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ASP Scan (Weekly) for May 21, 2021

ASP Scan (Weekly) for May 21, 2021

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

High level of antibiotic use found in dying organ donors

In a first-of-its-kind study, a team of US researchers reported this week in Clinical Infectious Diseases that nearly all of more than 400 deceased organ donors received at least one antibiotic dose during their terminal hospitalization, a finding that study authors say highlights the need for antibiotic stewardship in this population.

While there is concern about the use of donated organs that are infected or colonized with multidrug-resistant organisms (MDROs) and the potential for donor-derived infection (DDI), to date there have been no studies on antibiotic use among deceased organ donors, which is considered an important risk for MDRO colonization or infection. To investigate the level of antibiotic use in this group, a team led by researchers with the University of Pennsylvania Perelman School of Medicine examined data on 440 organ donors at four transplant centers in the Philadelphia region. Details on all antibiotics administered during terminal hospitalization, including those given leading up to and during organ procurement, were included.

Of the 440 organ donors, 427 (97%) received at least one course of antibiotics during terminal hospitalization, and 400 (91%) received at least one dose outside of the peri-procurement period. A total of 312 donors (71%) received a broad-spectrum antibiotic, with 299 (68%) receiving a broad gram-negative agent and 103 (23%) receiving a broad gram-positive agent. Sixty-three donors (14%) received potentially redundant antibiotics. The most frequently used antibiotics were first-generation cephalosporins (337 donors, 77%), and the median number of total antibiotic days of therapy was 4.

“In conclusion, our study identified widespread use of broad-spectrum antibiotics and many instances of potentially redundant antibiotic prescription among deceased organ donors,” the study authors wrote. “Since brief antibiotic exposures may increase the risk for donor MDRO colonization and subsequent MDRO DDIs in the recipient, the organ donor population is an important future target of antibiotic stewardship interventions.” 
May 20 Clin Infect Dis abstract

Stewardship helped limit antibiotics early in pandemic, hospital study finds

Strategies implemented by the antimicrobial stewardship team (AMST) at a hospital in Spain to minimize antibiotic use during the first wave of the COVID-19 pandemic contributed to an overall reduction in antibiotic use in 2020, researchers reported today in Infection Control & Hospital Epidemiology.

In a letter to the editor, clinicians and pharmacists at Moises Broggi Hospital in Barcelona report that antibiotic consumption at the hospital in 2020 was lower than in 2019, except for March, when the onset of the pandemic caused in increase in the use of azithromycin and ceftriaxone. Measured in defined daily doses (DDD) per 100 bed-days, the mean global consumption of antibiotics during hospitalization was 57.8 DDD/100 bed-days in 2020, compared with 64.7 DDD/100 bed-days in 2019.

The study authors say that while the AMST was unable to carry out its work from March through May 2020, protocols established for the management of COVID-19 patients, including recommended antibiotic regimens (azithromycin and ceftriaxone) and recommended durations (5 and 3 days, respectively) and review of antibiotic treatment by the AMST pharmacist, made it possible to control antibiotic consumption during the first wave.

“After the first wave, hospital activity began to normalize and allowed for the usual individualized AMST intervention,” the study authors wrote. “This made it possible to maintain the levels of antibiotic consumption below those observed in the previous year.”
May 21 Infect Control Hosp Epidemiol abstract


Pneumococcal vaccines may affect use of kids’ antibiotics

Originally published by CIDRAP News May 20

Antibiotic prescribing for young children in Israel sharply declined following implementation of pneumococcal conjugate vaccine (PCV), Israeli researchers reported today in Clinical Infectious Diseases.

Using data from the country’s largest health maintenance organization, the researchers conducted an interrupted time series analysis of dispensed antibiotic prescription (DAP) rates for Israeli children under the age of 5 from July 2005 through June 2018. The 7-valent vaccine (PCV7) was introduced into Israel’s National Immunization Plan (NIP) in 2009, and the 13-valent vaccine (PCV13) has gradually replaced it since 2010. Since then, a marked reduction in respiratory tract infections (RTIs) in Israeli children has been observed, but the impact on antibiotic prescribing has not been investigated.

