Remdesivir linked to lower COVID-19 mortality

Hospitalized COVID-19 patients who were treated with remdesivir within 2 days of admission had lower mortality rates than their matched cohort, according to a study today in Clinical Infectious Diseases. The observational cohort consisted of US adults hospitalized with COVID-19 from August to November 2020; 28,855 received remdesivir and 16,887 did not.

About 10.6% of patients who received remdesivir died within 14 days, and 15.4% died within 28 days, while those who didn't receive remdesivir had 14- and 28-day mortality rates of 15.4% and 19.1%, respectively. The researchers estimate that the antiviral drug reduces risk of death by 24% for 14-day mortality and by 11% at 28 days (95% CIs, 0.70 to 0.83 and 0.82 to 0.96, respectively).

This benefit was also seen across patients with no supplementary oxygen, low-flow oxygen, and invasive mechanical ventilation or extracorporeal membrane oxygenation treatment for both 14- and 28-day mortality (hazard ratios [HRs] ranged from 0.68 to 0.70 and 0.77 to 0.80, respectively). For those who received remdesivir and also needed high-flow oxygen or non-invasive ventilation, risk of death was reduced for 14-day mortality (HR, 0.81) but not 28-day mortality.

"While unmeasured confounding cannot be excluded, these findings provide further support that RDV antiviral therapy is a foundational treatment approach for COVID-19," the researchers conclude.

Remdesivir is the first antiviral fully approved by the US Food and Drug Administration to treat COVID-19 in critically ill patients, and it has received conditional authorization by the European Medicines Agency. It is not currently approved by the World Health Organization.
Sep 30 Clin Infect Dis study

People with disabilities face barriers around COVID vaccines, survey says

People with disabilities reported more willingness to receive a COVID-19 vaccine but had lower vaccination rates than people without disabilities, according to survey results published in today's Morbidity & Mortality Weekly Report (MMWR).

The researchers used data from a randomized telephone survey conducted May 30 to Jun 26, of which about 9% of 56,749 US adult respondents were considered as having disabilities. Those who had disabilities were more likely to report that they would definitely get vaccinated (age-adjusted prevalence ratio [aPR], 1.86) but less likely to have received at least one dose of a COVID-19 vaccine (aPR, 0.88).

In the same vein, unvaccinated adults with disabilities were more likely to say that the vaccine would offer protection (aPR, 1.29) as well as more likely to say that it would be difficult to get vaccinated (aPR, 2.69). This subgroup cited difficulties around getting an appointment online (aPR, 2.14, vs unvaccinated people without disabilities), not knowing where to get vaccinated (aPR, 1.95), getting to vaccination sites (aPR, 3.43), and vaccination sites not being open at convenient times (aPR, 1.69).

The study notes that 15.2% of adults in the United States had at least one reported functional disability in the 2019 American Community Survey.

"Reducing barriers to scheduling and making vaccination sites more accessible might improve vaccination coverage among persons with disabilities," conclude the researchers.
Oct 1 MMWR study

Giving flu, COVID vaccines at same time appears to be safe, effective

Giving the flu vaccine at the same time as the second dose of the AstraZeneca/Oxford or Pfizer/BioNTech COVID-19 vaccine appeared to be safe and induce immunogenicity, according to a non–peer-reviewed study in The Lancet yesterday.

From Apr 1 to Jun 26, the researchers divided 679 UK adults into six cohorts, with each concomitantly receiving their second COVID-19 vaccine dose and either a placebo or one of three influenza vaccines (a trivalent, adjuvanted vaccine [aTIV], or a cellular or recombinant quadrivalent vaccine [QIVc or QIVr]). Three weeks later, those who received the placebo received their flu vaccine and vice versa, and total follow-up concluded 6 weeks after that.

The phase IV, blinded, multicenter randomized controlled trial showed non-inferiority among those who received the AstraZeneca and QIVc vaccine (-1.29%), the Pfizer and QIVc vaccine (6.17%), the Pfizer and aTIV vaccine (-12.9%), and the AstraZeneca and QIVr vaccine (2.53%). In the other two cohorts, the upper limit of the 95% confidence interval [CI] exceeded 25% by no more than 1 percentage point.

