WHEN TYPHOID fever broke out in Pakistan in late 2016, doctors noticed that many patients were not responding to an antibiotic, ceftriaxone, that had worked before. Now we know why. Scientists reported Feb. 20 that the organism that caused the illness, Salmonella enterica serovar Typhi, had become extensively resistant to antibiotics. This development should be another warning that the global threat of antimicrobial resistance remains real, and urgent.
Typhoid fever is a major public-health menace in low- and middle-income countries ; it is often transmitted by contaminated water and causes an estimated 200,000 deaths a year. Prevention is best accomplished through vaccination, access to clean water and improved sanitation, but when the disease strikes, antibiotics are critical for treatment. Already, strains of the organism in Asia and Africa were resistant to some antibiotics, but so-called third- generation antibiotics, such as ceftriaxone, seemed to be working. Then came the outbreak. Three hundred thirty-nine isolates from patients in the Sindh region in southeastern Pakistan, including Karachi and Hyderabad, taken from November 2016 to September 2017, revealed that third-generation antibiotics were failing. Thankfully, a few of the more modern, fourth-generation antibiotics still worked.
To understand how the resistance spread so quickly, scientists mapped the genetic blueprint of the organism. They found it had embraced a piece of genetic material, probably from another species, that conferred the ability to resist ceftriaxone. In essence, bacteria were trading instructions across species on how to fight antibiotics. It has long been known that bacteria can exchange genetic material like this, but the Pakistan study underscored how the process may be accelerating antibiotic resistance. The scientists say in their report, published in the journal mBio, that ceftriaxone “is no longer reliable in the region.”
Antibiotics are a pillar of modern medicine and have saved lives for decades, but the rise of resistance threatens a back-to-the-future moment when small infections could become fatal, as they once were. This reckoning was postponed for a long time because a robust pipeline of new antibiotics was discovered and brought to market. But then the flow began to dry up. Antibiotics are often not as profitable as other drugs, making costly development less attractive for pharmaceutical companies.
The Pew Charitable Trusts and the World Health Organization published analyses in December of the worldwide pipeline of products in clinical development with the potential to treat drug-resistant infections, and they called the findings “grim.” They said too few new antibiotics are under development, and too few represent new classes of drugs. Recently, researchers reported on a new antibiotic found in soil, and with luck there will be more discoveries to follow. Separately, an ambitious public-private program, CARB-X, is attempting to speed up the development of promising early-stage antibiotics and diagnostics.
Just as vital, the overuse of antibiotics in human and animal health must be curbed. Fortunately, there is more attention these days to providing better stewardship of existing drugs. No less is at stake than preserving these miracle medicines, now and for future generations.