Epidemiology and outcome of bacteraemia in neutropenic patients in a single institution from 1991-2012.

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Epidemiology and outcome of bacteraemia in neutropenic patients in a single institution from 1991-2012.

Epidemiol Infect. 2014 Jun 30;:1-7

Authors: Ortega M, Marco F, Soriano A, Almela M, Martínez JA, Rovira M, Esteve J, Mensa J

Abstract
SUMMARY This study was part of a bloodstream infection surveillance programme that prospectively collected data on consecutive patients with bacteraemia in our institution from 1991 to 2012. We included 2092 bacteraemias in neutropenic patients. Shock and mortality accounted for 299 and 349 cases, respectively (14% and 17%). The main microorganisms isolated were coagulase-negative staphylococci (CoNS, 634, 30%), Escherichia coli (468, 22%) and Pseudomonas aeruginosa (235, 11%). During 2006-2012, there were 155 (27%) E. coli isolates; of these, 73% were fluoroquinolone resistant and 26% cefotaxime resistant. The independent risk factors for mortality were shock on presentation, rapidly fatal prognosis of underlying disease, corticosteroid use, and polymicrobial bacteraemia. Factors associated with lower mortality were the isolation of CoNS [odds ratio (OR) 0·38, 95% confidence interval (CI) 0·20-0·73, P = 0·004] and empirical therapy with amikacin (OR 0·50, 95% CI 0·29-0·88, P = 0·016). The progressive increase of Gram-negative microorganisms resistant to antibiotics influences the choice of empirical treatment in febrile neutropenia and in our experience, the addition of amikacin could be beneficial for such patients.

PMID: 24977667 [PubMed – as supplied by publisher]

The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

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The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

MBio. 2013;4(6):e00723-13

Authors: Douglas LM, Wang HX, Konopka JB

Abstract
UNLABELLED: Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis.
IMPORTANCE: The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane contributes to virulence, we analyzed a set of eight genes encoding MARVEL family proteins that are predicted to function in membrane organization. Interestingly, deletion of one gene, NCE102, caused a strong defect in formation of invasive hyphal growth in vitro and decreased virulence in mice. The nce102Δ mutant cells showed defects in actin organization that underlie the morphogenesis defect, since mutation of a known regulator of actin organization caused a similar defect. These studies identify a novel way in which the plasma membrane regulates the actin cytoskeleton and contributes to pathogenesis.

PMID: 24281718 [PubMed – indexed for MEDLINE]

Presence of Candida cell wall derived polysaccharides in the sera of intensive care unit patients: relation with candidaemia and Candida colonisation.

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Presence of Candida cell wall derived polysaccharides in the sera of intensive care unit patients: relation with candidaemia and Candida colonisation.

Crit Care. 2014 Jun 29;18(3):R135

Authors: Poissy J, Sendid B, Damiens S, Ichi Ishibashi K, François N, Kauv M, Favory R, Mathieu D, Poulain D

Abstract
INTRODUCTION: Prompt diagnosis of candidaemia and invasive candidosis is crucial to the early initiation of antifungal therapy. The poor sensitivity of blood cultures (BCs) has led to the development of fungal glycan tests as a diagnostic adjunct. We analysed the performance of tests for the detection of circulating beta-D-1,3-glucan (BDG) and mannan in the intensive care unit (ICU) setting.
METHODS: This retrospective, case-control study included 43 ICU patients with candidaemia and 67 controls, hospitalised on the same ward and assessed weekly for yeast colonisation with simultaneous serum sampling; 340 sera taken before and after positive BCs were available for the cases group and 203 for the controls. BDG and mannan levels were determined using the Fungitell(R) and Platelia TM Candida Ag tests, respectively.
RESULTS: BDG was detected early in sera from cases patients but was also present in several sera from controls. Increasing the cut-off from 80 pg/mL to 350 pg/mL and 800 pg/mL resulted in sensitivity/specificity ratios of 0.97/0.31, 0.65/0.74, 0.30/0.86, respectively. Detection of mannan was more specific but lacked sensitivity. No obvious correlation was found between BDG and colonisation, but a trend existed between high colonisation and high BDG. Candidaemia relapses were associated with a rise in BDG and mannan but, in contrast to the transient nature of mannan, BDG persisted up to 7 weeks after positive BCs.
CONCLUSION: A combination of mannan and BDG tests could be used to guide pre-emptive therapeutic decisions in ICU patients.

