Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

The biology of cancer: metabolic reprogramming fuels cell growth and proliferation

The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.

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Antibacterial resistance worldwide: causes, challenges and responses.

Timothy H. Dellit, Robert C. Owens, John E. McGowan, Jr., Dale N. Gerding, Robert A. Weinstein, John P. Burke, W. Charles Huskins, David L. Paterson, Neil O. Fishman, Christopher F. Carpenter, P. J. Brennan, Marianne Billeter, and Thomas M. Hooton Harborview Medical Center and the University of Washington, Seattle; Maine Medical Center, Portland; Emory University, Atlanta, Georgia; Hines Veterans Affairs Hospital and Loyola University Stritch School of Medicine, Hines, and Stroger (Cook County) Hospital and Rush University Medical Center, Chicago, Illinois; University of Utah, Salt Lake City; Mayo Clinic College of Medicine, Rochester, Minnesota; University of Pittsburgh Medical Center, Pittsburgh, and University of Pennsylvania, Philadelphia, Pennsylvania; William Beaumont Hospital, Royal Oak, Michigan; Ochsner Health System, New Orleans, Louisiana; and University of Miami, Miami, Florida

/pdf/infectious-diseases-society-of-america-and-the-society-for-34gfecer7v.pdf

Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship

https://www.cdc.gov/coronavirus/mers/downloads/Isolation2007.pdf

2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings.

OA-519 is a prognostic molecule found in tumor cells from breast cancer patients with markedly worsened prognosis. We purified OA-519 from human breast carcinoma cells, obtained its peptide sequence, and unambiguously identified it as fatty acid synthase through sequence homology and enzymology. Tumor fatty acid synthase is an approximately 270-kDa polypeptide which specifically abolished immunostaining of human breast cancers by anti-OA-519 antibodies. Tumor fatty acid synthase oxidized NADPH in a malonyl-CoA-dependent fashion and synthesized fatty acids composed of 80% palmitate, 10% myristate, and 10% stearate from acetyl-CoA, malonyl-CoA, and NADPH with a specific activity of 624 nmol of NADPH oxidized per min per mg. Tumor cell lines with elevated fatty acid synthase showed commensurate increases in incorporation of [U-14C]acetate into acylglycerols demonstrating that fatty acid synthase increases occur in the context of overall increases in endogenous fatty acid synthesis. Cerulenin inhibited acylglycerol synthesis in tumor cells and fibroblast controls in a dose-dependent fashion and also caused a growth inhibition which generally paralleled the level of endogenous fatty acid synthesis. Supraphysiologic levels of palmitate, 14 microM in dimethyl sulfoxide, significantly reversed the growth inhibition caused by cerulenin at concentrations of up to 5 micrograms/ml, indicating that cerulenin-mediated growth inhibition was due to fatty acid synthase inhibition.

https://www.pnas.org/content/pnas/91/14/6379.full.pdf

Fatty acid synthesis: a potential selective target for antineoplastic therapy

Mechanisms of latency in Mycobacterium tuberculosis

We report a case of a surgical site infection caused by clindamycin-susceptible, erythromycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) that did not respond to treatment with clindamycin. The MRSA isolate obtained after treatment was resistant to clindamycin but was found to be identical by pulsed-field gel electrophoresis to the clindamycin-susceptible isolate obtained before treatment. A post hoc erythromycin-induction test (D test) confirmed the presence of in vitro inducible macrolide-lincosamide-streptogramin B resistance (iMLS) in the pretreatment isolate. Erythromycin induction testing confirmed in vitro iMLS in 90 (56%) of 161 erythromycin-resistant, clindamycin-susceptible clinical S. aureus isolates overall and in a significantly higher proportion (78%) of methicillin-susceptible S. aureus isolates from pediatric patients. Our clinical laboratory currently tests all S. aureus isolates for iMLS before reporting clindamycin susceptibility.

/pdf/failure-of-clindamycin-treatment-of-methicillin-resistant-544a25wo1a.pdf

Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro.

Vancomycin resistance has been reported in clinical isolates of both coagulase-negative staphylococci and Staphylococcus aureus. The emerging threat of widespread vancomycin resistance poses a serious public health concern given the fact that vancomycin has long been the preferred treatment of antibiotic-resistant gram-positive organisms. Though major efforts are now being focused on improving our understanding of vancomycin resistance, there is much that remains unknown at this time. This article reviews the major epidemiologic, microbiologic, and clinical characteristics of vancomycin resistance in both coagulase-negative staphylococci and S. aureus. The review begins with a discussion of issues common to both coagulase-negative staphylococci and S. aureus, such as definitions, laboratory detection of vancomycin resistance, and infection control issues related to vancomycin-resistant staphylococci. The rest of the article is then devoted to a discussion of issues unique to each organism, including epidemiology, risk factors for infection, mechanisms of resistance, and management options.

Vancomycin Resistance in Staphylococci

Objective. —To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates. Design. —Febrile transfusion reactions were prospectively monitored over 42 months. Units involved in reactions were evaluated with Gram's stain and culture tests. Setting. —Comprehensive cancer center. Patients. —Patients receiving platelet transfusions for thrombocytopenia secondary to bone marrow failure. Result. —Seven cases of transfusion-associated sepsis were observed. Multidonor platelet products stored for 5 days resulted in an incidence of sepsis five times higher than those stored for 4 days or less ( P Conclusions. —Contamination of platelet concentrates remains a significant clinical problem. Septic episodes may be reduced by transfusion of platelets with shorter storage intervals. ( JAMA . 1991;266:555-558)

James D. Dick

Papers

Fatty acid synthesis: a potential selective target for antineoplastic therapy

Mechanisms of latency in Mycobacterium tuberculosis

Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro.

Vancomycin Resistance in Staphylococci

Septic reactions to platelet transfusions. A persistent problem.