Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
MCR-1 gene detected in Scottish Salmonella patient
Health officials in Scotland have announced the country's first detection of antibiotic-resistant bacteria harboring the MCR-1 gene.
According to a report from Health Protection Scotland, investigators with the Scottish Salmonella, Shigella and C. difficile Reference Laboratory identified the gene in an isolate from a Salmonella Enteritides patient who had travelled to Southeast Asia. The agency said the patient is currently recovering and did not require any antimicrobial therapy.
The MCR-1 gene, which can confer resistance to the powerful antibiotic colistin, was first identified in Escherichia coli strains in China in November 15, and since then has been detected in more than 30 countries. MCR-1 has alarmed public health officials because colistin is considered an antibiotic of last resort and is mainly used for bacterial infections that won't respond to other drugs. In addition, the gene can quickly spread colistin resistance to other bacteria because it's located on mobile pieces of DNA called plasmids.
The concern is that MCR-1 will latch onto multidrug-resistant bacteria and create infections that doctors can't treat.
Aug 2 Health Protection Scotland news release
USDA: Antimicrobial resistance ranges from 36% to 44% in E coli
A study by the US Department of Agriculture (USDA) has detected moderate levels of antimicrobial resistance (AMR) in illness-producing Escherichia coli strains from food animals and humans.
The strains were from six serogroups of non-O157 Shiga toxin–producing E coli (n-STEC)—O26, O45, O103, O111, O121, and O145. These serogroups have been identified by the Centers for Disease Control and Prevention as those responsible for the greatest numbers of n-STEC illnesses, hospitalizations, and deaths in the United States. Under USDA rules, any raw ground beef found to contain these bacteria is prohibited from sale to consumers.
Researchers found that 40% of the 138 E coli strains showed resistance to 1 of 15 antimicrobial agents, with AMR prevalence being lower in food animals (36%) than in humans (44%). One animal strain (from serogroups O121 and O145) and one human strain (from serogroup O26) showed extensive resistance.
In the same study, the human and animal E coli strains showed similar susceptibility to 24 disinfectants that were evaluated, with all strains being susceptible to triclosan.
August J Food Prot abstract
Reports note steps for streamlining antibacterial clinical trials
Originally published Aug 4.
A series of articles in a supplement to the latest issue of Clinical Infectious Diseases address what is termed a "crisis" in antibiotic development with recommendations to improve a critical stage in the process—clinical trials.
The journal supplement, titled "Facilitating Antibacterial Drug Development in a Time of Great Need," focuses on advancing and streamlining clinical trials, which are a critical part of the drug development process but which for antibiotics have become overly complicated, expensive, and lengthy to conduct. In particular, the supplement features articles that address the challenges of designing such trials for hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), which are hampered by low enrollment, protocol complexities, and high costs.
The recommendations from the Clinical Trials Transformation Initiative (CTTI)—a public-private partnership that includes government officials, academics, and pharmaceutical industry executives—focus on four keys area areas that could improve HABP/VABP clinical trials: informed consent, protocol design, choice of institutional review board, and efficacy outcome measures. In another paper, CTTI offers suggestions to streamline the process of collecting safety data. These approaches will be tested in an upcoming pilot study.
"The need for new therapeutic and diagnostic options to address the public health crisis of antibiotic resistance and the need to modernize the design and conduct of clinical trials are international issues," Leanne Madre and Pamela Tenaerts of CTTI write in the introduction to the supplement. "Our hope is that the recommendations, activities, and ideas presented highlight the importance of public-private partnerships that are patient-centric and provide proof that streamlining HABP/VABP trials is possible."
Aug 2 Clin Infect Dis supplement
Drug-resistant Salmonella isolates identified in imported food products
Originally published Aug 4.
A new study by the Food and Drug Administration has found antibiotic resistance in more than 20% of Salmonella enterica serovars isolated from food products imported into the US between 2011 and 2013.
The study, published this week in the Journal of Food Protection, found that 23 of 110 nontyphoidalS enterica (NTS) isolates showed resistance to various classes of antibiotics, including beta-lactams and fluoroquinolones, with 12 of the 23 showing resistance to more than three classes. One strain in particular was resistant to all antimicrobial agents tested except amoxicillin and clavulanic acid. The most common strains identified among the 23 drug-resistant isolates were S senftenberg and S enteritidis.
The contaminated food products included vegetables, fruits, meats, and seafood imported mainly from Southeast and East Asian countries. Drug-resistant NTS strains were predominantly found in products imported from Taiwan, Vietnam, Indonesia, and China.
According to the authors, NTS strains are considered the most common foodborne causes of gastroenteritis, enteric fever, diarrhea, and bacteremia. But only some NTS serovars are commonly associated with outbreaks. Serotyping NTS isolates is important for monitoring and tracking these pathogens, the researchers said, and this type of monitoring data could be used to improve food safety programs.
August J Food Prot abstract
Rapid bacterial infection test reduces unnecessary antibiotic use
Originally published Aug 3.
A new study in The Lancet shows that C-reactive protein (CRP) testing performed at the point of care safely reduced antibiotic use in patients with acute respiratory infections in Vietnam, without compromising patients' recovery.
In a randomized, controlled trial performed at primary care centers in northern Vietnam, researchers from the Oxford University Clinical Research Unit in Hanoi assigned more than 2,000 patients who had at least one symptom of an acute respiratory infection into one of two groups: One that received a point-of-care test for C-reactive protein (a biomarker for bacterial infection), and a control group that received routine care.
