ASP Scan (Weekly) for Jun 08, 2018

News brief

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

UK study details 118 cases of high-level antibiotic-resistant gonorrhea

In what appears to be an underreported outbreak, officials with Public Health England (PHE) yesterday in Eurosurveillance detailed 118 laboratory-confirmed cases of high-level azithromycin-resistant Neisseria gonorrhoeae, noting that cases emerged among heterosexuals in Leeds but then spread across England and into networks of men who have sex with men (MSM).

The cases occurred from November 2014 through May 2018, and cases per month, after initially staying level, increased from 2.6 to 3.4 from 2015 to the present time. The 118 patients include the man first reported by the PHE whose infection was also resistant to ceftriaxone, a particularly worrisome development.

The outbreak began in late 2014 and early 2015 among young heterosexuals living in "deprived areas" of Leeds, the authors said. Among 15 patients, the median age was 18 (range, 16 to 53). As the outbreak spread geographically, "cases among MSM were first identified in November 2015 mainly from a large, high-throughput clinic in London, which serves a substantial MSM population," the authors write. MSM patients had a median age of 30 years but also lived in disadvantaged areas.

The researchers found few direct epidemiologic links between heterosexual cases and none between MSM cases. They were able to establish 11 separate transmission networks, the largest linking four of the earlier Leeds cases.

"The few epidemiological links identified indicate substantial under-diagnosis of cases and this, along with the upturn in cases in 2017, highlights the difficulties in controlling the outbreak," the authors conclude.
Jun 7 Eurosurveillance report
Mar 28 CIDRAP News story "In world first, UK reports high-level gonorrhea resistance"

CDC issues alert over Shigella infections with low antibiotic susceptibility

The Centers for Disease Control and Prevention (CDC) yesterday published a Health Alert Network (HAN) update on managing and reporting Shigella infections that may have reduced susceptibility to not only ciprofloxacin but also azithromycin.

The HAN guidance is a follow-up to a HAN advisory last April. Officials are especially concerned about people who are at high risk for multidrug-resistant Shigella infections and are more likely to require antibiotic treatment.

The CDC "continues to identify an increasing number of Shigella isolates that test within the susceptible range for the fluoroquinolone antibiotic ciprofloxacin (minimum inhibitory concentration [MIC] values of 0.12-1 μg/mL), but harbor one or more resistance mechanisms. CDC remains concerned about potential clinical failures with fluoroquinolone treatment," the agency said.

Clinicians should carefully monitor patients who have Shigella infections and require fluoroquinolone treatment and report any possible treatment failures, the CDC said. "CDC has also identified an increasing number of Shigella isolates with azithromycin MICs that exceed the epidemiological cutoff value (ECV), and is requesting reports of any possible treatment failures occurring among patients with Shigella infections treated with azithromycin," the update said.

The agency said people at highest risk include MSM, homeless patients, and immunocompromised people. These individuals often have more severe disease, prolonged shedding, and recurrent infections.
Jun 7 HAN update
Apr 18, 2017 HAN advisory

China's XDR-TB status termed an emerging crisis

The authors of a Chinese study published yesterday in BMC Infectious Diseases—who previously claimed that the incidence of extensively drug-resistant tuberculosis (XDR-TB) in their country has been underestimated—determined that in reality, the situation is alarming owing to a sizable proportion of newly transmitted cases, high mortality, and patients' remaining in the community setting for long periods.

The patient population comprised all 67 patients diagnosed with XDR-TB for the first time in four specialized TB centers between March 2013 and February 2015. Patients were actively tracked through February 2017 by means of phone calls or home visits to them or to family members to ascertain survival information. Factors associated with death were evaluated with multivariable Cox regression models.

Mean patient age was 48.7 years, and 51 (76%) were men. Fourteen patients (21%) were treatment-naive so were considered to have been infected through primary transmission. At hospital discharge, 58 (86.8%) of patients remained positive on sputum smear or culture.

