Antibiotic-Resistant Bacteria Reach U.S.

 

A dangerous new form of antibiotic resistance has spread to the United States, according to a report published Thursday. Researchers at the Department of Defense announced that a Pennsylvania woman developed a urinary tract infection (UTI) with bacteria that fought off an antibiotic of last resort called colistin, and had  15 genes for resistance to other antibiotics. Until now, many bacteria have been vulnerable to colistin, even if they have been able to survive other medications. Since this type of resistance can easily spread between bacteria, the findings have sounded alarm bells among scientists over fears that common infections will soon be untreatable.
Bacteria have exhibited colistin resistance in the past, but this time it is different: Previous forms of the resistance weakened the microbes, and the resistance genes were located on DNA that was not easily shared among bacteria. But in November 2015, Chinese and British researchers discovered that mcr-1, a new gene for colistin resistance, was circulating among animals and people in China and was housed on a circular piece of bacteria DNA called a plasmid. Bacteria carrying this plasmid can share copies of it with other bacteria when they come into contact, which allows the colistin resistance to spread widely and rapidly. Because colistin is commonly used in food animals in China, but not in people, “the emergence of mcr-1 likely occurred because of extensive use of colistin in food animal production—which is yet another example of how injudicious use of antimicrobials comes back to hurt us,” explains James Johnson, an infectious disease specialist at the University of Minnesota.  
Soon after the Chinese study was published, researchers in Europe and Canada announced that they had found mcr-1-mediated colistin resistance, too. And now, thanks to newly launched Department of Defense surveillance efforts, it has been discovered here in the U.S. as well. In May researchers at the Walter Reed Army Institute of Research and the Walter Reed National Military Medical Center began testing drug-resistant Escherichia coli bacteria isolated from U.S. patients who had been treated at various institutions. That is when they identified the first instance of mcr-1-mediated colistin resistance in bacteria, collected from a woman treated for a UTI in late April at an outpatient military medical center. It also seems to have reached America’s livestock: In a blog post published on Thursday, the U.S. Department of Agriculture and the Department of Health and Human Services announced that they had discovered colistin-resistant bacteria in a sample taken from the intestine of an American pig.
People may pick up these bacteria in various ways, including from their food. Although the types of E. coli that cause UTIs are found within the urinary tract, they typically end up there because they have migrated from the gut. Research suggests that these types of E. coli often contaminate raw meat; in 2010 the National Antimicrobial Resistance Monitoring System, a collaborative governmental project, reported that more than 75 percent of retail chicken and turkey meat was contaminated with E. coli and that many of these bacteria were resistant to multiple antibiotics. A separate 2011 study based on this data reported that more than one-fifth of E. coli found on poultry meat were of the type that can—if ingested when food is not cooked properly—migrate from the gut and cause serious infections such as UTIs.
Ultimately, the big fear is that the newly discovered mcr-1 gene will end up being picked up by other multi-drug-resistant bacteria--particularly  a kind known as Carbapenem-resistant Enterobacteriaceae, or CRE. These microbes are resistant to a class of drugs called carbapenems, which are reserved to treat certain resistant infections. Infections with CRE are “becoming more and more common,” says Lance Price, a microbiologist who directs the Antibiotic Resistance Action Center at George Washington University’s Milken Institute School of Public Health—and right now, colistin is among the only drugs that can cure them. If CRE end up intermingling with bacteria containing the mcr-1 gene inside a person or animal’s gut, or even on a piece of meat—and this could already be happening unbeknownst to anyone—the world could suddenly be faced with pan-drug-resistant bacteria. “Then it’s a royal flush—the infection has an unbeatable hand,” Price says. “It’s untreatable."

A new review of surveillance data reveals that rates of highly drug-resistant infections are on the increase among children in the United States. The findings reinforce the need for better ways to track, prevent, and treat these serious infections in children and for bolstering stewardship programs.

The researchers say as highly drug-resistant infections rise, they leave healthcare providers with limited choices in effective antibiotics to treat them, and these antibiotics are less safe and more toxic in children.

