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

High levels of drug resistance found in Eastern Mediterranean region

An analysis of data on bloodstream infections (BSIs) from countries in the World Health Organization (WHO) Eastern Mediterranean Region shows a high prevalence of antimicrobial resistance (AMR) in the region and limited capacity to prevent the emergence and spread of resistant pathogens, WHO researchers reported yesterday in Emerging Infectious Diseases.

Using data reported to the WHO through the Global Antimicrobial Resistance Surveillance System (GLASS) by 11 to 14 countries in the region from 2017 through 2019, the researchers assessed the proportion of BSIs—which are among the most serious and life-threatening infections and are the main sustainable development goal indicator for AMR—that were caused by six resistant organisms.

They also measured the prevalence of antimicrobial use in hospitalized patients and evaluated the regional capacities of antimicrobial stewardship (AMS) and infection prevention and control (IPC) programs.

In 2019, the median proportion of BSIs caused by carbapenem-resistant Acinetobacter spp (CRAsp) was highest, at 70.3%, followed by third-generation cephalosporin (3GC)-resistant Klebsiella pneumoniae (66.3%). The lowest median proportion was for carbapenem-resistant Escherichia coli (4.6%).

The proportion of resistance tended to increase over time, from 71.4% in 2017 to 74.5% in 2019 for CRAsp, from 55.3% to 65.4% for 3GC-resistant K pneumoniae, from 36.6% to 45.8% for methicillin-resistant Staphylococcus aureus, and from 24.2% to 37.5% for carbapenem-resistant K pneumoniae. Egypt and Pakistan had the highest proportion of resistance for five of the six pathogens.

Data from 128 hospitals in 7 countries showed that 53.3% of hospitalized patients received one or more antimicrobial agents, ranging from 38.7% to 77.7% across countries, with high prescribing of 3GC and carbapenems.

Among 22 countries in the region, 13 had a national IPC program, but in 8 of those countries, the existing structures were not functioning. Assessment of national AMS core capacities in 20 countries found only 1 had dedicated funding for AMS, 4 had established national AMS technical working groups, and 1 had developed an AMS implementation plan.

The study authors note that the proportion of BSIs caused by CRAsp in the region is extremely high compared with the United States (33.9%) and the European Union (32.6%).

"Overall, the magnitude of the problem and the limited capacity to respond emphasize the need for regional political leadership in addressing AMR," they wrote.
Mar 3 Emerg Infect Dis study

Study ties antibiotics in pregnancy with higher risk of preterm birth

A study of first pregnancies in Sweden found that antibiotic use during pregnancy or 3 months before conception was associated with an increased risk of preterm birth, particularly during the first and second trimesters and in mothers with chronic diseases, researchers reported this week in the Journal of Antimicrobial Chemotherapy.

In the population-based cohort study, a team of Swedish and Belgian researchers analyzed data on all first pregnancies and maternal prescription drug exposure in Sweden from 2006 through 2016 using multivariable logistic regression to assess the risk of preterm birth associated with gestational or recent preconception antibiotic exposure. Other covariates considered in the analysis included common maternal chronic comorbidities (hypo- and hyperthyroidism, hypertension, or diabetes mellitus), trimester, antibiotic class, and treatment duration.

Compared with non-users, antibiotic exposure was associated with increased risks of preterm birth in mothers with comorbidities (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18 to 1.48) and without (OR, 1.09; 95% CI 1.06 to 1.13). Preconception use showed no association, while risk was increased for first- and second-trimester use and decreased for third-trimester use.

Increased risks were seen for the following antibiotic groups in mothers without and with comorbidities, respectively: macrolides, lincosamides, and streptogramins (OR, 1.63; 95% CI, 1.45 to 1.83 and OR, 2.48; 95% CI, 1.72 to 3.56); quinolones (OR, 1.60; 95% CI, 1.32 to 1.94 and OR, 2.11; 95% CI, 1.12 to 4.03); non-penicillin beta-lactams (OR, 1.15; 95% CI, 1.07 to 1.24 and OR, 1.39; 95% CI, 1.07 to 1.83); other antibacterials (OR, 1.09; 95% CI, 1.03 to 1.14 and OR, 1.38; 95% CI, 1.16 to 1.63); and penicillins (OR, 1.04; 95% CI, 1.01 to 1.08 and OR, 1.23; 95% CI, 1.09 to 1.40). Antibiotic indications, which could also affect preterm birth, were not available.

