Samantha Jacobs

Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens.

With increased use of expanded‐spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer‐Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post‐IFI mortality. All patients received antifungal prophylaxis. Fifty‐three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft‐versus‐host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g−1 dl−1 increase in albumin). The 90‐day mortality rate after IFI was 57%. Non‐cytomegalovirus systemic viral co‐infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

Human rhinovirus infections of the lower respiratory tract in hematopoietic stem cell transplant recipients.

Human rhinoviruses (HRVs) are a common cause of upper respiratory infection (URI) in hematopoietic stem cell transplant (HSCT) recipients; yet, their role in lower respiratory illness is not well understood.

Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT.

Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy

Abstract Background Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. Objectives This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. Study design From April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. Results One hundred and ten HM patients presented with HRV URTI (n =78) and HRV LRTI (n =32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0–9.2; p =0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. Conclusions HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.

Successful Treatment of Allergic Bronchopulmonary Aspergillosis With Isavuconazole: Case Report and Review of the Literature

Abstract Isavuconazole is a new triazole that is approved for primary therapy of invasive aspergillosis. We provide the first report of a patient with allergic bronchopulmonary aspergillosis (ABPA) who was successfully treated with isavuconazole with marked improvement and minimal adverse effects. We further review the literature on antifungal management of ABPA.

The Brief Case: Disseminated Mycobacterium haemophilum Infection in a Kidney Transplant Recipient

CASE A65-year-old woman from Thailand was hospitalized in May 2016 with fevers and rash. The patient had end-stage renal disease and hypertension and received a deceased-donor kidney transplant in 2009. The induction immunosuppression agent was rabbit anti-thymocyte globulin, and she took tacrolimus and mycophenolate mofetil for maintenance immunosuppression. The patient was diagnosed with polymorphic, Epstein-Barr virus-positive posttransplant lymphoproliferative disorder (PTLD) of the central nervous system 5 weeks prior to admission. She completed two doses (375 mg/m2 each) of rituximab with dexamethasone (10 to 24 mg/day in divided doses), and mycophenolate mofetil was discontinued after the PTLD diagnosis. On physical examination, the patient was ill appearing but alert and oriented. Her temperature was 38°C. The right eye conjunctiva was injected with nodular conjunctival lesions. On skin examination, there were erythematous papules, some with central pustules, on the forehead, face, neck, arms, anterior thighs, knees, and lower back (Fig. 1A). Human immunodeficiency virus antibody and tuberculosis gamma interferon release assays were performed, and both were negative. A computed tomography scan of the chest demonstrated several bilateral subcentimeter pulmonary nodules in the lower lobes and lingula. Skin biopsies were performed on the right arm, cheek, and thigh, and the samples were sent for histopathologic examination and bacterial, fungal, and mycobacterial cultures. Histopathology revealed a superficial and granulomatous reaction with a neutrophilic infiltrate involving the dermis and subcutaneous fat (Fig. 1C). Numerous acid-fast bacilli (AFB) were visualized after staining with Fite-Faraco stain (Fig. 1D). Rare AFB were observed by acid-fast fluorescent staining of tissue submitted to the clinical microbiology laboratory, and a portion of the specimen was inoculated onto chocolate agar and incubated at 30°C. Imipenem, azithromycin, levofloxacin, isoniazid, pyrazinamide, and ethambutol were administered as empirical therapy for rapidly growing mycobacterial species (Mycobacterium chelonae/Mycobacterium abscessus group and Mycobacterium fortuitum group), slowly growing mycobacterial species (Mycobacterium haemophilum and Mycobacterium marinum) that are often associated with skin lesions, and Mycobacterium tuberculosis. Aminoglycosides and rifamycins were initially avoided, given the potential for nephrotoxicity and drug interaction with tacrolimus, respectively. Two weeks after the skin biopsy, mycobacterial cultures demonstrated no growth. The skin lesions had progressed to extensive erythematous plaques and yellow/black crust covering the forehead, cheeks, both arms, and thighs. Painful ulcerations develCitation Jacobs SE, Zhong E, Hartono C, Satlin MJ, Magro CM, Jenkins SG, Westblade LF. 2018. The Brief Case: Disseminated Mycobacterium haemophilum infection in a kidney transplant recipient. J Clin Microbiol 56:e00561-17. https://doi.org/10.1128/JCM.00561-17. Editor Carey-Ann D. Burnham, Washington University School of Medicine Copyright

