S. typhi and shigella resistance increasing!!!

A recent article documented the emergence of potentially epidemic, highly resistant strains of Salmonella typhi, the organism associated with typhoid fever (see http://mbio.asm.org/content/9/1/e00105-18.full.pdf​ ). Thanks to Paul Susman for bringing this to my attention.

Details:
-- there was an outbreak in Hyderabad, Pakistan of more than 300 cases of extensively drug-resistant (XDR) typhoid in a 10 month period between 2016 and 2017.
-- Prior reports have documented relatively common resistance to the three first-line antibiotics (chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole), a multidrug resistant (MDR) organism prevalent in parts of South and Southeast Asia, Africa, and Oceania since the late 1970s.
-- This new XDR strain is now also resistant to fluoroquinolones and third-generation cephalosporins (those typically used were parenteral ceftriaxone and cefotaxime, as well as oral cefixime)
-- previously, there have been just sporadic cases of the XDR

Results:
-- 339 isolates in the Sindh region of Pakistan , which includes Hyderabad and Karachi, were found to be resistant to ceftriaxone, ciprofloxacin, ampicillin, and trimethoprim sulfamethoxazole, and susceptible to imipenem, meropenem, and azithromycin.
-- Whole genome sequencing in 87 of the strains revealed that the likely cause for the development of XDR was a ubiquitous antibiotic-resistance plasmid, likely from E. coli

Commentary:
-- typhoid fever is a huge public health problem in low and middle income countries, with approximately 200,000 deaths per year
-- S. typhi is transmitted by fecal-oral route, typically by contaminated water. Vaccination, access to clean water, and improved sanitation are effective in preventing typhoid fever. Antibiotics, however, are necessary to treat infections
-- MDR typhoid has been treated with fluoroquinolones, third-generation cephalosporins, and azithromycin.  But, there have been sporadic cases of resistance to ceftriaxone and azithromycin over the years.
-- In Pakistan, empiric therapy with third-generation cephalosporins has been the standard of therapy, with only very few cases of ceftriaxone resistance (0.08%, specifically in two children from Karachi from 2009 to 2011).
-- From November 2016, a large number of ceftriaxone-resistant cases have been reported in the province of Sindh. Previously there had just been sporadic cases of XDR reported, this being the first large group of ill patients.
-- A case of XDR S. typhi was also identified in the United Kingdom from a traveler returning from Pakistan.

So, pretty scary stuff, with this highly-resistant S typhi strain evolving, probably from a common plasmid from E. coli, and affecting large numbers of patients. It was mildly reassuring that in this outbreak, the XDR strain, was sensitive to azithromycin. However, azithromycin resistance has been reported previously (as noted above) and it seems only a matter of time until we see largely untreatable numbers of patients developing typhoid fever...

For prior relevant blogs:

http://gmodestmedblogs.blogspot.com/2014/05/who-report-on-antimicrobial-resistance.html  the WHO report detailing their data on global antibiotic resistance of many bacteria (though, notably, they only include nontyphoidal salmonella, not the one above)
http://gmodestmedblogs.blogspot.com/2018/06/increasing-gonorrhea-and-syphilis-in.html for increasing gonococcal and syphilis infections, with reference to a prior blog on GC resistance
http://gmodestmedblogs.blogspot.com/2018/04/antibiotic-overuse-in-animals-and.html which reports on antibiotic overuse in animals and humans, along with more resistant GC
http://gmodestmedblogs.blogspot.com/2017/07/take-full-course-of-antibiotics.html , reviews an interesting article suggesting that for many infections, it is probably better NOT to take the full course of prescribed antibiotics
http://gmodestmedblogs.blogspot.com/2016/06/response-and-further-comments-on-e-coli.html  for a blog on the emergence of the E. coli superbug
http://gmodestmedblogs.blogspot.com/2017/06/decreasing-antibiotic-resistance-by.html which describes an effective antibiotic stewardship program

and,
http://gmodestmedblogs.blogspot.com/search/label/antibiotic%20resistance  and for the array of blogs on antibiotic resistance


and, coincidentally, the CDC just issued an update on their recommendations for treating shigella infections because of reduced susceptibility to ciprofloxacin and azithromycin, and this resistance seems to be increasing exponentially (see https://emergency.cdc.gov/han/han00411.asp​ ).

Details:
--2016: surveillance data showed 8.2% of shigella isolates were resistant to ciprofloxacin and 9.5% to azithromycin
--2017: surveillance: 16.5% were cipro-resistant and 22.1% have reduced azithro susceptibility

Commentary:
--it should be emphasized that increased laboratory resistance in shigella does not necessarily translate to either worse clinical outcomes or changes in the risk of transmissibility (the laboratory data do, however, predict response rates to salmonella)
--as with salmonella (above), the major cause of shigella resistance seems to be plasmid-mediated (which really allows for rapid emergence of resistance), and quinolone-resistance is commonly associated with resistance to azithromycin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid, and ampicillin.
--there was a multistate outbreak of multi-drug resistance Shigella flexneri, mostly in adult men (often self-identified as MSM).
--as per usual, do not routinely prescribe antibiotics for shigella. Shigellosis is typically self-limited (5-7 days), overtreatment could increase resistance,  and antibiotics may prolong viral shedding
--but, treat those immunocompromised or with severe illness

Recommendations:
--avoid cipro if you know the MIC for cipro is 0.12 mcg/ml or higher
--get follow-up stool cultures if patients are getting worse despite antibiotic treatment
--consult state or local public health dept to see if/when kids can go to school/daycare, adults can return to work
--and routine sanitation measures: wash hands well for at least 20 seconds with soap/water, do not prepare foods for others, and no sex for 2 weeks after diarrhea resolved.
--let public health officials know if MIC is high (shigellosis is also a reportable condition, but this information is particularly important for public health officials)