The study also included a comparison of the DAP rate between Jewish and Bedouin populations in southern Israel, as prior to PCV implementation, pneumococcal diseases and RTIs were more prevalent among Bedouin children. PCV uptake was similar in Jewish and Bedouin children.

Following the implementation of PCV7/PCV13, DAP rates for children under 5 abruptly and significantly declined, largely driven by a decrease in amoxicillin and amoxicillin-clavulanate prescriptions, which prior to PCV implementation accounted for 75% of pediatric DAPs. The decline continued and stabilized at a reduced level within 5 years.  Children younger than 2 and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates, but also with a faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups.

Among all children under 5, the annual mean reduction (per 1,000 child-years) of DAPs ranged between an absolute incidence rate ratio of 344.7 and a relative incidence rate ratio of 110.4. For amoxicillin/amoxicillin-clavulanate, the respective reductions were 300.2 and 142.3. Azithromycin was the only drug with increasing trends following PCV implementation.

“The overall DAP reduction rate translates into reduced pressure on the entire body microbiota,” the study authors wrote. “However, consumption still remains high. Therefore, although PCV implementation is an important tool against antimicrobial resistance, efforts to develop other tools such as improvement of stewardship programs must be continued.” 
May 20 Clin Infect Dis abstract

New expert panel to advise global health leaders on zoonotic disease

Originally published by CIDRAP News May 20

Four international organizations today announced the formation of a new expert panel to improve understanding, and stop the emergence and spread, of zoonotic diseases.

Operating under the One Health approach, which recognizes the links between the health of people, animals, and the environment, the One Health High-Level Expert Panel will advise the United Nations Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health, the United Nations Environment Programme, and the World Health Organization (WHO) on the development of a long-term action plan to avert outbreaks of infectious diseases that emerge in animals.

According to a WHO press release, the ultimate aim of the panel will be to develop evidence-based recommendations for global, regional, national, and local action to help prevent zoonotic disease outbreaks that could trigger pandemics. Among the first steps will be conducting systematic analyses of research around factors that lead to disease transmission between animals and humans, developing risk assessment and surveillance frameworks, and identifying good practices for preventing zoonotic disease outbreaks.

The panel plans to focus on a few critical areas that could contribute to the emergence of diseases similar to H5N1 avian flu, Middle East respiratory syndrome (MERS), Ebola, and Zika, including food production and distribution, urbanization and infrastructure development, international travel and trade, and activities that affect biodiversity loss and climate change.

“This panel will contribute to advancing the One Health agenda, by helping to better understand the root causes of disease emergence and spread, and informing decision-makers to prevent long-term public health risks,” FAO Director General Qu Dongyu said at a press conference announcing the panel. “I encourage it to be a shining example of silo-breaking, systems thinking and open dialogue.”
May 20 WHO press release


CARB-X funds development of novel antibiotic for gram-negative infections

Originally published by CIDRAP News May 19

CARB-X announced today that it is awarding Swiss drug maker Basilea Pharmaceutica International up to $2.7 million to develop a novel class of antibiotics to treat gram-negative bacterial infections.

The award from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) will help Basilea develop small-molecule inhibitors of the DXR enzyme, which is essential for the survival of many gram-negative pathogens, including carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii and multidrug-resistant Pseudomonas aeruginosa.

“The Basilea project is in the early stages of development, with a novel chemical class working with a novel mechanism of inhibition of bacterial growth,” CARB-X Research and Development Chief Erin Duffy, PhD, said in a CARB-X press release.

“Together, these offer a potential advantage where the development of resistance is concerned and—as such—offer great promise for a new therapy to treat serious hospital infections.”
May 19 CARB-X press release


Hospital stewardship linked to reduced MDR pathogen colonization

Originally published by CIDRAP News May 19

A systematic review and meta-analysis of more than 60 studies found that antimicrobial stewardship programs (ASPs) were associated with reduced multidrug-resistant Enterobacterales (MDR-E) colonization in hospital patients, researchers reported last week in the Journal of Infection.

