Disseminated cryptococcal infection in allogeneic stem cell transplant patients: a rare cause of acute kidney injury.

Hematopoietic stem cell transplantation (HSCT) can be lifesaving for some of the deadliest hematologic diseases. However, immunosuppression, polypharmacy and risk of infectious complications associated with HSCT can increase morbidity and mortality for recipients. Incidence of acute kidney injury (AKI) after HSCT can be as high as 70%, and concomitant infection can be a therapeutic challenge for oncologists, nephrologists and infectious disease specialists. We illustrate this challenge in the case of a 31-year-old man with acute lymphoblastic leukemia who underwent a double cord HSCT complicated by GvHD, systemic cryptococcal and BK virus infections and AKI. Kidney biopsy showed round to cup-shaped organisms with occasional budding, consistent with Cryptococcus and thrombotic microangiopathy. We discuss our findings and a literature review of disseminated cryptococcal infection with renal involvement after HSCT.

The first case of acute unilateral pan-ureteritis caused by BK polyomavirus in an allogeneic stem cell transplant patient.

Several cases of ureteral obstruction have been reported in stem cell transplant (SCT) patients; however, they were bilateral and concomitant with or preceded by hemorrhagic cystitis. We describe, to our knowledge, a first case of acute unilateral pan-ureteritis caused by BK polyomavirus (BKPyV) in an SCT patient. This case may represent an early phase of BKPyV reactivation. BKPyV infection should be considered as a potential cause of acute unilateral ureteritis even among SCT recipients.

Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.

Efficacy and safety of antiretrovirals in HIV-infected patients with cancer.

At 30 years into the HIV infection epidemic, the optimal antiretroviral (ARV) regimen for infected patients with cancer remains unknown. We therefore sought to retrospectively study different ARV regimens used in this population. Data from HIV-infected patients seen at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, from 2001 to 2012 were reviewed. Patients received nucleoside reverse transcriptase inhibitors (NRTIs) plus protease inhibitors (PIs), non-NRTIs (NNRTIs), integrase strand-transfer inhibitors (INSTIs), or combinations of these. A total of 154 patients were studied. Most patients were male (80%), white (51%) and had haematological malignancies (HMs) (58%). NRTIs were combined with PIs (37%), NNRTIs (32%), INSTIs (19%) or combinations of these (11%). INSTIs were the most commonly used in patients with HM and in those receiving high-dose steroids or topoisomerase inhibitors (p <0.05). Side-effects occurred in 35%, 14%, 3% and 6% of patients receiving PIs, NNRTIs, INSTIs and combinations, respectively (p 0.001). Grade 3-4 adverse events were uncommon. Multivariate logistic regression analysis demonstrated that INSTIs and NNRTIs were nine times (95% confidence interval (CI), 1.4-50.8) and 11 times (95% CI, 1.9-64.7) more likely to be effective at 6 months, respectively, than PIs. This is the largest reported analysis studying different ARV regimens in HIV-infected cancer patients. Combinations that included PIs were the least favourable. NNRTIs and INSTIs had comparable efficacy, but INSTIs appeared to be the better tolerated ARVs in patients with HM or those receiving various chemotherapeutic agents.

Toxoplasmosis in allo-SCT patients: risk factors and outcomes at a transplantation center with a low incidence.

Toxoplasmosis in allo-SCT patients is rare in the United States but has a mortality of 60-90%. In this retrospective study, we identified patients with definite and probable toxoplasmosis after allo-SCT at our institution from 1994 to 2009 using ICD-9 codes and the pathology database. Of 3626 patients who underwent allogeneic SCT, we identified 8 with definite toxoplasmosis and 1 with probable toxoplasmosis, an incidence of 0.25%. International patients had a significantly higher incidence of toxoplasmosis than did US patients (1.6 versus 0.15% (P=0.002)). Three patients presented with toxoplasmosis <30 days after transplantation and six developed toxoplasmosis within 100 days of starting high-dose corticosteroids. Two patients were diagnosed postmortem. Six of the remaining seven patients died despite ≥2 weeks of therapy. Co-morbidities, particularly infections, were the primary cause of death in one case and a contributing factor in the remaining six cases. On the basis of these results, we conclude that all allo-SCT patients from countries with high Toxoplasma seropositivity and seropositive patients from the United States should undergo serial PCR screening during the first month after transplantation and during corticosteroid use. All patients who test positive should undergo preemptive therapy.

