News Scan for Dec 15, 2017

News brief

Canadian E coli outbreak linked to romaine lettuce sickens 30, 1 fatally

An Escherichia coli outbreak in Canada linked to romaine lettuce now involves five provinces, with 30 cases reported so far, 1 of them fatal, the Public Health Agency of Canada (PHAC) said yesterday in an update.

In its original announcement on Dec 11, the PHAC said there were 21 cases under investigation from three provinces: Quebec, New Brunswick, and Newfoundland and Labrador. In the update yesterday, it said 9 more cases have been added, with Ontario and Nova Scotia now reporting cases.

Many of the patients said they ate romaine lettuce before their symptoms began. So far no food recalls are linked to the outbreak, and the investigation is ongoing.

Most of the patients got sick in November or December, and 12 were hospitalized. Patient ages range from 4 to 80 years old, and 70% of them are female.
Dec 14 PHAC update

 

New H5N6 avian flu reassortant detected in Dutch wild birds

In the latest avian flu outbreak developments, the Netherlands today said the new highly pathogenic H5N6 reassortant was detected in mute swans found dead in a wetland area, and the Dominican Republic, Taiwan, and South Africa each reported new outbreaks involving different strains, some of which pertain to events in September and October.

In a report to the World Organization for Animal Health (OIE), Dutch veterinary officials said seven wild swans were found dead on Dec 9 at two different locations in Gelderland province in the east central part of the country. Tests revealed that the virus is an H5N6 reassortant, presumably similar to the virus—a mix of H5N8 and a low-pathogenic Eurasian avian flu—that has recently turned up in Dutch poultry, as well as in birds from Greece, South Korea, Japan, and Taiwan.

In an update today, Wangeningen Bioveterinary Research Institute said the wild birds were found along the shores of Lake Veluwe, several miles from where the reassortant was found in a recent outbreak at a duck farm in Flevoland province, according to a report translated and posted by Avian Flu Diary (AFD), an infectious disease news blog.
Dec 15 OIE report on H5N6 in the Netherlands
Dec 15 AFD post

In other reports from the OIE, two counties reported more H5N2 outbreaks, with the Dominican Republic noting the mid-October detections of the low-pathogenic form of the virus at three poultry farms in two different provinces, and Taiwan noting two recent highly pathogenic virus detections at poultry farms in Yunlin County and the city of Kaohsiung.

Meanwhile, in South Africa, the pace of new highly pathogenic H5N8 outbreaks has slowed, but the country reported one more outbreak that occurred in September at an ostrich farm in Western Cape province.
Dec 13 OIE report on low-pathogenic H5N2 in the Dominican Republic
Dec 14 OIE report on highly pathogenic H5N2 in Taiwan
Dec 15 OIE report on H5N8 in South Africa

 

Probing the impact of poultry market closures across 3 H7N9 waves

An analysis of human exposure to H7N9 avian influenza in China's Zhejiang province over the past three waves found that patterns haven't changed much since live poultry markets were shuttered in central urban areas and that a spike in infections during the fifth wave was mainly linked to areas where the poultry markets weren't closed, such as in suburban areas. A team based in Zhejiang province, which has the highest proportion of cases since the virus was first detected in 2013, reported their findings today in Influenza and Other Respiratory Viruses.

In an attempt to curb human illnesses, Zhejiang province in July 2014 permanently closed live poultry markets in the biggest urban areas. Across all three waves, most cases were reported from rural areas, and a similar percentage in all three waves reported exposure to poultry markets, raising poultry at home, or in occupational settings. However, during the fifth wave, the team saw a shift toward exposure at markets that weren't closed.

Researchers found no major demographic changes over the three waves that might shed light on the surge of illnesses seen in the fifth wave. However, like earlier reports from China as a whole, they did see a wider geographic distribution of cases. They also noted that an increasing proportion of rural cases were linked to contact with sick and dead poultry.