During the median follow-up period of 32 months, 20 patients died, for an overall mortality rate of 128 per 1,000 person-years. Among these, 17 (85%) had returned to the community setting and died at home; median survival duration was 5.4 months. Factors predictive of death were body mass index less than 18.5 kg per square meter (adjusted hazard ratio [aHR], 4.5; 95% confidence interval [CI], 1.3-15.7), smoking (aHR, 4.7; 95% CI, 1.7-13.2), and clinically significant comorbidity (aHR, 3.5; 95% CI, 1.3-9.4).

The authors conclude that the situation "calls for urgent actions . . . including providing regimens with high chances or cure and palliative care, and enhanced infection control measures."
Jun 7 BMC Infect Dis article

CDC: Injecting drug users 16 times more likely to contract MRSA

Originally published by CIDRAP News Jun 7

People who inject recreational drugs are 16.3 times more likely to develop invasive methicillin-resistant Staphylococcus aureus (MRSA) infections than people who do not inject drugs, according to data published today in the Centers for Disease Control and Prevention's (CDC's) Morbidity and Mortality Weekly Reports (MMWR).

CDC scientists looked at MRSA in drug users from 2005 to 2016 to assess how and if the opioid epidemic has affected MRSA case counts. Using six surveillance sites across the country, the researchers calculated the risk ratio of MRSA among drug users.

During the study period, 39,050 invasive MRSA cases were reported from six sites, with 2,093 (5.4%) occurring in persons who injected drugs. The estimated rate of invasive MRSA among injected drug users older than 13 years was 472.2 per 100,000 in 2011, and the estimated rate among those who did not inject drugs in the previous year was 29.0 per 100,000.

In addition, the researchers found that invasive MRSA in injected drug users rose from 3.5% to 9.2% from 2010 to 2016.

"Although much attention has focused on the transmission of blood-borne pathogens such as HIV and hepatitis B and C viruses related to injection drug use, infections from skin flora such as Staphylococcus aureus are also important and might not be prevented solely by programs focused on preventing blood-borne pathogen transmission," the CDC authors said. "Increases in nonsterile injection drug use are likely to result in increases in the occurrence of invasive MRSA infections among persons who inject drugs, underscoring the importance of public health measures to curb the opioid epidemic."
Jun 8 MMWR study

UK poultry industry has cut antibiotics 82% in 6 years, report says

Originally published by CIDRAP News Jun 7

The UK poultry sector has cut antibiotic use 39% from 2016 to 2017 and 82% over the past 6 years, according to a report this week from the British Poultry Council (BPC).

In addition to the overall reduction, the British poultry industry has slashed the use of fluoroquinolones (deemed critically important antibiotics [CIAs] in humans by the World Health Organization) by 91%, CIA macrolides by 76%, amoxicillin by 60%, and tetracyclines by 93%. In 2012, the poultry sector accounted for 21% of total antibiotic use for food-producing animals in Great Britain, but by 2016 the percentage had dropped to 9.7%.

The BPC also noted that the industry has stopped using antibiotics for growth promotion, as well as ceased using third- and fourth-generation cephalosporins and polymyxins (colistin).

BPC Chairman John Reed said in a news release, "Through BPC Antibiotic Stewardship, the British poultry meat sector is delivering excellence in bird health and welfare by monitoring and reviewing on-farm management practices and ensuring responsible use of antibiotics throughout our supply chain. Our farmers and veterinarians need antibiotics in their toolbox to preserve the health and welfare of our birds. Responsible use of antibiotics is about so much more than reduction targets. Zero use is neither ethical nor sustainable."

UK Chief Veterinary Officer Christine Middlemiss, BVMS, MBA, said, "The achievements made by members of the BPC are remarkable. Continuously reviewing on-farm biosecurity and disease management practices whilst ensuring prudent use of antibiotics is integral to the sustainability of British agriculture."
Jun 4 BPC news release

Study reveals docs' openness, barriers to feedback on antibiotic use

Originally published by CIDRAP News Jun 7

A survey conducted by Vanderbilt researchers found that physicians treating inpatients are open to receiving information on their antibiotic prescribing patterns but are concerned about barriers to that reporting, according to a study today in Infection Control and Hospital Epidemiology.