The study authors say that while the findings do not establish causality and that the underlying mechanism of the association between antibiotic use and preterm birth could not be assessed, they add more weight to recent evidence on the role of microbiome changes and the risk of preterm birth and highlight the need to reconsider the risks and benefits of antibiotics in pregnant women.
Mar 2 J Antimicrob Chemother study

WHO handbook aims to help countries implement AMR action plans

Originally published by CIDRAP News Mar 3

The WHO this week published new technical guidance to help countries implement national action plans (NAPs) for antimicrobial resistance in the human health sector.

Written for national health authorities, policymakers, technical experts, and other stakeholders, the WHO implementation handbook aims to help fill significant gaps in countries' implementation of NAPs. A recent survey by the WHO, the World Organisation for Animal Health, and the United Nations Food and Agriculture Organization showed that, of the 117 countries with NAPs, only 20%had fully financed those plans.

"For most countries, the greatest challenge is not developing a NAP; rather, it is achieving NAP implementation that is evidence-based and demonstrates sustained action," the document states.

The handbook lays out six steps for sustainable implementation of NAPs in the healthcare system. The steps include strengthening governance, prioritizing activities based on an assessment of the current situation, estimating costs and developing a budget for prioritized activities, mobilizing resources to fund the plan, implementing the prioritized activities, and monitoring and evaluating progress in implementing the plan.

Each chapter in the handbook provides specific instructions on the six steps, links to existing WHO guidance and tools to support implementation, and checklists. An online version of the handbook will contain case studies.

Future handbooks will provide technical guidance for NAP implementation in the animal health, food safety, and environment sector.
Feb 28 WHO implementation handbook

Study finds high levels of multidrug-resistant E coli on Chinese pig farms

Originally published by CIDRAP News Mar 3

A surveillance study of Chinese pig farms found a high level of multidrug resistance in E coli samples from pigs and their breeding environments, Chinese researchers reported yesterday in Nature Communications.

For the study, researchers from Huazhong Agricultural University collected and conducted antimicrobial susceptibility testing (AST) on 1,871 E coli isolates from pig farms in 31 Chinese provinces from October 2018 through September 2019. China is the largest pig-rearing country in the world, and E coli is a commonly used biomarker of antimicrobial resistance (AMR) on pig farms. The most representative provinces by isolate were Hubei (250 isolates) and Henan (191), the two largest pig-farming provinces in the country.

AST results showed that 90.5% of the 1,871 isolates were multidrug-resistant (MDR) strains. A large proportion of isolates were resistant to tetracycline (96.2%), chloramphenicol (82%), moxifloxacin (81.6%), and trimethoprim/sulfamethoxazole (80.3%). Resistance was also detected to last-resort antibiotics such as tigecycline (37.3%), colistin (3.8%), and carbapenems (imipenem [2.6%], meropenem [2.3%], and ertapenem [2.5]). Most colistin-resistant and carbapenem-resistant isolates came from Henan province.

The study also identified a heterogeneous group of O-serogroups and sequence types among the MDR isolates. These isolates harbored multiple resistance genes, virulence factor-encoding genes, and putative plasmids. In addition, phylogenetic analysis showed that 515 of the MDR E coli isolates from the pig farms were closely related to 287 publicly available draft genomes of human commensal E coli strains from across China. These findings suggest a high genetic propensity spread from pig farms to humans that poses health risks.

"Our AST results suggest a worrisome AMR situation on pig farms, as evidenced by the common recovery of MDR E. coli isolates from both pigs and their breeding environments on farms in different provinces, including Tibet, Xinjiang, and Qinghai," the study authors wrote. "This worrisome situation is widely accepted to be the result of antibiotic overuse and misuse in the Chinese pig industry."

The authors say the data may help inform governmental efforts to reduce antibiotic use and AMR in the Chinese pig industry.
Mar 2 Nat Commun study

Stewardship package linked to fewer antibiotics for dogs, cats

Originally published by CIDRAP News Mar 1

Implementation of a comprehensive AMS package at 135 general-practice veterinary clinics in Australia resulted in a decline in overall antimicrobial use and a shift towards use of low-importance antimicrobials, researchers reported last week in JAC-Antimicrobial Resistance.

