WHO report on antimicrobial resistance

world health org just came out with report on antimicrobial resistance (see antimicrobial resistance WHO 2014 in dropbox for summary, or URL: http://apps.who.int/iris/bitstream/10665/112647/1/WHO_HSE_PED_AIP_2014.2_eng.pdf ). remarkably scary report. their findings:

--very high levels of resistance in all WHO regions for many common bacteria. eg (with 20-50% of the 194 member states providing data):

    --e coli with >50% resistance both to 3rd generation cephalosporins and to fluoroquinolones in 5/6 WHO regions

    --klebsiella pneumoniae with >50% resistance to 3rd generation cephalosporins in 6/6 regions and to carbapenems in 2/6 WHO regions

    --staph aureus with >50% resistance to methicillin in 5/6 regions

    --strep pneumoniae with >25% resistance to penicillin in 6/6 regions

    --nontyphoidal salmonella with >25% resistance to fluoroquinolones in 3/6 regions

    --n gonorrhea with >25% resistance to 3rd generation cephalosporins in 3/6 regions

--there are significant gaps in information about important pathogens. surveillance not coordinated or harmonized

--multidrug resistant TB is a growing concern, and is under-reported, compromising control efforts. at this point 3.6% of new TB cases and 20.2% of previously treated have multi-drug resistance (and much higher in eastern europe and central asia)

--foci of artemisinin resistance in malaria have be found in a few countries. further spread could jeopardize important recent gains in malaria control. esp a problem in southeast asia (eg cambodia, vietnam, thailand, myanmar)

--increasing levels of HIV drug resistance has been found in patients about to start meds, with 10-17% of patients without prior treatment in europe, japan, US, australia resistant to at least one drug [this has led to recommendation a few years ago by CDC that all newly diagnosed HIV patients get a genotype, since the level of background resistance is so high]

--the data for antibacterial resistance presented above does not explain the full picture: routine surveillance in most countries is often based on patients with severe infections or when treatment has failed. community-acquired infections are underrepresented. mostly hospital data available.

--the increased resistance raises several important issues: when other drugs exist to treat these infections, they are more expensive and less available in resource-limited countries; when available, these drugs (which had been used in the past for very severe infections) are now needed much more frequently for less severe infections; some of these common infections (eg gonorrhea) are developing significant resistance to "the treatment of last resort" (3rd generation cephalosporins).

--major gaps in knowledge exist about antibiotic resistance in foodborne bacteria. need much more developed surveillance to assess levels of antibiotic resistance in bacteria carried by food-producing animals and in the food chain 

--systemic candidiasis is also found to have increasing resistance to fluconazole. and even starting to show resistance to new antifungal agents (echinocandins)

general conclusion: "antimicrobial resistance (AMR) is a global health security threat that requires action across government sectors and society as a whole. surveillance that generates reliable data is the essential foundation of global strategies and public health actions to contain AMR"

other issues, as noted in NY times editorial on sunday:

--FDA has come out with very weak guidelines regarding overuse of antibiotics in agriculture and medicine: only voluntary guidelines to stop indiscriminate use of antibiotics in humans and livestock

--at this point we really need new antibiotics developed. there have been no new class of antibiotics since 1987. issue is that the $$ is in chronic meds. even over-charging for antibiotics doesn't help much if it's for only a 10 day course.  and, will append below a blog from 1/31/2013 which shows that the vast majority of R&D by big pharma is for look-alike drugs and not for important break-throughs (though their arguments supporting the huge costs of drugs hinges on the expense of R&D)

--and, i would add, the whole ecology of infectious diseases is changing with climate change: diseases that once were localized to certain areas (eg dengue and other mosquito-borne diseases) are appearing in new areas (eg, southern US). many of these are likely to spread quickly in naive population.

blog from 1/31/2013:

striking article in BMJ about the image and reality of pharmaceutical research and development (see pharmaceutical R&D bmj 2012 in dropbox, or doi: 10.1136/bmj.e4348).  the $400 billion/yr drug industry has promoted an "innovation crisis" myth that they are too strapped to do the very expensive R&D. reality is that overall there has been a constant rate of new drugs over the past 60 years. the real innovation crisis is in the fact that the percentage of new medications which really offer important therapeutic advantage is on the order of 15% (ie, vast majority of new drugs are "look-alikes", ie yet another ACE inhibitor, statin, etc). this has not changed since i saw data in the 70s. the authors of the BMJ note "since the mid-1990s, independent reviews have also concluded that about 85-90% of all new drugs provide few or no clinical advantages for patients". and still, of the large amount of money spent on R&D, 80% of basic research comes from public sources. they also note that the drug company claims of huge amounts spent by them on R&D are dramatically overstated (eg, 1/2 of amount stated by them comes from "estimating how much profit would have been made if the money had been invested in an index fund of pharmaceutical companies that increased in value 11%/yr, compounded over 15 yrs.") and the down side in companies pushing for look-alike type drugs in order to extend their patents is that many of them are not as good as the original and/or less safe (eg vioxx, rosiglitazone, gatifloxacin...)

geoff