PMID: 24975380 [PubMed – as supplied by publisher]

Variation in Resource Utilization for the Management of Uncomplicated Community-Acquired Pneumonia across Community and Children’s Hospitals.

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Variation in Resource Utilization for the Management of Uncomplicated Community-Acquired Pneumonia across Community and Children’s Hospitals.

J Pediatr. 2014 Jun 25;

Authors: Leyenaar JK, Lagu T, Shieh MS, Pekow PS, Lindenauer PK

Abstract
OBJECTIVE: To describe patterns of diagnostic testing and antibiotic management of uncomplicated pneumonia in general community hospitals and children’s hospitals within hospitals and to determine the association between diagnostic testing and length of hospital stay.
STUDY DESIGN: We conducted a retrospective cohort study of children 1-17 years of age hospitalized with the diagnosis of pneumonia from 2007 to 2010 to hospitals contributing data to Perspective Database Warehouse, assessing patterns of diagnostic testing and antibiotic management. We constructed logistic regression models of log-transformed length of stay (LOS) and grouped treatment models to ascertain whether performance of blood cultures and viral respiratory testing were associated with LOS.
RESULTS: A total of 17 299 pneumonia cases occurred at 125 hospitals, with considerable variability in pneumonia management. Only 40 (0.2%) received ampicillin/penicillin G alone or in combination with other antibiotics, and 1318 (7.4%) received macrolide monotherapy as initial antibiotic management. Performance of blood culture and testing for respiratory viruses was associated with a statistically significant longer LOS, but these differences did not persist in grouped treatment models.
CONCLUSIONS: We observed greater rates of diagnostic testing in this cohort of structurally diverse hospitals than previously reported at freestanding children’s hospitals, with extremely low rates of narrow-spectrum antibiotic use. Tailored antibiotic stewardship initiatives at these hospitals are needed to achieve adherence to national guideline recommendations.

PMID: 24973795 [PubMed – as supplied by publisher]

Prevention of meticillin-resistant Staphylococcus aureus bloodstream infections in European hospitals: moving beyond policies.

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Prevention of meticillin-resistant Staphylococcus aureus bloodstream infections in European hospitals: moving beyond policies.
J Hosp Infect. 2014 Jun 5;
Authors: Borg MA, Hulscher M, Scicluna EA, R…

[Adequacy of antifungal agents in a teaching hospital: Too many inappropriate prescriptions despite training.]

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[Adequacy of antifungal agents in a teaching hospital: Too many inappropriate prescriptions despite training.]

Presse Med. 2014 Jun 24;

Authors: Fabien L, Foroni L, Brion JP, Maubon D, Stahl JP, Pavese P

Abstract
OBJECTIVES: The aim of this study was to assess adequacy and conformity of systemic antifungal drugs prescriptions in comparison with local, French, European and international recent guidelines in the Grenoble Teaching Hospital.
METHODS: Each prescription of itraconazole, liposomal amphotericin B, voriconazole, caspofungin, micafungin, posaconazole and anidulafungin made between February and October 2010 were reviewed by an infectious diseases specialist. Fluconazole prescriptions’ were reviewed only for 15 days.
RESULTS: Two hundred and eight patients received 295 systemic antifungal prescriptions. Most of them had at least one risk factor and immunodeficiency was one of the most common. Antifungal treatment starting, molecules choice, administrations conformity (dosage, administration way) were appropriate in 126 cases on 208 (60.5 %) at the treatment beginning evaluation and in 171 cases on 295 (58 %) at the treatment ending evaluation. Antifungal combinations (9.4 %) were less frequent than in the study carried out in Grenoble teaching hospital in 2007 (16.3 %). Most common non-conformities encountered were use of caspofungin instead of fluconazole, antifungal combinations prescription, administration modalities misguiding. The economy that could have been generated by appropriate prescriptions represented 18 % of the antifungal budget of 2010 in the Grenoble Teaching Hospital.
CONCLUSION: An improvement was highlighted in the antifungal prescriptions in comparison to the previous study led in 2007 in the Universitary Grenoble Hospital. However, the antifungal use was not optimal and further training is planned.

PMID: 24972851 [PubMed – as supplied by publisher]