Stewardship / Resistance Scan for Nov 26, 2018

News brief

Researchers re-estimate annual deaths from multidrug-resistant infections

Infectious disease specialists from Washington University School of Medicine estimate that the number of deaths caused by multidrug-resistant organisms (MDROs) is more than six times higher than widely cited figures from the Centers for Disease Control and Prevention (CDC).

In a letter published in Infection Control and Hospital Epidemiology, the researchers looked at data on inpatient and outpatient deaths in 2010 and estimated that a minimum of 153,113 deaths that year were caused by MDRO infections, with a worst-case scenario of 162,044. That would make MDROs the third-leading cause of death in the United States in 2010. The CDC estimated in a 2013 report that drug-resistant infections are responsible for 23,000 deaths a year, but because hospital codes don't specify deaths caused by MDROs, the true burden remains uncertain.

The researchers based the number of inpatient deaths caused by MDROs—70,837—on a conservative estimate of inpatient deaths due to sepsis (34.4%, 245,960) and the reported rate of MDR pathogens in sepsis cases (28.8%). The numbers for outpatient deaths—82,276 to 91,207—was determined by estimating how many outpatients died from infections in 2010 (17% to 19% of all cases, or 285,680 to 316,690 deaths) and then assuming that 28.8% were caused by MDROs.

The authors of the letter say the estimates illustrate the need for better surveillance and reporting mechanisms for MDROs infections.

"With rampant overuse of antibiotics, establishment of MDRO breeding and transmission centers (long-term acute-care hospitals and nursing facilities), and increasing rates of iatrogenic immunosuppression, the population at risk for MDRO infections and the likelihood of drug resistance will continue to increase," they write. "To address this critical issue, establishing the burden of MDROs is crucial to guide research funding allocation."
Nov 22 Infect Control Hosp Epidemiol letter


Japanese ASP reduces use of broad-spectrum antibiotics, study finds

Japanese researchers report in Open Forum Infectious Diseases that an antimicrobial stewardship program (ASP) centered around post-prescription review with feedback (PPRF) was tied to a reduction in the use of broad-spectrum antibiotics and the average length of stay at a Tokyo hospital over 4 years.

The before-after study conducted at Tokyo Metropolitan Tama Medical Center evaluated the impact of the ASP on antimicrobial use, patient-related outcomes, and changes in antimicrobial resistance in the inpatient setting by comparing two periods—the pre-intervention period (April 2012 to March 2014) and the intervention period (April 2014 to March 2018). The main activity in the ASP was a once-weekly PPRF meeting focused on auditing patients who were on carbapenems and piperacillin-tazobactam for more than 72 hours. Antimicrobial use was expressed as days of therapy (DOT) per 1,000 patient-days (PD).

An interrupted time series analysis showed that the monthly average use of both carbapenems (from 17.33 DOT per 1,000 PD to 8.67) and piperacillin-tazobactam (25.43 DOT/1,000 PD to 20.95) was lower in the intervention period than in the pre-intervention period. But the change in slope for carbapenem use significantly diminished over the course of the intervention period (from -0.73 to -0.003 DOT/1,000 PD [P < 0.001]), and the change in slope for piperacillin-tazobactam did not reach statistical significance (-0.04 to -0.24 DOT/1,000 PD [P = 0.16]). Post-intervention use of narrower spectrum antimicrobials was higher, but only ampicillin-sulbactam use reflected a statistically significant change (+0.58 DOT/1,000 PD [P < 0.001]).

The analysis also found that the monthly average length of hospital stay declined by -0.04 days per month (P < .001) and antimicrobial costs declined by -37.4 USD/1,000 PD per month (P < .001). Few post-intervention changes in the incidence of drug-resistant organisms were observed.

The authors conclude, "While the trends in antimicrobial use seen in the current study failed to demonstrate statistical significance, the results do suggest that PPRF for broad-spectrum antimicrobials can contribute to a sustained reduction in the use of antimicrobials and conduce to a hospital-wide de-escalation in antimicrobial use without compromising patients’ clinical outcomes."
Nov 22 Open Forum Infect Dis abstract


Review: Stewardship studies lack quality

A comprehensive systematic review of studies on antimicrobial stewardship has found that the overall quality is low and has not improved over time, a team of Dutch and British researchers report in Clinical Microbiology and Infection.

For the study, the researchers searched for all studies evaluating antimicrobial stewardship interventions published from 1950 through 2017. All studies underwent full-text evaluation, with reviewers assessing studies based on pre-specified design quality features (including use of randomized research design, multiple centers, and external controls) and factors that may influence design choices (including clinical setting, age-group studied, and financial support received.)

In total, 825 studies were included for review; 205 were in the community setting and 620 were in the hospital setting. Studies in the community setting fulfilled a median of 5 of 10 quality features, while studies in hospital settings fulfilled 3 of 10 quality features; none of the studies fulfilled all 10 quality features. Community setting studies were more likely to use randomization (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.8 to 9.2), external controls (OR, 5.6; 95% CI, 3.6 to 8.5), and multiple centers (OR, 10.5; 95% CI, 7.1 to 15.7). Most studies focused exclusively on process measures, with only 48% of all studies reporting clinical outcomes and only 23% reporting microbiologic outcomes. No improvement in quality design over time was observed.