The investigators surveyed 211 physicians in various specialties who provided inpatient care at Vanderbilt University Hospital. They found that 89% preferred that their own institutions determine provider use attribution as opposed to external personnel, 64% wanted to be compared with other providers within their service, 64% preferred quarterly feedback, and 73% wanted the feedback via email.

The study also found that providers agreed upon attribution of antimicrobial use early on in a hospital stay scenario but disagreed once care became more complex, with some deferring and others accepting responsibility. In general, they expressed concern that quantitative feedback would not account for the complexity of clinical care and severity of illness.

Overall, 51% of providers anticipated changing practice based on antibiotic use feedback.

"Data can help drive change, however in order to implement meaningful change, we must overcome barriers and use this data to improve the use of antibiotics," said lead author Tara Lines, PharmD, in a news release from the Society for Healthcare Epidemiology of America (SHEA), which publishes the journal.
Jun 7 Infect Control Hosp Epidemiol abstract
Jun 7 SHEA news release

BARDA initiative to address systemic health concerns, including sepsis

Originally published by CIDRAP News Jun 7

The Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) has launched DRIVe (Division of Research, Innovation and Ventures) to accelerate innovations for addressing systemic health concerns through an approach similar to that being taken for addressing man-made health threats, and one of its first focuses is sepsis, FierceHealthcare reports.

DRIVe will take advantage of powers granted to BARDA under the 21st Century Cures Act to fund innovation through grants and venture capital investment. It will also unite a network of accelerators to identify promising interventions, according to the story.

"It's now time to address those systemic problems, the ones common to most illnesses and injuries," said BARDA Director Rick Bright, PhD."Those need to be resolved to save even more lives. With DRIVe, we're focusing on solving sepsis in our lifetime. Too many lives are lost because of sepsis, and if a national health emergency arises, sepsis will surely take more."

DRIVe has already established eight partnerships with institutions across the United States.
Jun 5 FierceHealthcare story
DRIVe website
BARDA news releases page, which includes the 8 partnerships

Global Burden of Disease Study to include antimicrobial resistance data

Originally published by CIDRAP News Jun 5

University of Washington and University of Oxford experts yesterday announced the inclusion of mortality and morbidity data related to drug-resistant infections into the annual Global Burden of Disease Study, part of a new antimicrobial resistance (AMR) project "to provide rigorous quantitative evidence of the burden of AMR, to increase awareness of AMR, to support better surveillance of AMR, and to foster the rational use of antimicrobials around the world," according to a commentary in BMC Medicine.

"There are many challenges to estimating the burden of AMR," the authors write. "Primarily, there is limited and unreliable current and historical information on the geographical distribution, prevalence, and incidence of AMR and its health burden, making the burden of AMR difficult to measure and limiting our ability to devise geographically explicit strategies for its control."

The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study at the University of Washington's Institute for Health Metrics and Evaluation is the largest known repository of epidemiology data and can help researchers estimate the impact of a condition or health disparity like AMR on various populations. The GBD provides comparable estimates of mortality and disability resulting from 328 disease and injury causes and from 84 risk factors.

"Including AMR in the GBD will ensure that the resulting estimates comply with the rigorous, evidence-based framework that characterizes the GBD effort," the authors conclude, adding that the effort will provide "essential health intelligence to guide interventions and policies, as well as a benchmark for measuring the impact of interventions on future burden."

The effort is funded by the UK Department of Health and Social Care, the Fleming Fund, the Wellcome Trust, and the Bill and Melinda Gates Foundation.
Jun 4 BMC Med commentary

Review of One Health training finds lapses, makes recommendations

Originally published by CIDRAP News Jun 5

A systematic review of 45 One Health educational programs in the United States found that few have set core competencies or have consistent standards for applying them, along with other gaps, but offered recommendations for training future practitioners.

