Infections Succumbs to Blue Light
Blue light can selectively eradicate Pseudomonas aeruginosa infections of the skin and soft tissues, while preserving the outermost layer of skin, according to a proof-of-principle study led by Michael R. Hamblin of the Massachusetts General Hospital, and the Harvard Medical School in Boston. The research is published online ahead of print in the journal Antimicrobial Agents and Chemotherapy.
"Blue light is a potential non-toxic, non-antibiotic approach for treating skin and soft tissue infections, especially those caused by antibiotic resistant pathogens," says Hamblin.
In the study, animal models were infected with P. aeruginosa. All of the animals in the group treated with blue light survived, while in the control, 82 percent (9 out of 11) of the animals died.
Skin and soft tissue infections are the second most common bacterial infections encountered in clinical practice, and represent the most common infection presentation—more than 3 percent—in patients visiting emergency departments, says Hamblin. The prevalence of skin and soft tissue infections among hospitalized patients is 10 percent, with approximately 14.2 million ambulatory care visits every year and an annual associated medical cost of almost $24 billion (equivalent to $76 for every American), says Hamblin.
Treatment of skin and soft tissue infections has been significantly complicated by the explosion of antibiotic resistance, which may bring an end to what medical scientists refer to as the antibiotic era, says Hamblin. "Microbes replicate very rapidly, and a mutation that helps a microbe survive in the presence of an antibiotic drug will quickly predominate throughout the microbial population. Recently, a dangerous new enzyme, NDM-1, that makes some bacteria resistant to almost all antibiotics available has been found in the United States. Many physicians are concerned that several infections soon may be untreatable."
Besides harming public health, antibiotic resistance boosts health care costs. "Treating resistant skin and soft tissue infections often requires the use of more expensive, or more toxic drugs, and can result in longer hospital stays for infected patients," says Hamblin.
Reference: Dai T, Gupta A, et al. 2013. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antim. Agents Chemother. Published ahead of print Dec. 21, 2012 ,doi:10.1128/AAC.01652-12)
Labels: Antibiotic resistance, blue light, enzyme, Infection, NDM-1, Pseudomonas aeruginos, skin infections, soft tissue infections, treatment
A systematic review of validation studies of the use of administrative data to identify serious infections.
Formerly a the Division of Rheumatology, Department of Medicine, University Health Network, and the Division of Health Care and Outcome Research, Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Rheumatology, Department of Medicine, University of Calgary. cehbarbe@ucalgaryca.
To conduct a systematic review of the literature on the validation of algorithms identifying infections in administrative data for future use in populations with rheumatic diseases.
Medline and Embase were searched using the themes "administrative data" and "infection", between 1950 to October 2012. Inclusion criteria: validation studies of administrative data identifying infections in adult populations. Article quality was assessed using a validated tool.
5941 articles were identified, 90 articles underwent detailed review and 24 studies were included. The majority (17/24) examined bacterial infections and nine examined opportunistic infections. Eighteen studies were from the United States and all but four studies used ICD-9 codes. Rheumatoid arthritis patients were studied in 6/24. The studies on bacterial infections in general reported highly variable sensitivity and PPV for the diagnosis of infections using administrative data (sensitivity range 4.4-100%, PPV range 21.7-100%). Algorithms to identify opportunistic infections similarly had a highly variable sensitivity (range 20-100%) and PPV (1.3-99%). Thirteen studies compared the diagnostic accuracy of different algorithms which revealed that strategies including comprehensive algorithm using a greater number of diagnostic codes or codes in any position had the highest sensitivity for the diagnosis of infection. Algorithms which incorporated microbiologic or pharmacy data in combination with diagnostic codes had improved PPV for identification of tuberculosis.
Algorithms for identifying infections using administrative data should be selected based on the purpose of the study with careful consideration as to whether a high sensitivity or PPV is required.
Labels: Infections, validation studies
The lymph index: a potential hematological parameter for viral infection.
Center of Clinical Laboratory Medicine, the Second Affiliated Hospital of Nantong University, Nantong, 226001, China.
An LH750 hematology analyzer with VCS (volume, conductivity, and light scatter) technology can determine morphologic properties of peripheral leukocytes, known as cell population data (CPD). We have previously demonstrated that the lymphocyte CPD exhibit significant changes in acute hepatitis B virus infection. A simplified lymphocyte CPD, the lymph index, was proposed. We conducted the current study to further evaluate the clinical usefulness of the lymph index, and included patients with various viral infections, as well as those with acute bacterial infections.