New H7N9 cases were also reported from major urban areas in Zhejiang province's fifth wave, hinting at possible illegal trade. Also, they said massive closures in central urban areas could be driving the distribution of infected poultry to markets in outlying areas. They concluded that more efforts are needed to educate the public about the risk of exposure to sick and dead poultry and that stronger surveillance is needed in rural areas. Also, they said further expansion of live poultry market closures should be considered, if possible.
Dec 15 Influenza Other Respir Viruses abstract

 

PAHO confirms yellow fever cases in Brazil, Peru

The Pan American Health Organization (PAHO) this week noted that both Brazil and Peru have confirmed yellow fever cases in the second half of 2017. PAHO said both countries should be closely monitored in the new year.

Since Oct 27, officials have confirmed 3 cases of yellow fever in Brazil, 2 in Sao Paulo and 1 in Rio de Janeiro state. In Sao Paulo, the Itatiba municipality was the probable site of infection, and Guapimirim municipality was the probable site of infection in Rio de Janeiro. One of the patients in Sao Paolo, a 76-year-old man, died.

A total of 43 probable yellow fever cases are still under investigation in Brazil.

Peru has had 17 confirmed and probable cases this year, including 3 fatalities. Six of the cases have occurred in the Junin department, more than in any other department.

PAHO said 2016 yielded the highest number of human and epizootic yellow fever cases seen in decades. "The observed increase is as much related to an ecosystem favorable to the dissemination of the virus as to the unimmunized populations," PAHO said.
Dec 13 PAHO report

 

More polio reported in Pakistan, Syria

According to the latest Global Polio Eradication Initiative (GPEI) report, health officials confirmed one new wild poliovirus 1 in Pakistan last week. The child had symptom onset on Nov 9. Also, Syria has four new vaccine-derived polio cases, all in the previously affected Deir ez-Zur governorate.

There are now six officially reported wild poliovirus cases in Pakistan in 2017. The GPEI said next week's report will contain details on another case in Balochistan province. Pakistan, along with Afghanistan and Nigeria, is one of three countries in the world where wild poliovirus is still circulating. Last year Pakistan had 18 wild poliovirus cases.

Syria now has 74 type 2 circulating vaccine-derived poliovirus (cVDPV2) cases in 2017. The most recent patient had symptom onset on Sep 21. According to the GPEI, local authorities in Raqqa will administer inactivated polio vaccine (IPV) in the Ein Esa camp, which was missed in earlier IPV vaccination activities.

In other polio news, a study yesterday in Emerging Infectious Diseases showed that during surveillance during the West African Ebola outbreak of 2014-2015, 13 cVDPV2 viruses were isolated from 6 polio patients and 7 healthy contacts. All cases were identified in Guinea.

The researchers said the main risk factor was a low vaccination rate, which was 41% in Guinea in 2014.
Dec 13 GPEI report
Dec 14 Emerg Infect Dis study

Stewardship / Resistance Scan for Dec 15, 2017

News brief

Study: No benefit from adding rifampicin to S aureus bacteremia treatment

The results of a large randomized trial show that adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with Staphylococcus aureus bacteremia, UK researchers reported yesterday in The Lancet.

For many years, the researchers explain, it's been hypothesized that adding rifampicin to the standard treatment for S aureus bacteremia (either an anti-staphylococcal penicillin or a glycopeptide if the bacteria are resistant to methicillin) might improve outcomes for the infection, which is one of the most common and serious community- and hospital-acquired infections worldwide. That belief has led to widespread use of rifampicin for treatment of S aureus bacteremia, even though the evidence to support the benefit is weak.

To test the hypothesis that adjunctive rifampicin is beneficial for S aureus bacteremia patients, the researchers conducted a multicenter, randomized, double-blind, placebo-controlled trial of adults with S aureus bacteremia treated at 29 UK hospitals from December 2012 through October 2016. The participants were randomized 1:1 to receive either rifampicin or a placebo for 2 weeks, plus standard antibiotic therapy as chosen by the attending physician. The primary outcome was bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomization to 12 weeks.