The researchers came to this conclusion after analyzing a large reference-laboratory database of samples collected from pediatric patients all over the U.S. between 1999-2012. The samples were of an important infection-causing bacteria called Pseudomonas aeruginosa.
P. aeruginosa is a common cause of healthcare-associated infections that can result in prolonged illness, require longer hospital stays, and, ultimately, raise the risk of death.
The researchers report their findings in the Journal of the Pediatric Infectious Diseases Society.
First and corresponding author Latania K. Logan, assistant professor at Rush University Medical Center in Chicago, IL, says:
"Infections with P. aeruginosa can be serious and are associated with significant morbidity and mortality."
Antibiotics have transformed medicine - they have made it possible to treat once deadly infections and paved the way for advances like transplant surgery and chemotherapy for cancer. They have reduced disease and saved lives.
However, misuse of the drugs has also contributed to the increasing problem of antibiotic resistance, now a serious and growing threat to public health.

Multi-drug resistant P. aeruginosa a 'serious threat'

The Centers for Disease Control and Prevention (CDC) include antibiotic-resistant P. aeruginosa among the top 18 drug-resistant threats to Americans.
The CDC class multi-drug resistant P. aeruginosa as a serious threat - that is, "not considered urgent" but the threat "will worsen and may become urgent without ongoing public health monitoring and prevention activities."
Their estimates show 51,000 healthcare-associated P. aeruginosa infections in adults and children occur in the U.S. each year. This includes 6,700 cases where the bacterium is resistant to multiple types of antibiotic, resulting in 440 deaths a year.
The CDC suggest hospital antibiotic stewardship programs should contain the following core elements:

• Commitment from leaders: dedicate the human, financial, and information technology resources necessary to implement the program
• Accountability: appoint a single leader responsible for getting results - evidence from successful programs shows this works
• Drug expertise: appoint a single pharmacist leader who works to improve antibiotic use
• Action: implement at least one recommended action - such as evaluate the need for continuing treatment after a set period (for example, "antibiotic time-out" after 48 hours)
• Monitoring: track patterns of drug prescribing and resistance
• Informing: keep doctors, nurses, and relevant staff up-to-date about antibiotic use and resistance
• Education: educate clinicians about resistance and optimal prescribing.

Highly resistant P. aeruginosa infections rising in children

However, the researchers behind the new study note that - despite many papers warning about rising national rates of antibiotic resistance - few investigate the trends of drug-resistant P. aeruginosa in children specifically.
They looked at data from a surveillance network of laboratories serving around 300 hospitals across the U.S. The laboratories analyze patient samples of P. aeruginosa for resistance to several types of drugs.
For their analysis, the researchers included data on children aged 1-17 who were in outpatient, inpatient, intensive care unit, and long-term care settings from January 1999 - July 2012. They excluded children under 1 year old and patients with cystic fibrosis.
The researchers found the proportion of P. aeruginosa samples that were resistant to at least three classes of antibiotics - that is, multi-drug resistant - increased from 15.5 percent in 1999 to 26 percent in 2012.
The proportion that were resistant to carbapenems rose from 9.4 percent to 20 percent over the same period. Carbapenems are a class of antibiotic that is considered a treatment of last resort for highly resistant infections.
The researchers found both multi-drug resistant and carbapenem-resistant P. aeruginosa were more common in patients in intensive care units, in children aged 13-17, in respiratory samples, and among patients in the Midwest states (Iowa, Kansas, Minnesota, Missouri, Nebraska, and the Dakotas).

They conclude their findings highlight the need for "aggressive prevention strategies, including instituting antimicrobial stewardship programs in pediatric settings, are essential for combating antimicrobial resistance."
They suggest healthcare facilities should also consider using rapid molecular diagnostics to help make decisions about use of antibiotics.

"Highly drug-resistant P. aeruginosa infections leave healthcare providers with limited - or sometimes no - antibiotic choices available, and these antibiotics are less safe and more toxic in children."

Co-author Sumanth Gandra, Center for Disease Dynamics, Economics & Policy