Peripheral blood was collected from 72 patients with viral infections, 46 patients with acute bacterial infections, and 204 controls. The lymphocyte CPD included the mean volume (LV) with its standard deviation (LV-SD) and the conductivity (LC). The lymph index was calculated as LV×LV-SD ÷ LC.
The lymph index was significantly increased in viral infections and only mildly increased in acute bacterial infections compared to controls. Using a lymph index cutoff value of ≥12.92, we achieved 91.67% sensitivity and 97.2% specificity for diagnosing viral infection.
The findings may be clinically useful since these morphological parameters are readily obtained by hematology analyzer during automated leukocyte differentials. They are quantitative, objective, and fast. The lymph index could be a potential hematological parameter for viral infection.
Labels: conductivity, CPD, LH750 hematology analyzer, light scatter, lymph index, lymphocyte, VCS, viral infection, volume
Bacteriophages and their role in food safety.
Institute for Biotechnology and Bioengineering (IBB), Centre for Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
The interest for natural antimicrobial compounds has increased due to alterations in consumer positions towards the use of chemical preservatives in foodstuff and food processing surfaces. Bacteriophages fit in the class of natural antimicrobial and their effectiveness in controlling bacterial pathogens in agro-food industry has led to the development of different phage products already approved by USFDA and USDA. The majority of these products are to be used in farm animals or animal products such as carcasses, meats and also in agricultural and horticultural products. Treatment with specific phages in the food industry can prevent the decay of products and the spread of bacterial diseases and ultimately promote safe environments in animal and plant food production, processing, and handling. This is an overview of recent work carried out with phages as tools to promote food safety, starting with a general introduction describing the prevalence of foodborne pathogens and bacteriophages and a more detailed discussion on the use of phage therapy to prevent and treat experimentally induced infections of animals against the most common foodborne pathogens, the use of phages as biocontrol agents in foods, and also their use as biosanitizers of food contact surfaces.
Labels: antimicrobial compounds, bacteriophages, biocontrol, biosanitizers, food safety, USDA, USFDA
Suggested guidelines for using systemic antimicrobials in bacterial skin infections: part 2-- antimicrobial choice, treatment regimens and compliance.
Cabinet Vétérinaire, Spa, Belgium.
Systemic antimicrobials are critically important in veterinary healthcare, and resistance is a major concern. Antimicrobial stewardship will be important in maintaining clinical efficacy by reducing the development and spread of antimicrobial resistance. Bacterial skin infections are one of the most common reasons for using systemic antimicrobials in dogs and cats. Appropriate management of these infections is, therefore, crucial in any policy for responsible antimicrobial use. The goals of therapy are to confirm that an infection is present, identify the causative bacteria, select the most appropriate antimicrobial, ensure that the infection is treated correctly, and to identify and manage any underlying conditions. This is the second of two articles that provide evidence-led guidelines to help practitioners address these issues. Part 1 discussed the use of clinical signs, cytology and culture in diagnosis. This article will cover the rationale for topical and systemic antimicrobial therapy, including choice of first-, second- and third-line drugs, the dose, duration of therapy, compliance and identification of underlying predisposing conditions. In addition, there is guidance on cases of therapeutic failure and environmental hygiene. These guidelines will help veterinarians avoid the development and propagation of antimicrobial-resistant bacterial strains.
Labels: antimicrobial choice, bacterial skin infections, systemic antimicrobials, treatment regimen
Suggested guidelines for using systemic antimicrobials in bacterial skin infections: part 1--diagnosis based on clinical presentation, cytology and culture.
Cabinet Vétérinaire, Spa, Belgium.
Systemic antimicrobials are critically important in veterinary healthcare, and resistance is a major concern. Antimicrobial stewardship will be important in maintaining clinical efficacy by reducing the development and spread of antimicrobial resistance. Bacterial skin infections are one of the most common reasons for using systemic antimicrobials in dogs and cats.
Appropriate management of these infections is, therefore, crucial in any policy for responsible antimicrobial use. The goals of therapy are to confirm that an infection is present, identify the causative bacteria, select the most appropriate antimicrobial, ensure that the infection is treated correctly, and to identify and manage any underlying conditions. This is the first of two articles that will provide evidence-led guidelines to help practitioners address these issues. This article covers diagnosis, including descriptions of the different clinical presentations of surface, superficial and deep bacterial skin infections, how to perform and interpret cytology, and how to best use bacterial culture and sensitivity testing.
