CDC: updated threats of antibiotic-resistant bugs

The CDC just released their 2019 report documenting the increasing threat of antibiotic-resistant bacteria (see https://www.cdc.gov/drugresistance/biggest-threats.html , as well as the full 2019 report https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf ), updating their 2013 report (https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf )

Details:

-- overall, there are more than 2.8 million antibiotic-resistant infections in the US every year

-- and, more than 35,000 people die from these infections every year (a revised and higher estimate)

-- they breakdown the threats into 4 categories:

    -- urgent threats:

        -- carbapenem-resistant Acinetobacter: nearly all in patients were in a healthcare facility; 8500 cases in 2017, 700 deaths. A concern here is that these bugs have mobile genetic elements which can pass rapidly to other types of bacteria, creating resistance in them. Some species are resistant to nearly all antibiotics

        -- Candida auris: multidrug-resistant yeast, can cause severe infections in hospitalized patients and those in nursing homes; 323 cases in 2018. Also, see http://gmodestmedblogs.blogspot.com/2019/04/antibiotic-resistant-fungi-c-auris.html

        -- Clostridioides difficile (previously called Clostridium difficile): mostly in people have had recent medical care and antibiotics; 223,900 cases in 2017 and at least 12,800 people died. Also see http://gmodestmedblogs.blogspot.com/2019/11/c-diff-increasing-and-using.html which highlights the increasing % of community-acquired infections

        -- carbapenem-resistant Enterobacteriaceae (CRE): Mostly of patients in healthcare facilities, some are resistant to nearly all antibiotics; 13,100 cases in 2017, estimated deaths 1100. these bacteria also carry mobile genetic elements that are easily shared between bacteria.

        -- drug-resistant Neisseria gonorrhoeae: estimated drug-resistant infections 550,000 per year. Also see http://gmodestmedblogs.blogspot.com/2016/07/gonorrhea-resistance-increasing.html

    -- serious threats:

        -- drug-resistant Campylobacter: a cause of diarrhea (often bloody), fever and cramps, and can spread through contaminated food (especially raw or undercooked chicken); 48,400 infections per year, 70 deaths. Increasing resistance to fluoroquinolones and macrolides. Now, almost 30% of isolates have decreased susceptibility to ciprofloxacin

        -- drug-resistant Candida: found in mild oral and vaginal infections as well as severe invasive infections; 34,800 cases in hospitalized patients in 2017, 1700 deaths (one quarter of patients with bloodstream infections die). Increased infections when antibiotics are used for bacterial infections.[ie, decreasing unnecessary antibiotics might decrease infection with drug-resistant Candida}

        -- ESBL-producing Enterobacteriaceae (ESBL=extended-spectrum beta-lactamase): a problem in both healthcare settings and the community, can spread rapidly and cause infections in healthy people. 197,400 cases in hospitalized patients in 2017, 9100 deaths. ESBL’s produce enzymes that break down penicillins and cephalosporins

        -- vancomycin-resistant Enterococci (VRE): occur mostly in hospitalized patients; 54500 cases in 2017, 5400 deaths. 30% of healthcare-associated enterococci infections are resistant to vancomycin, and there is increasing resistance to additional antibiotics

        -- multidrug-resistant Pseudomonas aeruginosa, mostly in people with chronic lung disease or with  weakened immune systems, mainly in hospitalized patients; in 2017 32,600 cases with 2700 deaths. Some cases resistant to nearly all antibiotics, including carbapenems

        -- drug-resistant non-typhoidal Salmonella: spreads from animals to people through food, usually causing diarrhea, fever, abdominal cramps; 212,500 drug-resistant infections per year, 70 deaths. Ciprofloxacin resistance has been skyrocketing.