Infections in non-myeloablative hematopoietic stem cell transplantation patients with lymphoid malignancies: spectrum of infections, predictors of outcome and proposed guidelines for fungal infection prevention.

The overall risk of infections is lower in patients undergoing non-myeloablative allogeneic stem cell transplantation (NST) than in conventional stem cell transplant recipients. We sought to evaluate conditions associated with increased risk of infections after NST. In 81 patients, 187 infection episodes were noted; chronic lymphocytic leukemia (138 episodes/100 person-years) and recipients of matched unrelated donor graft (128 episodes/100 person-years) had higher risk of infection. Only half of the cytomegalovirus (CMV) infections occurred 31-100 days after transplantation. Most patients with CMV infection were non-neutropenic (100%), had lymphoma (76%), were younger (<55 years; 72%) and had received matched related donor (MRD) graft (72%). However, graft-versus-host disease (GVHD) was present in only 15% of these patients. Seven (78%) of nine invasive fungal infections (IFI) were diagnosed >100 days after NST and were associated with high mortality (78%). Most patients with IFI were also not neutropenic (100%), had received MRD graft (100%), had lymphoma (78%) and were given systemic steroids (78%); unlike CMV infection, 67% of these patients also had GVHD. On the basis of our results, we propose that NST recipients with lymphoma treated with high-dose corticosteroids for GVHD be considered for antifungal prophylaxis or pre-emptive antifungal therapy.

Severe parainfluenza virus type 2 supraglottitis in an immunocompetent adult host: an unusual cause of a paramyxoviridae viral infection.

Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.

A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I).

BACKGROUND: No clinical trial results directly comparing two nucleoside analog pairs in a drug regimen for HIV that includes a protease inhibitor are available. OBJECTIVE: To compare the safety and efficacy of stavudine (d4T) + lamivudine (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (IDV). DESIGN: Randomized, open-label, multi-center. SETTING: Fifteen HIV clinical research centers. PATIENTS: Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts > or = 200 x 10(6)/l and HIV-1 RNA > or = 10,000 copies/ml (bDNA assay), modified to 5000 copies/ml. INTERVENTION: d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV. MEASUREMENTS: Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additional endpoints: HIV-1 RNA < or = 50 copies/ml; change from baseline in HIV-1 RNA and CD4 cell counts; safety and adverse events. RESULTS: For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patients on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [90% confidence interval, -0.204 to 0.036; P= 0.213], with 49% and 47% respectively achieving < or = 50 copies/ml at 48 weeks (90% CI, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks was +227 x 10(6)/l and +198 x 10(6)/l for the d4T- and ZDV-containing arms, respectively. The median time-weighted average change from baseline in CD4 cell counts was significantly greater at 48 weeks in the d4T-containing arm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were significant differences for frequency of adverse events of all severity with increased nausea and vomiting in the ZDV-containing arm, and increased diarrhea and rash in the d4T-containing arm. CONCLUSIONS: These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV treatment regimen.

Effects of tapering doses of oral prednisone on viral load among HIV-infected patients with unexplained weight loss.

In an exploratory study of virologic and immunomodulatory effects of corticosteroid therapy for wasting syndrome, four HIV-infected adults with recent unexplained weight loss were given tapering doses of prednisone over a 2-month period. Serum neopterin and TNF receptor II levels decreased from baseline after 7 days. An antiretroviral effect was observed initially, peaking on days 14-21 (mean change in HIV-1 branched chain DNA assay on day 21 of -0.52 log10; mean change, from baseline to nadir for each individual, of -0.63 log10); subsequent bDNA levels returned toward baseline as prednisone was tapered. No patient lost weight and there was a mean weight gain of 3.5 kg. Anecdotal reports of corticosteroid benefits in the wasting syndrome may result in part from decreased T cell activation leading to decreased HIV replication, an effect that may be self-limited or that may occur only at higher prednisone doses. Studies involving more targeted immunomodulatory agents for wasting syndrome are warranted.

Cryptococcal empyema: case report and review.

A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans. He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed. We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS. Only three other cases of empyema, one of them in an HIV-infected patient, have been reported. A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients.