Chinese surveillance study finds multidrug-resistant E coli in food
A surveillance study by Chinese scientists has found multidrug-resistant Escherichia coli strains in food products carrying the MCR-1 and blaNDM-1 resistance genes, and mobile genetic elements similar to those found in human strains, according to a paper yesterday in Eurosurveillance.
Among the 1,166 non-repeated cephalosporin-resistant E coli isolates recovered from 2,137 samples of pork, beef, chicken, and shrimp bought at markets in Shenzen, China, from 2015 through 2017, the scientists identified 390 and 42, respectively, that were resistant to colistin and meropenem, and 5 isolates that were resistant to both antibiotics.
Among the 390 colistin-resistant E coli isolates, the rate of resistance to colistin rose from 26% in 2015 to 46% in 2017, while rates of meropenem resistance in the 42 meropenem-resistant isolates increased from 0.3% in 2015 to 17% in 2017.
Further screening found that all of the colistin-resistant isolates carried the MCR-1 gene and 36 of the 42 meropenem-resistant isolates carried the blaNDM-1 gene, with six harboring the blaNDM-5 gene; the five isolates that were resistant to both colistin and meropenem were carrying both MCR-1 and blaNDM genes. Notably, the scientists identified plasmids—in particular the ca 46kb IncX3 plasmid—that have been commonly reported in colistin- and carbapenem-resistant clinical isolates but not in isolates from animals and food. Conjugation experiments revealed that the colistin and meropenem resistance phenotypes of the 5 MCR-1 and blaNDM-bearing strains were transferable to other E colistrains of food origin.
The authors of the study say the isolation of E coli strains harboring blaNDM-1 and MCR-1 that structurally resemble clinical strains has not previously been reported, and warn that the rising prevalence of these strains could mean an increase in severe, multidrug-resistant foodborne infections.
"The increasing prevalence of Enterobacteriaceae strains carrying bla NDM and mcr-1 in food products will lead to increased colonisation of the human gastrointestinal tract with these Enterobacteriaceae strains, a phenomenon that has been associated with the high prevalence of drug-resistant infections in clinical settings," they write. "Further surveillance of bla NDM-1 and mcr-1 in other food products is warranted."
Mar 28 Eurosurveill study
Study in Georgia finds poor long-term outcomes for XDR-TB treatment
A study today in Open Forum Infectious Diseases reports high mortality among patients with extensively drug-resistant tuberculosis (XDR-TB) in the former Soviet republic of Georgia, with most deaths occurring post-treatment.
In the retrospective population-based cohort study, researchers from Emory University and Georgia's National Center for Tuberculosis and Lung Diseases assessed end-of-treatment and long-term outcomes in patients with XDR-TB. They also evaluated risk factors for poor outcomes. Patients were treated by directly observed therapy in accordance with 2011 World Health Organization (WHO) treatment guidelines for drug-resistant TB; the drug regimen did not include the newer agents bedaquiline and delamanid, which are now recommended under current WHO guidelines.
From 2011 through 2013, 111 patients initiated treatment for XDR-TB; end-of-treatment outcomes were available for 106. Of those patients, 35 (33%) had a favorable outcome from initial XDR-TB treatment and 71 (67%) had an unfavorable outcome, with 16 (15.1%) dying. After cessation of initial XDR-TB treatment, an additional 20 of 90 (22.2%) patients who were alive at the end of treatment died, increasing the overall mortality rate to 34% (36 of 106). In multivariable analysis, the main factor for post-treatment mortality was unfavorable initial end-of-treatment outcome (adjusted odds ratio, 14.41; 95% confidence interval, 1.78 to 117.3).
"The results of our study highlight the need for better surveillance during and after treatment for highly drug resistant TB," the authors of the study write. "After treatment cessation, public health resources should focus on continual monitoring of patients given a significant risk of mortality and relapse."
Mar 29 Open Forum Infect Dis abstract
Darden commits to buying chicken raised without antibiotics
Multi-brand restaurant operator Darden Restaurants yesterday announced it will phase out the routine use of medically important antibiotics in its chicken supply chain by 2023.
