Antibiotic plus probiotic combination may kill off superbugs

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Every year, over 2 million people in the United States develop infections that are resistant to treatment, and approximately 23,000 people die as a result.

These statistics have prompted the Centers for Disease Control and Prevention (CDC) to deem drug resistance “one of the biggest public health challenges of our time.”

Therefore, researchers are hard at work trying to develop ingenious ways of tackling so-called superbugs — bacteria that have become immune to antibiotic treatment.

Lately, researchers have added probiotics to their arsenal against superbugs. Probiotics are beneficial bacteria found in foods, such as yogurt, kefir, pickles, or miso soup.

Only a month ago, for example, a study suggested that simply consuming probiotics on a regular basis could reduce the need for antibiotics, thus helping to curb the drug resistance crisis. Continue reading Antibiotic plus probiotic combination may kill off superbugs

Telavancin Promising Potential Treatment Option for MRSA in Cystic Fibrosis Patients

By Kristi Rosa

Responsible for several issues ranging from skin infections and sepsis to pneumonia and bloodstream infections, methicillin-resistant Staphylococcus aureus continues to plague patients in the health care and community setting, as well as the providers who treat them.

When acquired in patients with cystic fibrosis, clinical outcomes are known to be even worse, affecting several organs—primarily the lungs—and resulting in an increased rate of declined respiratory function as well as infections that can have severe, and sometimes deadly, consequences.

Now, however, for the first time, investigators have found that telavancin—a drug that is currently used to treat skin infections and hospital-acquired pneumonia—has potent in vitro activity and low resistance development potential when used against S aureus isolates in patients with cystic fibrosis, making it a promising potential treatment option for this population.

“Telavancin (TLV) is a lipoglycopeptide antibiotic approved by the US Food and Drug Administration in 2009 for the treatment of complicated skin and skin structure infections and in 2013 for the treatment of cases of nosocomial pneumonia, however its application for the treatment of CF-MRSA pneumonia infections was not known, so our studies are contributing to extending the application of TLV for CF treatment,” Adriana E. Rosato, PhD, associate professor in the department of Pathology and Genomic Medicine at Houston Methodist Research Institute told Contagion®. “We were also inspired by the fact that CF patients have a short life time—until 40 to 50 [years]—so our priority is to contribute to better treatment in this patient population.”

Dr. Rosato and her team hypothesized that TLV might be a promising treatment option for CF-patient-derived MRSA and MSSA infections, as in vitro studies have shown that TLV has activity against MRSA.

To prove this, the investigators screened a total of 333 strains of CF patient-derived S aureus of the wild-type or small-colony-variant phenotype, collected from both adults and children at 3 different cystic fibrosis centers: Houston Methodist Research Institute, UW Health and the Center for Global Infectious Disease Research. TLV was found to display activity against all 333 strains collected.

When testing the activity of the drug against 23 MRSA strains, the investigators observed intermediate resistance to ceftaroline (CPT)—a new beta-lactam antibiotic that targets PBP 2a in MRSA—in 20 of the strains, and high-level resistance to CPT in 3 of the strains. The authors note that although high levels of resistance to CPT is rare, intermediate resistance is more common in patients who have chronic infections.

“Among all strains, the TLV MIC90 was 0.06 mg/liter, i.e. 8-fold lower than the daptomycin (DAP) and CPT MIC90 and 25-fold lower than the linezolid (LZD) and vancomycin (VAN) MIC90,” the authors write.

Using time-kill experiments, the investigators assessed the in vitro effectiveness of TLV compared with DAP, VAN, and CPT. They found that TLV showed activity against all tested strains and displayed rapid bactericidal activity as well. The activity profile for the drug at a free serum concentration of 8 mg/liter showed that TLV performed better than VAN (16 mg/liter), LZD (10.4 mg/liter), and CPT (16 mg/liter).

The investigators also set out to determine the fate of mutation selection that could be projected by the potential prolonged use of TLV in patients with cystic fibrosis. To do this they looked at 3 specific strains: AMT 0114-48, WIS 664, and TMH 5007. They found that due to the ease of mutation selection which had been noted in control strains, TLV mutant resistance is independent of the CF patient background of the strains.

“We demonstrated that TLV has bactericidal activity against the S aureus strains tested, including those against which CPT and LZD displayed reduced activity, which might provide TLV a significant advantage over the drugs currently used to eradicate those strains and prevent future exacerbations,” the study authors write.

A clinical trial is currently underway to assess the pharmacokinetic profile of TLV in patients with cystic fibrosis, who usually need dose adjustment because of an increase in the volume of distribution and clearance.

“[The next step for our research is] to perform in-vivo analyses studies that could lead to translational application/clinical trial,” Dr. Rosato added. “However, we are limited in research funds to continue our investigations.”

Original article here.

