antibiotic-resistant fungi: C auris

The NY Times recently highlighted a very scary story of a fungus found in hospitals that is not only resistant to all meds but also to the usual antiseptic hospital procedures (see https://www.nytimes.com/2019/04/06/health/drug-resistant-candida-auris.html?smid=nytcore-ios-share ). 

Details: 

--the case was an elderly man admitted to Mt Sinai Hospital in Brooklyn for abdominal surgery, who contracted Candida auris, an incurable infection that led to his death 90 days later 

--tests found the fungus everywhere in his room (including ceiling, walls, window shades, mattress, bed rails, doors, curtains, sink, phone, whiteboard, the IV poles, pump …) and they “needed special cleaning equipment and had to rip out some of the ceiling and floor tiles to eradicate it” 

--in the US, the CDC has reported cases in New York, New Jersey, and Illinois, and noted this bug is an “urgent threat”. So far 587 cases have been reported, with 309 in New York (first case was in 2013!!!), 104 in New Jersey, and 144 in Illinois (50% of residents in some Chicago nursing homes have tested positive for it) 

-- the NY Times article has a world map of C. auris outbreaks, which includes Canada, US, Panama, Venezuela, Colombia, UK, France, Spain, Germany, Saudi Arabia, Oman, Kenya, South Korea, South Africa, Russia, China, India, Australia, Singapore

--however, there is essentially no publicity about these infections. The NY Times notes:

    --"With bacteria and fungi alike, hospitals and local governments are reluctant to disclose outbreaks for fear of being seen as infection hubs. Even the C.D.C., under its agreement with states, is not allowed to make public the location or name of hospitals involved in outbreaks. State governments have in many cases declined to publicly share information beyond acknowledging that they have had cases."

   --even a former CDC outbreak investigator who dealt with resistant infection outbreaks in Kentucky, where the hospitals were not publicly disclosed, said, “It’s hard enough with these organisms for health care providers to wrap their heads around it” … “It’s really impossible to message to the public.” (!??!!)

    -- By the end of June 2016, a scientific paper reported an outbreak of 50 C. auris cases at Royal Brompton hospital in the UK, and the hospital shut down its I.C.U. for 11 days, again with no public announcement; there were eventually 72 total cases, though some patients were only carriers and were not infected by the fungus.

    -- Valencia, Spain: 372 people were colonized, and 85 developed bloodstream infections. Also, no public announcement

Commentary: 

--History of Candida auris:

    --Candida auris: first described in Japan in 2009; responsible for rapidly increasing hospital-acquired invasive infections, can survive normal decontamination procedures

    --C. auris: >90% are resistant to at least 1 drug and 30% to 2 or more 

--Why is this a problem:

    --fungi have highly plastic genomes and reproduce quickly, a recipe for developing resistance  

    --there are 9x as many antifungal agents available for crops than for systemic animal infections 

    --there are 4 frontline antibiotics for humans, all with different mechanisms of action: polyenes (eg amphotericin B), pyrimidine analogs (eg 5-fluorocytosine), echinocandins (the newest class), and azoles 

    --azoles are the most widely used class of fungicides in crop protection in the EU; there is now more azole resistance in humans to Aspergillus fumigatus (25% of A. fumigates in Netherlands carry the azole resistance alleles). Not surprisingly, azole-resistant aspergillus appears where lots of azole fungicides are used in agriculture 

    -- monoculture crops, as in industrial farming, leads to feeding grounds for the rapid emergence of fungicide-resistant bacteria (crop diversity tends to limit spread of disease) 

    -- one effect of broad-scale antifungal use in plants is inadvertently breeding out the plants’ own natural defenses against fungi 

    --also there are increases in the human population more susceptible to fungi: increasing age, more immunodeficiency (HIV, more surviving cancer patients/transplant on immunosuppressives)

    --rate of emergence of fungicide resistance is greater than the pace of fungicide discovery 

--Overview:

    --CDC estimated in 2010 that about 2 million people developed resistant infections in the US and 23,000 died from them. More recent numbers suggest 162,000 deaths in the US and 700,000 annually worldwide

    --a British study projected the possibility that with the array of superbugs developing (ie, highly resistant bugs), about 10 million people will die from them in 2050, more than the projected 8 million deaths from cancer, unless there is a concerted effort to decrease the development of antibiotic resistance 

    --total global mortality rate for fungal diseases exceeds malaria and breast cancer, and is comparable to TB and HIV 

--Other concerns:

    --in the setting of population increases and food insecurity, one concern is that crop-destroying fungi account for 20% crop yield losses and a further 10% post-harvest 

    --Candida glabrata: now resistant to important classes of antifungals (echinocandins and azoles), is becoming the predominant bloodstream fungal pathogen 

    --filamentous pathogenic fungi (Aspergillus terreus Scedosporium spp, Fusarium spp, Mucorales) are intrinsically resistant to a broad range of antifungals 

--?role of antibiotic stewardship programs. ? role of using multiple fungicides having dfferent mechanisms of action (as with HIV, TB). ?use of more non-chemical control programs, including development of innate resistance (selection of pathogen-resistance alleles), ??gene editing, ??human vaccines (one against C. albicans is in development).   ???fundamental changes in industrial farming and their use of antibiotics/pesticides

So, this article highlights 2 very important findings: 

--Our general societal development has led to increasingly severe outbreaks of drug-resistant infections, in specific: 

    --the widespread use of antibiotics, especially in agriculture where >80% of those produced are used, ultimately  leading to antibiotic resistance and notable cases of animal/human infections 

    --the widespread use of large-scale commercial agriculture, leading to vast swaths of land with single crops (monoculture) and increased volume/density of crop, leading to higher probability of developing resistance,and greater ease of spread of resistant organisms since organisms may not thrive as well if other crops’ naturally resistant to that organism are well-represented there 

    --the lack of drug company interest in developing new antibiotics, despite written pledges to the WHO to do so. For drug companies, antibiotics (even expensive ones) are not worth it. It costs lots of money to bring a drug to market, and unfortunately (for them) these drugs are used only for a short time and typically not in lots of people in the near-term [they really like the expensive new drugs for common chronic diseases that have the potential for life-long therapy] 

    --and a general popular culture of expectations that we have immediate drug therapy for illnesses (even if antibiotics are not indicated), again stressing short-term possible individual gains over long-term environmental/population concerns 

    --see references below to prior blogs on antibiotic resistance, future concerns, and some approaches and headway in this quite perilous issue 

--and, perhaps most strikingly, is the lack of transparency by the hospitals. Yes, it might scare away some patients to know that there is an untreatable bug in the hospital that is really hard to eliminate (and, in fact it should scare people…)

     --And the argument that it really only affects immunocompromised patients is patently absurd: there are increasing numbers of immunocompromised patients, with more people on cancer chemotherapy and post-transplants, and also with huge shifts in state-of-the art treatments in rheumatology, dermatology, pulmonary, and many other branches in medicine that use (remarkably expensive) immunomodulator drugs. And, it seems to me, there is a pretty high likelihood that a healthy person in the hospital for a fracture or pneumonia might well transport these resistant organisms home and into the community where immunocompromised patients live, since these organisms are not eliminated by routine hospital cleaning procedures 

        --and who is immunocompromised, anyway?? For many organisms, this includes newborns, elderly, diabetics, smokers as well as the more blatantly ones noted above 

    --so, it seems to me to border on the frankly criminal for hospitals not to disclose the finding of drug-resistant bugs, especially those that are resistant to all known antibiotics 

see http://gmodestmedblogs.blogspot.com/search?q=antibiotic+resistance for an array of articles on antibiotic resistance, antibiotic overprescribing, some data that antibiotic prescribing is decreasing, and an interesting perspectvie suggesting that antibiotics often should not be taken for the full prescribed course of therapy even when antibiotic therapy is indicated

geoff​

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