neonates with severe haemophilia. AIM: To determine the efficacy of a single dose of factor replacement before circumcision to prevent bleeding complications in neonates with severe haemophilia. METHODS: We conducted a retrospective chart review of male infants born between January 2000 and June 2019. Male neonates with severe haemophilia diagnosed at the Iowa Hemophilia and Thrombosis Center (n = 22) and healthy newborn controls who underwent circumcision at the University of Iowa Hospitals were included. Data were collected from the electronic medical record. Neonates with severe haemophilia were separated into two groups-those pretreated with one dose of factor replacement before circumcision and those without pretreatment. RESULTS: We observed that neonates with severe haemophilia pretreated with a single dose of factor VIII or factor IX replacement had significantly reduced bleeding complications, shorter hospital stay and required less therapeutic intervention compared with untreated patients. Importantly, pretreated patients had outcomes similar to healthy controls. CONCLUSIONS: Our results demonstrate that a single dose of factor replacement before circumcision is effective to prevent bleeding in neonates with severe haemophilia.

Secondary Plasma Cell Leukemia: A Case Report.

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma and has a poor prognosis. It needs prompt recognition in order to institute timely treatment. Given its relatively low incidence, it is an evolving area of research as well. This case report describes a patient with PCL in the setting of a previously treated myeloma. The report also reviews the clinicopathologic, cytogenetic, and immunophenotypic characteristics of PCL and its management.

Sleep Disordered Breathing in Hospitalized African-Americans.

RATIONALE: Sleep-disordered breathing (SDB) is a common disorder in general population, with higher prevalence in population with comorbid cardiovascular disease, and yet it remains frequently undiagnosed. Prior published data show that hospitalized obese patients have a high incidence of unrecognized SDB. However, limited data exists on the incidence, prevalence, and impact of SDB in hospitalized obese African-American (AA) patients. This study was performed to better understand the burden of undiagnosed SDB in hospitalized AA patients and its implications on readmission. METHODS: A total of 1243 consecutive obese AA patients admitted to medical or telemetry service were screened utilizing a screening questionnaire (STOP/STOPBANG) from October 2016 to October 2017. If the results of the screening questionnaire were positive, the patients were offered inpatient testing with either High Resolution Pulse Oximetry (HRPO), or a type 3 portable monitor (PM). SDB was suspected if the Oxygen Desaturation Index (ODI) or Apnea Hypopnea Index (AHI) ≥ 5. We collected 30-day readmission and emergency department (ED) visit data on all patients and requested a formal outpatient sleep study for patients identified as SDB positive. RESULTS: Of the 1243 AA patients screened, 852 (68.5%) patients screened positive for SDB. Of these high-risk screens, 538 (63.1%) patients underwent inpatient testing with either High Resolution Pulse Oximetry (HRPO) or PM. Of these 538 patients, 319 (59.3%) were found to have suspected obstructive sleep apnea (OSA) based on ODI/AHI >5. Mild SDB (AHI 5-14) was present in 149 (46.7%) patients; moderate (AHI 15-29) in 74 (23.2%) patients; and severe (AHI >30) in 96 (30.1%) patients. The patients with suspected SDB were educated and encouraged to get an out-patient polysomnogram (PSG) but only 32 (10.0%) returned to undergo a formal PSG. The 30-day readmission rate/ED visits for patient with SDB was 13.5% compared to 13.7% of patients without SDB. CONCLUSION: This is the largest SDB registry that included obese hospitalized AA patients in a tertiary care academic center and reveals a high prevalence of undiagnosed SDB in this cohort. Despite proactive screening and patient education only 3.8% (32/852) of patients returned post-discharge for formal polysomnography. The presence of SDB did not impact the 30-day readmission rate/ED visit rate in this cohort.

Oesophageal Variceal-Pulmonary Venous Fistula A Rare Cause of a Right-to-Left Shunt.

Oesophageal varices are a dilated submucosal venous plexus in the lower third of the oesophagus which result from increased pressure in the portal venous system. The portal system is connected to the systemic circulation in specific locations referred to as sites of portosystemic anastomosis. An increase in portal venous pressure is therefore reflected at these anastomotic sites, causing manifestations such as oesophageal varices, rectal varices, caput medusae and splenorenal shunts. Varices do not cause symptoms until they leak or rupture and this is the main complication which requires prompt treatment. Here, we present a post-liver transplant patient with metastatic hepatocellular carcinoma who had oesophageal varices that fistularized with a left pulmonary vein, thus creating a right-to-left shunt. Right-to-left shunts are usually intracardiac or intrapulmonary in location. The complications of a right-to-left shunt include predominantly hypoxia, cyanosis and, sometimes, paradoxical emboli in the case of intracardiac shunts. This patient had a very uncommon cause of such a shunt caused by a direct fistulous connection. LEARNING POINTS: Right-to-left shunts create a ventilation-perfusion mismatch.Recognizing situations where there is a connection between the systemic circulation and pulmonary circulation without intermediate oxygenation is important because of possible clinical implications such as hypoxia.

Pneumomediastinum in a Heavy Weightlifter.

The presence of air in the mediastinal cavity (i.e., pneumomediastinum) is an uncommon condition. It is usually precipitated by an event such as penetrating trauma, barotrauma or increased intrathoracic pressure caused by severe vomiting or coughing. We present the case of a 32-year-old man who developed pneumomediastinum as a result of heavy weightlifting. LEARNING POINTS: Pneumomediastinum should be considered in the differential diagnosis of acute onset shortness of breath and chest pain.Pneumomediastinum can be precipitated without any obvious trauma as in cases of increased coughing/vomiting or heavy weightlifting.It is generally managed conservatively and resolves spontaneously.

Caregiver's Health Locus of Control and Medication Adherence in Sickle Cell Disease.

ACKNOWLEDGEMENTS: The authors would like to thank Dr. Morisky for giving us permission to use the Morisky Medication Adherence Scale PURPOSE: To explore caregivers' Health Locus of Control's relationship to self-reported adherence to penicillin prophylaxis or hydroxyurea in children with sickle cell disease (SCD). PROCEDURE: A questionnaire-based study was conducted of caregivers of children with SCD who visited a comprehensive sickle cell center in an inner city hospital, who were either on penicillin prophylaxis or hydroxyurea or both. Multidimensional Health Locus of Control Scale (MHLC) and the Morisky Medication Adherence Scale (MMAS-8) questionnaires were used for the study. RESULTS: Caregivers of 43 children (27 on penicillin prophylaxis, 13 on hydroxyurea, and 3 on both) completed the MHLC and the MMAS-8. There was no significant difference in adherence between the penicillin and the hydroxyurea groups. The mean Powerful Others score of caregivers of the hydroxyurea only group (25.5+5.6) was higher than that of the penicillin only group (21.2+6.1, p=0.043). Regression analysis revealed an inverse relationship of Chance Locus of Control to adherence in the entire group (Beta = -0.306, R2=0.093, F[1,40]=4.12, p=0.049). CONCLUSION: Chance Locus of control may identify caregivers of children with SCD at risk for non-adherence to treatment.