ASP Scan (Weekly) for Sep 13, 2019

India joins antibiotic R&D hub
;
Resistant infections in African infants
;
Antibiotics in UK poultry
;
Chick-fil-A antibiotic-free
;
Resistant E coli in sewage
;
Fluoroquinolones and leaky heart valves
;
Meropenem for bacterial meningitis
;
Antibiotics and flu vaccine response
;
Treating complex abdominal infection

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

India joins global effort to spur antibiotic research and development

India announced yesterday that it has joined the Global Antimicrobial Resistance (AMR) Research and Development (R&D) Hub, becoming the 16th nation to join the global partnership.

The Global AMR R&D Hub, launched in May 2018 at the World Health Assembly, aims to provide more effective funding for research and development of new treatments and diagnostics for resistant pathogens by identifying and prioritizing R&D gaps, promoting increased investment in push and pull incentives, and fostering international collaboration. The European Commission, Bill & Melinda Gates Foundation, and Wellcome Trust are also members of the group, which is financed through grants from Germany's Federal Ministry of Education and Research and Federal Ministry of Health.

"By partnering with the Global AMR R&D Hub, India looks forward to working with all partners to leverage their existing capabilities and resources and collectively focus on new R&D intervention to address drug resistant infections," India's Ministry of Science and Technology said in a press release.
Sep 12 Government of India press release

 

Bacterial infections and AMR in newborns in sub-Saharan Africa

A systematic review and meta-analysis of data on bacterial infections in newborns in sub-Saharan Africa highlights the causative pathogens in bacteremia, sepsis, and meningitis and the burden of AMR.

In a study published yesterday in The Lancet Infectious Diseases, researchers from the London School of Hygiene and Tropical Medicine reviewed studies in sub-Saharan Africa published from 1980 through 2018 that reported the cause of invasive bacterial infections. For their analysis, the team included 151 studies comprising data on 84,534 neonates from 26 countries, almost all of which were hospital-based. The studies were arranged into two groups according to year of publication: 1980-2007 and 2008-2018, but only the 82 studies published from 2008 through 2018 were included in the meta-analysis.

The meta-analysis found that, from 2008 through 2018, Staphylococcus aureus infections accounted for 25% (95% confidence interval [CI], 19 to 31) of all reported cases of neonatal bacteremia or sepsis, Klebsiella spp. accounted for 21% (95% CI, 16 to 27), and Escherichia coli accounted for 10% (95% CI, 8 to 10). For meningitis, group B streptococcus was identified as the cause in 25% of cases (95% CI, 16 to 33), while Streptococcus pneumoniae accounted for 17% (95% CI, 9 to 16), and S aureus accounted for 12% (95% CI, 3 to 25).

Resistance to World Health Organization–recommended beta-lactam antibiotics was reported in 614 of 914 infections (68%), and resistance to aminoglycosides was reported in 317 of 1,176 cases (27%). For S aureus infections, resistance to cloxacillin and methicillin was reported in 40% and 50% of isolates, respectively.

The authors write, "These data provide useful insights into the pathogens associated with neonatal invasive bacterial infection in sub-Saharan Africa and the status of AMR. Interventions that focus on hospital-based care around the time of birth could prevent millions of neonatal and maternal deaths, stillbirths, and disability. With poor quality care, dangers of infection transmission and AMR threaten the gains of neonatal survival."

They suggest that a multipronged approach of infection prevention, expanded and improved clinical microbiology services, tailored local antimicrobial guidelines, implementation of antimicrobial stewardship policies, and new maternal vaccines against group B streptococcus and S pneumoniaecould help reduce the burden of neonatal infection morbidity and mortality.
Sep 12 Lancet Infect Dis study

 

Report notes 80% drop in antibiotics in UK poultry in 7 years

The British Poultry Council (BPC), in a report this week, says Britain's poultry meat sector has cut antibiotics 80.2% from 2012 to 2018 and "critically important" antibiotics 82.6%, despite a 12.4% increase overall in 2018.