The primary end point of the study was the number of patients in the two groups receiving antibiotics within 2 weeks of enrollment. The expectation, based on studies performed in Europe, was that CRP testing would reduce antibiotic prescribing by 20%.
Overall, the researchers found that 541 of 908 patients in the CRP-guided group (64%) used an antibiotic within 14 days of follow-up, compared with 738 out of 947 patients in the control group (78%), with significant differences seen in both children and adults. This constituted an 18% reduction in antibiotic prescribing.
In both groups, clinical recovery rates were similar. Adverse events were rare, with no deaths and 14 hospitalizations.
The study is significant because it's the first to gauge the effects of CRP testing on antibiotic prescribing in a low- or middle-income country , the authors wrote. The findings indicate that the intervention—which has the potential to be scaled up with affordable and reliable CRP tests becoming more available—could be effective in countries with resource constraints.
"With this easy-to-use tool, primary healthcare providers can safely limit the unnecessary antibiotic use for viral respiratory infections," investigator Nguyen Van Kinh, MD, PhD, of the National Hospital for Tropical Disease in Hanoi said in a news release. "The study provides important evidence for simple solutions in antibiotic stewardship programmes."
Aug 2 Lancet Glob Health study
Aug 2 Oxford University news release
Patient sharing among hospitals might foster spread of CRE
Originally published Aug 3.
A new study indicates that hospitals that are more likely to share patients with other hospitals have higher rates of carbapenem-resistant Enterobacteriaceae (CRE).
In the study, published in Clinical Infectious Diseases on Aug 1, researchers used a social network analysis of 185 Illinois hospitals in a statewide patient-sharing network to evaluate the influence of patient sharing on hospital-specific rates of CRE.
What they found was that hospitals that were more connected or central—ie, were more likely to share patients with other hospitals—had higher burdens of CRE, and that each additional hospital connection increased that burden. In rural counties, for example, each hospital connection was associated with a 6% increase in the CRE rate. In Chicago and other urban parts of the state, the associated increase was 3%.
In addition, sharing four or more patients with a long-term acute care hospital, where CRE infections are particularly problematic, was also linked to higher CRE rates.
Although the study does not prove that more interconnectedness causes higher CRE rates, the authors said the finding have immediate public health implications. "Our results provide an important way of identifying hospitals at highest risk of CRE exposure," the authors wrote.
An accompanying editorial adds that the study highlights the need for greater understanding of the role that hospital transfers play in infection control, and that the findings have "profound implications" for infectious disease surveillance efforts.
Aug 1 Clin Infect Dis abstract
Aug 1 Clin Infect Dis commentary
French study finds loss of plasmid-related drug resistance rare
Originally published Aug 2.
A new study from a team of French researchers suggests that when bacteria acquire plasmids containing drug-resistant genes, they rarely lose them.
In the study, published in Antimicrobial Agents and Chemotherapy, the researchers inoculated pigs with a strain of non-pathogenic Escherichia Coli (E coli M63) carrying plasmids—small strands of DNA—encoded for resistance to cephalosporin antibiotics and other antimicrobials, and placed the pigs with non-inoculated pigs. The purpose was to document how plasmid-encoded resistance spreads and how persistent it is. Because the pigs weren't treated with any extended-spectrum cephalosporin (ESC) antibiotics, there was no selection pressure favoring the persistence of ESC-resistant bacteria.
The researchers then collected fecal samples from the pigs and grew 353 E coli isolates. Genomic sequencing determined that out of the 353 isolates, only 3 lost the plasmid and were ESC-susceptible.
"Our results show that once a plasmid encoding resistance genes is transferred to a bacterial host, the probability that the bacteria will lose the encoded resistances is quite low, even absent a selective pressure," corresponding author Isabelle Kempf, DVM, from the Universite de Bretaigne Loire in France, said in a news release from the American Society for Microbiology (ASM), which publishes the journal.
Kempf and her colleagues say the finding is significant because cephalosporin antibiotics are critical to human health, and the gene for cephalosporin resistance is frequently carried on plasmids. They say developing a better understanding of how plasmids work, along with tools to counteract them, could lead to the creation of new tools to combat antimicrobial resistance.
Aug 1 Antimicrob Agents Chemother study
Aug 1 ASM news release
Microbiome treatment for C diff fails in phase 2 trial
Originally published Aug 1.
Biotechnology firm Seres Therapeutics announced late last week that SER-109, a drug designed to treat patients with recurring Clostridium difficile infections (CDIs), failed in a phase 2 study.
The randomized, double-blind, placebo-controlled study was intended to determine whether SER-109—essentially a collection of good bacteria from the human microbiome in pill form—could reduce the risk of CDI over an 8-week period. A total of 89 subjects were enrolled in the trial, with 59 receiving SER-109 and 30 receiving a placebo. Based on the 8-week data, CDI recurrence occurred in 44% of the subjects who received treatment with SER-109, compared with 53% in the placebo group—a difference that was not statistically significant.
The company said that the results were unexpected in light of the positive data from earlier trials, and that it plans to make appropriate adjustments to development plans for the drug in consultation with the Food and Drug Administration.
"C. difficile infection treatment options, including unregulated fecal microbial transplants, remain poor," Seres Therapeutics President and CEO Roger Pomerantz, MD, said in a company news release. "We will take our learnings from this study and continue in our pioneering efforts to develop meaningful new microbiome therapeutics for C. difficile infection and other serious diseases."
The Centers for Disease Control and Prevention estimates that C difficile caused nearly 500,000 infections in 2011, and 29,000 patients died within 30 days of the initial diagnosis.
Jul 29 Seres Therapeutics news release