The clinics were enrolled in the implementation trial in October 2018 and assigned to one of three levels of an antimicrobial stewardship program: a control group that received education only (CON), an intermediate group (AMS1), and an intensive group (AMS2).

AMS1 and AMS2 clinics were asked to appoint a stewardship champion to lead implementation of the ASP and to color-code antimicrobials according to their importance, and AMS2 clinics were required to restrict use of antimicrobials with a high-importance rating. To evaluate the impact of the three AMS levels, researchers analyzed antimicrobial prescribing data from October 2016 through October 2020.

In the pre-trial period (October 2016 through September 2018), the overall incidence rate (IR) of antimicrobial prescribing for dogs and cats was 3.7 per 1,000 consultations. During the implementation period, the IR of antimicrobial prescribing fell 36% from the pre-trial period to 2.4 per 1,000 consultations, then declined to 1.9 per 1,000 consultations in the post-implementation phase—a 50% decline from the pre-trial period.

Compared with the CON clinics, AMS2 clinics saw a 4% and 6% decrease in the IR of overall antimicrobial prescribing during the implementation and post-implementation periods. They also saw a 24% decline in the IR of high-importance antimicrobial prescribing in both periods compared with CON clinics. A greater mean difference in the IR of antimicrobial prescribing was seen in high-prescribing clinics.

"In conclusion, we have shown a positive impact of three different AMS programmes in a large group of general veterinary practices, resulting in both a decline in overall antimicrobial use and a shift in use towards prescribing of low-importance antimicrobials, with the greatest impact seen in high-prescribing clinics," the study authors wrote. "Further research is needed to evaluate the experience of veterinarians involved in the trial and to investigate the impact that these interventions may have in practices that see horses and/or food production animals in addition to dogs and cats."
Feb 25 JAC-Antimicrob Resist study

Trial finds azithromycin does not reduce post-RSV wheezing in kids

Originally published by CIDRAP News Feb 28

A randomized trial conducted among infants with severe respiratory syncytial virus (RSV) bronchiolitis found that administration of azithromycin did not prevent future wheezing, researchers reported yesterday in The New England Journal of Medicine–Evidence.

For the double-blind, placebo-controlled trial, a team led by researchers from Washington University School of Medicine in St. Louis and Vanderbilt University enrolled 200 otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis, which is a well-known risk factor for the development of childhood asthma. The infants were randomized 1:1 to receive either oral azithromycin—which the researchers hypothesized might attenuate airway inflammation during RSV bronchiolitis—or placebo for 14 days. The primary outcome was the occurrence of recurrent wheeze over the following 2 to 4 years.

A total of 188 infants (96 in the azithromycin group and 92 in the placebo group) had at least one follow-up visit. While children who received azithromycin had lower levels of interleukin 8 (a marker of airway inflammation) compared with those who received placebo, azithromycin did not reduce the risk of post-RSV recurrent wheeze. Forty-five percent of children in the azithromycin group developed recurrent wheeze, compared with 37% in the placebo group (adjusted hazard ratio, 1.45; 95% CI, 0.92 to 2.29; P = 0.11).

Azithromycin also did not reduce the risk of recurrent wheeze among infants already receiving other antibiotic treatment at the time of enrollment (44.8% in the azithromycin group vs 46.2% in the placebo group; hazard ratio, 0.94; 95% CI, 0.43 to 2.07). In contrast, among antibiotic-naïve participants (133), azithromycin therapy resulted in a risk of subsequent recurrent wheeze compared with placebo (47.8% vs 31.8%; hazard ratio, 1.79; 95% CI, 1.03 to 3.10).

"In conclusion, azithromycin therapy during early-life acute severe RSV bronchiolitis did not reduce recurrent wheeze occurrence over the following 2 to 4 years," the study authors wrote. "Our findings are consistent with national bronchiolitis guidelines, which recommend against the use of antibiotics during acute bronchiolitis because of a lack of effect on the acute illness, and they extend this recommendation by demonstrating the lack of a salutary effect on recurrent wheeze."
Feb 27 N Engl J Med Evidence study 

High levels of drug resistance found in Eastern Mediterranean region

An analysis of data on bloodstream infections (BSIs) from countries in the World Health Organization (WHO) Eastern Mediterranean Region shows a high prevalence of antimicrobial resistance (AMR) in the region and limited capacity to prevent the emergence and spread of resistant pathogens, WHO researchers reported yesterday in Emerging Infectious Diseases.

