Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Trial finds no mortality benefit from azithromycin for kids' diarrhea
A randomized trial involving more than 8,000 children in low-income settings found that azithromycin did not improve mortality in children with acute diarrhea, an international team of researchers reported yesterday in JAMA Network Open.
The Antibiotics for Children with Diarrhea (ABCD) trial, conducted in 36 healthcare facilities in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania, randomly assigned 8,226 high-risk children ages 2 to 23 months (54% boys, mean age 11.6 months) with acute non-bloody diarrhea to receive 3 days of oral azithromycin or placebo.
The aim of the trial was to determine whether the addition of azithromycin to standard case management of acute, non-bloody diarrhea—which is mainly caused by bacterial pathogens such as Shigella, Escherichia coli, and Campylobacter—could reduce mortality and improve linear growth.
A total of 20 of 4,133 children in the azithromycin group (0.5%) and 28 of 4,135 children in the placebo group (0.7%) died within 180 days of enrollment (relative risk, 0.72; 95% confidence interval [CI], 0.40 to 1.27).
The mean change in length for age z scores—a measurement of linear growth—was –0.16 in the azithromycin group and –0.19 in the placebo group (risk difference 0.03; 95% CI, 0.01 to 0.06)—a small difference that the study authors concluded was unlikely to be of clinical or public health significance. No evidence of modification of treatment effect with respect to participant age, sex, wealth quintile, or reason for enrollment was observed for either primary outcome.
Overall mortality was much lower than anticipated, the study authors noted, and the trial was stopped for futility at the prespecified interim analysis. They hypothesize that the trial requirement of rigorous adherence to the World Health Organization's (WHO's) guidelines for diarrhea management contributed to the low mortality.
"These results support rigorous adherence to the current WHO guidelines on the management of diarrhea and do not suggest that a change to global diarrhea management guidelines or policy is merited," they concluded.
Dec 16 JAMA Netw Open study
Doubling preventive antibiotics not always tied to fewer surgical infections
In another study published this week in JAMA Network Open, Swiss researchers reported that a double dose of cefuroxime administered prior to surgery was not consistently associated with a lower rate of surgical site infections (SSIs).
The cohort study involved 37,640 patients weighing at least 80 kilograms (kg) (about 176 pounds) who received surgical antibiotic prophylaxis (SAP) with cefuroxime prior to surgery at 142 Swiss hospitals from January 2015 through December 2019. The researchers were trying to determine whether national guidelines introduced in 2015 to lower SSI rates—which advocated for an optional increase of the standard SAP dose in patients weighing at least 80 kg—were associated with a reduction in SSIs.
A total of 1,203 (3.2%) patients had an SSI. Double-dose cefuroxime was administered to 13,246 patients (35.2%) and was not significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.89; 95% CI, 0.78 to 1.02; P=.10).
After stratification by weight category, double-dose SAP versus single-dose SAP was associated with lower SSI rates among 16,605 patients weighing at least 80 to less than 90 kg (aOR, 0.76; 95% CI, 0.61 to 0.97; P = .02) but not in the other weight categories. After stratification by contamination class, double-dose SAP was associated with lower SSI rates among 1,946 patients with contaminated wounds (aOR, 0.49; 95% CI, 0.30 to 0.84; P=.008), but not those with clean wounds or clean-contaminated wounds, compared with a single dose.
A subgroup analysis also found that a double dose of cefuroxime was significantly associated with a lower risk of SSI in surgical procedures not involving implants (aOR, 0.83; 95% CI, 0.69 to 0.99; P=.04).
"Our results suggest that general routine administration of a double SAP dose in patients weighing at least 80 kg has no general additional benefit," the authors wrote. "The observed signal in the weight category of 80 to 90 kg and the lower rate in patients with contaminated wounds and in surgical procedures without implants must be further confirmed."
Dec 15 JAMA Netw Open study
Study finds non-adherence to perioperative antibiotic guidelines
In a third study published this week in JAMA Network Open, US researchers reported that more than a third of surgical encounters did not adhere to perioperative antibiotic prophylaxis guidelines.
To describe adherence to each component of the Infectious Diseases Society of America's (IDSA's) perioperative antibiotic guidelines, researchers from Yale University looked at data on a national cohort of adult patients who underwent noncardiac surgery at 31 institutions from January 2014 through December 2018.
The primary endpoint was overall adherence to the IDSA guidelines, including appropriateness of antibiotic choice, weight-based dose adjustment, timing of administration with respect to surgical incisions, and timing of redosing, when indicated. The researcher also analyzed the data for specific factors associated with guideline non-adherence.
Of the 414,851 surgical encounters evaluated, 51.8% of patients were women, the mean age was 57.5 years, 1.2% of patients were of Hispanic, and 10.2% were Black. In this cohort, 148,804 encounters (35.9%) did not adhere to guidelines: 19.7% for antibiotic choice, 17.1% for weight-adjusted dosing, 0.6% for timing of first dose, and 26.8% for redosing.