Of the 758 eligible participants, 370 received rifampicin and 388 received a placebo in addition to standard therapy. Standard antibiotics were given for a median duration of 29 days, and 619 participants (82%) received flucloxacillin. By week 12, bacteriologically confirmed treatment failure or disease recurrence, or death, had occurred in 62 participants (17%) in the rifampicin group compared with 71 patients (18%) in the placebo group (absolute risk difference -1.4%, hazard ratio 0.96). While there was a small but significant reduction in disease recurrence associated with rifampicin, that effect had no impact on short-term or long-term mortality. In addition, patients treated with rifampicin had more adverse events than those treated with placebo (17% vs. 10%) and were more likely to have drug interactions that complicated their treatment (6% vs. 2%)

"In summary, adjunctive rifampicin did not improve outcomes from S aureus bacteraemia, with the exception of a modest reduction in disease recurrence," the authors conclude. 
Dec 14 Lancet study
Dec 14 Lancet commentary

 

Irish study finds VRE contamination common in the ICU

Irish researchers report that intensive care unit (ICU) environmental contamination with vancomycin-resistant enterococci (VRE) in areas near patients is common, even in non-outbreak settings, according to a study yesterday in Infection Control and Hospital Epidemiology.

In the single-center study, conducted in the ICU of an 820-bed teaching hospital in Dublin, investigators took samples from the ICU environment and patients during seven sampling periods from October 2012 through June 2014. The aim of the study was to identify potential reservoirs of VRE, investigate the clinical and molecular epidemiology of VRE outside of outbreaks, and assess the role of active surveillance cultures (ASCs) in identifying VRE patients in this setting. Ireland has the highest rate of VRE bloodstream infections in Europe at 45.8%.

Of 289 sampling occasions involving 157 patients and their bed spaces, VRE isolates were recovered from patient bed spaces, clinical samples, or both on 114 of 289 sampling occasions (39.4%). The patient and their bed space were positive for VRE on 34 of 114 VRE-associated sampling occasions (29.8%). Thirty of the 157 patients (19%) were VRE-colonized.

Of 1,647 environment samples, 107 sites (6.5%) were VRE positive, with significantly greater VRE recovery from isolation rooms than from the open-plan area (9.1% vs 4.1%). The most frequently VRE-contaminated sites were the drip stand, bed control panel, and chart holders, which together accounted for 61% of contaminated sites. The use of ASCs resulted in a 172% increase in identification of VRE-colonized patients. Molecular typing revealed two environmental clusters, one involving three patients and generally greater heterogeneity of patient isolates compared to environmental isolates.

The authors conclude that better infection control policies that limit environmental transmission of VRE in the ICU are needed.
Dec 14 Infect Control Hosp Epidemiol study


Palestinian study finds good response to ICU stewardship intervention

A prospective audit-and-feedback antimicrobial stewardship program (ASP) in a Palestinian ICU found a high acceptance rate for the ASP team's recommendations, according to a study this week in the British Journal of Clinical Pharmacology.

The ASP program was begun at the Palestinian Medical Complex in September 2015. The investigators analyzed data from the 4 months before and the 4 months after implementation.

They found that, of 176 recommendations made by the ASP team, 78.4% were accepted. The most often accepted interventions were dose optimization (87%) and de-escalation based on culture results (84.4%). In addition, interventions were associated with a 24.3% reduction in antimicrobial use, shorter length of stay, and significantly reduced duration of therapy.
Dec 13 Br J Clin Pharmacol study

ASP Scan (Weekly) for Dec 15, 2017

News brief

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

Study: No benefit from adding rifampicin to S aureus bacteremia treatment

The results of a large randomized trial show that adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with Staphylococcus aureus bacteremia, UK researchers reported yesterday in The Lancet.

