Yeast infection four times as likely with penicillin use

 Only certain classes of antibiotics increased the risk of yeast infections in a study of 650 women followed for 18 months to see what factors were associated with new-onset vulvovaginal candidiasis.

Penicillins increased the risk the most (adjusted hazard ratio, 4.1), followed by cephalosporins (aHR, 3.3) and metronidazole (aHR, 2.8), compared with women who did not report antibiotic use. Other classes of antibiotics were not associated with yeast infections.

"Many women and physicians believe that if you take an antibiotic, you’re just bound to get yeast. The message is that not all antibiotics are associated with yeast vaginitis; it’s certain classes of antibiotics that carry the highest risk," said senior investigator Sharon L. Hillier, Ph.D., a professor of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.

"When women are given antibiotics, I think it’s useful to help them understand they have some likelihood of getting a yeast infection with these three, and less so with quinolones or tetracyclines or something else," she said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The 650 subjects – 18-40 years old, not pregnant, and with no signs or symptoms of yeast at baseline – were followed at 2-month intervals during the investigation, and had a total of 4,934 follow-up office visits. Each time, they were asked what antibiotics they had been on, if any, among other questions.

There were 82 clinical yeast vaginitis diagnoses and 58 self-diagnosed infections with documented antifungal use. The results were largely similar when the team limited analysis to just clinically diagnosed cases.

A total of 312 women used an antibiotic at least once. Macrolides, metronidazole, and penicillins were used most often among the nine classes of reported antibiotics. The most common indications were upper respiratory tract infections, bacterial vaginosis, urinary tract infections, and sexually transmitted infections.

Having two or more male sexual partners was also a strong predictor of yeast vaginitis (aHR, 5.0), "and that was something that was a little bit surprising because it’s not a sexually transmitted infection. It’s useful maybe to tell women that limiting their numbers of sex partners will also decrease their risk," Dr. Hillier said.

Using depot medroxyprogesterone acetate (Depo-Provera), meanwhile, had a protective effect (aHR, 0.3), compared with women not using hormonal contraceptives. "Depo-Provera has a very strong progestin; some women who get the shot actually have estrogen depletion in the vaginal epithelium. The finding suggests that when you remove the estrogen from the [vaginal] epithelium, it can reduce your risk for yeast vaginitis," Dr. Hillier said.

Other forms of hormonal contraception were not associated with yeast vaginitis. Although "many women believe oral contraceptives and other hormonal methods increase the risk, there was no evidence of increased risk in this study," she said.

Tomado de: familypracticenews.com

Blockade of Pathogen's Metabolism

In the search for new antibiotics, researchers are taking an unusual approach: They are developing peptides, short chains of protein building blocks that effectively inhibit a key enzyme of bacterial metabolism. Now, scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, a branch of the Helmholtz Center for Infection Research (HZI), have published their findings and the implications for potential medical application in the scientific journal ACS Chemical Biology.

The road from gene to protein has an important stop along the way: ribonucleic acid, or RNA. This molecule is essentially a "negative copy" of DNA, the cell's hereditary material, and serves as a blueprint for the cell to make proteins, the basic building blocks of life. This "template" is assembled by the enzyme RNA polymerase, whose job it is to read off the information that is stored within the DNA molecule.

Bacterial RNA polymerase consists of several subunits. The core enzyme has to first bind a certain protein molecule called "sigma factor" which essentially allows the enzyme to begin production of the RNA molecule. The sigma factor locates the starting point of the gene to be copied -- as soon as its job is done, it once again detaches from the enzyme complex. The next time, the sigma factor and the core enzyme have to bind to each other again. If this is no longer possible, new RNA cannot be synthesized and no more proteins will be made by the cell. Cellular processes come to a complete standstill, and the bacterium dies.

Which is exactly the reason why the point of contact between the sigma factor and the core enzyme represents a potential target for new therapies against bacterial infections. Another feature makes this a particularly attractive target: "Sigma factors are unique to bacteria and are not found in mammalian cells," explains Kristina Hüsecken, Ph.D. student at the HIPS and the publication's first author. "This way, we are able to specifically target the bacteria without putting the body's own cells at risk." Which also means potential side effects are not to be expected.

