Long-Term Antibiotic Use May Up Women's Odds for Heart Trouble

Antibiotics can be lifesaving, but using them over a long period might raise the odds of heart disease and stroke in older women, a new study suggests.

Researchers tracked the health of nearly 36,500 U.S. women over an average follow-up of nearly eight years. During that time, more than a thousand developed heart disease.

The study found that women aged 60 and older who used antibiotics for two months or longer were 32% percent more likely to develop heart disease than those who did not use antibiotics.

Women aged 40 to 59 who took antibiotics for longer than two months had a 28% higher risk than those who did not take the drugs, said a team led by Lu Qi. He directs the Tulane University Obesity Research Center in New Orleans.

Said another way, the results mean that for older women who take antibiotics for two months or more, 6 per 1,000 would go on to develop heart disease, compared with 3 in 1,000 among those who did not take the drugs.

There was no increased risk of heart disease among women aged 20 to 39 who took antibiotics, according to the study published April 24 in the European Heart Journal.

"This is an observational study and so it cannot show that antibiotics cause heart disease and stroke, only that there is a link between them," Qi said in a journal news release. "It's possible that women who reported more antibiotic use might be sicker in other ways that we were unable to measure, or there may be other factors that could affect the results that we have not been able take account of."

However, the researchers did take into account other factors, including age, race, sex, diet and lifestyle, reasons for antibiotic use, overweight or obesity, other diseases and medication use.

The most common reasons for antibiotic use among women in the study were respiratory infections, urinary tract infections and dental problems.

So what could be the link between antibiotics and heart risk?

One possible reason could lie in the fact that antibiotics do alter the balance of gut microbes, destroying good bacteria and increasing the proportion of viruses, bacteria or other microbes that can cause disease, Qi suggested.

"Antibiotic use is the most critical factor in altering the balance of microorganisms in the gut," he said, and "previous studies have shown a link between alterations in the microbiotic environment of the gut and inflammation and narrowing of the blood vessels, stroke and heart disease."

Study first author Yoriko Heianza is a research fellow at Tulane University. She noted that, as the women in the study aged, "they were more likely to need more antibiotics, and sometimes for longer periods of time, which suggests a cumulative effect may be the reason for the stronger link in older age between antibiotic use and cardiovascular disease."

According to Qi, the take-home message from the new study is that "antibiotics should be used only when they are absolutely needed. Considering the potentially cumulative adverse effects, the shorter time of antibiotic use, the better."

Dr. Eugenia Gianos directs Women's Heart Health at Lenox Hill Hospital in New York City. She wasn't involved in the new research, but said the findings are "interesting and warrant further analysis."

Gianos agreed that the study couldn't prove cause and effect. "It is very possible that patients who require antibiotics for an infection have a worse underlying infectious or inflammatory process, and that the systemic effects of these diseases are what cause cardiovascular disease," she reasoned.

But the interplay between antibiotics, the gut's "microbiome" and the cardiovascular system could be important as well, Gianos said.

Long-Term Antibiotic Use May Up Women's Odds for Heart Trouble 

New type of antibiotic kills multidrug-resistant germ common to health care settings

A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.

The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.

The pathogen (germ) - called Acinetobacter - can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary cathetersor patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.

In the study in today's Journal of Infectious Diseases, PPMOs  peptide-conjugated phosphorodiamidate morpholino oligomer, (link for PMOs only) designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.

"We set out to target specific genes in Acinetobacter in an effort to inhibit the bacterium-s growth," said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. "With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development."

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.

"We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria," said Dr. Greenberg.

New type of antibiotic kills multidrug-resistant germ common to health care settings

Azithromycin can be effective treatment option for patients with BOS

In continuation of my update on azithromycin

Azithromycin can be effective treatment option for patients with BOS: Researchers in the United Kingdom have determined that azithromycin, a broad-spectrum antibiotic that also has anti-inflammatory properties, can be an effective treatment option for patients suffering from bronchiolitis obliterans syndrome (BOS), a life-threatening complication that occurs in the majority of patients following lung transplantation.