The authors of the review say the findings will be used to formulate recommendations in a white paper that will "support investigators with key decisions, support funders assessing proposals for stewardship studies, and enhance the quality and impact of research in this crucial area."
Nov 23 Clin Microbiol Infect study

News Scan for Nov 26, 2018

News brief

Romaine in latest E coli outbreak likely came from California

Romaine lettuce suspected in Escherichia coli O157:H7 illnesses in the United States and Canada probably came from California, based on growing and harvesting patterns, Scott Gottlieb, MD, US Food and Drug Administration (FDA) commissioner, said in a Nov 23 Twitter post.

The next step is to withdraw the product that's at risk from the market, then restock the market, he said.

New romaine lettuce from different growing regions, including Florida and Arizona, will soon be harvested, Gottlieb said, adding that officials are working with growers and distributors on labeling produce for location and harvest date as a way of informing consumers that the products are "post purge." Authorities are considering making the labels the new standard to improve product identification and traceability.

Meanwhile, California Leafy Greens Marketing Agreement (LGMA), an industry group centered around government food safety audits, said on Nov 20 that it supports government advisories and the withdrawal of all romaine, which it says is the fastest way to clear the supply chain of contaminated product and make a clean break from harvesting and shipping until the source of the outbreak is identified. It said a group of food safety experts from the produce industry is coming together to help pinpoint the specific source, and it noted that whole-genome sequencing by federal agencies has shown that the same E coli isolate was closely related to two similar outbreaks in 2016 and 2017 linked to leafy greens.

The LGMA said in a Nov 21Twitter post that the industry recently underwent a seasonal transition, wrapping up production in Central California and moving to Yuma, Ariz., a growing cycle designed to provide consumers with lettuce year round.
Nov 23 Scott Gottlieb Twitter thread
Nov 20 LGMA
Nov 21 LGMA

In a related development, the Public Health Agency of Canada (PHAC) on Nov 23 said three more cases have been linked to the outbreak, lifting its total to 22 in three provinces: Ontario, Quebec, and New Brunswick. The number of infections in the United States so far remains at 32 in 11 states.
Nov 23 PHAC update


Six more polio cases recorded in Papua New Guinea, Nigeria, DRC

According to the latest update from the Global Polio Eradication Initiative (GPEI), three countries reported vaccine-derived polio cases in the last week.

Papua New Guinea, which is battling its first polio outbreak in nearly 20 years, recorded three cases of circulating vaccine-derived poliovirus type 1 (cVDPV1), with onsets of paralysis reported from Aug 17 to Sep 30. The cases come from East Sepik and Enga provinces and raise the country's total number of polio cases this year to 25.

In Nigeria, two circulating vaccine-derived poliovirus type 2 (cVDPV2) were reported in Jigwa and Borno states. The patients reported an onset of paralysis on Oct 13 and 17. The cases raise Nigeria's yearly total to 27.

Finally, the Democratic Republic of the Congo (DRC) also recorded a cVDPV2 case in a previously uninfected province, Sankuru. The patient had onset of paralysis on Sep 25. There have now been 19 cases of polio in the DRC in 2018, compared with 10 at this point in 2017.
Nov 23 GPEI


China reports human H5N6 avian flu case, more poultry outbreaks

China has reported another H5N6 avian flu infection, this time involving a 10-year-old girl from the city of Suzhou in Jiangsu province, according to a Nov 23 statement from Hong Kong's Centre for Health Protection (CHP).

The girl's symptoms began on Oct 29, and she was hospitalized on Nov 3. The report did not say if she had contact with poultry or their environments. Jiangsu province is in the east central part of China.

H5N6 has been reported in poultry in a few Asian countries, but China is the only one to report human infections, which are often severe or fatal. Since the first human H5N6 illness was detected in 2014, China has reported 23 cases. The last was reported at the end of October and involved a man from Guangxi province who died from his infection.
Nov 23 CHP statement

In other H5N6 developments, China recently reported three more outbreaks in poultry, according to notifications from the World Organization for Animal Health (OIE) late last week. One of them occurred at a commercial farm in the village of Huinan in Jiangsu province. The event began on Nov 10, killing 320 of 31,649 birds.

The other two outbreaks struck commercial farms at different locations in Yunnan province in southwestern China, with start dates on Oct 28 and Nov 3. Taken together, the outbreaks killed 9,820 of 20,100 susceptible birds. In both provinces, the remaining poultry were culled to curb the spread of the virus.
Nov 23 OIE report on H5N6 in China
Nov 22 OIE report on
H5N6 in China


CDC: Flu activity still low but picking up a bit

Though flu activity in the United States is still low, the US Centers for Disease Control and Prevention (CDC) today reported small increases, with all three seasonal strains circulating, though 2009 H1N1 has been most commonly reported.

Two of the CDC's regions are above their specific baselines for flu-related clinic visits: region two, which mainly includes New York, New Jersey, and the US territories, and region eight, which covers six west central states. Nationally, the percentage of clinic visits for influenza-like illness (ILI) was at 1.9%, which is below the national baseline of 2.2%.

Geographic spread of flu was regional for one state, Kentucky, while Guam and 14 states reported local geographic spread. Georgia, Louisiana, and Oklahoma experienced moderate ILI activity.

One more pediatric flu death was reported, which involved the 2009 H1N1 virus and raises the season's total to three. Overall deaths from pneumonia and flu remained below the seasonal baseline.

Of samples analyzed at public health labs, 98.7% that tested positive for flu were influenza A, and, of subtyped influenza A viruses, 81.7% were 2009 H1N1 and 18.3% were H3N2.
Nov 26 CDC FluView report

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