Nocardiosis following hematopoietic stem cell transplantation.

BACKGROUND: Nocardia species are ubiquitous environmental organisms that can cause a diverse spectrum of disease. Clinical manifestations range from localized skin and soft tissue infections to life-threatening pulmonary, central nervous system, and/or disseminated infections. Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) are at risk for nocardiosis, and further data in regard to characteristics of disease in this population are warranted. METHODS: We performed retrospective chart review of patients post allogeneic HSCT at Moffitt Cancer Center in Florida diagnosed with nocardiosis from 2003 to 2013. RESULTS: In a decade, 15 cases of nocardiosis were identified. The majority of patients were men (11/15). The median age was 55 years (range 25-65). The most common type of transplant was matched-related donor (n = 8), followed by matched-unrelated donor (n = 3), mismatched-unrelated donor (n = 3), and double umbilical cord (n = 1). Ten received myeloablative conditioning (MAC) regimens. Twelve of 15 patients were on prednisone, 10 of which were on a total daily dose ≥20 mg. The median time from transplant to first positive culture was 10 months (range 1.5-93). Pulmonary nocardiosis was the most prevalent manifestation at 87%. Disseminated disease (2 or more sites of infection) was seen in 47%, whereas blood cultures were positive in 27% of the total cohort. The most common species was Nocardia nova (n = 4). At the time of diagnosis, 20% of the patients were receiving prophylaxis for Pneumocystis jirovecii pneumonia (PJP) with trimethoprim-sulfamethoxazole (TMP-SMX). Susceptibility data were available for 8 patients: all 8 samples were susceptible to TMP-SMX. Nocardiosis was treated with 2 or more active drugs in 93% of the patients. Overall mortality was 53%, with nocardiosis attributed as the cause in 62.5% (5/8). The absolute lymphocyte count at time of diagnoses was significantly lower in patients who ultimately experienced treatment failure. CONCLUSION: Infection with Nocardia species in allogeneic HSCT recipients appears to be a late complication of transplantation and most commonly involves the lung. Two-thirds of the cohort received a MAC regimen and the majority of the patients were receiving steroids at the time of diagnosis. Most patients were not receiving TMP-SMX for PJP prophylaxis at the time of nocardiosis diagnosis, and TMP-SMX may therefore have a protective effect.

Randomized controlled trial of high-dose intradermal versus standard-dose intramuscular influenza vaccine in organ transplant recipients.

The immunogenicity of standard intramuscular (IM) influenza vaccine is suboptimal in transplant recipients. Also, recent studies suggest that alloantibody may be upregulated due to vaccination. We evaluated a novel high-dose intradermal (ID) vaccine strategy. In conjunction, we assessed alloimmunity. Transplant recipients were randomized to receive IM or high-dose ID vaccine. Strain-specific serology and HLA alloantibody production was determined pre- and postimmunization. In 212 evaluable patients (105 IM, 107 ID), seroprotection to H1N1, H3N2 and B strains was 70.5%, 63.8% and 52.4% in the IM group, and 71.0%, 70.1%, 63.6% in the ID group (p=ns). Seroconversion to ≥1 antigen was 46.7% and 51.4% in the IM and ID groups respectively (p=0.49). Response was more likely in those≥6 months posttransplant (53.2% vs. 19.2%; p=0.001). Use of mycophenolate mofetil was inversely associated with vaccine response in a dose-dependent manner (p<0.001). Certain organ subgroups had higher response rates for influenza B in the ID vaccine group. Differences in anti-HLA antibody production were detected in only 3/212(1.4%) patients with no clinical consequences. High-dose intradermal vaccine is an alternative to standard vaccine and has potential enhanced immunogenicity in certain subgroups. In this large cohort, we also show that seasonal influenza does not result in significant alloantibody production.

Morphine, opioids, and the feline pulmonary vascular bed.

BACKGROUND: Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects. METHODS: This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of L-N(5)-(1-iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H(1)-receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. RESULTS: In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of L-NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine. CONCLUSION: The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways.