The Infectious Disease Society of America (IDSA) has released a list of the six drug-resistant pathogens scientists should be most concerned about.
The AATF (Antimicrobial Availability Task Force) created a list of high-priority bacterial and fungal pathogens on the basis of ⩾1 of the following characteristics: current clinical and/or public health concern in the United States because of a high incidence of infection and substantial morbidity; infection with high attributable mortality rates, even if the population-based incidence is low (e.g., the majority of infections occur in immunocompromised patients in tertiary care medical centers); and unique virulence or resistance factors that could circumvent the usual therapeutic effect of antimicrobial therapy. An additional criterion was the presence of few or no novel candidates in the late-stage US drug-development pipeline for treatment of infection due to these pathogens. We chose to focus only on compounds in phases 2 or 3 of development (i.e., studies of therapy for specific infections, with well-defined inclusion and exclusion criteria), given the high failure rate of compounds that have not successfully navigated phase 1 studies (i.e., initial single- or multiple-dose studies involving healthy adult volunteers conducted primarily to collect pharmacokinetic and safety data). For each organism proposed for the list, a rationale for inclusion was drafted and the needs for drug development identified. The list of pathogens was not conceived of as exhaustive but rather as illustrative of pathogens considered to be most important.
What'd they find? Continued...
Members of the AATF identified the following particularly problematic pathogens: Acinetobacter baumannii, Aspergillus species, extended spectrum Î²-lactamase (ESBL)âproducing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium (VRE), Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA).
Most people have heard of the last three, so I'm not going to go into any detail on those in this post. The first one--Acinetobacter--has gotten some coverage lately:Mike's covered it several times. Aspergillus is the only one on the list that's not a bacterium--it's a fungus. These are often difficult to treat since they have complex life cycles, and often appear in immunocompromised hosts, and have a high mortality rate.
Entobacteriaceae isn't a species--it's a family consisting of a number of species you're probably familiar with (E. coli, Yersinia, Klebsiella, Salmonella, etc.) Those that produce the extended-spectrum beta lacatamase mentioned are endemic in hospitals with no sign of decrease on the horizon.
The article itself is well worth reading, going into a lot more background on why these organisms are high priority. They end with a plea:
The discovery and development of new antimicrobials is an expensive and time-consuming process requiring a long-term commitment to maintaining a substantial and sophisticated infrastructure. Once dismantled, such programs cannot be restarted in weeks or months. Clinicians and public health officials, working in collaboration with the pharmaceutical industry, must act now to ensure a robust pipeline of compounds for the next decade. IDSA's membership, including specifically those clinicians who serve on the front line caring for patients with nosocomial infection due to multidrug-resistant pathogens, can make their needs known via IDSA's advocacy efforts, as found on the IDSA Web site (available at: http://www.idsociety.org).
I'm obviously not a clinician myself, nor do I do any work specifically dealing with antibiotic resistance, but there's a large, multi-year study run by colleagues here at the university that focuses on surveillance for resistant organisms (the SENTRY program). You know when you go to a presentation on the topic, the news just ain't gonna be good. And while it's notable to have some "high priority" organisms, obviously the scope of the problem goes far beyond the six described above. We need to not only develop new drugs, but prudently use the ones we have.
[Edited to add: Mike has a new summary of Acinetobacter info here.]
Hmmmm, interesing stuff.
Are there any new powerful antimicrobial drugs just over the horizon ready to be unleashed, or are such things still way down the pipeline?
They do give a whole list of compounds in Phase 2 or 3 trials (Table 2 of the paper). How long it would take them to make it to the market (assuming they're effective), I'm not sure.
And of course, the vanctomycin-resistant Enterococcus faecium are likely to be the consequence of feeding analogues of medical antibiotics to farm animals as 'growth promotants'.
Also, I would put good money on that list of organisms expanding quite a bit in future.