The commitment to buying chicken raised without medically important antibiotics is part of a wider animal welfare policy that the company, whose brands include Olive Garden and The Capital Grille, is adopting. The policy aims to increase mobility, lower injury and mortality rates, and reduce stress and fear among the farm animals in its supply chain.
In addition to responsible use of antibiotics, Darden has identified humane housing, avoidance of pain, slaughter practices, and farm animal transportation as priority areas for improvement.
Darden operates more than 1,700 restaurants in North America.
Mar 28 Darden Restaurants press release
Wendy's urged to cut use of medically important antibiotics in beef supply
Originally published by CIDRAP News Mar 28
Consumer and public health advocacy group U.S. PIRG Education Fund is calling on the nation's third-largest burger chain to reduce its reliance on beef raised with the routine use of medically important antibiotics.
The group held events today in front of Wendy's franchises in New York and Chicago to urge the restaurant chain to follow the lead of McDonald's, which announced in December 2018 that it would partner with its beef suppliers to reduce the use of medically important antibiotics for disease prevention in its beef supply chain. McDonald's was the first major burger chain to release a policy on antibiotic use in beef.
Wendy's is one of several fast-food chains that have stopped serving chicken raised with medically important antibiotics, and it currently sources up to 20% of its beef from suppliers that have cut the use of the antibiotic tylosin in their cattle. But Matt Wellington, director of U.S. PIRG's Stop the Overuse of Antibiotics campaign, which has pushed several restaurant chains to reduce routine use of medically important antibiotics in their meat supply chains, says the company can do more.
"We can't waste life-saving medicines to produce cheap beef," Wellington said in a U.S. PIRG (Public Interest Research Group) press release. "The cost to our health is too high, and Wendy's can use its buying power to help move the beef industry away from overusing antibiotics."
Mar 28 U.S. PIRG press release
Former UK advisor on antibiotic resistance criticizes drug industry
Originally published by CIDRAP News Mar 28
Lord Jim O'Neill, an economist and former advisor to the British government on antibiotic resistance, suggested yesterday that nationalizing part of the pharmaceutical industry may be a way to stimulate new antibiotic development.
O'Neill—former chair of the British government's Review on Antimicrobial Resistance—told BBC News that he was shocked that pharmaceutical companies have failed to develop new antibiotics for drug-resistant infections. He suggested that the answer may be for the government to create a new public body to acquire the antibiotic research and development programs that many drug companies have been abandoning.
"If you had asked me three years ago, I would have thought that would have been a bit crazy," O'Neill told the BBC. "But nearly three years after our review came out, there's endless talk but there's no progress in waking up the pharmaceutical industry to want to do this.
"So, by default, I find my mind thinking why not explore the idea of some public utility that's got public-purpose ownership of it, just take it away from them and take it over," he said.
A 2015 report by the Review on Antimicrobial Resistance called for creating a $2 billion global innovation fund to boost investment in new antibiotic research and development, and suggested that from $1.6 billion to $3.7 billion a year would be needed to provide "pull" incentives to encourage drug companies to develop new antibiotics. The first report by the group warned that antimicrobial resistance could kill an extra 10 million people a year, and cost up to $100 trillion, by 2050 if nothing is done to slow or halt it.
In January, the British government announced a new payment model for antibiotics, under which the National Health Service would pay pharmaceutical companies up front for access to effective antibiotics. The government hopes the model, which aims to delink the value of antibiotics from sales volume, could help spur new antibiotic development.
Mar 27 BBC News story
Review: Cefazolin an option for methicillin-sensitive staph bacteremia
Originally published by CIDRAP News Mar 28
A systematic review and meta-analysis of data from more than 11,000 patients published yesterday in Clinical Microbiology and Infection suggests that cefazolin is at least equally effective as anti-staphylococcal penicillins (ASP) in treating methicillin-sensitive Staphylococcus aureus bacteremia (SAB), and associated with less nephrotoxicity.
