Visceral leishmaniasis in hematopoietic cell transplantation: Case report and review of the literature.

Visceral leishmaniasis has been recognized as an opportunistic infection affecting people with cellular-immunity impairment, including hematopoietic cell transplantation (HCT) recipients. We describe the case of a young Italian man with Hodgkin lymphoma, who developed visceral leishmaniasis after multiple lines of chemotherapy and allogenic HCT. Literature review of visceral leishmaniasis in HCT recipients was also performed. Eleven patients (median age 50 years, 9 male) developed visceral leishmaniasis after allogenic (n = 9) and autologous (n = 2) HCT. Most of them presented with fever and pancytopenia. Bone marrow examination was the main diagnostic technique; liposomal amphotericin B was the treatment of choice. Four out of eight patients (for whom data are available) experienced visceral leishmaniasis relapse. Visceral leishmaniasis in HCT recipients is a rare event that should be suspected in patients with persistent fever, pancytopenia and possible exposure to Leishmania spp., remembering that - as well as South-East Asia, East Africa and South America - it is endemic in several European regions.

Bloodstream infections are an improbable cause of positive serum (1,3)-ß-D-glucan in hematology patients.

Ninety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-ß-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results.

Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study.

Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.

Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome.

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor's immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.

Piperacillin/tazobactam (Tazocin™) seems to be no longer responsible for false-positive results of the galactomannan assay.

OBJECTIVES: Galactomannan (GM) testing is extremely useful for diagnosing invasive aspergillosis in high-risk patients, but false-positive results have been reported in patients treated with piperacillin/tazobactam. The aims of this study are to test if the recent piperacillin/tazobactam (Tazocin™; Pfizer) preparation still contains GM, and if serum GM positivity in haematopoietic stem cell transplant (HSCT) recipients receiving piperacillin/tazobactam can be attributed to this treatment. PATIENTS AND METHODS: Serum samples obtained from 1 October 2009 to 31 October 2010 from HSCT recipients for GM testing were analysed. The difference in the rate of positive results (defined as GM ≥ 0.5) in patients receiving and not receiving piperacillin/tazobactam was evaluated. Piperacillin/tazobactam vials from randomly selected batches were tested. RESULTS: Of 1606 samples drawn in the absence of piperacillin/tazobactam therapy, 25 (1.6%) tested positive for GM versus 10 of 394 samples (2.5%) drawn while on piperacillin/tazobactam (P = 0.18). The median GM result of samples drawn on piperacillin/tazobactam was slightly higher than that of samples drawn in the absence of piperacillin/tazobactam (0.141 versus 0.122; P < 0.001). All 90 piperacillin/tazobactam vials from 30 randomly selected batches tested negative for GM, with a median GM value of 0.057 (range: 0.011-0.320). CONCLUSIONS: Although some residual GM might still be present in piperacillin/tazobactam, currently available brand piperacillin/tazobactam preparations seem no longer responsible for false-positive GM results.

Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients.