        -- drug-resistant Salmonella serotype typhi: cause of typhoid fever, most cases from traveling abroad; 4100 drug-resistant infections per year, less than 5 deaths per year. 75% are resistant to ciprofloxacin. 11-21 million infections worldwide

        -- drug-resistant Shigella: spread through feces, most people develop diarrhea, fever, stomach cramps; 77,000 drug-resistant infections per year, less than 5 deaths. 24% decreased susceptibility to azithromycin, 10% to ciprofloxacin, and 3% to both

        -- methicillin-resistant Staphylococcus aureus (MRSA): 323,700 cases in hospitalized patients in 2017, 10,600 deaths

        -- drug-resistant Streptococcus pneumoniae: 900,000 infections in 2014, 3600 deaths. Significant decreases in infections associated with vaccination (especially in kids, though also true for adults). 30% are now resistant to one or more antibiotics (was 40% in 2000)

        -- drug-resistant tuberculosis: 847 cases in 2011 and 62 deaths

    -- concerning threats:

        -- erythromycin-resistant group A Streptococcus: increasing resistance to erythromycin and clindamycin; 5400 infections in 2017, 450 deaths

        -- clindamycin-resistant group B Streptococcus: especially problematic in pregnant women; 13000 infections in 2016 and 720 deaths, clindamycin-resistant in 42% of cases of invasive infection,  

    -- watchlist:

        -- azole-resistant Aspergillus fumigates: lots of azoles used in agriculture, likely contributing to resistance

        -- drug-resistant Mycoplasma genitalium: sexually-transmitted infection with increasing azithromycin resistance. Also, see http://gmodestmedblogs.blogspot.com/2019/02/new-test-for-m-genitalium-frequent.html for an updated review of M genitallium

        -- drug-resistant Bordetella pertussis

Commentary:

-- a rather scary report from the US CDC about antibiotic resistance and the increasingly limited effective antibiotic arsenal for resistant bacteria.  BUT, a few of limitations of this study:

    -- it does not include non-bacterial infections

    -- it is limited to the US. The WHO had a report a few years ago on the global threat, which is much scarier than this one: see http://gmodestmedblogs.blogspot.com/2014/05/who-report-on-antimicrobial-resistance.html. the CDC report does note that these international threats are also US threats given that 1 billion people cross the international borders each year, including 350 million arriving in the US through more than 300 points of entry

    -- And, these numbers of cases above are mostly from hospital-based data. Lots of infections (eg MRSA) are diagnosed and treated in the community, where (unlike essentially every other industrialized country with an organized health care system) we do not have systematic reporting of cases [ie, many of these cases are likely markedly underreported]

--a few US governmental reports have come out detailing efforts to decrease antibiotic resistance: see see the 2015 https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf , as well as the 2014 https://www.cdc.gov/drugresistance/pdf/report-to-the-president-on-combating-antibiotic-resistance.pdf , or my review http://gmodestmedblogs.blogspot.com/2015/03/us-effort-to-combat-antibiotic.html​

--the recent report (see https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf ) is the updated cdc report, noting their concern about rising resistant infections in the community (eg gonorrhea, and ESBL-producing Enterobacteriaceae, the former with no available treatment for highly resistant strains per https://www.cdc.gov/std/gonorrhea/arg/default.htm , and the latter with the unfortunate ability of spreading their resistance to other types of bacteria, as noted above) 

    --and, per the new report, several new organisms have bubbled up to the serious threat list (eg Candida auris and carbapenem-resistant Enterobacteriaceae), and the new 3 added to the “watch list”

-- some goodish news

    -- the CDC has ramped up their efforts: as of 2018 they have tested lots of bacteria for antibiotic resistance (106,000, with the rate of detecting a new resistant bug every 4 hours), as well as giving support to 350 global partners in the fight

    -- 16% decrease in outpatient antibiotic prescribing to kids since 2011

    -- 5% overall decrease in antibiotics

    -- 18% decreased death rates from antibiotic-resistant bacteria since the 2013 report and 28% decreased hospital rates

    -- the FDA reports decreased domestic sales and distribution of medically important antimicrobials approved for use in food-producing animals, including OTC ones (see https://www.fda.gov/media/119332/download ), though there have been increases in fluoroquinolones (24%) and lincosamides (eg clindamycin, 7%). However,  these changes need to be put into the context of the mega-huge 70-80% of all antibiotics that have been used in farming (mostly livestock) and were done so without any clinical indication (though there was a financial one: animals are larger/generate more income with antibiotics….). It should be noted that fluoroquinolones have only recently been used in farming, are still not a major antibiotic used (largest current users are still tetracyclines and ionophores, the latter not considered medically important for humans), but this increase in fluoroquinolone use is potentially a huge issue given the importance of fluoroquinolones for many serious human infections and the markedly increasing resistance in many bacteria, as above