Total antibiotics used in the UK poultry sector amounted to 81.8 tons in 2012, but usage fell to 14.4 tons in 2017 before climbing slightly to 16.2 tons in 2018, according to the report, which attributed the uptick to seasonal illness in birds. "Having reached a low level of usage, it is inevitable that our annual figure will fluctuate up and down in response to the challenges we face during that period," the BPC report said. "What is key is that we continue to be open and honest about the reasons behind these fluctuations and what we are doing to mitigate them in the future."

Also, the industry saw a 19% reduction in critical antibiotics from 2017 to 2018, the report authors noted. In 2012 the UK poultry meat industry used 21% of the total antibiotics licensed for food animals, but that portion dropped to 7.1% in 2017.

British Poultry Council Chairman Graeme Dear said in a news release, "With poultry being half the meat eaten in the country, the British poultry meat industry's Antibiotic Stewardship is playing a crucial role in delivering good bird health and welfare; ensuring responsible use of antibiotics, safeguarding the efficacy of antibiotics, and helping produce food consumers trust."

During the study years, the British poultry industry has stopped preventive use of antibiotics, stopped polymyxin (colistin) use in 2016, used fluoroquinolones and macrolides as a last resort, and in 2012 ceased using third- and fourth-generation cephalosporins, the authors of the report wrote.
Sep 11 BPC report and news release

 

Chick-fil-A reached goal of antibiotic-free chicken in all its restaurants

Originally published by CIDRAP News Sep 12

Chick-fil-A today announced it has reached its goal of serving only chicken raised without the routine use of antibiotics, an ambition it set in 2014, according to a company news release.

Chick-fil-A reached its "no antibiotics ever" milestone in May and will be touting the achievement on packaging in its restaurants next month. Matt Abercrombie, director of menu and packaging for the company, said, "Our goal was to pursue the highest standard and partner with the USDA [US Department of Agriculture] to verify it." He added, "We worked with our suppliers to convert our chicken supply to No Antibiotics Ever, which was an industry-changing move, as the supply of No Antibiotics Ever chicken previously did not exist to match our scale."

Other restaurant chains that have reached the same milestone are Chipotle, Panera, McDonald's, Subway, and KFC, according to a blog post today by Avinash Kar and Lena Brook with the New York City–based Natural Resources Defense Council (NRDC).

The pair said, "This reflects a stunning antibiotics success story that has unfolded across the U.S. chicken industry in the last decade," pointing to the fact that 92% of US chicken sold last year was produced without the use of medically important antibiotics.
Sep 12 Chick-fil-A news release
Sep 12 NRDC blog post

 

Study finds similar antibiotic resistance rates in sewage, clinical samples

Originally published by CIDRAP News Sep 12

A study today in Eurosurveillance suggests analysis of sewage samples has the potential to be used for population-level surveillance of antibiotic resistance, complementing current monitoring systems and providing clinically relevant data for countries where clinical surveillance is lacking.

In the study, a team of Swedish researchers collected hospital and municipal sewage on eight and six occasions, respectively, in 2016, then analyzed 1,252 E coli isolates from the samples for resistance to eight different antibiotics. The annual mean resistance rates measured in hospital sewage were higher than in the municipal sewage for seven of the eight antibiotics, and a higher prevalence of extended-spectrum beta-lactamase (ESBL) producers was also observed in the hospital sewage. In addition, E coli showing resistance to at least one of the antibiotics were twice as prevalent in the hospital sewage (36.6% vs 17.9%), and 10 of the 11 most resistant isolates were found in the hospital sewage.

Comparison of the resistance rates in the hospital and municipal sewage isolates showed a strong correlation with resistance rates in corresponding clinical isolates from hospital patients and from primary care urine samples, with the stronger correlation observed between resistances rate in hospital sewage and hospital clinical isolates (r² = 0.95 and 0.89 for urine and blood samples, respectively) and a slightly weaker correlation between resistance rates in municipal sewage and primary care isolates (r² = 0.82). The resistance rates in isolates from hospital sewage were overall close to those observed in hospital patient isolates, while the resistance rates from municipal sewage were about half of those measured in primary care isolates.

