Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin, and C-reactive protein.

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Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin, and C-reactive protein.

Support Care Cancer. 2014 Jan;22(1):269-77

Authors: Kitanovski L, Jazbec J, Hojker S, Derganc M

Abstract
PURPOSE: In febrile neutropenia (FN), no reliable marker has been identified to discriminate between severe infection and other causes of fever early in the clinical course. Since lipopolysaccharide-binding protein (LBP) has proven to be an accurate biomarker of bacteremia/clinical sepsis in critically ill non-immunocompromised infants and children, we performed a prospective study to determine the diagnostic accuracy of LBP in children with FN.
METHODS: Concentrations of LBP, procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) were prospectively measured on two consecutive days in 90 FN episodes experienced by 47 children. Receiver operating characteristic curve analysis was performed for each biomarker to predict bacteremia/clinical sepsis and severe sepsis.
RESULTS: Eighteen of the 90 episodes were classified as bacteremia/clinical sepsis. On both days 1 and 2, all biomarkers had a low to intermediate diagnostic accuracy for sepsis, and no significant differences were found between them (area under the curve (AUC) for LBP, 0.648 and 0.714; for PCT, 0.665 and 0.744; for IL-6, 0.775 and 0.775; and for CRP, 0.695 and 0.828). Comparison of their AUCs to the AUC of maximum body temperature on admission (AUC = 0.668) also failed to show any significant differences. In severe sepsis, however, the best diagnostic accuracies were found for IL-6 and PCT (AUC 0.892 and 0.752, respectively), and these were significantly higher than those for LBP (AUC 0.566) on admission.
CONCLUSIONS: On admission and 24 h later, the LBP concentration is less accurate for predicting bacteremia/clinical sepsis compared to IL-6, PCT, and CRP.

PMID: 24057110 [PubMed – indexed for MEDLINE]

Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia.

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Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia.

Cochrane Database Syst Rev. 2014 Feb 24;2:CD004707

Authors: Jørgensen KJ, Gøtzsche PC, Dalbøge CS, Johansen HK

Abstract
BACKGROUND: Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.
OBJECTIVES: To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.
SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.
SELECTION CRITERIA: Randomised clinical trials comparing voriconazole with amphotericin B or fluconazole.
DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.
MAIN RESULTS: Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors’ prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.
AUTHORS’ CONCLUSIONS: Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.

PMID: 24563222 [PubMed – as supplied by publisher]

Polymorphisms in Tumor Necrosis Factor-α Increase Susceptibility to Intra-Abdominal Candida Infection in High-Risk Surgical ICU Patients*

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Polymorphisms in Tumor Necrosis Factor-α Increase Susceptibility to Intra-Abdominal Candida Infection in High-Risk Surgical ICU Patients*

Crit Care Med. 2014 Feb 19;

Authors: Wójtowicz A, Tissot F, Lamoth F, Orasch C, Eggimann P, Siegemund M, Zimmerli S, Flueckiger UM, Bille J, Calandra T, Marchetti O, Bochud PY, and the Fungal Infection Network of Switzerland (FUNGINOS)

Abstract
OBJECTIVES:: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients.
DESIGN:: Prospective observational cohort study.
SETTING:: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland.
PATIENTS:: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis).
MEASUREMENTS AND MAIN RESULTS:: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient’s DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined «heavy» colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p = 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008).
CONCLUSION:: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.

PMID: 24557424 [PubMed – as supplied by publisher]

Evaluation of treatment of invasive fungal infections.

Evaluation of treatment of invasive fungal infections.