Reactions were mostly mild or moderate and didn't significantly differ in frequency between those who received the concomitant vaccines and those who didn't (85.2% and 81.7%, respectively). Similarly, immunogenicity was similar across anti-S immunoglobulin G geometric mean units and seroconversion rates 21 days after the COVID-19 dose. No significant differences were seen in hemagglutination inhibition (HAI) geometric mean titer ratios against any flu strain 21 days after receiving the flu vaccine either concomitantly or alone. (People vaccinated against the flu develop HAI antibodies that bind and neutralize the flu virus.)

"In some parts of the world, COVID-19 and seasonal influenza vaccination programmes will overlap, and so administration of both vaccines at the same appointment, concomitantly, would lessen the burden on healthcare systems, support vaccine uptake and afford timely protection against both infections," the researchers write.

"Our findings demonstrate that concomitant administration of six different combinations of COVID-19 and influenza vaccines raises no safety concerns, produces acceptable reactogenicity profiles and preserves immunogenicity."
Sep 30 Lancet preprint study

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

New antimicrobials added to WHO essential medicines list

New antimicrobials to treat severe bacterial and fungal infections were among the drugs that the World Health Organization (WHO) included in its new Essential Medicines list, which is updated annually and serves as its recommended list of medicines that every health system should have.

For infectious diseases, new inclusions include cefiderocol, listed as a "reserve" drug that should be accessible but is reserved for treatment of confirmed or suspected multidrug-resistant infections. The reserve designation is part of the WHO's AWaRe (Access, Watch, and Reserve) classification database, developed in 2017 to guide antimicrobial stewardship actions.

Other infectious disease additions include echinocandin antifungals, as well as monoclonal antibodies for rabies prevention. The list includes new formulations of medicines for common bacterial infections, including tuberculosis, to better meet dosing and administration needs for children and adults.

The WHO also classified 81 more antibiotics under the AWaRe framework.
Oct 1 WHO statement

Global point-prevalence survey helps hospital stewardship, survey finds

Originally published by CIDRAP News Sep 30

Results from a worldwide survey of hospitals suggests that the Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) has helped inform stewardship activities, Belgian researchers reported this week in Antimicrobial Resistance and Infection Control.

Launched in 2015, Global-PPS provides hospitals with a standardized method of collecting and assessing antimicrobial prescribing data and has been used by more than 700 hospitals around the world. But little is known about how hospitals are using it to inform antimicrobial stewardship (AMS) activities. To assess its role in AMS efforts and identify barriers to implementing AMS in different resource settings, researchers from the University of Antwerp sent a cross-sectional survey to hospitals within the Global-PPS network.

A total of 248 hospitals from 74 countries participated in the survey; of these, 192 (77.4%) had conducted the PPS at least once. In 96.9% of these 192 hospitals, Global-PPS participation had led to the identification of problems with antimicrobial prescribing. The most common prescription-related problems were a high relative use of certain classes of antibiotics (62%), prolonged surgical antibiotic prophylaxis (60.9%), and a high antimicrobial use prevalence (60.4%). In 69.3% of hospitals, at least one AMS component was related to findings from the Global-PPS. The Global-PPS was mostly used to inform education and communication and the development and review of guidelines.

The level of AMS implementation in hospitals varied by region. Up to 43.1% of all hospitals had a formal AMS strategy, ranging from 10.8% of hospitals in Africa to 60.9% of hospitals in North America. Another 29.7% reported that they were planning to develop a formal AMS strategy. The main barriers to implementing AMS programs were a lack of time (52.7%), knowledge on good prescribing practices (42.0%), and dedicated funding (39.9%). Hospitals in low- and middle-income countries more often reported a lack of prescribing guidelines, insufficient laboratory capacity, and suboptimal use of available lab services.