The review looked at 14 non-randomized studies on the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB, and a meta-analysis was conducted to estimate relative risk (RR) of the two treatments on the primary end point—90-day all-cause mortality. Secondary end points included 30-day all-cause mortality, treatment failure/relapse, and nephrotoxicity. The researchers also looked at outcomes in a subset of patients with high pathogen loads, including those with endocarditis and abscesses.
Seven of the studies reported the primary end point and showed an overall 90-day mortality of 25.1% (703/2,802) in the ASP group and 18.2% (289/1,589) in the cefazolin group, resulting in an RR of 0.71 (95% confidence interval [CI], 0.50 to 1.02). For the secondary end points, the researchers found that cefazolin may be associated with lower 30-day mortality (RR, 0.70; 95% CI 0.54 to 0.91) and less nephrotoxicity (RR, 0.36; 95% CI, 0.21 to 0.59), but they were uncertain whether cefazolin and ASP differ regarding treatment failure/relapse (RR, 0.84; 95% CI, 0.59 to 1.18), as the quality of the evidence was very low.
The subgroup analysis showed that cefazolin may be associated with equal 30-day and 90-day mortality for patients with endocarditis (RR, 0.71; 95% CI, 0.12 to 4.05) and abscesses (RR, 1.17; 95% CI, 0.30 to 4.63).
The authors say the main limitation of the review is that all the available evidence comes from non-randomized, single-center studies with an inherent high risk of bias. They suggest multicenter randomized controlled trials are needed to identify the safest and most effective treatment for patients with SAB.
Mar 27 Clin Microbiol Infect abstract
Study finds disconnect in clinic docs' antimicrobial resistance knowledge
Originally published by CIDRAP News Mar 27
A survey of physician attitudes about antibiotic use in clinic settings found that nearly all agree that antimicrobial resistance (AMR) is a national problem, but only 63% thought the issue is a problem at their own facilities. A group based at Wayne State University reported its findings yesterday in the American Journal of Infection Control.
The researchers focus on clinic settings because of the high volume of antibiotic prescribing at physician discretion. The cross-sectional survey consisted of a self-administered 34-item questionnaire to eligible US physicians from May 2018 to August 2018. The voluntary anonymous survey was delivered through email and online forums such as Facebook. The most common ambulatory settings were hospital outpatient clinics and emergency departments, urgent care centers, surgical centers, oncology clinics, mental health clinics, and hospice.
Of 323 doctors who completed the survey, 271 (84%) were attending physicians, with 62% in primary care and the rest residents or fellows. The survey revealed that 99% agreed that AMR is a national problem and 99% reported that overprescribing or use of antibiotics for self-limiting nonbacterial infections are important causes of AMR. However, respondents voiced less agreement on other factors perceived to play a role in AMR, such as overuse of broad-spectrum medications and patients' expectations.
Only 63% of respondents reported AMR as a problem in their facilities, and 23% still believe aggressive prescribing is needed to avoid clinical failures. Prescribing guidelines had a low to moderate impact on antibiotic choice, and measures that respondents say reduce AMR include education, institution guidelines, and regular audits.
Aside from underestimating the significance of the problem in their own clinics, respondents seem to have significant knowledge gaps and ambivalence about resistance mechanisms, the authors concluded. "Global and national AMR awareness campaigns and antibiotic stewardships that incorporate interactive education and feedback, along with input of local experts are critically needed to successfully address the mounting problem of AMR in both inpatient and ambulatory settings," they wrote.
Mar 26 Am J Infect Control abstract
No treatment failure difference noted in IV vs oral meds for UTI bacteremia
Originally published by CIDRAP News Mar 27
A comparison of intravenous (IV) and IV-transitioned-to-oral antibiotic treatment in hospital patients with gram-negative bacteremia from a urinary tract infection (UTI) found no difference in treatment failure, researchers based at the Mayo Clinic in Rochester, Minnesota, reported yesterday in the Journal of Global Antimicrobial Resistance.
The single-center retrospective cohort study included hospitalized noncritically ill adults patients who received culture-susceptible antibiotic therapy for 7 to 12 days. The most common treatments were ciprofloxacin and levofloxacin.
