Statin Therapy and Decreased Incidence of Positive Candida Cultures Among Patients With Type 2 Diabetes Mellitus Undergoing Gastrointestinal Surgery

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OBJECTIVE

To assess whether statin therapy decreases the incidence of cultures positive for Candida species among high-risk hospitalized patients with type 2 diabetes mellitus (DM).

PATIENTS AND METHODS

We performed a retrospective cohort study analyzing the records of all patients with type 2 DM who were admitted to Massachusetts General Hospital for lower gastrointestinal tract surgery between January 1, 2001, and May 1, 2008. We defined statin exposure as the filling of at least 1 prescription of statins during the 6 months before hospitalization or during the current hospital stay. The primary outcome was a culture positive for Candida species during hospitalization. Clinical information on a wide range of covariates was collected. Logistic regression analysis was used to adjust for possible confounders.

RESULTS

Of the 1019 patients who were eligible for the study, 493 (48%) were receiving statins. A total of 139 patients (14%) had at least 1 culture positive for Candida species during hospitalization. An adjusted multivariate model based on a backward stepwise elimination procedure showed that statin therapy significantly decreased the incidence of cultures positive for Candida species (odds ratio, 0.60; 95% confidence interval [CI], 0.38-0.96; P=.03) with a statistically significant prolonged time to event compared with no statin therapy (adjusted hazard ratio, 0.62; 95% CI, 0.44-0.88; P=.01). The benefit of statins was more prominent in patients with type 2 DM who had greater comorbidities (Charlson Comorbidity Index ≥2) (adjusted odds ratio, 0.47; 95% CI, 0.27-0.79; P=.01).

CONCLUSION

Among patients with type 2 DM who underwent gastrointestinal surgery, use of statins correlated with a decreased incidence of cultures positive for Candida species.

Antifungal activity of statins against Aspergillus species

Content Source – National Institutes for Health

The cholesterol-lowering agents known as statins have in vitro activities against human pathogenic fungi, such as Candida species, Cryptococcus neoformans, and Zygomycetes. Synergy between statins and azoles against these fungi has also been reported. We evaluated the in vitro activities of two statins, lovastatin and simvastatin, alone and in combination with azoles and amphotericin B, against clinical isolates of Aspergillus spp. A disk diffusion assay showed that both statins were active against Aspergillus spp. The minimal inhibitory concentration (MIC) ranges for lovastatin and simvastatin against Aspergillus spp. were 16 to >256 microg/ml and 4 to >256 microg/ml, respectively. Although both statins were fungicidal for A. fumigatus, the MICs were vastly higher than clinically achievable concentrations. The results of a combined agar dilution-Epsilometer test as well as a disk diffusion assay showed that neither statin had any effect on the in vitro activities of itraconazole, voriconazole, or amphotericin B against Aspergillus spp.

Blurred Lines: Aspergillosis Mimicking Metastatic Lung Cancer

Invasive Aspergillosis Mimicking Metastatic Lung Cancer

In a patient with a medical history of cancer, the most probable diagnosis of an 18FDG avid pulmonary mass combined with intracranial abnormalities on brain imaging is metastasized cancer. However, sometimes a differential diagnosis with an infectious cause such as aspergillosis can be very challenging as both cancer and infection are sometimes difficult to distinguish.

Pulmonary aspergillosis can present as an infectious pseudotumour with clinical and imaging characteristics mimicking lung cancer. Even in the presence of cerebral lesions, radiological appearance of abscesses can look like brain metastasis. These similarities can cause significant diagnostic difficulties with a subsequent therapeutic delay and a potential adverse outcome.

Awareness of this infectious disease that can mimic lung cancer, even in an immunocompetent patient, is important. We report a case of a 65-year-old woman with pulmonary aspergillosis disseminated to the brain mimicking metastatic lung cancer.

PDF: Invasive Aspergillosis Mimicking Metastatic Lung Cancer

Blurred Lines-Pulmonary Aspergillosis and Lung Cancer

[18F]Fluorodexyglucose (FDG) positron emission tomography (PET) scans have significantly improved the diagnosis and staging of lung cancer, but false-positive scans are known to occur due to inflammatory and infectious diseases.