Despite the substantial variation in hospital AMS programs and the barriers to implementation, the authors say the results show how Global-PPS can contribute to AMS activities.

"Providing all participating hospitals with a personalised feedback report, the Global-PPS allows local teams to identify targets for antimicrobial stewardship without the need to invest time and resources in complex data analyses," they wrote. 
Sep 28 Antimicrob Resist Infect Control study

Short-course antibiotics shown effective for Pseudomonas bloodstream infections

Originally published by CIDRAP News Sep 30

A retrospective study of patients with Pseudomonas aeruginosa bloodstream infections (BSIs) found that short-course antibiotic therapy may be as effective as long-course therapy, South Korean researchers reported today in the Journal of Antimicrobial Chemotherapy.

The researchers looked at data on all patients admitted to a tertiary care hospital with uncomplicated P aeruginosa BSIs from April 2010 through April 2020. They compared the primary outcome (a composite rate of recurrent P aeruginosa infection and mortality 30 days after discontinuing antibiotics) among patients who received short-course (7 to 11 days) and prolonged (12 to 21 days) antibiotic therapy. The secondary outcome was a recurrence of P aeruginosa infection at any site within 180 days.

A total of 290 patients met the eligibility criteria. Among them, 97 received short-course therapy (median of 9 days) and 193 underwent prolonged therapy (median of 15 days). Eleven patients in the short-course group (11%) and 30 patients in the long-course group (16%) had recurrent P aeruginosainfection or died within 30 days of completing therapy. Propensity scoring analysis using the inverse probability of treatment weighting (IPTW) method showed that prolonged therapy did not significantly reduce the risk of recurrent infection or death compared with short-course therapy (IPTW-adjusted hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.34 to 1.36).

Recurrent P aeruginosa infection at any site within 180 days of completing therapy occurred in 12 patients in the short-course group (12%) and 37 patients in the prolonged-course group (19%). Prolonged-course therapy did not significantly reduce the risk of this outcome (IPTW-adjusted HR, 0.57; 95% CI, 0.29 to 1.10).

The study authors acknowledge several limitations, including the single-center nature of the study, residual bias, rigorous exclusionary criteria, and wide confidence intervals, and say the study needs to be repeated as a randomized trial with a larger sample size. But they believe the findings could be applied to select patients with uncomplicated P aeruginosa BSIs.

"Our findings reinforce the current tendency to lean toward shorter duration of antimicrobial therapy," they write. 
Sep 30 J Antimicrob Chemother abstract

Study finds CDC-based stewardship intervention is cost-effective

Originally published by CIDRAP News Sep 29

An intervention based on the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antibiotic Stewardship yielded cost savings at 10 outpatient Veterans Healthcare Administration (VHA) sites, researchers reported today in Infection Control & Hospital Epidemiology.

The intervention, implemented in September 2017, used a provider-directed audit feedback and academic detailing approach to promote appropriate diagnosis and treatment of uncomplicated acute respiratory tract infections (ARIs). To evaluate the cost-effectiveness of the intervention, researchers developed an economic simulation model from the health system perspective and compared antibiotic prescribing, appropriate treatment, adverse drug events, and hospitalizations at intervention sites and control (usual care) sites. The effectiveness measure was quality-adjusted life-years (QALYs). Costs included those related to treatment of ARIs and associated care, and costs incurred to implement the intervention.

A total of 16,712 and 51,725 patient visits occurred at the intervention and control sites, respectively. The proportion of ARI patient-visits with antibiotics prescribed at intervention sites was lower (62% vs 74%), appropriate treatment was higher (51% vs 41%), and hospitalization was lower (1.6% vs 1.9%) compared with control sites. The estimated intervention cost over a 2-year period was $133,604. The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared with usual care. The cost savings were mainly driven by reductions in antibiotic prescribing and hospitalization.