Of 346 patients enrolled in the study, 82 (23.7%) were in the IV group and 264 (76.3%) were in the group transitioned from IV to oral medication. The researchers said the transition from IV to oral antibiotics has been a successful strategy for battling several infections, but there is little data on outcomes in patients with bacteremia from UTIs.
Of six treatment failures, two (2.4%) occurred in the IV group and four (1.5%) occurred in the oral treatment group. All failures were linked to recurrence of the index organism.
When the team looked at secondary outcomes, they found that the IV group had significantly higher rates of IV line-associated complications, with shorter hospital stays for the patients in the oral cohort.
Mar 26 J Glob Antimicrob Resist abstract
Scientists note low clinical yield of molecular diagnostic panels for diarrhea
Originally published by CIDRAP News Mar 27
A study today in Open Forum Infectious Diseases found a low clinical yield for molecular diagnostic panels as an antimicrobial stewardship tool for outpatients with diarrhea.
Molecular diagnostic panels for enteric pathogens offer increased sensitivity and reduced turnaround time, the authors of the study, primarily from the University of Virginia, write. But they come at a steep price, and often pathogen detections do not change clinical management and enteric disease is self-limited.
To explore the panels more in depth, the researchers analyzed 629 tests from adult outpatients with diarrhea in 2015 and 2016, among which a pathogen was detected in 127 tests, or 20.2%.The most common pathogens were enteropathogenic E coli (7.5%), norovirus (3.8%), enteroaggregative E coli (2.2%), Campylobacter (1.4%), and Salmonella (1.4%).
The investigators noted that the clinical yield of diagnostic panels was low, with antimicrobial treatment clearly indicated for only 18 subjects (2.9%) and any change in clinical management indicated for 33 subjects (5.2%). In contrast, following the clinical criteria for diagnostic testing from 2017 guidelines from the Infectious Diseases Society of America (IDSA) would have reduced testing by 32.3% without significantly reducing the clinical yield.
Mar 27 Open Forum Infect Dis study
Vietnamese study shows limits of rapid diagnostics technology
Originally published by CIDRAP News Mar 26
A randomized controlled trial of rapid diagnostics technology in two hospitals in Vietnam found no improvement in antimicrobial therapy compared with traditional microbiologic methods, according to a study in the Journal of Infection.
The study aimed to determine whether matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS), which can accurately identify cultured bacteria or fungi within minutes, increased the number of patients with confirmed infection on optimal antimicrobial therapy when compared with conventional microbiological identification. While MALDITOF-MS has been shown to improve clinical decision-making in high-income settings when combined with antimicrobial stewardship programs (ASPs), the benefits of the technology in relation to clinical end points have not been explored in low-income settings.
To compare the two diagnostic methods, researchers recruited patients with a pathogen cultured from a normally sterile sample and randomly assigned samples to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion of patients on optimal antimicrobial therapy within 24 hours of positive culture.
Among 1,005 randomized patients, pathogens were isolated from 628, with 326 in the MALDITOF-MS arm and 302 in the control arm. The proportion receiving optimal therapy within 24 hours was not significantly different between the two arms (135/326, 41.4% vs 120/302, 39.7%; adjusted odds ratio [aOR], 1.17; P = 0.40). There was also no difference in the secondary outcome, which was the proportion of patients on optimal therapy within 48 hours of positive culture (151/326, 46.3% vs 141/302, 46.7%; aOR, 1.05; P = 0.79). Nor did MALDITOF-MS have any impact on other outcomes explored, including time taken to provide optimal antibiotic therapy, total antibiotic therapy, patient outcomes, or time in intensive care.
The authors of the study say the findings indicate that technological advances in rapid diagnostics technology, in the absence of an ASP, do not always lead to improvements in clinically relevant outcomes.
"In conclusion, our study showed no improvement in antimicrobial prescribing or other patient or provider centred outcomes through MALDITOF-MS, though MALDITOF-MS did produce results rapidly in our setting," they write. "While MALDITOF-MS has many other compelling advantages, our findings suggest that it is unlikely to lead to improvements in prescribing on its own."
