Growing threat from multidrug-resistant shigella in the U.S.

Highly Contagious, Antibiotic-Resistant Food Poisoning Establishes U.S. Presence

The kinds of bacteria that can cause food poisoning lurk all around us. These germs can be especially easy to pick up when traveling internationally as well as in places, such as children's day cares, which are hard to keep clean. The infections usually clear up on their own but sometimes require hospitalizations and hefty doses of antibiotics to expunge. Unfortunately, the bacteria are becoming increasingly resistant to treatment.

The latest bad news came in April when the U.S. Centers for Disease Control and Prevention reported an outbreak of Shigella sonnei that has become resistant tociprofloxacin—one of the last remaining medications in pill form that can kill the germ. Since then a Scientific American investigation shows the worrisome strain is still circulating in the U.S. a year after it first emerged.

Shigella bacteria typically cause about 500,000 diarrheal illnesses and 40 deaths in the U.S. every year. Children who are malnourished and people with compromised immune systems are particularly at risk of developing severe cases. Symptoms include diarrhea that is sometimes bloody, fever and abdominal pain, and typically last about a week.

The bacteria occur naturally in the U.S. but, heretofore, people typically caught ciprofloxacin-resistant strains while traveling internationally. In the current outbreak, however, many people who became sick had not recently been out of the country, which proves that the multidrug-resistant bug has now established a firm domestic presence.

The CDC has confirmed 275 cases of ciprofloxacin-resistant shigella across the country from May 2014 to May 2015, according to data obtained exclusively by Scientific American (see chart below). Although these figures appear small, they almost certainly represent but a tiny fraction of the true number of ciprofloxacin-resistant cases. Shigella infections are supposed to be reported to the CDC but a lot of people who get sick do not go to the doctor. And those who do are sometimes not tested for the presence of shigella, let alone drug resistance.

Vulnerable populations are some of the hardest hit in this outbreak, including cases linked to a day care center, homeless people in San Francisco and HIV-positive individuals in Philadelphia. As few as 10 shigella germs can cause an infection—making the bacteria virtually undetectable as it quickly spreads in contaminated food and water or from person to person.

Other drugs that the pathogen has overcome in the past include ampicillin, streptomycin and tetracycline. Anna Bowen, a medical officer in the CDC's Waterborne Diseases Prevention Branch and lead author of the April study, says the CDC has identified some cases in this outbreak that were resistant to all of the oral treatment options currently available. The next line of defense is a broader-spectrum, more expensive antibioticthat must be administered via injection or an intravenous line.

Whereas labs can test for ciprofloxacin resistance, there are currently no standardized tests to identify if a shigella infection is resistant to azithromycin, which is the go-to drug for children. (The U.S. Food and Drug Administration has approved ciprofloxacin only for adults.) "Almost no clinical labs are doing this sort of testing," Bowen says, "and so patients are being treated kind of blindly since the providers don't know if azithromycin is an appropriate choice or not."

Lag time in reporting is another issue. San Francisco, for example, is tracking nearly two times the number of cases that the CDC counts as confirmed for the city—228 cases versus 119. Cora Hoover, director of Communicable Disease Control and Prevention for the San Francisco Department of Public Health, says they have slightly different case definitions because as the city agency on the ground investigating this outbreak they want assurance all possible patients are identified; also it takes so long to confirm a case. Public health officials normally follow up with each patient, and lab tests can take weeks.

It can take around a month to confirm a case of shigellosis is both antibiotic-resistant and part of the same outbreak, though it varies. Generally, once a doctor identifies a shigella infection, he or she reports it to the city or state public health agency and sends a stool sample to the lab to confirm the diagnosis. The lab grows or "cultures" the bacteria and reports its findings back to the doctor and agency in about a week. The health agency then reports the case to the CDC, which tests a selection of cases for antibiotic resistance via the National Antimicrobial Resistance Monitoring System and its national laboratory network, PulseNet. Results from PulseNet's genetic testing of sample cases can be complete within a couple of weeks.

By the time the full picture of a single case is confirmed, the patient is usually better. Caroline Johnson, director of the Division of Disease Control at Public Health for the City of Philadelphia, says her division usually suspects that a case is part of an outbreak but does not know for sure until the full results are in.

Peter Gerner-Smidt, chief of the CDC's Enteric Diseases Laboratory Branch and PulseNet, says labs will gradually move away from having to culture bacteria to identify them. As genetic testing becomes cheaper and more accessible, state labs will eventually be able to get that information by determining the whole DNA sequence of each sample. This approach will hopefully reveal antibiotic-resistance more quickly, he says, but it will likely take years before these tests are widely used.

Because of the increasing threat of multidrug-resistant shigella, the CDC and other health agencies recommend doctors only prescribe antibiotics for severe cases. Shigellosis can actually clear up on its own with proper hydration and rest. Prevention is therefore the best weapon for controlling resistant shigella, Bowen says, particularly because the U.S. cannot regulate antibiotic overuse in other countries, but it still affects patients here.

"Problems with antibiotic resistance anywhere are problems with antibiotic resistance everywhere," she says. "There are no borders when it comes to antibiotic resistance, and we have all got to be vigilant."

The numbers in this chart do not fully represent the shigellosis burden in the U.S. because not all cases are reported. The weekly case totals in this graphic were calculated by subtracting the previous week's cumulative total from the current week's cumulative total as reported in the CDC's Morbidity and Mortality Weekly Report. These cumulative totals can fluctuate up or down based on new information.