Lior Nesher

Cytomegalovirus diseases after hematopoietic stem cell transplantation: A mini-review

Cytomegalovirus (CMV) infection remains a significant complication after hematopoietic stem cell transplantation (HSCT) and may have a deleterious impact on the overall outcome after transplantation. In addition to the direct effects of CMV infection, tissue-invasive CMV diseases may be associated with increased risk of graft versus host disease, myelosuppression, and invasive bacterial and fungal infections. Because of these direct and indirect adverse effects, prevention of CMV infection, mostly through pre-emptive therapy, is one of the essential strategies that may improve outcomes of HSCT recipients. Management of CMV infection relies mainly on intravenous (IV) antiviral therapy with ganciclovir and foscarnet, with or without IV polyclonal immunoglobulins. Although viral resistance remains rare, better tolerated antiviral agents with less serious side effects are needed, and a few will be evaluated in phase III clinical trials in the near future.

Neutropenic Enterocolitis, a Growing Concern in the Era of Widespread Use of Aggressive Chemotherapy

Neutropenic enterocolitis (NEC) is a life-threatening disease with substantial morbidity and mortality, seen primarily in patients with hematologic malignancies. The frequency of NEC has increased with the widespread use of chemotherapeutic agents such as the taxanes, which cause severe gastrointestinal mucositis. Neutropenic patients with fever and abdominal symptoms (cramping, pain, distention, diarrhea, GI bleeding), should undergo evaluation of the abdomen for bowel wall thickening of >4 mm, the hallmark of NEC. Clostridium difficile infection should be ruled out, as well as other etiologies such as graft-versus-host disease. Complications include bacteremia, which is often polymicrobial, hemorrhage, and bowel wall perforation/abscess formation. Management includes bowel rest, correction of cytopathies and coagulopathies, and broad spectrum antibiotics and antifungal agents. Surgical intervention may be necessary to manage complications such as hemorrhage and perforation and should be delayed, if possible, until recovery from neutropenia.

Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections

We developed an immunodeficiency scoring index for respiratory syncytial virus (ISI-RSV) infection, based on a cohort of 237 allogeneic hematopoietic cell transplant (allo-HCT) recipients, that can predict the risk of progression to lower respiratory tract infection (LRTI) and RSV-associated mortality. A weighted index was calculated using adjusted hazard ratios for immunodeficiency markers. Based on the ISI-RSV (range, 0-12), patients were stratified into low (0-2), moderate (3-6), and high (7-12) risk groups. A significant trend of increasing incidence of LRTI and RSV-associated mortality was observed as the risk increased from low to moderate to high (P < .001). Patients in the high-risk group had the greatest benefit of ribavirin-based therapy at the upper respiratory tract infection stage and the highest risk for progression to LRTI and death when antiviral therapy was not given (6.5 [95% confidence interval (CI), 1.8-23.6] and 8.1 [95% CI, 1.1-57.6], respectively). The ISI-RSV is designed to stratify allo-HCT recipients with RSV infection into groups according to their risk for progression to LRTI and RSV-associated mortality. Identification of high-risk groups using this index would distinguish patients who would benefit the most from antiviral therapy, mainly with aerosolized ribavirin. The ISI-RSV should be validated in a multi-institutional study.

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

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.

Utility of the Enzyme-Linked Immunospot Interferon-γ–Release Assay to Predict the Risk of Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients

The ability to distinguish allogeneic hematopoietic cell transplant (allo-HCT) recipients at risk for cytomegalovirus (CMV) reactivation from those who are not is central for optimal CMV management strategies. Interferon γ (IFN-γ) produced by CMV-challenged T cells may serve as an immune marker differentiating these 2 populations. We prospectively monitored 63 CMV-seropositive allo-HCT recipients with a CMV-specific enzyme-linked immunospot (ELISPOT) assay and for CMV infection from the period before transplantation to day 100 after transplantation. Assay results above certain thresholds (50 spots per 250 000 cells for immediate early 1 or 100 spots per 250 000 cells for phosphoprotein 65) identified patients who were protected against CMV infection as long as they had no graft-versus-host disease and/or were not receiving systemic corticosteroids. Based on the multivariable Cox proportional hazards regression model, the only significant factor for preventing CMV reactivation was a CMV-specific ELISPOT response above the determined thresholds (adjusted hazard ratio, 0.21; 95% confidence interval, .05–.97; P = .046). Use of this assay as an additional tool for managing allo-HCT recipients at risk for CMV reactivation needs further validation in future studies. Application of this new approach may reduce the duration and intensity of CMV monitoring and the duration of prophylaxis or treatment with antiviral agents in those who have achieved CMV-specific immune reconstitution.

