Stewardship / Resistance Scan for Mar 29, 2021

News brief

Trial suggests shorter antibiotic course for hospitalized pneumonia

The results of a randomized clinical trial conducted in France indicate that 3 days of beta-lactam therapy is non-inferior to 8 days of treatment in patients hospitalized with community-acquired pneumonia who meet clinical stability criteria after 3 days, French investigators reported last week in The Lancet Infectious Diseases.

The Pneumonia Short Treatment (PTC) trial was conducted in 16 hospitals in France and involved non-immunocompromised adult patients admitted to the hospital with moderately severe community-acquired pneumonia who met prespecified clinical criteria after 3 days of treatment with beta-lactam therapy. The trial participants were randomly assigned to receive either 5 days of additional beta-lactam therapy (oral amoxicillin plus clavulanate) or 5 days of placebo, with participants, clinicians, and study staff blinded to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, with a non-inferiority margin of 10 percentage points.

From December 2013 to February 2018, 310 eligible patients were assigned to receive placebo (157) or beta-lactam treatment (153). Seven patients withdrew consent before treatment started. In the intention-to-treat analysis (ITT), cure at day 15 occurred in 117 of 152 patients (77%) in the placebo group and 1o2 of 151 (68%) in the beta-lactam group (between-group difference, 9.42 percentage points; 95% confidence interval [CI], -0.38 to 20.04), indicating non-inferiority.

Results of the per protocol analysis also indicated non-inferiority, with 113 of 145 placebo patients (78%) and 100 of 146 in the beta-lactam group (68%) cured at day 15 (between-group difference, 9.44 percentage points; 95% CI, -0.15 to 20.34). Incidence of adverse events was similar in the placebo group (11%) and the beta-lactam group (19%). By day 30, 3 patients (2%) in the placebo group and 2 (1%) in the beta-lactam group died.

"These data support the concept that antibiotic therapy can be safely discontinued in patients who have moderately severe community-acquired pneumonia who have early clinical response to therapy, which could allow an important reduction in antibiotic exposure among patients being treated in hospital for community-acquired pneumonia," the authors wrote.
Mar 25 Lancet Infect Dis abstract

Report highlights R&D, access gap for pediatric drugs

A new report from the Access to Medicine Foundation finds significant gaps in treatments aimed specifically at children under 12, highlighted by a lack of access to a child-friendly Clostridioides difficile treatment and a dearth of drugs that address diarrheal diseases in infants in low- and middle-income countries (LMICs).

According to the report, among the five treatments that could be "game-changers" for children in LMICs is an oral suspension of fidaxomicin for C difficile-associated diarrhea in children over 6 months of age. The treatment, developed by MSD and Astellas Pharma Europe, was approved by the US Food and Drug Administration in 2o20 but does not show any evidence of an access plan that would help ensure it is accessible and affordable in all the markets where it's needed.

The report shows that of the 1,073 pharmaceutical research and development (R&D) projects assessed, less than 7% (69) target children under the age of 12 and are focused mainly on lower respiratory infections, cancer, HIV/AIDS. Only five projects target neonatal sepsis, and the pipeline for certain diarrheal infections such as Escherichia coli and cholera is completely empty, despite being identified as a priority R&D target by the World Health Organization.

The authors of the report suggest that stakeholders can address these gaps by simplifying regulatory procedures for pediatric drugs, establishing targeted economic incentives to encourage pediatric R&D, integrating access plans into the R&D process, and increasing funding for innovative approaches to expanding access to pediatric drugs in LMICs.

"For the millions of children waiting in line for medicines that are taken for granted in high-income countries, it is not enough that a few projects are in development," the report states. "It is not enough that a few more mechanisms are in place to ensure some of these projects will reach children who need them. It is time to close the gaping disparities in access that persist."
Mar 25 Access to Medicine Foundation report

Spanish stewardship intervention linked to reduced carbapenem use

A multifaceted antimicrobial stewardship program (ASP) was associated with reduced carbapenem use and decreased incidence of carbapenem-resistant Acinetobacter baumannii, according to a study last week in the Journal of Antimicrobial Chemotherapy.

The quasi-experimental time-series study involved seven hospitals in Andalusia, Spain, with carbapenem use above the region's average. A team of Spanish researchers looked at carbapenem use and identification of carbapenem-resistant gram-negative bacilli (CR-GNB) from January 2014 through September 2018, comparing the 11 quarters prior to the introduction of the ASP with the 8 quarters after.

The ASP intervention had four components addressing carbapenem prescribing, with the core activity being educational interviews between stewardship teams and prescribing physicians after they prescribed carbapenems. During the intervention period, 6,046 interviews on antibiotic prescriptions were carried out, and 1,747 involved carbapenem prescriptions.

The use of carbapenems decreased throughout the study period (average quarterly percentage change [AQPC], -1.5%), with a level change of -8.170 observed following the start of the intervention. The total number of educational interviews per hospital was correlated with a decrease in carbapenem use. While the overall incidence density (ID) of CR-GNB remained stable during the study period (AQPC, -0.4%), the ID of CR-A baumannii decreased (AQPC, -3.5%). CR-GNB, CR-A baumannii, and CR-Pseudomonas aeruginosa IDs per hospital correlated with the local consumption of carbapenems.