New class of antibiotics with a novel mode of action (against drug resistant bacterii)

Many Gram-negative bacteria have become multi-drug resistant in recent years, as they have developed mechanisms to escape the therapeutic effects of current antibiotic drugs. New antibiotics against drug resistant bacteria are thus urgently needed as the current arsenal of drugs becomes ineffective against such resistant pathogens. Many research groups are trying different approaches, but now Polyphor Ltd., has come up with an interesting finding, they have discovered  a new class of antibiotics with a novel mode of action (Science 19 February 2010: Vol. 327. no. 5968, pp. 1010 - 1013). As per the claim by the lead researcher, Prof. John Robinson at the University of Zürich (in collaboration with Polyphor Ltd.,) the  new class of antibiotics is effective against multi-drug resistant Gram-negative bacteria, opening up new treatment options for serious and often life-threatening infections. The most advanced drug candidate in this new class,  POL7080, selectively kills the dangerous bacteria Pseudomonas aeruginosa. 

Polyphor applied its proprietary Protein Epitope Mimetics Technology (PEM Technology) to identify new antibiotics that either act against a broad-spectrum of bacteria or selectively target one particular bacterial strain. This joint research effort resulted in the discovery of a new drug target and mechanism of action by which Gram-negative bacterii are killed effectively. 

About Protein Epitope Mimetics (PEM Technology) :

Using a biologically relevant peptide or protein structure as a starting point for lead identification represents one of the most powerful approaches in modern drug discovery. In  protein epitope mimetic (PEM) approach, where folded 3D structures of peptides and proteins are taken as starting points for the design of synthetic molecules that mimic key epitopes involved in protein–protein and protein–nucleic acid interactions. By transferring the epitope from a recombinant to a synthetic scaffold that can be produced by parallel combinatorial methods, it is possible to optimize target affinity and specificity as well as other drug-like ADMET properties (Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties by Quantitative Structure-Activity Relationships, QSAR). The PEM technology is a powerful tool for target validation, and for the development of novel PEM-based drugs.

As per the claim by the lead researcher Prof. J. A. Robinson, one major target recently has been the development of PEMs with antibiotic activity against Gram negative bacteria, in particular, Pseudomonas aeruginosa. Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms. 

Researchers, synthesized a family of peptidomimetic antibiotics (fully synthetic, medium-size cyclo peptide-like molecules), based on the antimicrobial peptide protein I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against gram-negative Pseudomonas sp.,  

Researchers conclude that, the leading antibiotic PEMdrug candidate POL7080 represents an important new weapon to combat life threatening infections with Pseudomonas aeruginosa which frequently occur in the hospital setting or in chronic lung infections.

Polyphor is currently preparing the start of Phase I clinical trials with POL7080 to rapidly advance the clinical development and has initiated out-licensing negotiations with Pharma partners.  The company is optimistic  about  the  positive clinical results and there by making way for this new class of antibiotics...

Ref : http://www.polyphor.com/PolyphorInhalt/Infogate/PressReleases/PressRelease20100219_en.pdf

Bacterially produced antifungal on skin of amphibians may protect against lethal fungus

Bacterially produced antifungal on skin of amphibians may protect against lethal fungus

Minocycline for stroke patients?

Minocycline hydrochloride, also known as minocycline (right structure), is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bactriostatic antibiotic. As a result of its long half-life it generally has serum levels 2-4 times that of most other tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24–48 hours). It is primarily used to treat acne and other skin infections. Apart from the antibacterial activity, 'minocycline' is recognized as a DMARD (Disease-Modifying Anti-Rheumatic Drug) by the American College of Rheumatology, which recommends its use as a treatment for mild rheumatoid arthritis.

A recent study by the Dr. Cesar V. Borlongan (University of South Florida, USA) has lead to some interesting result, i.e., minocycline can be used to treat the stroke patients !. As per the claim by the researchers this drug might be a better option, when compared with the thrombolytic agent tPA (the only effective drug for acute ischemic stroke) and more over only 2 % of ischemic stroke patients benefit from this treatment due to its limited therapeutic window.

During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications. This study recorded the effect of intravenous minocycline in both isolated neurons and animal models after a stroke had been experimentally induced. At low doses it was found to have a neuroprotective effect on neurons by reducing apoptosis of neuronal cells and ameliorating behavioral deficits caused by stroke. The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy claims the researchers. Congrats for this interesting finding...

Ref : http://www.biomedcentral.com/1471-2202/10/126/abstract