For many years, the researchers explain, it's been hypothesized that adding rifampicin to the standard treatment for S aureus bacteremia (either an anti-staphylococcal penicillin or a glycopeptide if the bacteria are resistant to methicillin) might improve outcomes for the infection, which is one of the most common and serious community- and hospital-acquired infections worldwide. That belief has led to widespread use of rifampicin for treatment of S aureus bacteremia, even though the evidence to support the benefit is weak.

To test the hypothesis that adjunctive rifampicin is beneficial for S aureus bacteremia patients, the researchers conducted a multicenter, randomized, double-blind, placebo-controlled trial of adults with S aureus bacteremia treated at 29 UK hospitals from December 2012 through October 2016. The participants were randomized 1:1 to receive either rifampicin or a placebo for 2 weeks, plus standard antibiotic therapy as chosen by the attending physician. The primary outcome was bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomization to 12 weeks.

Of the 758 eligible participants, 370 received rifampicin and 388 received a placebo in addition to standard therapy. Standard antibiotics were given for a median duration of 29 days, and 619 participants (82%) received flucloxacillin. By week 12, bacteriologically confirmed treatment failure or disease recurrence, or death, had occurred in 62 participants (17%) in the rifampicin group compared with 71 patients (18%) in the placebo group (absolute risk difference -1.4%, hazard ratio 0.96). While there was a small but significant reduction in disease recurrence associated with rifampicin, that effect had no impact on short-term or long-term mortality. In addition, patients treated with rifampicin had more adverse events than those treated with placebo (17% vs. 10%) and were more likely to have drug interactions that complicated their treatment (6% vs. 2%)

"In summary, adjunctive rifampicin did not improve outcomes from S aureus bacteraemia, with the exception of a modest reduction in disease recurrence," the authors conclude. 
Dec 14 Lancet study
Dec 14 Lancet commentary

 

Irish study finds VRE contamination common in the ICU

Irish researchers report that intensive care unit (ICU) environmental contamination with vancomycin-resistant enterococci (VRE) in areas near patients is common, even in non-outbreak settings, according to a study yesterday in Infection Control and Hospital Epidemiology.

In the single-center study, conducted in the ICU of an 820-bed teaching hospital in Dublin, investigators took samples from the ICU environment and patients during seven sampling periods from October 2012 through June 2014. The aim of the study was to identify potential reservoirs of VRE, investigate the clinical and molecular epidemiology of VRE outside of outbreaks, and assess the role of active surveillance cultures (ASCs) in identifying VRE patients in this setting. Ireland has the highest rate of VRE bloodstream infections in Europe at 45.8%.

Of 289 sampling occasions involving 157 patients and their bed spaces, VRE isolates were recovered from patient bed spaces, clinical samples, or both on 114 of 289 sampling occasions (39.4%). The patient and their bed space were positive for VRE on 34 of 114 VRE-associated sampling occasions (29.8%). Thirty of the 157 patients (19%) were VRE-colonized.

Of 1,647 environment samples, 107 sites (6.5%) were VRE positive, with significantly greater VRE recovery from isolation rooms than from the open-plan area (9.1% vs 4.1%). The most frequently VRE-contaminated sites were the drip stand, bed control panel, and chart holders, which together accounted for 61% of contaminated sites. The use of ASCs resulted in a 172% increase in identification of VRE-colonized patients. Molecular typing revealed two environmental clusters, one involving three patients and generally greater heterogeneity of patient isolates compared to environmental isolates.

The authors conclude that better infection control policies that limit environmental transmission of VRE in the ICU are needed. 
Dec 14 Infect Control Hosp Epidemiol study

 

Palestinian study finds good response to ICU stewardship intervention

A prospective audit-and-feedback antimicrobial stewardship program (ASP) in a Palestinian ICU found a high acceptance rate for the ASP team's recommendations, according to a study this week in the British Journal of Clinical Pharmacology.

The ASP program was begun at the Palestinian Medical Complex in September 2015. The investigators analyzed data from the 4 months before and the 4 months after implementation.

