Activity of anidulafungin in a murine model of Candida krusei infection: evaluation of mortality and disease burden by quantitative tissue cultures and measurement of serum (1,3)-beta-D-glucan levels.

Experience with anidulafungin against Candida krusei is limited. Immunosuppressed mice were injected with 1.3 x 10(7) to 1.5 x 10(7) CFU of C. krusei. Animals were treated with saline, 40 mg/kg fluconazole, 1 mg/kg amphotericin B, or 10 and 20 mg/kg anidulafungin for 5 days. Anidulafungin improved survival and significantly reduced the number of CFU/g in kidneys and serum beta-glucan levels

Rationale and Methods of the Study Protocol: Streptococcus pneumoniae Serotypes in Adults 18 Years and Older with Radiographically-Confirmed Community-Acquired Pneumonia (CAP)

This study was an active, prospective surveillance study of adults 18 years and older hospitalized with community-acquired pneumonia (CAP) due to Streptococcus pneumoniae conducted at 21 hospitals in ten cities across the United States. This report describes the surveillance methodology applied between October 7, 2013 and September 30, 2016, including the identification and description of surveillance areas and populations at-risk for CAP hospitalization for estimation of incidence rates for selected study sites

Post-operative Aspergillus mediastinitis in a man who was immunocompetent: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Aspergillus </it>spp. infections mainly affect patients who are immunocompromised, and are extremely rare in immunocompetent individuals.</p> <p>Case presentation</p> <p><it>Aspergillus </it>post-operative mediastinitis is considered to be a devastating infection, usually affecting patients undergoing cardiothoracic surgery with specific predisposing factors. We describe the case of an immunocompetent 68-year-old Caucasian man with severe chronic thromboembolic pulmonary hypertension, who underwent pulmonary thromboendarterectomy and developed post-operative mediastinitis due to <it>Aspergillus flavus</it>. The environmental control did not reveal the source of <it>A. flavus </it>infection and, despite combined antifungal therapy, our patient died as a result of septic shock and multiple organ failure.</p> <p>Conclusion</p> <p><it>Aspergillus </it>mediastinitis mainly affects patients after cardiosurgery operations with predisposing factors, and it is unusual in patients who are immunocompetent. The identification of the <it>Aspergillus </it>spp. source is often difficult, and there are no guidelines for the administration of pre-emptive therapy in this population of at-risk patients.</p

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BACKGROUND: Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. METHODS: This observational, prospective surveillance study recruited hospitalized adults aged \u3e /=18years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. RESULTS: Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1years and 52.7% were aged \u3e /=65years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged \u3e /=65years. Among patients aged 18-64years PCV13 serotypes were detected in 3.8-5.3% of patients depending on their risk status. CONCLUSIONS: After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population

Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases.

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities

Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

Introduction: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).Objective: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.Design: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.Methods: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.Results: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score >= 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.Conclusions: the cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.Pfizer Inc.Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Med, Mexico City, DF, MexicoHosp Escuela Tegucigalpa, Tegucigalpa, HondurasUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilNatl Canc Inst, Div Infect Dis, Mexico City, DF, MexicoUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruHosp Vargas Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Texas Med Sch Houston, Mem Hermann Texas Med Ctr, Dept Med, Houston, TX USAUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilUniv Chile, Fac Med, Hosp Luis Calvo Mackenna, Dept Pediat, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Santiago, ChileHosp Clin Jose San Martin, Infect Dis Unit, Buenos Aires, DF, ArgentinaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilPfizer Inc.: INF-168Web of Scienc

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients

Background: Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods: A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was >= 1: 160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results: Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions: This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.This study has been supported by a Pfizer research gran

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Candidiasis caused by Candida kefyr in a neonate: Case report

<p>Abstract</p> <p>Background</p> <p>Systemic <it>Candidia </it>infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic <it>Candida </it>infection. We report a very rare case of candidiasis caused by <it>Candida kefyr </it>in a term neonate.</p> <p>Case Presentation</p> <p>Renal agenesis on the left side was diagnosed antenatally and anal atresia postnatally. Moreover, a vesico-ureteral-reflux (VUR) grade V was detected by cystography. The first surgical procedure, creating a protective colostoma, was uneventful. Afterwards our patient developed urosepsis caused by <it>Enterococcus faecalis </it>and was treated with piperacillin. The child improved initially, but deteriorated again. A further urine analysis revealed <it>Candida kefyr </it>in a significant number. As antibiotic resistance data about this non-<it>albicans Candida </it>species are limited, we started liposomal amphotericin B (AMB), but later changed to fluconazole after receiving the antibiogram. Candiduria persisted and abdominal imaging showed a <it>Candida </it>pyelonephritis. Since high grade reflux was prevalent we instilled AMB into the child's bladder as a therapeutic approach. While undergoing surgery (creating a neo-rectum) a recto-vesical fistula could be shown and subsequently was resected. The child recovered completely under systemic fluconazole therapy over 3 months.</p> <p>Conclusions</p> <p>Candidiasis is still of major concern in neonates with accompanying risk factors. As clinicians are confronted with an increasing number of non-<it>albicans Candida </it>species, knowledge about these pathogens and their sensitivities is of major importance.</p