Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients.

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Aerosolized ribavirin: the most expensive drug for pneumonia.

Dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. We highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.

Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center.

PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.

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.

Vaccination guidelines after hematopoietic stem cell transplantation: practitioners' knowledge, attitudes, and gap between guidelines and clinical practice.

BACKGROUND: Hematopoietic stem cell transplant (HCT) recipients are more susceptible to infections from vaccine-preventable diseases than the general population. Despite the development of international consensus guidelines addressing immunization after HCT, studies have shown that deviations from recommended immunization practices commonly occur. METHODS: An anonymous survey aimed at determining awareness of the guidelines and attitudes toward vaccination was distributed to our HCT clinicians. In parallel, we retrospectively evaluated patients' characteristics and post-HCT vaccine administration practices from 2010 to 2013. RESULTS: The majority of survey respondents (96%) were familiar with post-HCT vaccination protocols. Seventy-four percent of respondents reported that influenza vaccines were given to >70% of their patients, and 41% stated that they prescribed live vaccines to eligible patients. However, our pharmacy database review revealed that 38% of patients received the first series of vaccinations by the recommended 6 months post HCT, and 60% received them by 1 year after HCT. Most patients who had their vaccines withheld had relapsed disease or were undergoing treatment for graft-versus-host disease. Furthermore, we identified lower immunization rates in non-English speaking individuals, African-Americans, and Hispanic patients. CONCLUSIONS: Survey respondents reported being aware of current guidelines; however, adherence to the recommendations varied, likely connected to conflicting data on vaccine effectiveness and a lack of clear recommendations in complex clinical scenarios. Similar to the general population, patient barriers also could have contributed to lower vaccination rates in some cases. To decrease the large gap between the post-HCT vaccination guidelines and clinical practice, further studies on vaccine effectiveness and specific populations are warranted.

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.

Utility of galactomannan enzyme immunoassay and (1,3) beta-D-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients.

Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.

Anti-adherence activity and antimicrobial durability of anti-infective-coated catheters against multidrug-resistant bacteria.

OBJECTIVES: To investigate the anti-adherence and antimicrobial durability of anti-infective catheters against multidrug-resistant (MDR) Staphylococcus aureus (resistant to vancomycin, rifampicin and methicillin) and MDR Gram-negative bacteria (Stenotrophomonas maltophilia, Acinetobacter baumannii/calcoaceticus and Enterobacter agglomerans) that are often associated with catheter-related bloodstream infections (CRBSIs). METHODS: Catheters impregnated with minocycline and rifampicin (M/R) or with silver-platinum and carbon (SPC) or with chlorhexidine and silver sulfadiazine (CHX/SS) were compared with non-coated catheters. Adherence of organisms was tested by using an established biofilm colonization model. All isolates were rifampicin-resistant. Antimicrobial durability was tested by soaking 1 cm segments of the catheter in serum and determining zones of inhibition against the tested organisms at weekly intervals. RESULTS: The M/R catheters showed significantly superior anti-adherence activity and more prolonged antimicrobial durability when compared with CHX/SS-central venous catheter (CVC), SPC-CVC and uncoated control catheters against MDR and vancomycin-resistant S. aureus (MDR VRSA) (all P values < or = 0.02), MDR S. maltophilia (all P values < 0.005) and MDR A. baumannii/calcoaceticus (all P values < 0.002), respectively. M/R-CVC and CHX/SS-CVC had comparable anti-adherence and antimicrobial durability against MDR E. agglomerans, and these two were superior to SPC-CVC and the uncoated control catheters (all P values < 0.001). CONCLUSIONS: M/R-CVC demonstrated superior anti-adherence activity and more prolonged antimicrobial durability when compared with other approved anti-infective catheters against MDR VRSA and/or MDR Gram-negative bacteria that are often associated with CRBSIs. This finding could explain their efficacy and better performance in clinical studies.

The role of vitamin B6 in the prevention of haematological toxic effects of linezolid in patients with cancer.

