Stewardship / Resistance Scan for Apr 20, 2017

Novel antibiotic target
Penicillin-resistant pneumonia

New drug takes novel approach to inhibiting bacterial growth

A study today in the Canadian Journal of Physiology and Pharmacology describes a novel antibiotic agent that targets a different pathway than traditional antibiotics to inhibit bacterial growth.

In the first part of the study, a team of Canadian researchers explain how sodium ion circulation enzymes, or pumps, serve as a direct source of energy in many bacterial pathogens. They identified one enzyme in particular, the NQR pump, as critical for the growth and proliferation of Chlamydia trachomatis, a species of gram-negative bacteria that causes chlamydia infections. Identifying a novel target for antibiotic activity is considered critical to the development of new antibiotics.

In the second part of the study, the researchers showed that PEG-2 and PEG-2S, compounds extracted from the antibiotic korormicin (which is too toxic to be an effective treatment), inhibit the growth and proliferation of C trachomatis bacteria by suppressing the function of the NQR pump. And because the drugs only target bacteria harboring NQR enzymes, they don't affect healthy cells and non-pathogenic gastrointestinal bacteria.

The researchers say that since NQR enzymes are present in other bacterial pathogens, such as Pseudomonas aeruginosa and Neisseria gonorrhea, their findings have implications beyond the inhibition of growth in C trachomatis, and that PEG-2 and PEG-2S may potentially be used to suppress bacterial growth in a number of different diseases.

"The results from our collaboration are tremendously exciting," lead author and University of Manitoba professor Pavel Dibrov, MSc, PhD, says in a press release from journal publisher Canadian Science Publishing. "We are currently designing PEG-2S variations and hope to tailor PEG-based antimicrobials to each specific NQR-containing pathogenic bacterium."

PEG-2S has received a provisional patent, according to the press release
Apr 20 Can J Physiol Pharmacol study
Apr 20 Canadian Science Publishing press release


US study shows no increase in penicillin-resistant pneumonia

Researchers from Harvard University and the US Centers for Disease Control and Prevention (CDC) reported no significant change in the prevalence of penicillin resistance among nonvaccine pneumococcal strains after the introduction of the 13-strain pneumococcal conjugate vaccine (PCV13) in the United States, but with wide regional variations.

As noted in their report in Emerging Infectious Diseases, the investigators used data from the Active Bacterial Core surveillance system, a population- and lab-based collaborative system between the CDC and state health departments and academic institutions in 10 states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. They compared serotypes isolated in 2009 and 2012. PCV13 was implemented in 2010.

They found that PCV13 introduction was not associated with a significant change in the prevalence of penicillin resistance in nonvaccine serotypes "because of the variable success of highly resistant serotypes." They added that differences in regional serotype distribution and serotype-specific resistance contributed to geographic heterogeneity of penicillin resistance.

Georgia, New Mexico, and Minnesota had the highest level of penicillin resistance in 2012, while Oregon had the lowest, followed by California and Tennessee.
Apr 18 Emerg Infect Dis report

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