'Serious lack' of antibiotics in development to address resistance

Modesto Morganelli
Settembre 20, 2017

A new report today from the World Health Organization (WHO) argues that the antibiotics now in clinical development are not sufficient to counter rising antimicrobial resistance (AMR), particularly in the pathogens that present the greatest threat to human health. They are a particular danger to patients who are already sick and have fragile immune systems.

The agency also singled out gram-negative pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae, including Klebsiella pneumoniae and Escherichia coli, as "the most critical priority for antibiotic research and development" because "strains are emerging worldwide that can not be treated with any of the antibiotics now on the market".

"There is an urgent need for more investment in research and development for antibiotic-resistant infections including tuberculosis (TB), otherwise we will be forced back to a time when people feared common infections and risked their lives from minor surgery", World Health Organization director-general Tedros Adhanom Ghebreyesus said.

Most of the drugs now being developed to combat antimicrobial resistance are only modifications of existing antibiotics which are just short-term solutions. Some of these drugs are only in phase 1 clinical trials.

The only antibiotic active against all the critical priority pathogens is cefiderocol, a siderophore cephalosporin with a unique mechanism to penetrate the tough outer shell of gram-negative pathogens. Unless they are sparingly used, resistance will build to the new drugs as well.

As of now, the report titled, Antibacterial agents in clinical development, says about 51 new antibiotics are being developed to possibly treat antibiotic-resistant pathogens.

But drug development is lagging behind, especially for drug-resistant tuberculosis and other infections the WHO has designated as high priority, the United Nations health agency said. While discovering compounds that are part of a new chemical class, with new targets, novel modes of action, and no cross-resistance to current antibiotics, is more hard, these types of innovative drugs are viewed necessary for truly countering drug resistance.

Among the alarming diseases that are increasing and spreading is multi-drug resistant tuberculosis (TB), which requires treatment lasting between nine and 20 months. There are 250,000 deaths a year from drug-resistant TB and only 52% of patients globally are successfully treated.

There are also very few oral treatments in the works, which are essential for treating infections outside hospitals.

Experts say the findings of the World Health Organization report are not surprising, given the known economic and scientific challenges of new antibiotic development.

"This is the most comprehensive survey in existence on the clinical development pipeline", Kevin Outterson, LLM, JD, executive director of CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), told CIDRAP News. It has now examined new drugs in the development pipeline. The hope is that this funding will help get a new batch of innovative drug candidates into the pipeline more quicker and, ultimately, into clinical use.

It said cooperation by the pharmaceutical industry will be key to bringing new options onto the market and that new treatments must be combined with infection prevention and control and antimicrobial stewardship efforts.

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