Stewardship / Resistance Scan for Sep 09, 2021

News brief

VA study finds faster receipt of antibiotics in sepsis patients

A study of US veterans hospitalized with community-acquired sepsis shows an overall decline in time-to-antibiotics, with significant variation across hospitals, researchers reported this week in JAMA Network Open.

The observational cohort study examined the time from presentation to antibiotic administration in sepsis patients admitted to 130 Veterans Affairs (VA) hospitals from 2013 to 2018. Faster receipt of antibiotics has been associated with improved survival in sepsis patients, and sepsis quality improvement programs have resulted in faster administration of antibiotics, but it's unclear if antibiotic timing for sepsis has improved outside of formal performance incentive programs.

Among a total of 111,385 sepsis hospitalizations identified during the study period, 7,574 patients (6.8%) died in the hospital and 13,855 (12.4%) died within 30 days. Median time-to-antibiotics was 3.9 (2.4 to 6.5) hours, declining from 4.5 hours during 2013-2014 to 3.5 hours during 2017-2018—an absolute change of 54.6 minutes and a relative change of 22.2%. After adjusting for patient characteristics, median time-to-antibiotics declined by 9 minutes per year.

Analysis of hospital-level variation in time-to-antibiotics showed that the magnitude of decrease varied across hospitals, with hospitals that had faster baseline time-to-antibiotics experiencing less change over time. Hospitals in the slowest tertile decreased time to antibiotics by 16.6 minutes per year, while hospitals in the fastest tertile saw time-to-antibiotics decline by 7.2 minutes per year. Median time-to-antibiotics varied by 118.2% across hospitals during 2017-2018, ranging from 3.1 to 6.7 hours.

"This variation persisted after adjustment for granular patient characteristics, suggesting that sepsis practice patterns truly differ across hospitals," the study authors wrote. "This may represent a potential opportunity for practice improvement going forward, but the benefits of further accelerating time-to-antibiotics must be balanced against the risk of driving antibiotic overuse in patients with noninfectious illness."
Sep 7 JAMA Netw Open study

Trial data support shorter antibiotic course for bloodstream infections

The results of a randomized controlled trial conducted in Spain suggest that a 7-day course of antibiotics for Enterobacterales bloodstream infections (eBSIs) is preferable to 14 days, researchers reported yesterday in Clinical Microbiology and Infection.

The open-label, multi-center study enrolled patients diagnosed with eBSI from five Spanish hospitals to receive either 7 days (the experimental arm) or 14 days of antibiotic treatment (the control arm). Patients were followed for 28 days after stopping antibiotic treatment. The primary end point was days of treatment at the end of follow-up, and clinical outcomes were assessed through relapse of eBSI, relapse of fever, and clinical cure (resolution of all signs and symptoms of infection).

Secondary end points included crude mortality, superinfections, and adverse events. A superiority margin of 3 days was set for the primary end point, and a non-inferiority margin of 10% for clinical outcomes.

Of the 248 patients enrolled, 119 were assigned to 7 days of antibiotics and 129 to 14 days. The median length of antibiotic treatment in the intention-to-treat population was 7 days in the experimental arm and 14 in the control arm. No significant differences were observed for the other end points at the end of the 28-day follow-up, including mortality, relapse of eBSI, relapse of fever, superinfections, or drug-related adverse events. The non-inferiority margin was met for all clinical outcomes except relapse of fever, which was more frequent in the 7-day group (difference in absolute risk, —0.2%).

A Desirability of Outcome Ranking and Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) analysis showed that patients receiving 7 days of treatment had a 77.7% greater probability of achieving better results compared with those who received 14 days of treatment.

The study authors say the findings on relapse of fever suggest some patients may need more than 7 days of antibiotics, but that the overall benefit of shorter antibiotic treatments is clear.

"In conclusion, this trial points to 7-day course of antibiotics as the preferential treatment for eBSI, as long as the source is properly controlled," they wrote. "The potential impact of implementing this recommendation into clinical practice would be significant in the fight against bacterial resistance."
Sep 8 Clin Microbiol Infect study

News Scan for Sep 09, 2021

News brief

Colorectal cancer patients fared worse after COVID lockdowns, study finds

Patients diagnosed as having metastatic colorectal cancer (mCRC) after COVID-19 lockdowns in France had significantly higher tumor burdens and died sooner than those diagnosed before the pandemic, shows a multicenter study yesterday in JAMA Network Open.

In the study, a team led by researchers at the Universite de Montpellier evaluated the tumor burden of 80 patients at 18 centers with mCRC using circulating tumor DNA (ctDNA) in plasma, which the authors said rises with increasing tumor size. The patients (median age, 62 years) were enrolled in a phase 2 clinical trial comparing the activity of two drug combinations.

The 40 patients diagnosed after the spring 2020 lockdowns (May 14 to Sep 3, 2020) had median ctDNA concentrations of 119.2 nanograms per milliliter (ng/mL), compared with 17.3 ng/mL in the 40 patients screened before (Nov 11, 2019, to Mar 9, 2020). The post-lockdown ctDNA level constituted a 6.9-fold increase.

Patients with greater tumor burden also had significantly lower median survival than those with lesser tumor burden (14.7 months vs 20.0 months; hazard ratio, 1.74).

The researchers noted that the pandemic has been tied to large reductions and delays in screening, diagnosis, and hospital referrals for cancer patients, while the reprioritization of hospital staff and resources to COVID-19 patients has been linked to delayed or compromised care.

"The differences in tumor burden between patients who were diagnosed before vs after lockdown and the resulting risk of reduced survival point to the association between the pandemic-related lockdown and unfavorable consequences for patients with newly diagnosed mCRC, who may have delayed their first visit to an oncologist," the authors wrote. They added that patients may have been reluctant to visit a healthcare facility because of fears of COVID-19 infection or burdening the health system.

To prepare for any further coronavirus-related lockdowns, the researchers called for reinforced mass CRC screening using fecal occult blood testing, communicating the urgency of screening to patients, and providing adequate resources and planning to manage backlogs in diagnosis and treatment. "The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment," they wrote.
Sep 8 JAMA Netw Open study

Mental health improved somewhat after COVID vaccine, poll says

People who received at least one COVID-19 vaccination between December 2020 and March 2021 were a bit more likely to report lower mental distress levels, according to a study yesterday in PLOS One.

The researchers used the representative Understanding America Study cohort, and from Mar 10, 2020, to Mar 31, 2021, 8,003 adults answered at least 2 of the 26 surveys (average response rate per survey, 82%), which were conducted from weekly to monthly.

People who reported receiving at least one COVID-19 vaccination had a 1-percentage-point drop in mild depression probability and a 0.7-percentage-point drop in severe depression probability, a relative reduction of 4% and 15%, respectively. Overall, the results showed an average effect comparative to 4% of the standard deviation of PHQ-4 scores, or the four-item Patient Health Questionnaire that made up the framework of the survey.

Vaccinated respondents were more likely to be older (average age, 60.4 vs 47.1 years), college educated (68% vs 52%), and White (87% vs 82%).

"Those recently vaccinated may become less worried about getting infected, they may become more active socially, or they may venture into different work opportunities," the researchers write.

They add, however, "Since people who get the vaccines at different times are different in several dimensions, this implies that the effects may be different for the people who get vaccinated after the period studied here. Another reason why the effects may be different in a later period is that the conditions may be different."
Sep 8 PLOS One study