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Risk factors for refractory febrile neutropenia in urological chemotherapy.

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Risk factors for refractory febrile neutropenia in urological chemotherapy.

J Infect Chemother. 2013 Apr;19(2):211-6

Authors: Yasufuku T, Shigemura K, Tanaka K, Arakawa S, Miyake H, Fujisawa M

Abstract
During chemotherapy, patients are more susceptible to infectious complications as a result of bone marrow suppression, leading to neutropenia. The purpose of this study is to investigate risk factors for refractory febrile neutropenia (FN) during urological chemotherapy. Our method for suppressing FN is to use granulocyte colony-stimulating factor and prevent upper respiratory infection by masking and gargling. We studied 47 episodes of FN in 39 patients that occurred during urological chemotherapy for urothelial cancer, testicular cancer, and prostate cancer. Among our cases, there were 5 patients with refractory FN; we set risk factors for refractory FN and performed statistical analyses. The average age of the 39 patients was 60.6 years (range, 18-80 years). In 47 FN episodes, the chemotherapy regimen before the occurrence of FN included 15 (31.9 %) MVAC (methotrexate, vinblastine, adriamycin, cisplatin) for urothelial cancer, 5 (10.6 %) DE (docetaxel, estramustin) for prostate cancer, and 3 (6.4 %) TIP (paclitaxel, ifosfamide, cisplatin) for testicular cancer. The antibiotics used to treat FN included 17 (36.3 %) meropenem and 23 (49.0 %) cefepime, and the average duration of antibiotics was 4.4 days (range, 1-12). We investigated risk factors for refractory FN and showed a significant relationship between refractory FN and indwelling urinary catheter or smaller Multinational Association for Supportive Care in Cancer score by multivariate analysis. A future prospective study is needed for further evaluation for risk factors and establishing treatment protocols and guidelines for FN.

PMID: 23011233 [PubMed – indexed for MEDLINE]

Oral status of patients submitted to autologous hematopoietic stem cell transplantation.

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Oral status of patients submitted to autologous hematopoietic stem cell transplantation.

Support Care Cancer. 2014 Jan;22(1):15-21

Authors: Fernandes LL, Torres SR, Garnica M, de Souza Gonçalves L, Junior AS, de Vasconcellos ÁC, Cavalcanti W, Maiolino A, de Barros Torres MC

Abstract
PURPOSE: Oral infection may be a source of bacteremia in patients undergoing hematopoietic stem cell transplant (HSCT). The aim of this study was to evaluate the relationship between patients with poor periodontal status and complications after HSCT.
METHODS: A cohort of patients with hematological malignancies candidates for autologous HSCT was observed before and during the neutropenic phase of HSCT. A primary evaluation was performed before the HSCT procedure, including medical and socio-demographic data and physical examination (number of teeth and decayed, missing and filled teeth index (DMFT), oral mucosa, and full mouth periodontal assessment). During the neutropenic phase, data regarding the development of febrile neutropenia, bacteremia, and mucositis were also prospectively obtained.
RESULTS: Forty-eight patients were included. The most common baseline disease was multiple myeloma (70 %). In the primary evaluations, the median DMFT was 13 (ranging 0-27), and periodontitis and gingivitis were present in 29 and 60 % of the patients, respectively. During the neutropenic phase of HSCT, fever occurred in 96 % of patients, and bacteremia was documented in 29 %. Coagulase-negative Staphylococcus was the most common isolated bacteria. Patients who developed bacteremia had a higher frequency of oral disorders compared with those without bacteremia, but it was not statistically significant. Oral mucositis affected 89.6 % of the patients, and patients with gingivitis or periodontal disorders had a high frequency of mucositis.
CONCLUSIONS: The prevalence of oral pathologic conditions previous to HSCT procedures was very high in the studied population. A possible association was noted between previous gingivitis and the development of mucositis during the neutropenia of HSCT.

PMID: 23975228 [PubMed – indexed for MEDLINE]

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]

Excavated pneumonia: an unusual suspect.

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Excavated pneumonia: an unusual suspect.
Intensive Care Med. 2013 Jul;39(7):1318-9
Authors: Bellesoeur A, Chalumeau-Lemoine L, Blot F
PMID: 23571870 [PubMed – indexed for MEDLINE]