"We conclude that the intervention compared to usual care is the preferred strategy for patients with uncomplicated ARI visits conditional on the decreased chance of hospitalization because of the intervention," the study authors write. "These findings may provide decision makers with a comparable benchmark for evaluating the antibiotic stewardship intervention."
Sep 29 Infect Control Hosp Epidemiol abstract

Medical record message linked to improved C diff antibiotic prescribing

Originally published by CIDRAP News Sep 29

In another study published today in the same journal, researchers reported that antibiotic prescribing for Clostridioides difficile infections (CDIs) improved at a health system in Michigan after a clinical decision support message was added to the electronic medical record.

Researchers at the Henry Ford Health System analyzed patient treatment for an initial CDI episode before and after a best practice advisory (BPA) was added to the electronic medical record to assist with antibiotic prescribing for CDI in the system's outpatient medical centers. The BPA alert stated "Vancomycin or fidaxomicin are preferred over metronidazole for C. difficile infection" per guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America, and it displayed buttons to remove the order for metronidazole and place an order for a 10-day course of vancomycin.

The primary outcome of the study was the proportion of patients who received guideline-concordant CDI therapy. Secondary outcomes included clinical response, recurrence, and unplanned healthcare encounter.

A total of 189 patients were included in the study, with 92 treated before the BPA and 97 after the BPA. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. After implementation of the BPA, guideline-concordant therapy increased (72% before vs 91% after), vancomycin prescribing increased (72.8% vs 86.6%), and metronidazole prescribing decreased (28.3% vs 10.3%). There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14 to 56 days of the initial episode (27% vs 7%).

"A targeted BPA is an effective stewardship intervention that may be especially useful in settings with limited antimicrobial stewardship resources," the study authors conclude.
Sep 29 Infect Control Hosp Epidemiol abstract

Antibiotics after mastectomy common, but with small benefit, study finds

Originally published by CIDRAP News Sep 27

An analysis of US health insurance data found that post-discharge prophylactic antibiotics are commonly prescribed after mastectomy, but provide only a small reduction in surgical-site infections (SSIs), researchers reported today in Infection Control & Hospital Epidemiology.

Using a database that includes outpatient pharmacy claims for individuals covered by employer-sponsored and commercial health insurance plans, researchers from the Washington University School of Medicine in St. Louis studied a cohort of women ages 18 to 64 who underwent mastectomy from January 2010 through June 2015. Their aim was to investigate the factors associated with post-discharge prophylactic antibiotic use and the impact on SSIs.

Out of 38,793 mastectomies, 24,818 included immediate reconstruction. Prophylactic antibiotics were prescribed after discharge after 2,688 mastectomy-only procedures (19.2%) and after 17,807 mastectomies with immediate reconstruction (71.8%). Post-discharge prophylactic antibiotic use ranged from 18.9% in 2013 to 19.7% in 2015 after mastectomy only and 68.2% in 2010 to 74.4% in 2015 after mastectomy with immediate reconstruction. Factors associated with post-discharge antibiotics included history of Staphylococcus aureus infection, neoadjuvant chemotherapy, non-infectious wound complication during the mastectomy admission, and implant reconstruction, but physician preference appeared to be a bigger factor.

The 90-day incidence of SSI after mastectomy was 3.5% after mastectomy only and 8.8% after mastectomy with immediate reconstruction. Antibiotics with anti–methicillin-sensitive S aureus (MSSA) activity were the most commonly prescribed antibiotics after mastectomy and were associated with decreased SSI risk after mastectomy only (adjusted relative risk [aRR], 0.74; 95% CI, 0.55 to 0.99) and mastectomy with immediate reconstruction (aRR, 0.80; 95% CI, 0.73 to 0.88), respectively. The numbers needed to treat to prevent 1 additional SSI were 107 and 48, respectively.

The authors note that anti-MSSA antibiotics are associated with moderate risk of Clostridioides difficile infection and other adverse events, ranging from rashes to more severe events, including anaphylaxis and acute renal failure.

"The small apparent benefit of post-discharge oral antibiotics should be balanced with the risks associated with overuse of antibiotics, particularly given the relatively large number of women who would need to be treated to prevent one infection," they write.
Sep 27 Infect Control Hosp Epidemiol abstract