Plazomicin has received FDA approval to treat complicated urinary tract infections (cUTI), including pyelonephritis, due to certain Enterobacteriaceae bacteria in adults with limited or no alternative treatment options.
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The drug, which is being marketed as Zemdri by Achaogen, Inc., of South San Francisco, California), is administered once daily by intravenous infusion. According to an Achaogen press release, it is indicated for patients aged 18 years or older for cUTI caused the following susceptible bacteria: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.

The approval was supported in part by data from the phase 3 EPIC (Evaluating Plazomicin in cUTI) clinical trial, the first randomized controlled study of once-daily aminoglycoside therapy for treating cUTI, including pyelonephritis, the company said in the press release. In the trial, plazomicin demonstrated non-inferiority to meropenem for the co-primary efficacy endpoints of composite cure (clinical cure and microbiologic eradication) in the microbiological modified intent-to-treat population at day 5 and test-of-cure (TOC) visit. Composite cure rates at TOC were 81.7% for plazomicin vs 70.1% for meropenem, the company said. 

In addition, composite cure at the TOC visit in patients with concomitant bacteremia at baseline was achieved in 72% of plazomicin-treated patients compared with 56.5% of meropenem recipients.

New research reveals fresh clues on the infection-fighting properties of cranberries. Researchers in Canada showed how cranberry extract rich in a particular type of compound successfully disrupted cell-to-cell communication in bacteria responsible for hard-to-treat infections.
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The team - from McGill University in Montreal and INRS-Institut Armand-Frappier in Laval, both in Canada - reports the discovery in the journal Scientific Reports. Previous studies have already shown that cranberries contain proanthocyanidins (PACs), a class of compound that fends off illness through various antibacterial properties. For example, they can stop certain bacteria from sticking onto the wall of the bladder and causing a urinary tract infection.

However, the team behind the new study also wanted to find out if cranberry compounds can control the virulence of bacteria, and therefore reduce the severity of an infection. They suggest their findings not only give fresh clues on how PACs in cranberries fight bacteria, but they could also lead to new approaches to infection control.

Cranberry compounds disrupt bacterial cell communication

For their study, the team used fruit flies - a useful model for studying human infections at the level of cells and molecules. They found severity of bacterial infection was reduced in fruit flies fed on cranberry extract rich in PACs, compared with cranberry-free fruit flies. The cranberry-fed flies also lived longer.

Further investigation revealed the cranberry PACs disrupt a cell communication process called "quorum sensing" that forms an essential link in a chain of events involved in the spread and severity of chronic bacterial infections. The research focuses on a bacterium called Pseudomonas aeruginosa, which can cause infections in hospital patients and people with weak immune systems.

Patients on breathing machines, fitted with catheters, or with burns or surgical wounds are potentially at risk for serious, life-threatening infections.

Implications for antibiotic resistance

Pseudomonas infections are generally treated with antibiotics. However, because of increasing antibiotic resistance, these and other hospital-acquired bacterial infections are becoming harder to treat.

In the United States, there are an estimated 51,000 healthcare-associated P. aeruginosa infections every year. Of these, around 13 percent are multi-drug resistant, and about 400 deaths are due to these infections.

In their paper, the researchers discuss the relevance of their findings to the problem of drug resistance. They found that while the cranberry PACs disrupted bacterial quorum sensing, this did not kill the cells - it just disrupted their communication and spread.

They suggest this could be important because one reason conventional antibiotics lead to drug resistance is because they kill bacteria - which they note poses "strong selective pressure in any environment."

However, the authors also point out it would be "naive to presume" that by disrupting quorum sensing one would not be placing any selective pressures that might lead to resistance against drugs that work using this mechanism.

Nonetheless, the findings are still useful in that they "expand our strategies for combating pathogen resistance by identifying novel anti-microbial and anti-virulence agents," they conclude.

The study was funded by the Natural Sciences and Engineering Research Council of Canada, the Wisconsin Cranberry Board, and the Cranberry Institute.