Since 2002, many institutions and universities have developed programs related to the One Health approach, which centers around the connections between human health and that of animals and the environment. Authors from the One Health Institute at the University of California (UC), Davis, and the National Academies' One Health Action Collaborative published their findings yesterday in National Academies of Medicine (NAM) Perspectives.

Lead author Eri Togami, DVM, MPH, a fellow at the UC Davis' One Health Institute, said in a press release from the school that the group believes three main skill sets are important to give future public health professionals the tools to solve complex challenges: robust health science knowledge; an understanding of local and global issues related to human, animal, and environmental health; and professional skills such as communication. "We recognize there is a large variety of educational programs for different purposes. Having these three pillars will help aspiring One Health professionals go through high quality training," she said.

Of 45 programs, 27 (60%) did not explicitly state core competencies, and only 14 (31%) listed them publicly online. Epidemiology, as well as environmental health and ecology, were covered by 75% of programs, but underrepresented disciplines included plant biology, law, and antimicrobial resistance. Also, less than half of the programs focused on communication skills required to collaborate with team member, the public, policymakers, and people in different cultural settings.

On the positive side, most programs emphasized practical, applied training for students, including internships, capstone projects, and nonacademic work settings. The report's four main recommendations include clearly stating core competencies, educating future students across a range of disciplines, emphasizing hands-on training, and emphasizing communication.

Jonna Mazet, DVM, PhD, the study's senior author, said in the press release, "I am encouraged to see the country's top educational institutions taking up this charge and creating so many new programs. Our hope is to provide some guidance to help them achieve their goals and ultimately improve the health of our planet."
Jun 4 NAM Perspectives study
Jun 4 UC Davis press release

Study suggests potential antibiotic alternative for women's acne

Originally published by CIDRAP News Jun 4

A new study in the Journal of Drugs and Dermatology suggests that a diuretic drug may be as effective as antibiotics for treatment of women's acne.

In the study, researchers from the University of Pennsylvania Perelman School of Medicine conducted a retrospective analysis comparing data on 6,684 women and girls taking spironolactone to 31,164 who were prescribed oral tetracycline antibiotics. They were looking to determine the frequency of switching to a different systematic agent within the first year of treatment, a proxy for ineffectiveness.

Among the women who were started on spironolactone, 14.4% were prescribed a different systematic agent within a year, compared with 13.4% of the women treated with antibiotics. After adjusting for age, topical retinoid, and oral contraceptive, the odds ratio for being prescribed a different systematic agent within a year was 1.07 for those prescribed spironolactone when compared with antibiotics, and the risk difference was 0.007.

"These numbers suggest dermatologists should consider spironolactone first instead of antibiotics when it comes to women with acne," lead study author John Barbieri, MD, said in a University of Pennsylvania press release.

Oral antibiotics are the most common systematic treatment for acne. More than 50% of women in the United States between the ages of 20 and 29, and more than 35% of women between the ages of 30 and 39, are treated for acne. According to the Centers for Disease Control and Prevention, dermatologists prescribe the highest level of antibiotics per provider among all medical specialties.

Spironolactone is currently approved to treat high blood pressure, heart failure, and conditions that cause people to retain fluid.
June J Drugs Dermatol abstract
Jun 4 University of Pennsylvania press release

Small trial shows promise for fecal microbiota transplant for primary C diff

Originally published by CIDRAP News Jun 4

The results of a small proof-of-concept clinical trial in Norway suggest fecal microbiota transplantation (FMT) may be an alternative to antibiotics for primary treatment of Clostridium difficile infection (CDI).

The trial randomly assigned 20 patients with acute CDI at six hospitals in Norway to receive either the recommended treatment of oral metronidazole (400 mg three times a day for 10 days) or FMT. The primary end point was clinical cure with no evidence of recurrent CDI at day 70. Secondary end points were evaluations conducted at 4 and 35 days after initial treatment and adverse events.