The drug researchers from Saarbrücken have looked at a range of peptides, short chains of amino acids, capable of inhibiting the polymerase. Their structure corresponds to areas from the binding site of one of the enzyme parts: A perfect fit, the peptides dock either to the core enzyme or to the sigma factor, specifically at the exact location where the counterpart would normally attach to. This way, the components are prevented from combining to form a functional enzyme since the binding site is already occupied. Of the 16 total peptides the researchers examined, one in particular proved especially effective. The peptide called P07 was able to show in further tests that it actually does prevent transcription of DNA to RNA in bacterial cells by interfering with the interaction between sigma and core enzyme.

A number of current antibiotics target bacterial RNA polymerase, among them rifampicin, which was first introduced in the late 1960s. Yet these classic drugs are quickly losing their efficacy, as germs are evolving resistance to them. "Since we're looking at a new mode of action, it won't come to cross resistance, which is a much-feared issue with new antibiotics," says Dr. Jörg Haupenthal, the study's principal investigator. This could be the case with any new substance whose mode of action is similar to that of an antibiotic the bacteria have already evolved resistance to.

Whether or not P07 will be developed into a market-ready drug is something Haupenthal and his colleagues cannot predict. "Even though our research points the way to new and effective antibiotics, actually developing them into full-blown drugs for clinical use requires much additional research," says Haupenthal. As such, the researchers are working at optimizing P07 while also looking for other molecules capable of binding to the same spot on the polymerase enzyme.

Tomado de sciencedaily.com

New Antibiotic Cures Disease by Disarming Pathogens, Not Killing Them

 A new type of antibiotic can effectively treat an antibiotic-resistant infection by disarming instead of killing the bacteria that cause it. Researchers report their findings in the October 2 issue of mBio®, the online open-access journal of the American Society for Microbiology.

"Traditionally, people have tried to find antibiotics that rapidly kill bacteria. But we found a new class of antibiotics which has no ability to kill Acinetobacter that can still protect, not by killing the bug, but by completely preventing it from turning on host inflammation," says Brad Spellberg of the UCLA Medical Center and David Geffen School of Medicine, a researcher on the study.

New drugs are badly needed for treating infections with the bacteriumAcinetobacter baumannii, a pathogen that most often strikes hospital patients and immune- compromised individuals through open wounds, breathing tubes, or catheters. The bacterium can cause potentially lethal bloodstream infections. Strains of A. baumannii have acquired resistance to a wide range of antibiotics, and some are resistant to every FDA-approved antibiotic, making them untreatable.

Spelling and his colleagues found that in laboratory mice it was possible to mitigate the potentially lethal effects of the bacterium by blocking one of its toxic products rather than killing it.

"We found that strains that caused the rapidly lethal infections shed lipopolysaccharide [also called LPS or endotoxin] while growing. The more endotoxin shed, the more virulent the strain was," says Spellberg. This pinpointed a new therapy target for the researchers: the endotoxin these bacteria shed in the body.

Blocking the synthesis of the endotoxin with a small molecule called LpxC-1 prevented infected mice from getting sick. Unlike traditional antibiotics, Spellberg says, LpxC-1 doesn't kill the bacteria, it just shuts down the manufacture of the endotoxin and stops the body from mounting the inflammatory immune response to it that is the actual cause of death in seriously ill patients.

Spellberg says this is a direction few researchers have taken when exploring ways to treat infections but that it could make the difference in finding an effective drug. The results also highlight how important it is to find new, physiologically relevant ways of screening potential antibiotics for pathogens with a high degree of resistance, write the authors. Molecules like LpxC-1 that inhibit rather than kill bacteria wouldn't pass muster with traditional antibiotic screens that are based on killing effectiveness.

Liise-anne Pirofski of the Albert Einstein College of Medicine and a reviewer of the study for mBio® says neutralizing virulence factors is showing a lot of promise as an alternative route for treating infections. "There's a growing movement in infectious disease therapy to control the host inflammation response in treatment rather than just 'murdering' the organism," says Pirofski. "This is a very elegant and important validation that this approach can work -- at least in mice."

American Society for Microbiology. "New antibiotic cures disease by disarming pathogens, not killing them." ScienceDaily, 2 Oct. 2012. Web. 8 Nov. 2012.