Toxic Hepatitis Induced by Gymnema sylvestre, a Natural Remedy for Type 2 Diabetes Mellitus

Toxic hepatitis or drug-induced liver injury (DILI) encompasses a spectrum of conditions ranging from mild biochemical abnormalities to acute liver failure. Recent studies report that 35% to 48% of patients with diabetes use some form of complementary and alternative medical therapy. Moreover, >800 plants have been traditionally used for the treatment of diabetes. Despite this widespread use, only few were supported by rigorous clinical evidence. Gymnema sylvestre, also known as gurmar (sugar destroyer in Hindi), is a plant considered to be with potent antidiabetic effects and, hence, widely used in folk, ayurvedic and homeopathic systems in medicine. The authors were unable to find previous reports associating G sylvestre to liver injury. Herein, the authors report a case of DILI in a patient who was treated with G sylvestre for diabetes mellitus and review the literature to suggest possible mechanisms that led to this acute condition.

Left spontaneous pneumothorax presenting with ST-segment elevations: A case report and review of the literature

Common electrocardiogram (ECG) changes associated with left-sided pneumothorax include right axis deviation, reduced R-wave amplitude in precordial leads, QRS alterations (amplitude changes), and T-wave inversions. Few reports exist of ST-segment elevations or changes suggestive of acute myocardial infarction (AMI), and these involve older patients with tension pneumothorax and previous coronary heart disease. We report on a young man with no significant medical history, presenting with left-sided spontaneous pneumothorax and ECG changes that included ST-segment elevations and T-wave inversions in the precordial leads, reminiscent of AMI. All changes resolved after decompression of the pneumothorax. On the basis of the patients presenting symptoms, response to therapy, and our review of the literature, we propose a number of possible mechanisms explaining his electrocardiographic findings.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

In vitro activity of telavancin compared with vancomycin and linezolid against gram-positive organisms isolated from cancer patients

Telavancin is a dual action, bactericidal lipoglycopeptide. Its in vitro activity was compared with vancomycin and linezolid against 392 Gram-positive isolates from cancer patients. MIC90 values (μg ml−1) for telavancin, vancomycin and linezolid were determined for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible (MS), methicillin-resistant (MR), coagulase-negative staphylococci (CoNS), viridans group streptococci (VGS), Streptococcus pneumoniae, Bacillus species, Corynebacterium species and Micrococcus species. Telavancin had potent activity against β-hemolytic streptococci and Staphylococcus lugdunensis. Whereas 100% of MRSA and 98% of MSSA had vancomycin MICs ⩾1.0 μg ml−1 (minimum inhibitory concentrations (MICs) at which poor clinical responses have been reported), the highest telavancin MIC was 0.38 μg ml−1. For CoNS, 95% of MS and 100% of MR isolates had vancomycin MICs ⩾1.0 μg ml−1, whereas the highest telavancin MIC was 0.38 μg ml−1. Furthermore, 48% of VGS had vancomycin MICs ⩾1.0 μg ml−1, whereas the highest telavancin MIC was 0.064 μg ml−1. A similar pattern was noticed for S. lugdunensis, Bacillus species, Corynebacterium species and β-hemolytic streptococci. These data suggest that telavancin and linezolid have potent activity against most Gram-positive organisms that cause infections in cancer patients. Consequently, they may be considered as alternatives to vancomycin, especially in institutions wherein a substantial proportion of infections are caused by organisms with vancomycin MICs ⩾1.0 μg ml−1.

In vitro activity of dalbavancin and five comparator agents against common and uncommon Gram-positive organisms isolated from cancer patients

Dalbavancin is a long acting, bactericidal lipoglycopeptide. Its in vitro activity was compared with that of vancomycin, daptomycin, linezolid, trimethoprim/sulfamethoxazole (TMP/SMX) and levofloxacin against 241 Gram-positive organisms isolated from cancer patients. The rank order of potency for the glycopeptides based on MIC90 (μg ml−1), that is, the concentration of antimicrobial agent required to inhibit 90% of isolates tested was dalbavancin (0.12 μg ml−1)>daptomycin (1.0 μg ml−1)>vancomycin (2.0 μg ml−1) for coagulase-negative staphylococci and Staphylococcus aureus isolates (including methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains). Dalbavancin had potent activity against staphylococcal isolates with vancomycin MICs⩾1.0 μg ml−1. TMP/SMX also had potent activity against staphylococci including methicillin-resistant strains, whereas levofloxacin had moderate to poor anti-staphylococcal activity. Dalbavancin also exhibited more potent activity than vancomycin and daptomycin against Bacillus spp., Corynebacterium spp., Micrococcus spp. and various streptococci (including Streptococcus pneumoniae, viridans group streptococci (VGS), beta-hemolytic streptococci and gamma-hemolytic streptococci). MBC determinations showed that dalbavancin had potent bactericidal activity against MRSA with no tolerance being detected. These data suggest that dalbavancin may be considered as an alternative to vancomycin, especially in institutions wherein a substantial proportion of infections are caused by organisms with vancomycin MICs⩾1.0 μg ml−1.