A eulogy for Dr Francisco Miguel Marty Forero.

As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being.

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients.

Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown. We evaluated the infectious and noninfectious outcomes of 179 pancreas transplant recipients treated with alemtuzumab for induction and maintenance therapy (extended alemtuzumab exposure (EAE)) from 2/28/2003 through 8/31/2005, compared with 159 pancreas transplant recipients with standard induction and maintenance (SIM) therapy performed before (1/1/2002 until 12/31/2002) and after (1/1/2006 until 12/31/2006) the implementation of EAE. EAE was associated with higher risk of overall infections (hazard ratio (HR) 1.33 (1.06-1.66), P=0.01), bacterial infections (HR 1.33 (1.05-1.67), P=0.02), fungal infections (HR 1.86 (1.28-2.71), P < 0.01), and cytomegalovirus infections (HR 2.29 (1.39-3.77), P < 0.01). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46-2.99), P < 0.01). In conclusion, while a limited alemtuzumab dosing is safe and effective for induction therapy in pancreas transplantation, EAE combined with steroid and calcineurin minimization is associated with a high risk of infectious complications and acute cellular rejection.

Intestinal pathophysiological and microbial changes in sickle cell disease: Potential targets for therapeutic intervention.

There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso-occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD.

Brincidofovir (CMX001) for the Treatment of Severe Adenoviral Pneumonia in Kidney Transplant Recipient.

Adenovirus causes significant morbidity and mortality in solid organ and hematological transplant recipients. Treatment of adenovirus infections includes supportive care, reduction of immune suppression, and in patients with severe disease, intravenous cidofovir. Brincidofovir (CMX001) is a lipid conjugate of cidofovir, with good oral bioavailability, no associated nephrotoxicity, and higher intracellular levels of the active drug compared to cidofovir. We describe a case of severe adenoviral pneumonia in an adult renal transplant recipient who was successfully treated with oral brincidofovir after developing renal insufficiency with intravenous cidofovir. Brincidofovir (CMX001) along with other supportive therapy, may offer an efficacious, safe, and well-tolerated treatment for severe adenoviral infections in solid organ transplant recipients.

Anaplasma phagocytophilum presenting with orchitis in a renal transplant recipient.

Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, is an emerging tick-borne disease. It is spread by the black-legged deer tick Ixodes scapularis that serves as the vector for six human pathogens. HGA is still rarely reported in solid organ transplant recipients. In solid organ transplant recipients, orchitis has been reported secondary to chickenpox, tuberculosis and infections due to Listeria monocytogenes and Nocardia asteroides. Orchitis as a presenting feature of HGA infection has only been reported in animals. We present a unique case of a renal transplant recipient with HGA that presented as orchitis. We also compare the clinical presentation and laboratory findings of our patient with other cases of HGA in transplant recipients. To the best of our knowledge, our patient is one of the first cases of A phagocytophilum mono-infection causing a classical presentation of orchitis in a transplant patient.

Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors.

We carried out a retrospective cohort study on patients with advanced cancer treated with immune checkpoint inhibitors (ICIs) to determine whether antibiotics affect treatment outcome. Sixty consecutive patients were identified, and 17 received systemic antibiotics within 2 weeks before and/or after first dose of ICI. Antibiotic-treated patients were significantly younger (p = 0.0008) and less likely to receive nivolumab (p = 0.08) or had neutrophil:lymphocyte ratio < 5 (p = 0.08). They had a lower response rate (RR) (29.4% vs 62.8%) (p = 0.024) and more inferior progression-free survival (PFS) (p = 0.048). Narrow-spectrum antibiotics did not affect the RR. However, broad-spectrum antibiotics were associated with a lower RR (25% vs 61%) (p = 0.02) and a trend towards longer time to response (median: 14 weeks vs 12 weeks) (p = 0.1). They also had shorter PFS (p = 0.012). Multivariate analysis identified antibiotics as the only factor affecting RR (p = 0.0038) and PFS (p = 0.01). We next examined the 21 patients whose PFS lasted for 12 weeks or more. Five of the 21 patients received broad-spectrum antibiotics within 10 weeks before disease progression. There was a trend towards shorter PFS in these patients (p = 0.1). Finally, antibiotic-treated patients experienced shorter overall survival (OS) (median: 24 months vs 89 months) (p = 0.003). Multivariate analysis found age (p = 0.035) and antibiotics (p = 0.038) to be the only factors affecting OS. Our results point to a detrimental effect of broad-spectrum antibiotics on treatment outcome to ICI therapy.

Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?

Non-typhoidal Salmonella usually induces self-limiting gastroenteritis. However, in many parts of Africa, especially in individuals who are malnourished, infected with malaria, or have sickle cell disease, the organism causes serious and potentially fatal systemic infections. Since the portal of entry of non-typhoidal Salmonella into the systemic circulation is by way of the intestine, we argue that an increased gut permeability plays a vital role in the initiation of invasive non-typhoidal Salmonella in these patients. Here, we will appraise the evidence supporting a breach in the intestinal barrier and propose the mechanisms for the increased risks for invasive non-typhoidal Salmonella infections in these individuals.

Infections in patients on BCR-ABL tyrosine kinase inhibitor therapy: cases and review of the literature.

The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.

Relapsing EBV encephalitis in a renal transplant recipient.

In solid organ transplant recipients, Epstein-Barr virus (EBV) can cause active central nervous system (CNS) infection or malignant transformation of latently infected cells in the CNS, known as post-transplant lymphoproliferative disease (PTLD). Reduction of T-cell immunosuppression is the cornerstone of management. The role of antivirals with in-vitro activity against herpesviruses in EBV-related CNS syndromes is controversial, as they have no effect on latent virus. We report an unusual case of relapsing EBV encephalitis in a donor-positive, EBV-negative renal transplant recipient, with response to valganciclovir. Our report supports the utility of antiviral treatment for EBV encephalitis, as adjunct to reducing immunosuppression, and highlights the need for a systematic approach and long-term, multi-disciplinary follow-up of such patients.

Resolution of diarrhea in an immunocompromised patient with chronic norovirus gastroenteritis correlates with constitution of specific antibody blockade titer.

Norovirus gastroenteritis in immunocompromised hosts can result in a serious and prolonged diarrheal illness. We present a case of chronic norovirus disease during rituximab-bendamustine chemotherapy for non-Hodgkin's lymphoma. We show for the first time a correlation between norovirus strain-specific antibody blockade titers and symptom improvement in an immunocompromised host.

Transfusion-transmitted anaplasmosis from a leukoreduced platelet pool.

BACKGROUND: Human granulocytic anaplasmosis is an emerging tick-borne illness. Anaplasma phagocytophilum resides intracellularly, can cause asymptomatic infection, and can survive blood component refrigeration conditions for at least 18 days. To date, eight cases of transfusion-transmitted anaplasmosis (TTA) have been reported: seven attributed to red blood cell (RBC) units, five of which were prestorage leukoreduced using RBC leukoreduction filters, and one involving a process leukoreduced apheresis platelet (PLT) unit. Here, we report a case of TTA from a whole blood-derived PLT pool. STUDY DESIGN AND METHODS: Donation segments from the 7 units of RBCs and two PLT pools transfused were examined. Fast protocol multiplex real-time A. phagocytophilum polymerase chain reaction (PCR) and serologic testing for immunoglobulin (Ig)M and IgG antibodies to A. phagocytophilum by enzyme immunoassay were performed. RESULTS: Transmission was confirmed by positive A. phagocytophilum PCR and serology in one of 16 donors and by positive PCR and seroconversion in the recipient. CONCLUSION: This is the first confirmed case of TTA from a whole blood-derived PLT pool prepared from PLT concentrates leukoreduced by in-line filtration of PLT-rich plasma.

Myopericarditis associated with Fusobacterium nucleatum-caused liver abscess.

A wide clinical spectrum of bacteremic disease caused by Fusobacterium has been presented in this journal. We wish to extend this spectrum by presenting a case of myopericarditis resulting from a liver abscess caused by F. nucleatum. While F. nucleatum plays an important role in periodontal disease, and has been isolated from skin ulcers, liver abscesses, urinary tract infections, and endocarditis, a single case of F. nucleatum-induced pericarditis is documented in the literature.