PURPOSE: Bloodstream infections (BSIs) are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to identify predictors of mortality after BSI in patients who undergo HSCT. METHODS: Patients who underwent HSCT between 1 January 2004 and 31 January 2008 and developed BSI during the first year post-transplantation were included. Variables influencing overall mortality at 7 and 30 days after BSI were analysed. RESULTS: BSIs developed in 149 patients, within a median of 9 days after undergoing HSCT. Early and late mortality were 15 and 27%, respectively. Of the BSI, 54% were due to Gram-positive microorganisms, 33% were due to Gram-negative microogranisms, 10% were polymicrobial and 3% were fungal. The associated 7-and 30-day mortality was respectively 10 and 24% (Gram positive), 22 and 31% (Gram negative; Pseudomonas aeruginosa mortality 67%, all within 7 days), 13 and 27% (polymicrobial) and 40% (fungal, all within 7 days). Early mortality was higher in relapsed disease at HSCT (25.9%, p = 0.01), but lower in early (i.e. within 20 days of HSCT) BSI (11.7%, p = 0.03) and BSI due to Gram-positive infective agents (10%, p = 0.05). Multivariate analysis confirmed a higher mortality in late BSI [odds ratio (OR) 3.29, p = 0.03] and relapsed disease at HSCT (OR 2.2, p = 0.04). Late mortality was associated with the type of underlying disease (OR 0.44 for diseases other than acute leukaemia, p = 0.05) and its status (OR 6.04 for relapse at HSCT, p = 0.001). Appropriate empirical therapy was associated with lower early and late mortality in single Gram-negative BSI (16 vs. 45% for 7-day mortality, p = 0.09; 21 vs. 64% for 30-day mortality, p = 0.02). CONCLUSIONS: BSIs are frequent during the first year after HSCT and are associated with a high mortality rate. The aetiology influenced early mortality, while the type and phase of the underlying disease played a pivotal role in late mortality. Appropriate empirical therapy is crucial in BSI due to Gram-negative infective agents.

Rhino-cerebral zygomycosis after allogeneic transplant: case report and literature review.

The proportion of patients with hematological malignancies (HM) who develop rare invasive fungal infections (IFI) has increased worldwide over the past few decades. Zygomycosis is an opportunistic fungal infection, which begins in the nose and paranasal sinuses due to inhalation of fungal spores. Rhino-cerebral zygomycosis is the most common form of the disease, it typically develops in diabetic or immunocompromised patients and presents as an acute fulminate infection, which is often lethal. We report a case of rhino-cerebral zygomycosis in an allotransplanted patient to emphasize early diagnosis and treatment of this potentially fatal fungal infection. We discuss different risk factors, specific diagnosis procedures and review the current concepts in management of zygomycosis.

Persistence of a positive (1,3)-beta-D-glucan test after clearance of candidemia in hematopoietic stem cell transplant recipients.

In 6 hematopoietic stem cell transplant (HSCT) recipients with candidemia, the (1,3)-ß-d-glucan (BG) test was positive a median of 2.5 days after a positive blood culture. Only in 1 patient did BG positivity precede positive blood cultures. BG concentrations decreased in patients with clinical response, but positive BG results persisted long after blood cultures became sterile (median, 48 days).

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.

Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case-control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2-24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65-48.99 and OR=7.52, 95% CI, 1.56-36.31, respectively, P=0.047); severe (grades 3-4) mucositis (OR=9.04, 95% CI, 1.97-41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11-18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93-18.66 for 1-7 days of therapy, and OR=7.31, 95% CI, 1.78-30.12 for 8-23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06-0.97, P=0.045 and OR=0.11, 95% CI, 0.02-0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.

Risk factors for invasive aspergillosis and related mortality in recipients of allogeneic SCT from alternative donors: an analysis of 306 patients.

Invasive aspergillosis (IA) is a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), particularly from donors other than HLA-identical sibling. All 306 patients who underwent alternative donor HSCT between 01 January 1999 and 31 December 2006 were studied. Late IA was defined as occurring >or=40 days after HSCT. The median follow-up was 284 days (range, 1-2709). Donors were matched unrelated (n=185), mismatched related (n=69), mismatched unrelated (n=35) and unrelated cord blood (n=17). According to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, 2 patients already had IA at HSCT, 23 had early IA and 20 had late IA (IA incidence 15%). Eight patients had proven and 37 probable IA. Multivariate analyses showed that significant predictors of IA were delayed neutrophil engraftment, extensive chronic GVHD (cGVHD), secondary neutropenia and relapse after transplant. Early IA was associated with active malignancy at HSCT, CMV reactivation and delayed lymphocyte engraftment. Late IA was predicted by cGVHD, steroid therapy, secondary neutropenia and relapse after HSCT. IA-related mortality among IA patients was 67% and was influenced by use of anti-thymocyte globulin, steroids, higher levels of creatinine, and lower levels of IgA and platelets. The outcome of IA depends on the severity of immunodeficiency and the status of the underlying disease.