    -- and they even comment on the potential use of bacteriophages…. (see http://gmodestmedblogs.blogspot.com/2019/11/c-diff-increasing-and-using.html , which has a section on the use of bacteriophages, a potentially important and specific antibacterial)

So, 

a rather distressing report overall. There have been some improvements since the US developed the prior initiatives to decrease antibiotic resistance, but several of the above bacteria are becoming more resistant and with few available antibiotic options. And some (eg C diff) have become more prevalent in the community. The report does comment on the very important role of antibiotics used in the food supply, and that target still needs to be a primary one: both for developing antibiotic-resistant bacteria in the foodchain, contaminating water/other foods, and spreading to humans; and also more directly by contributing edible antibiotics to humans from the antibiotic-laced food products and leading to antibiotic resistance in humans.

As with climate change, there is a very real urgency to decrease the overuse of antibiotics in people and agriculture (the finding of a newly detected resistant bug in the CDC labs every 4 hours is a tad disturbing)...

Prior relevant blogs on antibiotic overprescribing, antibiotic resistance, microbiome changes, and some positive changes

blogs on microbiome changes:

    --a study finding similar outcomes and fewer adverse events in kids on narrower-spectrum antibiotics: http://gmodestmedblogs.blogspot.com/2018/01/antibiotic-use-in-kids-narrow-spectrum.html

    --a small study showing that there can be long-term effects (12 month) on the gut microbiome even after a single exposure to antibiotics: http://gmodestmedblogs.blogspot.com/2015/11/longterm-microbiome-changes-with.html 

    --increased colorectal adenomas, including advanced ones, in women exposed to antibiotics: http://gmodestmedblogs.blogspot.com/2017/04/antibiotics-microbiome-changes-and.html

   --increased risk of colon cancer in those exposed to antibiotics, perhaps moreso with penicillins: http://gmodestmedblogs.blogspot.com/2019/10/antibiotics-increased-colon-cancer-risk.html

    --increased obesity and allergy in kids exposed to antibiotics: http://gmodestmedblogs.blogspot.com/2018/12/antibiotics-ppish2ras-increase-obesity.html

    --and a blog with 2 articles, one showing an unfortunate shift from prescribing narrow to broad-spectrum antibiotics and another showing that clinicians tend to prescribe more antibiotics late in a clinical session ("clinician fatigue"): http://gmodestmedblogs.blogspot.com/2015/07/antibiotic-overprescribing.html

other blogs on antibiotic overprescribing 

    --4 articles noting high prescription rates of antibiotics for URIs, pharyngitis and acute rhinosinusitis: http://gmodestmedblogs.blogspot.com/2016/01/antibiotic-overprescribing-and-acute.html 

    --another with a CDC report from 2013 finding huge overprescription of antibiotics for respiratory infections: http://gmodestmedblogs.blogspot.com/2015/07/antibiotic-overprescribing.html

a couple of hopeful notes: 

    --we are moving (slowly) in the right direction, see http://gmodestmedblogs.blogspot.com/2017/08/antibiotic-use-decreasing.html

    --antibiotic resistance can be decreased by hospital antibiotic stewardship programs: http://gmodestmedblogs.blogspot.com/2017/06/decreasing-antibiotic-resistance-by.html 

but a somewhat less hopeful one: 

    --drug companies are largely abandoning antibiotic development (it is much more profitable to develop a long-term drug for a chronic condition than even a high-priced one used for a few weeks): http://gmodestmedblogs.blogspot.com/2018/07/novartis-dumps-antibiotic-research.html . 

    --And, http://gmodestmedblogs.blogspot.com/2014/05/who-report-on-antimicrobial-resistance.html  also summarizes a pretty great BMJ article debunking the really exaggerated statement that R&D costs come close to justifying the astronomical cost of new drugs

geoff

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