Stewardship / Resistance Scan for May 07, 2020

News brief

IDSA urges changes to national sepsis care measures

The Infectious Diseases Society of America (IDSA) and five other medical organizations are urging changes to a national set of care measures for sepsis patients, with the aim of reducing unnecessary antibiotic use in patients who may not need them.

In a paper published yesterday in Clinical Infectious Disease, members of the IDSA Sepsis Task Force argued that the Centers for Medicare and Medicaid Services' (CMS's) Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), which was implemented in 2015, has the potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. Of particular concern is that SEP-1 stipulates the same time-to-antibiotic goal for both sepsis and septic shock, even though the association between time-to-antibiotics and mortality is much stronger for septic shock than for sepsis without shock.

"IDSA believes the perception that any delays in antibiotic therapy lead to worse outcomes for patients with sepsis, regardless of the severity of illness, contributes to inappropriate antibiotic prescribing and is the wrong message to communicate to providers," the authors wrote.

Among the recommendations outlined in the paper is removing sepsis without shock from SEP-1 to mitigate the risk of inappropriate antibiotics for patients with signs and symptoms resembling sepsis but with a low likelihood of infection. The recommendations also urge that SEP-1 continue to focus on obtaining blood cultures before giving antibiotics, versus after, and that antibiotics be administered within 1 hour of septic shock being recognized. But they call for the criteria for septic shock to be simplified.

In an editorial, authors from CMS, the University of California, San Francisco School of Medicine, and Wayne State University say the IDSA has not met the burden of proof to establish that SEP-1 has increased unnecessary antibiotic usage, or shown that delaying antibiotics in patients with severe sepsis is safe.

"We are open to considering alternative antibiotic measurement strategies in severe sepsis and septic shock, but we cannot support a strategy of leaving severe sepsis patients without timely and appropriate antibiotic coverage," the authors wrote. CMS requires hospitals to publicly report their compliance with SEP-1 in order to receive additional payments.
May 6 Clin Infect Dis paper
May 6 Clin Infect Dis editorial

Randomized trial shows stewardship benefits of rapid ID, susceptibility test

In another study published yesterday in Clinical Infectious Diseases, the results of a randomized controlled trial found that use of a rapid organism identification and phenotypic antibiotic susceptibility test (AST) led to faster changes in antibiotic therapy in patients with gram-negative bloodstream infections (BSIs) when compared with conventional testing.

In the prospective trial, US researchers randomized 500 patients who had a positive blood culture showing gram-negative bacteria at two US academic medical centers to receive either standard-of-care (SOC) culture and AST or rapid organism identification and phenotypic AST using the Accelerate Pheno System (RAPID). All patients in both arms underwent prospective audit and feedback from antibiotic stewardship programs at the hospitals. The primary outcome was time to first antibiotic modification within 72 hours of randomization.

Among the 448 participants included in the final analysis, the mean time to organism identification was faster in the RAPID arm than in the SOC arm (2.7 hours vs 11.7 hours, P < 0.001), as was time to susceptibility results (13.5 hours vs 44.9 hours, P < 0.001). Median (interquartile range, [IQR]) hours to first antibiotic modification was faster in the RAPID vs SOC arm for overall antibiotics (8.6 hours vs 14.9 hours, difference 6.3 hours, P = 0.02) and for gram-negative antibiotics (17.3 hours vs 42.1 hours, difference 24.8, P < 0.001). Median (IQR) time to antibiotic escalation was also faster in the RAPID arm than the SOC arm for antibiotic-resistant BSIs (18.4 vs 61.7 hours, difference 43.3 hours, P = 0.01).

Analysis of patient outcomes found no statistically significant differences between the two arms for mortality, time to death, or length of hospital stay.

The authors of the National Institutes of Health–funded study say the results indicate that rapid ID and AST, implemented along with antibiotic stewardship measures, can help clinicians provide timely, effective therapy while also promoting more appropriate antibiotic use.