They found that, of 176 recommendations made by the ASP team, 78.4% were accepted. The most often accepted interventions were dose optimization (87%) and de-escalation based on culture results (84.4%). In addition, interventions were associated with a 24.3% reduction in antimicrobial use, shorter length of stay, and significantly reduced duration of therapy. 
Dec 13 Br J Clin Pharmacol study

 

More cases of puppy-linked Campylobacter reported in several states

Originally published by CIDRAP News Dec 13

The Centers for Disease Control and Prevention (CDC), in an update on an ongoing outbreak of multi-drug resistant Campylobacter infections linked to puppies sold in pet shops today, confirmed 30 new cases reported since the last outbreak update published on Oct 30.

As of yesterday, officials have reported that 97 people in 17 states have laboratory-confirmed infections or symptoms consistent with Campylobacter infection. A total of 22 people have been hospitalized, but no deaths have been reported. The first cases were reported to the CDC in June.

The vast majority of patients (98%) reported contact with a puppy in the week preceding illness. Ninety percent of people interviewed said they had contact with a puppy from a Petland store, or had contact with a person who became sick after contact with a puppy from a Petland store. Twenty-one ill people worked at a Petland store.

Using whole genome sequencing, the CDC identified multiple antimicrobial resistance genes and mutations in most isolates from 35 ill people and 9 puppies, including resistance to azithromycin, ciprofloxacin, clindamycin, erythromycin, nalidixic acid, telithromycin, and tetracycline.
Dec 13 CDC update

 

Clinicians call for more inclusive trials for new antibiotics

Originally published by CIDRAP News Dec 12

A letter today in the Journal of Infectious Diseases argues for relaxed criteria for patient exclusion in randomized controlled trials (RCTs) for new drugs to treat multidrug-resistant infections.

The letter, written by two Israeli clinicians, describes three patients with severe infections caused by carbapenem-resistant bacteria that presented during a single day at a hospital in Haifa. None of the three patients, the authors note, was eligible for an ongoing RCT at the hospital to assess the antibiotic cefiderocol—a novel siderophore cephalosporin in late-stage development—versus the best available therapy for bloodstream and other severe multidrug-resistant infections. All were treated with colistin as the only covering antibiotic.

These cases, the authors argue, point out a paradox. While it's estimated that more than 700,000 patients die each year from infections caused by multidrug-resistant pathogens, and plenty of patients with carbapenem-resistant infections are described in epidemiologic studies, finding patients for drug approval RCTs is difficult. That's because RCTs are often biased toward uncomplicated patients with a low risk of death, and the patients with the types of conditions described in their letter—neutropenia, severe sepsis, and organ failure—are often excluded from such studies. Yet these are the patients who may have the greatest need for new treatments.

While efforts to improve testing and approval requirements of new drugs for unmet needs have been commendable, the authors write, "We would like a discussion about the changes in regulatory guidance to the industry that would relax criteria for patient exclusion to ensure that the patients in [an] RTC resemble a bit more the patients in need of the antibiotic under study."
Dec 12 J Infect Dis letter

 

Commentary: Vaccines needed in the fight against AMR

Originally published by CIDRAP News Dec 12

Vaccines could and should play a key role in stemming the antimicrobial resistance (AMR) crisis, according to a commentary today in Nature.

The commentary, co-authored by the chief scientist at GlaxoSmithKline Vaccines and professors from Harvard T.H. Chan School of Public Health and Cincinnati Children's Hospital, calls for a global strategic effort to prioritize development of a portfolio of vaccines to target AMR.

Their reasoning is based on several factors. For one, they argue, vaccines almost never prompt bacteria to develop resistance. In addition, scientists have had much more success over the last 30 years developing new vaccines than they've had discovering new antibiotics. Since the 1980s, 22 new vaccines have been deployed in the clinic, while no new truly new class of antibiotics has been discovered or engineered. And vaccine technology continues to evolve.

