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

Antibiotic prescribing guidelines, diagnostics linked to reduced resistance

Implementing institution-specific guidelines (ISGs) for antimicrobial prescribing and use of diagnostics at a tertiary care hospital was associated with significant declines in antibiotic resistance rates and Clostridioides difficile infections (CDIs), German researchers reported yesterday in PLOS One.

In an interrupted time series analysis, the researchers assessed changes in antibiotic consumption, resistance rates, and CDI incidence over a 9-year period (2012 through 2020) at Leipzig University Hospital. The hospital introduced ISGs in 2014, first in a printed pocket guide and then in an electronic application. The researchers hypothesized that antibiotics prescribed commonly prior to the intervention but not often recommended in the ISGs, such as ciprofloxacin, would be reduced, and that resistance to those antibiotics would decline.

From 2012 to 2020, annual antibiotic consumption per 100 bed days (BD) fell by 14%, from 543 defined daily doses (DDD)/100 BD to 468 DDD/100 BD. The reduction mainly occurred prior to the introduction of the ISGs, most likely because of other antimicrobial stewardship interventions. But fluoroquinolone prescribing fell by 67% during the study period (from 104 DDD/100 BD to 35 DDD/100 BD), a reduction largely associated with introduction of the ISGs and an immediate drop in ciprofloxacin consumption.

The researchers also observed declining resistance rates to most tested antibiotics in all analyzed pathogens except enterococci, where no significant trends were observed. Declines in resistance to broad-spectrum penicillins of up to 25% were observed among Enterobacterales, Staphylococcus,and Pseudomonas. Annual CDI incidence fell by 65%.

"Despite many limitations it seems likely that the reductions in resistance are a result of the decreases and changes in antibiotic consumption," the study authors wrote. "Hence, we recommend the wider use of ISGs for empirical antibiotic therapy because they are relatively easy to implement, reach all clinicians, and have a significant impact on antibiotic prescribing."
Oct 14 PLOS One study

New online tool aims to help countries calculate cost of fighting AMR

Originally published by CIDRAP News October 13

The World Health Organization (WHO) today released a new tool to help countries calculate the costs of implementing multisectoral national action plans (NAPs) for antimicrobial resistance (AMR).

The modular online tool enables countries to prioritize activities included in their NAPs, which in many cases exist only on paper, and then calculates what those activities may cost, based on key parameters that are relevant to those countries. Users can also input existing national funds that will be used to cover the costs, which helps identify funding gaps and additional resources that might be needed to pay for AMR activities.

Funding for activities to address AMR, or lack thereof, remains a key issue for many countries. As of July 2021, 145 countries have developed AMR NAPs and an additional 41 are in the process of developing one. But according to a recent survey by the WHO, the World Organization for Animal Health, and the United Nations Food and Agriculture Organization, only 20% of these plans are fully funded and 40% have a budgeted operational plan.

"Leaders making funding decisions need to understand how much the activities included in the NAP will cost, how many activities are already being funded and how the budget can be increased," the WHO states in the user guide for the cost and budgeting tool. "A clear approach to costing and budgeting AMR NAPs is therefore a critical first step in ensuring that efforts are practical and can be implemented sustainably."
Oct 13 WHO AMR costing and budgeting tool and user guide

Stewardship rules, drug review tied to better antibiotic prescribing

Originally published by CIDRAP News Oct 11

Implementing a set of rules targeting antimicrobial stewardship (AMS) into a hospital-wide medication review service was associated with a dramatic decline in inappropriate antibiotic prescribing, Belgian researchers reported last week in the Journal of Antimicrobial Chemotherapy.

The interrupted time series (ITS) analysis looked at inappropriate antibiotic prescribing at a tertiary care hospital in Belgium in the year before and 2 years after 41 AMS-related clinical rules were added to the hospital's Check of Medication Appropriateness (CMA) service. The CMA is a pharmacist-led medication review service that screens electronic medical record data for potentially inappropriate prescriptions (PIPs). For each identified PIP, the pharmacist formulated a recommendation for the prescribing physician. The study aimed to estimate the effect of the CMA on AMS-related residual PIPs.

Pre-implementation, a median proportion of 75% residual PIPs per day was observed at the hospital. After the CMA intervention, the proportion was reduced to 8% per day. Use of the AMS-related clinical rules resulted in an immediate relative reduction of 86.7% in AMS-related residual PIPs. No significant underlying time trends were observed during the study period.

Post-implementation, 2,790 recommendations were provided, of which 81.32% were accepted. The clinical rule "inappropriate dosing of piperacillin-tazobactam" accounted for the highest proportion of recommendations (24.34%).

"Our ITS analysis showed that this approach is effective in supporting clinicians in antimicrobial prescribing, ultimately aiming to optimize clinical outcomes and minimize unintended consequences of antimicrobial use," the study authors wrote.
Oct 7 J Antimicrob Chemother abstract

Tanzanian study finds high antibiotic use in postnatal women, newborns

Originally published by CIDRAP News Oct 11

Point-prevalence surveys at three hospitals in Tanzania found substantial overuse of antibiotics in postnatal women and newborns, researchers reported late last week in Antimicrobial Resistance and Infection Control.

