Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

https://www.easy-immune-health.com/support-files/clin_practice_guidelines_candidiasis.pdf

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

/pdf/clinical-practice-guideline-for-the-use-of-antimicrobial-1cdrjevze2.pdf

Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

/pdf/clinical-practice-guideline-for-the-management-of-451dfbrsff.pdf

Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of immunosuppression that predisposes burn patients to infectious complications. A current summary of the classifications of burn wound infections, including their diagnosis, treatment, and prevention, is given. Early excision of the eschar has substantially decreased the incidence of invasive burn wound infection and secondary sepsis, but most deaths in severely burn-injured patients are still due to burn wound sepsis or complications due to inhalation injury. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis. The introduction of silver-impregnated devices (e.g., central lines and Foley urinary catheters) may reduce the incidence of nosocomial infections due to prolonged placement of these devices. Improved outcomes for severely burned patients have been attributed to medical advances in fluid resuscitation, nutritional support, pulmonary and burn wound care, and infection control practices.

Burn Wound Infections

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)67490-9.pdf

Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial

PF-05280014 was compared with trastuzumab sourced from the European Union (trastuzumab-EU), each plus paclitaxel, as first-line treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer in a phase III study. Equivalence between treatment groups was demonstrated.The aim of this study was to report long-term safety and overall survival (OS) over 6 years after the first patient was screened.Randomized patients received intravenous PF-05280014 or trastuzumab-EU, each plus paclitaxel, until objective disease progression. OS, long-term safety, subgroup safety (patients ongoing after day 378), and time-to-treatment discontinuation (TTD) were assessed based on the final statistical analysis plan amended for the ad-hoc analyses.Of 707 randomized patients (n = 352, PF-05280014; n = 355, trastuzumab-EU), 252 (71.6%) in the PF-05280014 and 251 (70.7%) in the trastuzumab-EU group discontinued treatment due to objective progression. Overall, 451 (63.8%) patients completed the study. Between groups (PF-05280014; trastuzumab-EU), estimated median TTDs were 12.25 and 12.06 months (p = 0.692); 61 (17.3%) and 67 (18.9%) patients died; stratified hazard ratio for OS was 0.929 (95% confidence interval 0.656-1.316; p = 0.339); estimated survival rates were 82.3 and 77.4% at 2 years and 77.2 and 75.3% at 3 years. The incidences of treatment-emergent adverse events (TEAEs) overall (98.6%; 96.6%) and for grades ≥3 (41.0%; 43.1%) were comparable between groups. In patients (n = 265; n = 264) ongoing after day 378, the incidences of any TEAEs, grade ≥3 TEAEs, and serious TEAEs were comparable between the treatment groups.Long-term safety and OS were consistent with previous results and demonstrated no clinically meaningful differences between treatment groups.ClinicalTrials.gov: NCT01989676 (21 November 2013); and EudraCT: 2013-001352-34 (18 December 2013). 

/pdf/long-term-safety-and-effectiveness-of-pf-05280014-a-1319f11r.pdf

Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study

/pdf/long-term-safety-and-effectiveness-of-pf-05280014-a-792k60tj.pdf

9088 Background: Cachexia is a multifactorial syndrome frequently associated with cancer characterized by anorexia and unintentional weight loss, including skeletal muscle loss, fatigue, functional impairment, poor quality of life, and worse survival. The objective of this post-hoc analysis was to examine the relationship between weight gain and overall survival (OS) in patients with NSCLC treated with first-line platinum-based regimens. Methods: Data were pooled from three phase 3 clinical trials (NCT00254891, NCT00254904, and NCT00596830) conducted between Nov 2005 and Mar 2011 in patients with advanced NSCLC (stage IIIB or stage IV) treated with first-line standard-of-care (SOC) chemotherapy (control arm). Weight was recorded at baseline, prior to dosing on day 1 of each 3-week treatment cycle (up to 6 cycles), and post-treatment according to each study’s schedule. Weight gain was categorized as > 0%, > 2.5%, and > 5% increase from baseline up to 4.5 months. Cox Proportional Hazards modeling of OS including time to weight gain and time to confirmed objective response (RECIST v1.0) and baseline covariates were used to estimate hazard ratios (HR) for each category. Results: The total 1,030 patients from the SOC control arms were predominantly male (70.5%) with Stage IV NSCLC (88.5%) and a mean age (SD) of 60.9 (9.4) years and BMI 24.6 (4.4) kg/m2. Overall, 486 (47.2%), 299 (29.0%), and 164 (15.9%) patients experienced weight gain from baseline of > 0%, > 2.5%, and > 5%, respectively. Median time to > 0%, > 2.5%, and > 5% weight gain was 24, 43, and 64 days, respectively. After adjusting for statistically significant time-dependent confirmed objective response, the risk of death was significantly less for patients with weight gain. For patients with > 0% vs. ≤0% weight gain, HR was 0.70 (95%CI 0.61, 0.82) with median OS of 13.6 vs. 8.3 months. For patients with > 2.5% vs. ≤2.5% weight gain, HR was 0.70 (95%CI 0.59, 0.83) with median OS of 15.3 vs. 9.1 months. For patients with > 5% vs. ≤5% weight gain, HR was 0.76 (95%CI 0.61, 0.94) with a median OS of 14.4 vs. 9.8 months. Conclusions: In this pooled analysis, weight gain during treatment with first-line platinum-based chemotherapy was associated with a significantly reduced risk of death in patients with advanced NSCLC, independent of tumor response defined by RECIST criteria. The survival benefit was comparable for > 2.5% vs. > 5% weight gain. Weight gain of 2.5% may be an earlier predictor of survival outcomes and may have implications for the design of cancer cachexia trials. Clinical trial information: NCT00254891, NCT00254904, and NCT00596830.

Evaluation of weight gain and overall survival of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.

F Hilton

Papers

Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial

Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study

Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study

Evaluation of weight gain and overall survival of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.