The study authors note that the reduced consumption of carbapenems was achieved without adopting restrictive measures, using educational interventions only, and despite a shortage of piperacillin/tazobactam, which increased carbapenem use in the third quarter of 2017.
Mar 26 J Antimicrob Chemother abstract

News Scan for Mar 29, 2021

News brief

Adults 20-49 key to last year's US COVID-19 resurgence, study says

Adults 20 to 49 years old may be sustaining the resurgence of COVID-19, according to a study published late last week in Science.

The researchers looked at age-specific mobility trends from more than 10 million Americans and used mathematical modeling to estimate the proportion of COVID-19 cases per age-group, finding that young adults less than 35 appeared to have comparable mobility compared with older age-groups as pandemic restrictions eased through Oct 29, 2020. However, the estimated viral reproduction number across 38 states, New York City, and the District of Columbia was highest in those 35 to 49 years old (1.39) and 20 to 34 (1.29). Comparatively, for people ages 10 to 19 and 50 to 64, the reproductive values were about 1.

"The primary mechanisms underlying the high reproduction numbers from 20- to 49-year-olds are that at the population level, adults aged 20 to 49 naturally have most contacts with other adults aged 20 and above, who are more susceptible to COVID-19 than younger individuals, paired with increasing mobility trends for these age groups since April 2020," the researchers write. They add that their model also indicated that those in this age-group may have a higher transmission risk per venue visit.

The researchers go on to estimate the number of COVID-19 cases each age group caused, finding that, until mid-August 2020, before most schools reopened, the percent contribution of virus reproduction was mostly from those 35 to 49 (41.1%) and those 20 to 34 (34.7%). After schools opened in the fall, 2,570 observation days revealed a modest shift, with a 38.2% contribution from those 35 to 49 and 34.0% from those 20 to 34.

Yet there is a caveat: As children and teenagers can cause infection in adults who transmit COVID-19 more easily, the researchers say that school openings are associated with an estimated 25.7% increase in COVID-19 infections and a 5.9% increase in related deaths.

"These findings indicate that adults aged 20 to 34 and 35 to 49 continue to be the only age groups that contribute disproportionately to COVID-19 spread relative to their size in the population, and that the impact of school reopening on resurgent COVID-19 is mitigated most effectively by strengthening disease control among adults aged 20 to 49," the researchers write.
Mar 26 Science study

Pre-symptomatic cases tied to substantial portion of COVID-19 spread

Close contacts of symptomatic COVID-19 index cases have a 3.8-fold greater likelihood of getting infected with COVID-19 than if they were exposed to an asymptomatic index case, but pre-symptomatic transmissions accounted for almost 40% of secondary cases, according to a study published late last week in Clinical Infectious Diseases.

The researchers looked at four provinces and one municipality in China, collecting information on transmission events for lab-confirmed cases. From Jan 5 to Apr 7, 2020, 393 symptomatic index cases led to 128 out of 3,136 infections among close contacts (4.1%), while the 185 asymptomatic index cases led to 12 infections out of 1,078 close contacts (1.1%). A shared household and meal sharing were associated with 8.27 and 2.90 increased risks of transmission, respectively, regardless of whether the index case-patient had symptoms.

The researchers also found that 38% of COVID cases stemming from a symptomatic index case occurred before the person developed symptoms. (The researchers acknowledge their attack rates are lower than other reported data, suggesting that different study settings or China's COVID mitigations may be part of the cause.)

Infections from asymptomatic index cases were more likely to be asymptomatic and less severe, according to the study: 1 in 2 close contacts (6/12) were asymptomatic if infected by an asymptomatic index case, compared with 1 in 4 (128/3,136) infected by a symptomatic index patient. Additionally, none of the symptomatic cases from asymptomatic index cases were severe or fatal, whereas 12 of 96 (12.5%) from a symptomatic index patient were.
Mar 27 Clin Infect Dis study

Vaccine-derived polio cases rose sharply in 2020

In an update on circulating vaccine-derived poliovirus type 2 (cVDPV2), the World Health Organization (WHO) said cases and environmental detections increased in 2020 compared with the previous year, and countries in Africa are at the greatest risk for spread or emergence.

In 2020, there were 959 human cases and 411 environmental detections, up from 2019, when there were 336 cases and 173 environmental detections.

For 2020, cases were reported by 27 countries spanning four regions, though 21 were in Africa, where several genetically distinct cVDPV2 outbreaks are under way. In the Middle East, cases in Pakistan have been linked to illnesses in Iran and Tajikistan. And in the Western Pacific region, outbreaks in the Philippines and Malaysia continue.

The WHO said it considers the African region to be at very high risk of spread or emergence, with the Eastern Mediterranean region at high risk and Europe and the Western Pacific at low-to-moderate risk.
Mar 26 WHO cVDPV2 update

In other polio developments, the WHO today said Somalia's circulating vaccine-derived poliovirus type 3 (cVDPV3) outbreak is over, 28 months after it was detected, with no international spread. And Afghanistan today launched its second polio vaccination drive of the year, a 5-day even that targets 9.9 million children younger than 5 years old.
Mar 29 WHO statement on Somalia's cVDPV3 outbreak
Mar 29 WHO statement on Afghanistan polio vaccine drive