"Development of rapid, innovative methods for detection of microorganisms and drug resistance in blood cultures is an important component in the fight against antimicrobial resistance," they wrote.
May 6 Clin Infect Dis abstract

News Scan for May 07, 2020

News brief

Study confirms risks of breastfeeding to infants of moms with Ebola

A systematic review published yesterday in The Lancet Infectious Diseases underscores the importance of precautions to minimize the risk of transmitting Ebola via breastfeeding.

Led by World Health Organization (WHO) researchers, the review of 52 studies published from 1976 to 2019 found that Ebola virus was still detectable via reverse transcription polymerase chain reaction in breast milk 26 days after the mother began having symptoms and in amniotic fluid as long as 32 days after the virus had cleared from the mother's blood.

Of 274 pregnant women with Ebola, 197 (72%) died, similar to the death rate of the general population infected with the virus. Almost all the women had adverse pregnancy outcomes, with only 31 of 267 (12%) resulting in a live birth and all but 3 babies dying within 19 days. Maternal death rates from Ebola before 2014 were higher (91 of 107 cases [85%]).

The 2019 outbreak of Ebola in the Democratic Republic of the Congo is ongoing, with 3,453 cases and 2,264 deaths as of Apr 5. Most cases have occurred in women, as they did in the 2014-16 outbreak in West Africa that killed more than 11,000 people.

Some pregnant women were denied supportive care in the 2014-16 outbreak because healthcare workers thought treatment was futile. "Our review, however, suggests that pregnancy is not associated with increased mortality or disease severity for women with Ebola virus disease," the authors wrote.

In a commentary in the same journal on WHO guidelines on the care of pregnant or breastfeeding women with Ebola issued in February, the same authors said that breastfeeding infants of infected mothers should be separated and given a breast milk substitute and should be considered contacts for the purposes of outbreak management.
May 6 Lancet Infectious Diseases study and commentary
February WHO guidelines

Undervaccination, crowded conditions fueled Jerusalem measles outbreak

An investigation into a large measles outbreak in Israel's Jerusalem district in 2018 and 2019 revealed challenges with contact tracing and isolating patients, due to high population density and that vaccination encouragement from rabbis helped turn the tide. The team reported its findings today in a Morbidity and Mortality Weekly Report (MMWR) note from the field.

The outbreak began following imported cases, mainly from Ukraine, in March 2018 in Central and Northern districts of Isreal, but it spread to Jerusalem in August 2018 because of two unvaccinated infected people, a 20-year-old boarding school student and a 2-year-old child. The outbreak spread rapidly though densely populated low-income orthodox Jewish neighborhoods where first-dose measles vaccine coverage is lower than for children in other communities.

Transmission intensified during the fall Jewish high holidays. Investigators found inadequate adherence to isolation recommendations among patients and their parents and were challenged by high numbers of close contacts to track.

The response also included postexposure prophylaxis and a vaccine campaign that targeted children ages 1 to 14 years old. High numbers of cases and the impact on young children triggered community concerns, and the rabbi community helped support the vaccine campaign, which encouraged acceptance and compliance with control activities.

Vaccine coverage climbed from 76.3% to 96.8%, and by December 2018, cases dropped considerably, ending in May 2019. The outbreak totaled 4,115 cases, about half from Jerusalem.
May 8 MMWR note from the field

Valneva to develop single-dose chikungunya vaccine

Valneva this week announced a partnership with Instituto Butantan, a producer of immunobiologic products, to develop, manufacture, and market, Valneva's single-injection chikungunya vaccine, VLA1553, in low- and middle-income countries (LMICs).

"Although millions of people have been affected by chikungunya, there is currently no vaccine and no effective treatment available against this debilitating disease," said Thomas Lingelbach, Valneva president and CEO. "We look forward to working with Instituto Butantan to help address this current public health crisis and speed up the development of a chikungunya vaccine in LMICs, which are high outbreak areas."

Valneva is set to begin phase 3 clinical trials on the vaccine in the United States this year, and all phase 4 trials will be handled by Instituto Butantan.

Since 2005, the mosquito-borne disease has caused 2 million deaths worldwide.
May 5 Valneva press release