J Pharmacol Pharmacother. 2014 1;5(1):47-52

Authors: Casucci I, Provenzani A, Polidori P

Abstract
OBJECTIVE: To identify the risk factors associated with invasive fungal infections (IFI) in immunocompromised patients (IP), and monitor antifungal therapy appropriateness and costs.
MATERIALS AND METHODS: The 1-year observational retrospective study was performed on 101 IP, who received antifungal intravenous therapy with fluconazole (F), liposomal amphotericin-B (A), caspofungin (C), itraconazole (I) for ≥4 days. Patient therapy was divided into three groups: Prophylactic, empirical, and target. Immunosuppressive therapy (IT), total parenteral nutrition (TPN), dialysis, central line, steroid therapy, stent use, neutropenia, and mechanical ventilation were evaluated. Variables were therapy duration, defined daily dose (DDD) consumption, DDD average cost.
RESULTS: Main risk factors were central line (65.3%), TPN (56.4%), dialysis (46.5%), IT (42.6%), mechanical ventilation (32.7%), neutropenia (24.8%), steroid therapy (23.8%), and stent use (14.9%). Average duration of prophylaxis was 7 days; F (61%), A (26%), and C (13%) were used. Average duration of empirical therapy was 8 days; F (52.9%), A (26.5%), C (8.8%), I (2.9%), and in association A + C, A + F, C + F (8.9%) were used. Average duration of target therapy was 9 days; F (40.4%), A (23.1%), C (15.4%), I (7.7%), and in association A + C, A + F, C + F (13.4%) were used. DDD consumption and DDD average-cost were: C 50 mg vial: 273 DDD, €381.1; C 70 mg vial: 33.6 DDD, €389.6; F 200 mg vial: 768 DDD, €11.8; F 100 mg vial: 89 DDD, €10.6; I 250 mg vials: 62.5 DDD, €68.8; and A 50 mg vial: 2200 DDD, €93.4; respectively.
CONCLUSIONS: Data showed an appropriate use of antifungals. Best alternative therapy (cheaper antifungal drug) was prescribed for most patients. The high cost of A and C was justified by IFI resolution.

PMID: 24554910 [PubMed – as supplied by publisher]

MSG-01: A randomized, double-blind, placebo controlled trial of caspofungin prophylaxis followed by pre-emptive therapy for invasive candidiasis in high-risk adults in the critical care setting.

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MSG-01: A randomized, double-blind, placebo controlled trial of caspofungin prophylaxis followed by pre-emptive therapy for invasive candidiasis in high-risk adults in the critical care setting.

Clin Infect Dis. 2014 Feb 18;

Authors: Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA, Schuster M, Judson MA, Revankar SG, Caeiro JP, Mangino JE, Mushatt D, Bedimo R, Freifeld A, Nguyen MH, Kauffman CA, Dismukes WE, Westfall AO, Deerman JB, Wood C, Sobel JD, Pappas PG

Abstract
Background. Invasive candidiasis is the 3rd most common bloodstream infection in the ICU and is associated with morbidity and mortality. Prophylaxis and pre-emptive therapy are attractive strategies for this setting. Methods. We conducted a multicenter, randomized, double-blind, placebo controlled trial of caspofungin vs. placebo as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had one additional risk factor: parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other Immunosuppressants. (1,3)-β-D-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive pre-emptive therapy with caspofungin. The pre-emptive approach analysis included patients all patients who received study drug, including those positive at baseline. Results. For prophylaxis, the incidence of proven or probable invasive candidiasis in the placebo vs. caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively (p= 0.14). For the pre-emptive approach analysis it was 30.4% (31/102) and 18.8% (22/117), respectively (p= 0.04), however this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. Conclusion. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis but the difference was not statistically significant. A pre-emptive therapy approach deserves further study.

PMID: 24550378 [PubMed – as supplied by publisher]

ESCMID & ECMM Joint Guidelines on Diagnosis and Management of Hyalohyphomycosis: Fusarium spp, Scedosporium spp, and others.

ESCMID & ECMM Joint Guidelines on Diagnosis and Management of Hyalohyphomycosis: Fusarium spp, Scedosporium spp, and others.

Clin Microbiol Infect. 2014 Feb 19;

Authors: Tortorano AM, Richardson M, Roilides E, van Diepeningen A, Caira M, Munoz P, Johnson E, Meletiadis J, Pana ZD, Lackner M, Verweij P, Freiberger T, Cornely OA, Arikan-Akdagli S, Dannaoui E, Groll AH, Lagrou K, Chakrabarti A, Lanternier F, Pagano L, Skiada A, Akova M, Arendrup MC, Boekhout T, Chowdhary A, Cuenca-Estrella M, Guinea J, Guarro J, de Hoog S, Hope W, Kathuria S, Lortholary O, Meis JF, Ullmann AJ, Petrikkos G, Lass-Flörl C

Abstract
Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation. This article is protected by copyright. All rights reserved.

PMID: 24548001 [PubMed – as supplied by publisher]

Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

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Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

J Chemother. 2014 Feb 18;:1973947814Y0000000164

Authors: Hawser S, Hoban DJ, Badal RE, Bouchillon SK, Biedenbach D, Hackel M, Morrissey I

Abstract
The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25 746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≧48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16·5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.

PMID: 24548089 [PubMed – as supplied by publisher]