Recognition of the conditions leading to false-positive scans is important. Single or multiple pulmonary nodules, with or without cavitation, are classical findings in acute and chronic pulmonary aspergillosis. Clinical features of pulmonary aspergillosis are very similar to those of lung cancer.

This report highlights pulmonary aspergillosis as an alternative diagnosis to lung cancer in patients with positive [18F] FDG PET scans and the need to strive for presurgical histological diagnosis.

PDF: Pulmonary Aspergillus & Lung Cancer

Fungal Genome Initiative-Aspergillus Genome Projects

PROJECT BACKGROUND

Perhaps no other fungal genus contains species that are so harmful and species that are so beneficial to humans as the genus Aspergillus (1), and a large number of Aspergillus species are of biomedical and industrial significance. For example, A. nidulans is a key fungal model system for genetics and cell biology (2, 3), A. niger is widely exploited by the fermentation industry for the production of citric acid, whereas A. oryzae plays a key role in the fermentation process of several traditional Japanese beverages and sauces (4). In contrast, A. flavus is a plant and animal pathogen that also produces the potent carcinogen aflatoxin (5), whereas several other species (most notably A. fumigatus and A. terreus) are important opportunistic pathogens of individuals with compromised immune systems (6).

The genome sequences of A. nidulans (7), A. fumigatus (6) and A. oryzae (4) represented an enormous advance in the study of Aspergillus, providing the foundation for comparative and functional genomics studies. As part of the Fungal Genome Initiative, we have sequenced and annotated an additional Aspergillus species, A. terreus. Four additional recently sequenced genomes also fall within this phylogenetic group: A. flavusA. nigerA. clavatus, and Neosartorya fischeri. The profoundly different lifestyles exhibited by each of this growing set of Aspergillus species for which genome sequences are available coupled with the varying degrees of evolutionary affinity shared by their genomes make Aspergillus a model clade to address fundamental questions in functional and comparative genomics.

References

1. Volk, T., (1997) Aspergillus in Fungus of the Month, http://botit.botany.wisc.edu/toms_fungi/feb97.html
2. Pontecorvo, G., Roper, J. A., Hemmons, L. M., Macdonald, K. D. and Bufton, A. W. (1953) The genetics of Aspergillus nidulans. Adv. Genet. 5, 141-238.
3. Morris, N. R. and Enos, A. P. (1992) Mitotic gold in a mold: Aspergillus genetics and the biology of mitosis. Trends Genet. 8, 32-37.
4. Machida, M. et al. (2005) Genome sequencing and analysis of Aspergillus oryzae. Nature 438, 1157-1161.
5. Payne, G. A. et al. (2006) Whole genome comparison of Aspergillus flavus and A. oryzae. Med. Mycol. 44 Suppl, 9-11.
6. Nierman, W. C. et al. (2005) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438, 1151-1156.
7. Galagan, J. E. et al. (2005) Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438, 1105-1115.

Advances in citric acid fermentation by Aspergillus niger: Biochemical aspects, membrane transport and modeling

Research Review Paper

Maria Papagianni ⁎
Department of Hygiene and Technology of Food of Animal Origin, School of Veterinary Medicine, Aristotle University of Thessaloniki,
54006 Thessaloniki, Greece
Received 8 October 2006; received in revised form 11 January 2007; accepted 11 January 2007
Available online 19 January 2007

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Citric acid is regarded as a metabolite of energy metabolism, of which the concentration will rise to appreciable amounts only under conditions of substantive metabolic imbalances. Citric acid fermentation conditions were established during the 1930s and 1940s, when the effects of various medium components were evaluated.

The biochemical mechanism by which Aspergillus niger accumulates citric acid has continued to attract interest even though its commercial production by fermentation has been established for decades. Although extensive basic biochemical research has been carried out with A. niger, the understanding of the events relevant for citric acid accumulation is not completely understood. This review is focused on citric acid fermentation by A. niger.

Emphasis is given to aspects of fermentation biochemistry, membrane transport in A. niger and modeling of the production process.

© 2007 Elsevier Inc. All rights reserved.

PDF: Advances in citric acid fermentation by Aspergillus niger: Biochemical aspects, membrane transport and modeling

Additional reading-PDF: Comparative genomics of citric-acid-producing
Aspergillus niger ATCC 1015 versus enzyme-producing
CBS 513.88