The surveys were conducted at three public-sector hospitals in Dar es Salaam in 2018 to collect data on antibiotic use and infections in maternity and neonatal wards. Researchers collected data on a total of 376 mothers and 162 newborns across three rounds.

Antibiotic prescribing was high in all three hospitals among women in caesarean section wards, ranging from 90% to 100%. Antibiotic use varied considerably among women in the postnatal vaginal delivery wards, ranging from 1.4% to 63%. Antibiotic use in newborns ranged from 89% to 100%. The most common reasons for antibiotic prescriptions at all three hospitals were medical or postoperative surgical prophylaxis (prevention).

The study authors said that they expected to see high levels of antibiotic use on caesarean section wards, given that the procedure carries a higher risk of infection and surgical prophylaxis is recommended, but they point out that those antibiotics should be given pre- rather than postoperatively. In addition, they note that, of the 76 newborns treated with antibiotics, 57% had no clear indication for antibiotic use.

"Irrational overuse of antibiotics is likely to ultimately lead to severe illness and death in mothers and newborns as a result of increasing levels of antibiotic resistance in low-income countries," they wrote. "Better infection control policies, local and national guidelines, and antimicrobial stewardship programs need to be implemented to avoid unnecessary prescription of the antibiotics and promotion of antibiotic resistance."
Oct 9 Antimicrob Resist Infect Control study

Vaccine effectiveness high against severe Delta-caused COVID-19

A 17-study literature review looking at vaccine effectiveness (VE) during the Delta (B1617.2) variant shows a pooled VE of 90.9% versus hospitalization with a 75.7% and 63.1% VE against symptomatic and asymptomatic infection, respectively.

The results, published yesterday in Eurosurveillance, were based on studies collected until Aug 25. Some studies looked at VE against Delta and Alpha (B117) using sequenced samples, while others looked at VE from time periods where Delta or Alpha was the dominant strain without sequencing samples. Asymptomatic infections (2 studies), symptomatic infections (9), the compound outcome of severe disease and hospitalization (3), and hospitalization alone (4) were looked at, as were VE against Alpha versus Delta (9) and waning immunity (2).

Ten studies looked at VE against infection but didn't demarcate asymptomatic versus symptomatic infections. Pooled VE was 66.9% (95% confidence interval [CI], 58.4% to 73.6%), with one study finding VE for 18- to 34-year-olds was 90%.

VE against mild outcomes was reduced by 10% to 20% when against Delta compared with Alpha but "fully maintained" against severe COVID-19, according to the researchers. Overall, VE against severe disease and hospitalization ranged from 81.5% to 100%, while VE against hospitalization ranged from 75% to 96%.

As for waning immunity, the first study found that Pfizer/BioNTech's vaccine had a 93% VE against infection (symptomatic or asymptomatic) at baseline that declined to 53% after at least 4 months of full vaccination (95% CIs, 85% to 97% and 39% to 65%, respectively). The other study looked at any COVID-19 vaccine given to US frontline workers and found a non-significant change from 85% to 73% VE after at least 5 full months of full vaccination (95% CIs, 68% to 93% and 49% to 86%, respectively).

"Current evidence shows that COVID-19 vaccines licensed in the [European Union] are moderately to highly effective in preventing SARS-CoV-2 infections with the Delta variant, while effectiveness against severe courses of COVID-19 remains high," the researchers conclude.
Oct 14 Eurosurveil study

Delta outbreak in Delhi shows immunity evasion, high transmission

Delhi's COVID-19 outbreak this past spring—the city's fourth since the pandemic began—showed the Delta variant's high transmissibility and higher ability to infect the previously infected, researchers say in a study published yesterday in Science.

The researchers used genomic and epidemiological data taken from Delhi from November 2020 to June 2021. During the 2020 outbreaks, they found that there were no variants of concern, and the Alpha variant was seen occasionally and usually in foreign travelers until January 2021. In March 2021, the Alpha variant surged to comprise about 40% of the cases, but Delta rapidly displaced its dominance in April. A Bayesian model indicated that the Delta variant was 30% to 70% more transmissible than the other COVID-19 lineages seen in Delhi thus far. And, importantly, prior COVID-19 infection provided 50% to 90% of protection against Delta compared with previous lineages.

To see how well the mathematical model held up against reality, the researchers then looked at a cohort recruited by the Council of Scientific and Industrial Research, India, which ranged from 832 to 1,012 people across three time periods. From February to July, the unvaccinated people who were positive for antibodies against COVID-19 went from 42% to 87.5%. Among 91 people who had COVID-19 before the Delta outbreak, 27.5% had increased levels of antibodies, indicating reinfection. Also, regarding breakthrough infections, a single center showed that of 24 cases, Delta was seven times more likely to be the cause.

"The concept of herd immunity is critical in ending outbreaks, but the situation in Delhi shows that infection with previous coronavirus variants will be insufficient for reaching herd immunity against Delta," said co-author Ravi Gupta, PhD, MPH, BMBCh, in a University of Cambridge press release. "The only way of ending or preventing outbreaks of Delta is either by infection with this variant or by using vaccine boosters that raise antibody levels high enough to overcome Delta’s ability to evade neutralisation."
Oct 14 Science study
Oct 14 University of Cambridge press release