"In conclusion, this study indicates that resistance data obtained from sewage samples reflects well the resistance situation in the studied populations. However, in order to use sewage monitoring to predict the clinical situation in other populations, including those for which such data are missing, further calibration is needed," the authors of the study write. "This calibration could be extended from E coli to additional important pathogens that can be present in faeces (such as Klebsiella pneumoniae and Salmonella enterica) and possibly from the study of human populations to husbandry animals."
Sep 12 Eurosurveill study

 

Study links fluoroquinolone use to higher risk of heart condition

Originally published by CIDRAP News Sep 11

A new study in the Journal of the American College of Cardiology found an association between current fluoroquinolone use and increased risk of leaky heart valves, adding to a number of adverse events linked to the drugs.

Using data from the Food and Drug Administration's (FDA) adverse reporting system database and a random sample of more than 9 million patients from a health claims database, a team of Canadian researchers conducted a disproportionality analysis to identify cases of fluoroquinolone-related aortic or mitral valve regurgitation—blood leakage that can cause blood backflow into the heart—reported to the FDA and a case-control analysis to compare these cases with valvular regurgitation reported for non-quinolone antibiotics.

Given fluoroquinolones' in vitro ability to damage connective tissue and collagen, and other reported adverse events that have been linked to their use, the researchers hypothesized that fluoroquinones could damage the connective tissue of the aortic and mitral valves and thus increase the risk for valvular regurgitation.

In the disproportionality analysis, the team noted102 reported events of fluoroquinolone-related valvular regurgitation and 6,099 reports with other drugs from 2004 to 2018, for an odds ratio of 1.45 (95% confidence interval [CI], 1.20 to 1.77). In the case-control study, which involved a total of 12,505 cases and 125,020 control subjects, the adjusted rate ratios [RRs] for current users of fluoroquinolones compared with amoxicillin and azithromycin users were 2.40 (95% CI, 1.82 to 3.16) and 1.75 (95% CI, 1.34 to 2.29), respectively. The adjusted RRs for recent and past fluoroquinolone users when compared with amoxicillin were 1.47 (95% CI, 1.03 to 2.09) and 1.06 (95% CI, 0.91 to 1.21), respectively. 

While noting that the findings need to be confirmed, the authors of the study say the increased risk observed in their study suggests "it might be prudent to consider antibiotics that are chemically distinct to FQs [fluoroquinolones] in patients with a previous history of valvular regurgitation who require antibacterial therapy."

In December 2018, the FDA warned that fluoroquinolones can increase the risk aortic dissension and should not be used in patients who have an increased risk of the condition. The agency has also added boxed warnings that fluoroquinolones can increase the risk of peripheral neuropathy and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system. 
Sep 9 J Am Coll Cardiol study

 

Study: Meropenem could be alternative treatment for bacterial meningitis

Originally published by CIDRAP News Sep 10

New data from a study by Swedish researchers indicates meropenem is an effective alternative empirical treatment option for adults who have community-acquired acute bacterial meningitis (ABM). The findings appeared yesterday in Antimicrobial Agents and Chemotherapy.

The study analyzed data on 623 Swedish adults diagnosed with ABM from 2008 through 2016 who were treated empirically with either cefotaxime plus ampicillin—which is recommended as the first-line treatment for ABM by the Swedish Infectious Disease Association—or meropenem. Propensity score matching was performed to adjust for baseline differences between the two groups. The primary end point was 30-day mortality, and secondary end points were 90-day mortality and unfavorable outcome at follow-up.

Among the 328 patients who received cefotaxime plus ampicillin, the 30-day mortality was 3.4%, compared with 6.4% in the patients treated with meropenem, and the corresponding figures for 90-day mortality were 4.6% and 8.1%, respectively. But the patients who received meropenem were older and more often presented with septic shock, and a lower proportion of them received adequate corticosteroids together with the initiation of antibiotics. In the propensity-matched patients, the 30-day mortality was 3.2% in the cefotaxime plus ampicillin group and 3.4% in the meropenem group.