Study Links CF Patients’ Airway Bacteria with Disease Outcomes

By: Diogo Pinto

Researchers have linked variations in the mix of microorganisms in cystic fibrosis patients’ airways to their disease outcomes.

The findings in the journal PLOS One were in an article titled “Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis.

CF patients typically have particular strains of bacterial and fungus in their airways. The usual bacteria suspects include PseudomonasAchromobacterBurkholderiaHaemophilusStaphylococcus, and Stenotrophomonas.

Other bacteria and fungi also inhabit CF patients’ airways, however. These include anaerobic species that do not need oxygen to grow and spread.

Not only do the microbial communities in CF patients’ airways vary by type of microorganism, but also in the relative abundance of each species.

Researchers decide to see if the prevalence and relative abundance of typical CF pathogens and anaerobic microorganisms play a role in the severity of patients’ disease and their lung function.

They analyzed 631 sputum samples collected over 10 years from 111 patients.

The team classified the stage of patients’ disease on the basis of their lung function scores. The yardstick they used was forced expiratory volume in one second, or FEV1. They considered an early stage of the disease to be an FEV1 score higher than 70, an intermediate stage a score of 40 to 70, and an advanced stage a score lower than 40.

Researchers classified disease aggressiveness — mild, moderate or severe — on the basis of change in FEV1 relative to age.

They discovered a link between variations in the prevalance of the six typical CF pathogens, plus nine anaerobic species, and changes in a patient’s disease stage and lung function.

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Potential Nitric Oxide Treatment for Resistant Bacterial Infections Gets Patent

A possible inhalable treatment for antibiotic-resistant bacterial infections in people with cystic fibrosis due to Pseudomonas aeruginosa now has a U.S. patent and is being readied for a first clinical trial, Novoclem Therapeutics announced.

The patent (No. 9,850,322) was issued to the University of North Carolina (UNC) at Chapel Hill where the potential therapy, BIOC51, was discovered, and covers a technology known as water-soluble polyglucosamine compositions that release nitric oxideContinue reading Potential Nitric Oxide Treatment for Resistant Bacterial Infections Gets Patent

Therapy for Reducing P. Aeruginosa Lung Infections Planned Phase 1 Trial

Arch Biopartners recently completed a good manufacturing practice (GMP) production campaign for AB569, a potential inhalation treatment for antibiotic-resistant bacterial lung infections in people with cystic fibrosis (CF) chronic obstructive pulmonary disease (COPD) and other conditions. The campaign, intended to ensure the quality of the investigative therapy, was directed by Dalton Pharma Services.

AB569 is composed of ethylenediaminetetraacetic acid (EDTA) and sodium nitrite, two compounds approved by the U.S. Food and Drug Administration (FDA) for use in people. AB569 can be administered alone or in combination with other compounds to treat multi-drug resistant bacterial infections that can cause reduced lung function.

Pseudomonas aeruginosa is one of the most common bacterial infections in patients with respiratory diseases, including CF, COPD, and pneumonia.

In preclinical studies, AB569 was shown to be capable of killing drug-resistant bacteria like P. aeruginosa and other common pathogens associated with chronic lung infections.

The company also announced that a Phase 1 clinical trial to investigate the safety and pharmacokinetic profile of AB569, planned to start in January, will be conducted at the Cincinnati Veterans Affairs Medical Center (CVAMC). According to an Arch Biopartners press release, Ralph Panos, chief of medicine at CVAMC, will lead the trial.

Three escalating doses of nebulized AB569 will be used to evaluate tolerance to the treatment in about 25 healthy volunteers. Each will be given a single administration of nebulized AB569  to characterize the pharmacokinetic profile of plasma nitrite and nitrate metabolites, exhaled nitric oxide, and circulating hemoglobin.

Pharmacokinetics studies how a drug is absorbed, distributed and metabolized in, and expelled by, the body.

Should the Phase 1 trial in volunteers be successful, Arch Biopartners plans to move its AB569 program into a Phase 2 trial to test its effectiveness in treating chronic P.aeruginosa infections in COPD patients.

AB569 received orphan drug status by the FDA in November 2015 as a potential treatment of P. aeruginosa lung infections in CF patients. Orphan drug status is given to investigative medicines intended for people with rare diseases to speed their development and testing.

Original article: https://cysticfibrosisnewstoday.com/2017/12/12/arch-biopartners-readies-ab569-potential-treatment-for-cf-copd-lung-infections-for-phase-1-trial/

Presentation of Positive New Data from Studies of VIBATIV at ASM Microbe

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Theravance Biopharma (TBPH) Announces Presentation of Positive New Data from Studies of VIBATIV at ASM Microbe

Theravance Biopharma, Inc. (NASDAQ: TBPH) (“Theravance Biopharma” or the “Company”) today announced the presentation of positive new data from Continue reading Presentation of Positive New Data from Studies of VIBATIV at ASM Microbe