Preoperative Nutritional Status as a Risk Factor for Major Postoperative Complications Following Anterior Lumbar Interbody Fusion

Study Design: Retrospective study. Objectives: To determine rates of medical and surgical postoperative complications in adults with hypoalbuminemia undergoing anterior lumbar interbody fusion (ALIF). Methods: This was a retrospective analysis of prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database of patients (≥18 years old) undergoing ALIF procedures, identified by CPT (Current Procedural Terminology) code from 2011 to 2014. Poor nutritional status was defined by a preoperative serum albumin level <3.5 g/dL, and albumin levels above this were considered normal. Multivariate logistic regression models were utilized to assess preoperative risk factors including nutritional status as predictors of specific postoperative complications. Significance was defined as P < .05 and odds ratios (ORs) were calculated with a 95% confidence interval (CI). This model was used to determine the strength of nutritional status as an adjusted predictor of adverse postoperative events. Results: There were 3184 ALIF cases, including 1,275 (40%) of which had preoperative serum albumin levels. 53 (4.15%) patients were classified as having poor nutrition status. Poor preoperative nutritional status was shown to be a strong independent predictor of length of stay ≥5 days (OR = 2.56, 95% CI 1.43-4.59, P = .002), urinary tract infection (OR = 5.93, 95% CI 2.11-16.68, P = .001), and sepsis (OR = 5.35, 95% CI 1.13-25.42, P = .035) compared to patients with normal preoperative serum albumin levels. Conclusions: Our analysis shows that patients with poor nutritional status before ALIF are independently at risk for sepsis as well as increased length of stay and urinary tract infection.

Risk Factors for Perioperative Complications in Morbidly Obese Patients Undergoing Elective Posterior Lumbar Fusion

Study Design: Retrospective cohort study. Objectives: The prevalence of obesity-related low back pain and degenerative disc disease is on the rise. Past studies have demonstrated that obesity is associated with higher perioperative complication rates, but there remains a gap in the literature regarding additional risk factors that further predispose this already high-risk patient population to poor surgical outcomes following elective posterior lumbar fusion (PLF). The aim of the study is to identify independent risk factors for poor 30-day perioperative outcomes in morbidly obese patients undergoing elective PLF. Methods: We identified 22 909 patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent elective PLF. There were 1861 morbidly obese patients. Baseline patient demographics and medical comorbidities were collected. Univariate analysis was performed to compare perioperative complication rates between non-morbidly obese and morbidly obese patients. The 5 most common complications in the morbidly obese group were then selected for multivariate regression analysis to identify independent risk factors for poor 30-day outcomes. Results: Morbidly obese patients had a higher perioperative complication rate. The 5 most common complications were prolonged hospitalization, blood transfusion, readmission, wound complications, and reoperation. Independent risk factors for these complications were age ≥65 years, super obesity (ie, BMI > 48.6), chronic steroid use, American Society of Anesthesiology classification ≥3, poor functional status, long length of fusion ≥4 levels, and extended operative time (ie, operative time ≥318 minutes). Conclusions: Morbidly obese patients are at higher risk of perioperative complications following elective PLF. Modifiable risk factors for the most common complications are obesity and preoperative steroid use.

Colonization With Levofloxacin-resistant Extended-spectrum β-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients

Background Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. Results We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. Conclusions HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Orphan drugs for the treatment of aspergillosis: focus on isavuconazole

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