For matched cases, the odds ratio (OR) for 30-day mortality for meropenem vs cefotaxime plus ampicillin was 1.15 (95% confidence interval [CI], 0.41 to 3.22, P = 0.79). The ORs for 90-day mortality and unfavorable outcome were 1.47 (95% CI, 0.62 to 3.52, P = 0.38) and 1.10 (95% CI, 0.75 to 1.63, P = 0.62).

The authors of the study say that while the findings support meropenem as an effective alternative for empirical treatment of ABM, cefotaxime plus ampicillin should remain the first-line treatment. "However, due to the importance of antibiotic stewardship, and the lack of benefit of meropenem on clinical outcomes in the majority of patients with ABM, third-generation cephalosporins should continue to be the cornerstone of empirical treatment of ABM," they conclude.
Sep 9 Antimicrob Agents Chemother abstract

 

Oral antibiotics linked to altered immune response to flu vaccine

Originally published by CIDRAP News Sep 10

A small study led by researchers from Stanford University and funded by the National Institutes of Allergy and Infectious Diseases (NIAID) suggests that oral antibiotics may alter the human immune response to the flu vaccine.

In the study, which was published in the journal Cell, the researchers set out to investigate the role of the human gut microbiota in shaping immune responses to the seasonal flu vaccine. They enrolled 22 healthy adults with high pre-existing immunity to the flu during the 2014-15 flu season, then randomized 11 participants to a 5-day oral cocktail of broad-spectrum antibiotics (neomycin, vancomycin, and metronidazole) 3 days prior to and 1 day after vaccination, with the aim of reducing gram-negative and anaerobic bacteria in the gut. They then collected biological samples for the following year and measured key aspects of the gut microbiome and the immune system.

Despite a significant reduction in gut bacterial load and bacterial diversity in the group that received antibiotics, there was no significant difference in antibody responses between the two groups. However, in a second study of 11 adults with low pre-existing flu immunity studied during the 2015-16 flu season, the researchers found a hindered response to the H1N1 A/California-specific strain of flu on day 90 and day 180 in the 5 participants who received antibiotics. No differences were observed for the two other flu strains.

The researchers also found that, in both groups that received antibiotics, there were changes to the immune system that promoted a pro-inflammatory state, similar to that seen in older adults who receive the flu vaccine.

"Here, we have demonstrated the potential for antibiotic-driven perturbation of the microbiome to influence immune responses to vaccination in healthy adults," the authors of the study write. "These findings should inform further research seeking to better understand mechanisms that control the interplay between the gut microbiota and our immune system."
Sep 5 Cell study
Sep 6 NIAID press release

 

Analysis: Beta-lactams effective alternative for intra-abdominal infections

Originally published by CIDRAP News Sep 9

A systematic review and meta-analysis of treatment for complicated intra-abdominal infections (cIAIs) found no difference in clinical outcomes between carbapenem antibiotics and non-carbapenem beta-lactams, Chinese researchers reported today in Open Forum Infectious Diseases.

In a search of literature published up to November 2018, the researchers identified 22 randomized controlled trials, involving 7,720 patients, comparing the safety and effectiveness of carbapenems versus alternative beta-lactam treatments for cIAIs. While both carbapenems and alternative beta-lactams alone or in combination are recommended for cIAIs by the Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America, the researchers say the rise of carbapenem-resistant infections reflects illustrates the need for better treatment options.

"Due to the current lack of new antibiotic agents without overlapping mechanisms of resistance, judicious use of these broad-spectrum agents for treatment of resistant gram-negative infections is critical to preserve their future utility," they write.

The meta-analysis found no differences in clinical treatment success (OR, 0.86; 95% CI, 0.71 to 1.05), microbiological treatment success (OR, 0.88; 95% CI, 0.71 to 1.09), adverse events (OR, 0.98; 95% CI, 0.87 to 1.09), or mortality (OR, 0.96; 95% CI, 0.68 to 1.35). Subgroup analyses found that patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative beta-lactams monotherapy or in combination.

"In conclusion, the current meta-analysis revealed that beta-lactams monotherapy or in combination can be an effective and safe treatment option for cIAI, similar to carbapenem," the researchers write.
Sep 9 Open Forum Infect Dis abstract

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