Mar 23 J Infect study
Study finds peer comparison helps reduce fluoroquinolone use
Originally published by CIDRAP News Mar 25
A new study in the Journal of the American College of Clinical Pharmacy shows that the use of peer comparison reports based on prescriber specialty was tied to less use of fluoroquinolone antibiotics throughout a large community-hospital system.
In the quasi-experimental study, which was conducted at 16 community hospitals in Florida in 2017, researchers evaluated the impact of 1,265 peer comparison reports issued to high-volume prescribers in three different medical specialty cohorts: internal medicine/hospitalists/family medicine, intensivists/pulmonologists, and infectious diseases. The reports provided feedback to each eligible prescriber on their prescribing patterns and compared them to others within their peer group.
The primary study outcome was fluoroquinolone days of therapy (DOT) per 1,000 patient-days (PD) in the intervention period compared with the baseline period. Additional outcomes included total antibiotic days of therapy, total percentage of antibiotic days attributable to fluoroquinolones, and cases of hospital-acquired Clostridioides difficile/1,000 PD.
During the intervention period, fluoroquinolone use declined 29% compared with the baseline period, from 83.9 DOT/1,000 PD to 58.3 DOT/1,000 PD. Declines were observed in all facilities included in the study, but fluoroquinolone use decreased most among the facilities with the highest baseline use. The percentage of antibiotic days attributable to fluoroquinolones fell from 15.4% in the baseline period to 11.3% in the intervention period. In addition, total antibiotic days of therapy fell by 6%, and use of other key antibiotic classes, including third-generation cephalosporins and anti-pseudomonal beta-lactams, remained unchanged. The rate of hospital-acquired C difficile fell by 20%.
The authors of the study say their findings are consistent with most of the previous studies that demonstrate that behavioral interventions can have a positive impact on antibiotic prescribing, and they conclude that providing prescribers with feedback on antibiotic use may be a useful behavior modification tool for inpatient stewardship programs.
Mar 23 J Am Coll Clin Pharm abstract
Antipseudomonal combo therapy for pneumonia linked to higher mortality
Originally published by CIDRAP News Mar 25
A study last week by researchers with the University of Texas and the University of Connecticut has found that older adults who received antipseudomonal combination therapy (PCT) for community-onset pneumonia had worse outcomes than those who received antipseudomonal monotherapy (PMT).
The population-based, retrospective cohort study, published in the American Journal of Infection Control, used data from more than 150 hospitals and 1,400 clinics in the Veterans Health Administration (VHA) system. The researchers used VHA electronic medical records to categorize pneumonia patients as having low, medium, or high risk of drug-resistant pathogens and to assign them to PCT or PMT treatment arms based on antibiotics received in the first 48 hours of hospital admission. They then compared all-cause 30-day mortality in the two groups.
Of the 31,027 patients who met the criteria for the study, 23% received PCT and 77% received PMT. The unadjusted mortality difference between PCT and PMT was most pronounced in the low-risk group (18% vs 8%), followed by the medium-risk group (24% vs 18%) and the high-risk group (39% vs 33%). PCT was associated with higher 30-day mortality than PMT overall (adjusted odds ratio [aOR], 1.54; 95% confidence interval [CI], 1.43 to 1.66) and in all three risk groups: low (aOR, 1.69; 95% CI, 1.50 to 1.89), medium (aOR, 1.30; 95% CI, 1.14 to 1.48), and high (aOR, 1.21; 95% CI, 1.04 to 1.40)
The findings are important, because community-acquired pneumonia guidelines from both the American Thoracic Society and IDSA recommend PCT when Pseudomonas pneumonia is suspected. The authors of the study say that the data from this study, and their previous study of empiric Pseudomonas therapy in patients with community-acquired pneumonia, indicate that the guidelines should be changed.
"We support the use of empiric PMT in high-risk patients, but we do not support the use of empiric PCT in pneumonia patients from any of the risk groups," they write. "PCT may be beneficial over PMT for patients with known Pseudomonas (ie, definitive therapy)—a question beyond the scope of this study—but PCT is not associated with additional benefit in patients simply suspected of having Pseudomonas (ie, empiric therapy)."
Mar 21 Am J Infect Control study