BACKGROUND: Linezolid is the first approved synthetic oxazolidinone with activity against multidrug-resistant gram-positive pathogens. However, haematological toxic effects of linezolid frequently limit its prolonged use, especially in patients with poor marrow reserves such as those with cancer receiving chemotherapy. Previous authors have reported that administration of vitamin B6 with linezolid reversed pancytopenia in two patients. METHODS: This is an open-label study of 31 patients with cancer who received linezolid at 600 mg twice daily and vitamin B6 at 50 mg/day for at least 2 weeks mean therapy duration and they were matched to 62 control patients who received linezolid without vitamin B6 to determine whether the concomitant use of vitamin B6 attenuates the haematological toxicity of linezolid in patients with cancer. RESULTS: Patients were matched according to age, underlying disease, duration of therapy, creatinine level and use of chemotherapy. We found no significant differences in the rate of haematological toxic effects between the two patient groups. The rate of thrombocytopenia was 13% in the vitamin B6 group and 15% in the control group (P = 0.82). Also, the rate of leucopenia was 7% versus 5%, respectively (P = 0.75). None of the patients in the vitamin B6 group had anaemia compared with 5% in the control group. CONCLUSIONS: Vitamin B6 given at 50 mg/day may have an impact on anaemia but did not prevent linezolid-induced thrombocytopenia or leucopenia in cancer patients.

Fistula Following Laparoscopic Sleeve Gastrectomy: a Proposed Classification and Algorithm for Optimal Management.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an accepted restrictive procedure with a hormonal component. There is no definitive course of treatment for post-LSG fistula; it remains a feared complication. We aimed to classify post-LSG fistulas and propose an algorithm to optimize their treatment. METHODS: Following primary and revisional LSG in obese patients, a retrospective observational study of fistulas was undertaken. Radiological studies were performed to identify anatomically distinct types of fistulas. An algorithm was elaborated for the classification and evolving treatment of each type of fistula. RESULTS: Twenty post-LSG fistulas were studied (13 [2.5%] from our center, 7 referred) with a mean body mass index of 43.1 ± 10.2 kg/m2 (32.0-76.0) and mean age of 33.1 ± 11.4 years (20.0-56.0). In all cases, the clinically suspected diagnosis was radiologically confirmed by water-soluble upper gastrointestinal series and double-contrast abdomino-pelvic CT scan. Three anatomical fistula types were characterized: type I, a small leak with no collection; type II, a leak with associated intra-abdominal abscess; and type III, a leak with multiple internal or external abscesses, a complex fistula. In accord with our algorithm, patients without sepsis received conservative treatment initially; this was sufficient for type I leaks. Type II abscesses received internal or external percutaneous drainage, and in some cases, stenting or endoprosthesis. Surgery was reserved for failure of conservative options and type III fistula. In cases of sepsis, surgery was mandatory. CONCLUSION: A radiologically defined, anatomically based classification system and treatment algorithm proved effective in clinical management of post-LSG fistula.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Risk factors associated with late cytomegalovirus reactivation after allogeneic stem cell transplantation for hematological malignancies.

We analyzed the clinical factors associated with late cytomegalovirus (CMV) reactivation in a group of 269 consecutive recipients of allogeneic stem cell transplant (SCT) for hematological malignancies. Eighty-four subjects (31%) experienced late CMV reactivation, including 64 with prior early reactivation and 20 with isolated late reactivation. Multivariate analyses were conducted in patients with early CMV reactivation to identify factors associated with late recurrence. Important risk factors included lymphoid diagnosis, occurrence of graft-versus-host disease (GVHD), greater number of episodes of early reactivation, persistent day 100 lymphopenia and the use of a CMV-seronegative donor graft. We combined these risk factors in a predictive model to identify those at relatively low, intermediate and high risk. The low-risk group (15% cumulative incidence, CI) encompassed patients without early CMV reactivation, and subjects transplanted for a myeloid malignancy from a matched-related (MR) donor without subsequent acute GVHD. The high-risk patients (73% CI) met all of the following criteria: (1) received an MR graft but developed GVHD, or received a non-MR graft irrespective of GVHD; (2) had more than two episodes of early reactivation; and (3) received a CMV-seronegative graft and/or remained persistently lymphopenic at day 100 after SCT. The remaining patients had an intermediate incidence of 32%.

Outcomes for and risk factors associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium bacteremia in cancer patients.

OBJECTIVE: Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR) Enterococcus faecalis bacteremia and VR Enterococcus faecium bacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes. METHODS: We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VR E. faecalis bacteremia and were matched with 32 patients with VR E. faecium bacteremia and 32 control patients. A retrospective review of medical records was conducted. RESULTS: Logistic regression analysis showed that, compared with VR E. faecalis bacteremia, VR E. faecium bacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98]; P=.046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3]; P=.004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8]; P=.09). Compared with control patients, patients with VR E. faecalis bacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6]; P=.03), whereas patients with VR E. faecium bacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6]; P<.001). In a multivariate model that compared patients with VR E. faecium bacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2]; P=.004) and VR E. faecium bacteremia (OR, 11 [95% CI, 2.7-45.1]; P<.001). No difference in outcomes was found between patients with VR E. faecalis bacteremia and control patients. CONCLUSIONS: VR E. faecium bacteremia in cancer patients was associated with a poorer outcome than was VR E. faecalis bacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VR E. faecium bacteremia, and recent receipt of aminoglycoside therapy was independent risk factor for E. faecalis bacteremia.

Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review.

This study reviewed retrospectively the clinical characteristics of 28 cancer patients with fungal osteoarticular infections (FOAIs) between 1995 and 2005. Most patients (26; 93%) had haematological malignancies (19 had leukaemia); half (14) were allogeneic stem-cell transplant recipients. Twelve patients (43%) had severe neutropenia (< or = 100/mm3) with a mean duration of 65 days (range 10-500 days), and ten (36%) patients had received a significant dose of corticosteroids. Most (19; 68%) FOAIs were caused by contiguous extension, while nine (32%) were associated with haematogenous spread. Pain, joint instability and local drainage were seen in 28 (100%), six (21%), and seven (25%) patients, respectively. Sixteen (57%) patients had symptoms for < 1 month. The sinuses (ten; 36%) and the vertebral spine (six; 21%) were the most common sites involved. Moulds were the predominant pathogens: Aspergillus fumigatus (two); non-fumigatus Aspergillus spp. (eight); non-specified Aspergillus spp. (three); Fusarium spp. (six); Zygomycetes (five); Scedosporium apiospermum (two); and Exserohilum sp. (one). Candida was the causative pathogen in four cases (including two cases of mixed FOAIs). Arthritis and post-operative FOAIs were both uncommon manifestations, occurring in two patients each. All patients received systemic antifungal therapy (combinations in 20 cases), and 19 cases underwent adjunctive surgery. The crude mortality rates (at 12 weeks) were 44% (9/20) in the patients who underwent surgery and antifungal therapy vs. 33% (2/6) in patients who received antifungal therapy alone (p not significant). FOAI is a rare, yet severe, manifestation of localised or systemic mycoses, caused predominantly by moulds, and is seen typically in patients with haematological malignancies.

Current drug therapy for multiple myeloma.

Recent years have witnessed tremendous advances in the molecular pathogenesis and management of multiple myeloma. Standard chemotherapy (melphalan and prednisone; MP) has been the mainstay of treatment of multiple myeloma for about 3 decades. However, it is no longer considered the 'gold standard', particularly for those patients who will subsequently undergo intensive chemotherapy with autologous or allogeneic peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT), or for patients with refractory myeloma. A variety of induction combination chemotherapy regimens have been developed, some of which have demonstrated an improved response rate and duration and a superior 5-year survival rate when compared with standard chemotherapy. The early use of high dose chemotherapy with autologous PBSC support or BMT has significantly increased the complete remission rate, and has prolonged event-free sur vival and overall survival. Allogeneic bone marrow or PBSC transplantation may be a good option for selected patients with poor prognostic features. The role of interferon-alpha in multiple myeloma is still inconclusive despite many years of clinical evaluation. The clinical application of chemosensitising agents that can inhibit P-glycoprotein (P-gp) expression and function, and particularly the development of more potent P-gp modulators such as valspodar (PSC 833) and elacridar (GF120918) has made it possible to reverse multidrug resistance in some refractory patients and to enhance the efficacy of chemotherapeutic agents. Immunotherapeutic approaches to purging of autologous bone marrow or PBSC, or as adjuvant therapy for minimal residual disease, show great promise. Finally, a number of new therapies specifically designed to treat many of the complications of multiple myeloma are improving clinical outcomes and quality of life for these patients.

[Frontal pseudo-tumoral form of adrenoleukodystrophy]. / Adrénoleucodystrophie à forme frontale pseudo-tumorale.

A case of adrenoleukodystrophy in a 9-year old boy revealed by a predominant frontal syndrome is reported. Brain MRI showed an unusual pseudo-tumoral frontal lesion. The diagnosis was confirmed by increased plasma levels of very long chain fatty acids. His young brother had an isolated adrenal insufficiency with normal brain MRI. The frontal predominance of the lesion and the clinical polymorphism of the disease in this family are discussed.

[Trichinosis and cerebral sinocavernous thrombosis]. / Trichinose et occlusions sino-veineuses cérébrales.

The authors report a case of sino-venous thrombosis occurring in the course of trichinella infection in a 43 year-old man. MRI and angio-MRI showed a right rolandic haemorrhagic infarct and thrombosis of the superior sagittal and left lateral sinuses. Sino-venous thrombosis in such infection appears to be extremely rare. We found 4 reported cases which we compared to the present case. The findings of sino-venous thrombosis in relation with neurotrichinosis is examined.