Using data reported to the WHO through the Global Antimicrobial Resistance Surveillance System (GLASS) by 11 to 14 countries in the region from 2017 through 2019, the researchers assessed the proportion of BSIs—which are among the most serious and life-threatening infections and are the main sustainable development goal indicator for AMR—that were caused by six resistant organisms.

They also measured the prevalence of antimicrobial use in hospitalized patients and evaluated the regional capacities of antimicrobial stewardship (AMS) and infection prevention and control (IPC) programs.

In 2019, the median proportion of BSIs caused by carbapenem-resistant Acinetobacter spp (CRAsp) was highest, at 70.3%, followed by third-generation cephalosporin (3GC)-resistant Klebsiella pneumoniae (66.3%). The lowest median proportion was for carbapenem-resistant Escherichia coli (4.6%).

The proportion of resistance tended to increase over time, from 71.4% in 2017 to 74.5% in 2019 for CRAsp, from 55.3% to 65.4% for 3GC-resistant K pneumoniae, from 36.6% to 45.8% for methicillin-resistant Staphylococcus aureus, and from 24.2% to 37.5% for carbapenem-resistant K pneumoniae. Egypt and Pakistan had the highest proportion of resistance for five of the six pathogens.

Data from 128 hospitals in 7 countries showed that 53.3% of hospitalized patients received one or more antimicrobial agents, ranging from 38.7% to 77.7% across countries, with high prescribing of 3GC and carbapenems.

Among 22 countries in the region, 13 had a national IPC program, but in 8 of those countries, the existing structures were not functioning. Assessment of national AMS core capacities in 20 countries found only 1 had dedicated funding for AMS, 4 had established national AMS technical working groups, and 1 had developed an AMS implementation plan.

The study authors note that the proportion of BSIs caused by CRAsp in the region is extremely high compared with the United States (33.9%) and the European Union (32.6%).

"Overall, the magnitude of the problem and the limited capacity to respond emphasize the need for regional political leadership in addressing AMR," they wrote.
Mar 3 Emerg Infect Dis study

Study ties antibiotics in pregnancy with higher risk of preterm birth

A study of first pregnancies in Sweden found that antibiotic use during pregnancy or 3 months before conception was associated with an increased risk of preterm birth, particularly during the first and second trimesters and in mothers with chronic diseases, researchers reported this week in the Journal of Antimicrobial Chemotherapy.

In the population-based cohort study, a team of Swedish and Belgian researchers analyzed data on all first pregnancies and maternal prescription drug exposure in Sweden from 2006 through 2016 using multivariable logistic regression to assess the risk of preterm birth associated with gestational or recent preconception antibiotic exposure. Other covariates considered in the analysis included common maternal chronic comorbidities (hypo- and hyperthyroidism, hypertension, or diabetes mellitus), trimester, antibiotic class, and treatment duration.

Compared with non-users, antibiotic exposure was associated with increased risks of preterm birth in mothers with comorbidities (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18 to 1.48) and without (OR, 1.09; 95% CI 1.06 to 1.13). Preconception use showed no association, while risk was increased for first- and second-trimester use and decreased for third-trimester use.

Increased risks were seen for the following antibiotic groups in mothers without and with comorbidities, respectively: macrolides, lincosamides, and streptogramins (OR, 1.63; 95% CI, 1.45 to 1.83 and OR, 2.48; 95% CI, 1.72 to 3.56); quinolones (OR, 1.60; 95% CI, 1.32 to 1.94 and OR, 2.11; 95% CI, 1.12 to 4.03); non-penicillin beta-lactams (OR, 1.15; 95% CI, 1.07 to 1.24 and OR, 1.39; 95% CI, 1.07 to 1.83); other antibacterials (OR, 1.09; 95% CI, 1.03 to 1.14 and OR, 1.38; 95% CI, 1.16 to 1.63); and penicillins (OR, 1.04; 95% CI, 1.01 to 1.08 and OR, 1.23; 95% CI, 1.09 to 1.40). Antibiotic indications, which could also affect preterm birth, were not available.

The study authors say that while the findings do not establish causality and that the underlying mechanism of the association between antibiotic use and preterm birth could not be assessed, they add more weight to recent evidence on the role of microbiome changes and the risk of preterm birth and highlight the need to reconsider the risks and benefits of antibiotics in pregnant women.
Mar 2 J Antimicrob Chemother study