Nine patients were assigned to FMT and 11 to metronidazole. Patients who were clinically cured after initial treatment and had no recurrence were defined as having a full primary response; patients who received additional treatment to achieve clinical cure but experienced no recurrence were defined as having a full secondary response.

A full primary response was observed in five patients in the FMT group (56%) and in five in the metronidazole group (45%). Three of the four remaining patients in the FMT group received antibiotics by day 4 after initial treatment, and two of them had a full secondary response. In the metronidazole group, none of the six remaining patients had a full secondary response. The overall response to treatment (full primary or secondary response) was achieved in seven of the FMT patients (78%), compared with five in the metronidazole group (45%).

While previous research has shown that FMT is an effective alternative to antibiotics for treating recurrent CDI, this is the first study to assess FMT for primary CDI treatment. The authors of the study, which was published in the New England Journal of Medicine, say a phase 3 trial is currently under way.
Jun 2 N Engl J Med correspondence

News Scan for Jun 08, 2018

News brief

Salmonella outbreaks tied to backyard poultry cause 124 cases in 26 states

The Centers for Disease Control and Prevent (CDC) today said it is investigating several Salmonella outbreaks totaling 124 cases in 36 states linked to contact with backyard poultry flocks.

Outbreak strains are Salmonella Seftenberg, Montevideo, Infantis, Enteritidis, Indiana, and Litchfield. Twenty-one people have required hospitalization, but no deaths have been reported, the CDC said. Illness-onset dates range from Feb 2 to May 14.

The patients tilt young, with 31% of them preschool-aged. Of 74 case-patients interviewed, 55 (74%) reported contact with chicks or ducklings in the week before they fell ill. People reported obtaining the baby poultry from several sources, including feed supply stores, websites, and hatcheries.

"Mail-order hatcheries should provide health-related information to owners and potential purchasers before they buy any birds," the CDC said. "This should include information about preventing Salmonella infections from contact with live poultry." The agency said stores should buy only from suppliers who have adopted best practices from the US Department of Agriculture.

Among advice to consumers, the CDC said poultry owners and handlers should always wash their hands after touching live poultry or anything in the birds' environment. The agency said 70 Salmonella outbreaks have been tied to backyard poultry since 2000.
Jun 8 CDC statement
CDC advice on keeping backyard poultry

CDC says pre-cut melon is likely source of 60 Salmonella cases in 5 states

Consumers in five Midwestern states should not eat pre-cut melon bought from several national retail chains because it is the likely source of 60 Salmonella infections in those states, the CDC announced today.

Cases have been reported in Illinois (6), Indiana (11), Michigan (32), Missouri (10), and Ohio (1), the agency said in an email to journalists. Thirty-one people have been hospitalized, but no deaths have been reported.

Sick people have reported eating pre-cut cantaloupe, watermelon, or a fruit salad mix with melon, according to the alert. Most people bought pre-cut melon at Walmart or Kroger stores in the Midwest. Yesterday Walmart and Kroger removed pre-cut melon linked to the outbreak from all Walmart, Kroger, Jay C, and Payless stores in the affected states.

The CDC said consumers should discard pre-cut melon bought from Walmart stores in any of the five states or from Kroger, Jay C, or Payless stores in Indiana and Michigan. The warning includes fruit salad mixes with pre-cut melon but does not include whole melons.

The Food and Drug Administration is working to identify a supplier of pre-cut melon to stores where sick people shopped, officials said. The CDC may expand its advice to consumers to include other stores where contaminated pre-cut melon was sold. State health officials are working with the two federal agencies on the investigation.
Jun 8 CDC notice

Pakistan announces second polio case of 2018

Health officials in Pakistan reported a new case of wild poliovirus in Balochistan. This is the second polio case in Pakistan in 2018; last year, the country recorded eight cases of the paralyzing disease.