Part 2 will discuss therapy, including choice of drug and treatment regimens.
Labels: bacterial skin infections, systemic antimicrobials
Growth Factor: How Bacterial Infections Persist Through Antibiotics
By Katherine Harmon | Scientific American
Some strains of nasty bacterial infections, such as MRSA (methicillin-resistant Staphylococcus aureus), come loaded with resistance to antibiotics built right into their genes. But certain infections seem to acquire an ability to persist in the face of drugs that should knock them out--without developing the genetic hallmarks of antibiotic resistance. For decades, researchers have thought this holdout occurred because many antibiotics target cell growth, so even though most of the bacteria were killed by the drug, a select group simply shut down, going into a sort of hibernation, thereby allowing the infection to persist. In other words: if the bacteria aren't growing, they're also not dying.
But a new study suggests that quite the opposite is occurring: some surviving bacteria are actually flourishing and multiplying while under antibiotic attack. The findings were published online January 3 in Science.
"We thought that surviving bacteria made up a fixed population that stopped dividing," Neeraj Dhar, of the Swiss Federal Institute of Technology in Lausanne and study co-author, said in a prepared statement. Instead, a stable overall population was hiding a "very dynamic" colony, he said.
The researchers studied Mycobacterium smegmatis, a species closely related to the bacterium that causes tuberculosis (Mycobacterium tuberculosis), which often resists antibiotic treatment and remains a major health threat in many countries. The traditional analysis of a persistent culture of these bacteria would reveal that the population was not growing, which is what had led scientists to think that the colony had been reduced to non-proliferating "persister cells" that could better ride out the antibiotic attack by laying low. But using time-lapse images taken through a microscope of cells in a microfluidic culture (allowing study of small-scale changes), the researchers saw quite a different story.
"Using microfluidics, we can now observe every bacterium individually, instead of having to count a population," John McKinney, also of the Swiss Federal Institute of Technology, said in a prepared statement. Not only were the surviving cells not playing dead, they were just as likely to be growing as cells that died off.
McKinney and his team observed that even after the introduction of an antibiotic and the death of most bacterial cells, a large percentage of the so-called persister cells continuing to divide--129 of 153 progenitor cells they followed divided at least once in the face of antibiotic treatment. And this cycle of growth, division and death kept up for at least 10 days of exposure to the antibiotic.
The antibiotic was isoniazid (known by the drug names Laniazid and Nydrazid), which has been a common first-line treatment for tuberculosis. This antibiotic becomes an activated bacterium killer when it comes into contact with an enzyme called KatG that the bacteria produces. The enzyme, however, was not produced consistently, the researchers found. Instead, individual cells generated it in seemingly random spurts. So the cells that happened to have had pauses in their KatG production at just the right time were often able to avoid activating the antibiotic--and thus were saved from certain death.
Tuberculosis cells that should have been essentially identical, genetically, showed different propensities for survival, pointing to a possible role of epigenetic differences (such as those in gene expression) in determining cell survival. "This diversity is critical for microbial persistence in fluctuating environments because it ensures that some individuals may survive a lethal stress that would otherwise extinguish the population," the researchers explained in their paper.
Because cell survival does not seem to be tied to permanent genetic change in this case, it means the bacterial colony should remain susceptible to future antibiotic treatment, which could be good news for treating infections. However, given the low level of continued growth and change during exposure to antibiotics, "the bacteria can mutate and thus develop resistance in the presence of the antibiotic," Dhar said.
This discovery now paints a clearer picture of how antibiotic resistance can develop in persistent bacterial infections. With so many individual bacteria reproducing, "some of them can adapt to stressors that they have not previously encountered, thanks to the selection of persistent individuals," McKinney said. Such findings could help inform the creation of more effective antibiotics and perhaps expand to other illnesses, such as the persistence of cancer cells, although the researchers acknowledge that the persistence behavior of other bacterial infections might be quite different.
Nevertheless, the insights offer "a new approach for trying to figure out why some infections are so difficult to eliminate," McKinney said.
Labels: antibiotics, bacterial infections, Laniazid, methicillin-resistant Staphylococcus aureus, MRSA, Mycobacterium tuberculosis, Nydrazid, persister cells