Given this reality, and the fact that several current vaccines—such as the pneumococcal and influenza vaccines—have already helped directly and indirectly reduce the need for antibiotics, the authors say vaccines must be considered an essential element of the fight against AMR, along with new antibiotics, diagnostics, surveillance, and stewardship. Launching an effort to develop a portfolio of vaccines against AMR, they say, will require policymakers and stakeholders to raise awareness about the potential of vaccines to combat AMR, to persuade governments and drug companies of the cost-effectiveness of investing in vaccines, and to prioritize which bacterial strains should be targeted.

"Over the past few years, key institutional stakeholders — notably the [World Health Organization], the [United Nations General Assembly], the World Bank, the G20 group of countries, the European Union and the UK and US governments — have called for researchers to develop new antibiotics to expand our arsenal in the war against superbugs," the authors write. "We appeal to these organizations to call now for a multi-layered strategy that prioritizes the development of vaccines to target resistant strains."
Dec 12 Nature comment

 

Interventions to reduce overtreatment of asymptomatic bacteriuria noted

Originally published by CIDRAP News Dec 11

A paper today in JAMA Internal Medicine proposes an evidence-based implementation guide to help reduce inappropriate treatment of asymptomatic bacteriuria (ASB).

Despite efforts to reduce the practice, treatment of ASB—defined as isolation of bacteria in an uncontaminated urine specimen in the absence of urinary tract infection symptoms—remains prevalent across settings and frequently leads to inappropriate antibiotic prescribing. A multicenter retrospective review of three US hospitals found that 38% of in patients with ASB were treated with antibiotics the day of a positive urine culture report, and 43% were treated by the fourth day.

To come up with an implementation guide that could help clinicians reduce ASB overtreatment, a team of researchers from Johns Hopkins, Sinai Health System, and the University of Toronto first reviewed the evidence behind supporting reduced treatment of ASB. Based on that evidence, they determined that efforts to reduce inappropriate treatment of ASB in low-risk populations (excluding pregnant women and patients undergoing invasive urologic procedures) can reduce preventable harm from unnecessary antibiotic exposure.

The team then looked at safety and quality outcomes data for different interventions aimed at reducing ASB treatment. From those data, they determined that the most successful interventions used a multimodal approach that combined the following elements: education, audit and feedback, withholding routine urine culture reports, and clinical decision support tools and protocols.

"While the interventions described in this guide have proven efficacy in certain settings, we acknowledge the importance of context and encourage teams to select and adapt specific interventions that best suit the needs and resources specific to the institution," the authors write. "In reality, a bundle of interventions may be needed to address different contributors to the problem specific to the local setting."
Dec 11 JAMA Internal Med paper

 

New National Academies publication details AMR workshop proceedings

Originally published by CIDRAP News Dec 11

The National Academies of Sciences, Engineering, and Medicine (NAS) have released a new document summarizing the presentations and discussions at a 2-day workshop on antimicrobial resistance (AMR) held earlier this year.

The workshop, held Jun 20 and 21 in Washington, DC, brought together experts in infectious disease, microbiology, and human and animal health to explore the issue of AMR through the One Health lens, which views the health of humans, animals, and the environment as interconnected. The workshop was convened to examine short-term actions and research needs that are feasible and cost-effective and will have the greatest effect on reducing AMR.

Among the topics explored were the implications and effects on human health of the movement of resistance genes across different ecosystems; the expected effect of new US regulatory policies regarding the use of antibiotics in food animals; the role and effectiveness of antibiotic stewardship programs in reducing and preventing AMR, and the importance of data availability and data sharing for evaluating stewardship strategies; strategies for maintaining the effectiveness of existing drugs, for developing new drugs and diagnostics, and for implementing disease prevention steps; and the need for national and international collaboration.

The document contains the opinion of the presenters, but it does not reflect the conclusions of the Health and Medicine Division of the NAS.
Dec 8 National Academies proceedings of AMR workshop

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