According to the Global Polio Eradication Initiative (GPEI) weekly report, the new case-patient in Pakistan experienced symptom onset on Apr 15. GPEI said vaccinators using the bivalent oral polio vaccine reached more than 20 million Pakistani children during May.

The Pakistani newspaper The Express Tribune, meanwhile, said today that a third case was recorded in Balochistan's Dakki district, when an 18-month-old toddler tested positive for the virus.

Pakistan, Nigeria, and Afghanistan are the reaming countries in the world with active, endemic wild poliovirus transmission. Afghanistan reported a new environmental sample of wild poliovirus in Kunar province, collected on Apr 24, GPEI noted. Afghanistan has had eight polio cases this year.
Jun 8 GPEI report
Jun 8 Express Tribune story

Lancet editors underscore need for more Nipah research

In light of the Nipah virus outbreak in Kerala, India, which has left 16 dead, the editors of The Lancet penned an editorial calling for more research on the emerging virus.

Like Ebola, the experts say, Nipah has pandemic potential, and the recent human-to-human transmission seen among healthcare workers and family members of patients in India provides more evidence that the virus is highly infective and often deadly. Some estimates show Nipah as having a 75% case-fatality rate.

The World Health Organization (WHO) has issued a roadmap for Nipah, the editors note, after the agency included the virus in the 2018 list of priority epidemic threats. And the Coalition for Epidemic Preparedness Innovations, announced on May 21 a $25 million investment in two US biotechnology firms working on a Nipah vaccine.

"However, for true countermeasures and preparedness, a broader and more comprehensive approach and investment are urgently needed. In addition to diagnostics, therapeutics, and vaccines, surveillance infrastructure must be improved to rapidly identify and verify cases, conduct detailed contact tracing, investigate spillovers, and better understand the ecology of bats and Nipah virus infection, especially outside of outbreak scenarios," the editors warn.

According to the WHO, there have been 600 human cases of Nipah from 1998 to 2015, all in South and East Asia. The virus's natural host is the fruit bat, but outbreaks have also infected livestock. The first human outbreak occurred in the late 1990s in pigs in Malaysia and Singapore and moved to humans, killing 106 people.
Jun 8 Lancet editorial
WHO Nipah R&D blueprint and roadmap

Combination drug treatment for malaria found not cardiotoxic

The effective and well-tolerated drug combination of dihydroartemisinin and piperaquine, which has faced concern over possible cardiotoxicity because of its proarrhythmic potential, carries a risk of sudden cardiac death no higher than baseline levels, found a study published yesterday in The Lancet.

The authors, from Thailand, Spain, and England, carried out a careful review and Bayesian meta-analysis of 94 human studies comprising 197,867 patients (501,156 courses of treatment; 1,396,494 doses) who had received the combination therapy for at least one 3-day regimen in mass drug administration programs, as a preventive treatment, or in case management of uncomplicated malaria. Patient follow-up in all studies was a minimum of 3 days.

Only one patient, a 16-year-old girl in Mozambique who had heart palpitations after a second dose of dihydroartemisinin-piperaquine and died en route to the hospital, was identified as having a potentially drug-related sudden death. Median pooled risk estimate of sudden unexplained death after the combination treatment was calculated at 1 in 757,950 (95% confidence interval, 1 in 2,854,490 to 1 in 209,114), not higher than the baseline rate of sudden cardiac death (1 in 1,714,280 to 1 in 100,835 over a 30-day risk period), according to the authors.

The apparently misplaced concern over potential cardiotoxicity of the combination drug rests of the fact that piperaquine can prolong cardiac ventricular repolarization duration and the electrocardiographic QT interval.

"Concerns about repolarisation-related cardiotoxicity need not limit its [dihydroartemisin-piperaquine] current use for the prevention and treatment of malaria," the authors write. An accompanying commentary further states that the combination "should be shed of its cardiotoxic reputation, so that malaria-endemic areas can benefit from its full potential and to decrease the toll that malaria still imposes globally."
Jun 7 Lancet article
Jun 7 Lancet commentary