The aim of the study, conducted by scientists from Israel, Germany, and Spain, was to evaluate the comparative effectiveness and safety of different interventions for the prevention of MDR-E colonization and infections in hospitalized patients. The co-primary outcomes were reduction in mortality and infections caused by MDR-E, and secondary outcomes included colonization with MDR-E.

A total of 63 studies were included, with 23 that assessed ASPs as the main intervention. Meta-analysis of those studies found no significant difference between ASPs and control groups for all-cause mortality (relative risk [RR], 1.o; 95% confidence interval [CI], 0.95 to 1.07), intensive care unit mortality (RR, 1.01; 95% CI, 0.93 to 1.10), or MDR-E infection (incidence ratio [IR], 0.88; 95% CI, 0.71 to 1.10). But significantly reduced MDR-E colonization was observed with ASPs (IR, 0.69; 95% CI, 0.57 to 0.82).

Seventeen studies examining decolonization strategies found no significant differences in any outcomes. Few other intervention strategies were studied.

The authors say that the finding of reduced colonization is noteworthy, since roughly one-third of patients with MDR-E colonization will develop an infection.

“Though effect on infection was not demonstrated in our meta-analysis, it is possible that additional future studies and a larger sample size would demonstrate a significant difference,” they wrote.
May 14 J Infect abstract


VHA survey finds stewardship programs reliant on pharmacists

Originally published by CIDRAP News May 19

Interviews conducted at Veterans Health Administration (VHA) hospitals without on-site infectious diseases (ID) support found that ASPs are largely a pharmacy-driven process, researchers reported this week in Infection Control & Hospital Epidemiology.

 A team led by researchers with the Iowa City Veterans’ Affairs Health Care System found that four themes emerged from site visits (two conducted virtually because of the pandemic) and interviews with 42 ASP team members at seven VHA hospitals lacking on-site ID support.

The first was that the ASP pharmacy champion wears many hats and fills many roles, and was consistently recognized as the leader of the ASP. The second was that ASP pharmacy champions had to build rapport with clinicians in order to get support for stewardship recommendations, a task that was difficult at hospitals that relied heavily on contract physicians.

The third theme that emerged was that access to an off-site ID specialist via electronic consultation helped give credibility to both the ASP pharmacists’ recommendations and to any stewardship initiatives the ASP team was trying to move forward. Finally, most ASP pharmacy champions spoke of the difficulty of gaining institutional buy-in and funding for their efforts.

The authors say the findings have broader implications, since a large proportion of US hospitals lack an on-site ID support but are still required to have an ASP.

“Given the ongoing need to improve antibiotic use and expand the implementation of ASPs across the spectrum of healthcare, our findings could inform future work on ASP implementation in these settings,” they wrote.
May 17 Infect Control Hosp Epidemiol abstract


CARB-X to fund development of novel antibiotic for CRE infections

Originally published by CIDRAP News May 18

CARB-X announced today that it is awarding up to $4.1 million to Summit Therapeutics of Cambridge, Massachusetts, to develop a first-in-class antibiotic to treat multidrug-resistant bacterial infections.

The money will help fund development of SMT-738, the first candidate from a novel class of antibiotics that target CRE via the LoICDE complex, an essential lipid transport system in gram-negative bacteria. The company says SMT-738 has shown potent in vitro activity against CRE isolates, including strains carrying the New Delhi Metallo-beta-lactamase (NDM) enzyme, and that it hopes to begin phase 1 clinical trials in 2023.

Under the award from CARB-X, Summit could receive an additional $3.7 million if certain project milestones are achieved.

“SMT-738 has the potential to save the lives of patients, as yet with untreatable infections through a novel drug class with a low propensity for resistance development,” Summit Chairman and Chief Executive Officer Robert Duggan said in a CARB-X press release. “We are excited and optimistic to take on the real challenge of antibiotic resistance and are grateful to CARB-X for partnering with us in support of this important mission.”

The Centers for Disease Control and Prevention (CDC) estimates that infections caused by CRE, dubbed “nightmare bacteria,” kill an estimated 1,100 hospital patients a year. 

CARB-X is now funding 58 active projects focused exclusively on drug-resistant bacteria.
May 18 CARB-X press release

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