Possible malignant transformation of benign lymphoepithelial parotid lesions in human immunodeficiency virus-infected patients: report of three cases.

Benign lymphoepithelial parotid lesions (BLL) are intraparotid pathological changes that are commonly thought to be an early manifestation of human immunodeficiency virus (HIV) infection. It is not well known whether BLL may undergo malignant transformation into B cell lymphoma and may therefore be a sort of precancerous lesion. We report 3 cases of possible malignant transformation of BLL in HIV-infected patients.

Benign lymphoepithelial parotid lesions in HIV-positive patients: spectrum of findings at gray-scale and Doppler sonography.

OBJECTIVE: Benign lymphoepithelial lesions are intraparotid nodules that develop as an early manifestation of HIV infection. The purpose of this study was to describe the spectrum of sonographic and Doppler findings of benign lymphoepithelial lesions in HIV-positive patients and to assess whether these findings are specific for the diagnosis of such lesions. SUBJECTS AND METHODS: Nine HIV-positive patients with swelling of the parotid gland caused by single or multiple parotid nodules were evaluated. Fourteen nodules were identified sonographically and proved to be benign lymphoepithelial lesions at cytologic examination. They were assessed with gray-scale, duplex, color Doppler, and power Doppler sonography. For each nodule, the echogenicity, grade and pattern of vascularity, and spectral tracings were evaluated. RESULTS: Benign lymphoepithelial lesions manifested as parotid nodules with a wide spectrum of sonographic appearances, ranging from simple cysts to mixed masses with predominantly solid components. Cystic lesions (10/14) were not purely anechoic; they had an internal network of thin septa supplied by vessel pedicles and, in four of 10 cases, a solid mural nodule. On the other hand, mixed nodules (4/14) had a higher conspicuity of solid tissue and thicker stromal septa, thus resembling a parotid neoplasm more than a cyst. The overall grade of vascularity of benign lymphoepithelial lesions varied from avascular to intensely hypervascular. Generally, mixed nodules were more hypervascular than were the cystlike ones. Spectral analysis showed slow velocity (peak systolic velocity range, 8-28 cm/sec; mean, 20 20 cm/sec) and low impedance (resistive index range, 0.36-0.70; mean, 0.57) arterial flows. CONCLUSION: The spectrum of sonographic and Doppler features of benign lymphoepithelial lesions in HIV-positive patients is broad. Sonographic findings are non-specific for the diagnosis of such lesions, especially in cases of mixed solid-cystic isolated nodules.

Immunization of HIV-infected patients with rgp160: modulation of anti-rgp120 antibody spectrotype.

HIV-1 infection results in progressive failure of the immune system with decline in the number and/or function of B-cell clones originally recruited in specific humoral responses. Spectrotypic analysis, done by isoelectric focusing and reverse blotting (IEF-RB), is one technique for evaluating the activity and the number of specific B-cell clones and is adaptable to the direct measurement of antibodies to conformationally intact epitopes. The anti-HIV-1 (IIIB) rgp120 spectrotype was measured in 30 early-stage HIV-infected volunteers undergoing vaccine therapy with recombinant gp160 (rgp160). Twenty-five of the patients displayed a clear oligoclonal banding pattern; seven (28%) showed the same pattern in all samples, while 18 (72%) showed changes. Ten of the latter had an increase in band intensity over the course of immunization, and eight had an increase in both band intensity and number of bands. In contrast, serum samples from eight patients receiving placebo (alum) showed no changes over a comparable period. These findings suggest that vaccine therapy with rgp160 may be able to expand the anti-HIV-1 (LAI) gp120 B-cell clone pool in some HIV-infected patients as well as increase antibody synthesis by established B-cell clones recruited during natural infection. These data provide further evidence that postinfection vaccination may provide an alternative strategy in the treatment of chronic viral diseases.