In adjusted analyses, overall nonadherence was associated with emergency surgery (odds ratio [OR], 1.35; 95% CI, 1.29 to 1.41; P<.001), surgery requiring blood transfusions (OR, 1.30; 95% CI, 1.25 to 1.36; P<.001), off-hours procedures (OR, 1.08; 95% CI, 1.04 to 1.13; P<.001), and procedures staffed by a certified registered nurse anesthetist (OR, 1.14; 95% CI, 1.11 to 1.17; P<.001).
Overall adherence to guidelines for antibiotic administration improved over the study period from 53.1% (95% CI, 52.7% to 53.5%) in 2014 to 70.2% (95% CI, 69.8% to 70.6%) in 2018.
"Although adherence to perioperative antibiotic administration guidelines has improved over time, the findings of this cohort study suggest that substantial nonadherence persists," the study authors wrote. "Future quality improvement efforts directed at improving antibiotic guideline adherence may lead to a decrease in SSIs and improved surgical outcomes."
Dec 14 JAMA Netw Open study
G7 finance ministers commit to addressing antibiotic market failure
Originally published by CIDRAP News Dec 15
Finance ministers for G7 countries yesterday issued a statement in support of actions to boost development of new antibiotics.
Citing the lessons of the COVID-19 pandemic and the need to prepare for the long-term health and economic consequences of antimicrobial resistance (AMR), the G7 finance ministers committed to taking "additional and appropriate" steps to address the failure of the antibiotic market, create the right economic conditions to preserve essential antibiotics, strengthen antibiotic research and development, and bring new drugs to market where they meet identified public health needs.
The steps outlined include exploring a range of market incentive options, with a particular emphasis on "pull" incentives, new pilot projects, and legislative and regulatory measures.
"We are committed to strengthen and intensify our action across the G7," the statement said. "Recognising that this is a multiyear and multi-stakeholder effort, we ask our finance and health officials to work with relevant technical agencies, international organisations, industry, and investors to continue this dialogue and share best practice."
The statement also committed all G7 members to implementing their existing strategies to address AMR, as outlined in their national action plans.
Dec 14 G7 finance ministers' statement
Study will explore ways to limit broad-spectrum antibiotics for pneumonia
Originally published by CIDRAP News Dec 15
The Cleveland Clinic announced last week that it has received funding from the Agency of Healthcare Research and Quality (AHRQ) to conduct a clinical trial to evaluate ways to reduce and target use of broad-spectrum antibiotics for community-acquired pneumonia (CAP).
The $2.5 million from AHRQ will fund a multicenter, randomized clinical trial that will test two approaches to limiting broad-spectrum antibiotics in hospitalized adult CAP patients: routine use of rapid diagnostic testing at the time of hospital admission, and pharmacist-led antibiotic de-escalation.
Approximately 1 million US adults are hospitalized for pneumonia each year, and 50,000 die from it. Though pneumonia is caused by bacteria, viruses, and fungi, most patients aren't tested for the cause and are typically treated with antibiotics.
"Our overall goal is to improve antimicrobial prescribing for patients with community-acquired pneumonia," trial co-lead Abhishek Deshpande, MD, PhD, a staff physician with Cleveland Clinic's Center for Value-Based Research, said in a press release. "Specifically, knowledge gained from this trial will allow physicians to limit the use of broad-spectrum antimicrobials and initiate targeted therapy."
Dec 9 Cleveland Clinic press release
Brazilian restriction on antibiotic sales linked to decline in resistance
Originally published by CIDRAP News Dec 14
A national policy restricting over-the-counter (OTC) antibiotic sales in Brazil was linked with a drop in AMR in two pathogens that frequently cause community-acquired infections, Brazilian researchers reported yesterday in Emerging Infectious Diseases.
To assess the impact on AMR from a 2010 National Health Surveillance Agency of Brazil policy that required a prescription to buy antibiotics from private pharmacies, the researchers analyzed sales of six oral antibiotics from private pharmacies in Sao Paulo, along with AMR data on E coli and Streptococcus pneumoniae isolates collected from Sao Paulo hospitals, from 2008 through 2016. They used a dynamic regression model based on a Bayesian approach to analyze the effect of the restriction policy on the association between antibiotic sales and resistance.
During the study period, sales of the six antibiotics—amoxicillin, azithromycin, cephalexin, ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole—combined in the Sao Paulo region fell from 7.86 defined daily doses per 1,000 inhabitants per day (DID) to 7.65, with a steep drop in sales observed after the implementation of the policy in 2010.
But the decline in sales was driven by amoxicillin and sulfamethoxazole. Sales of all the other antibiotics rose over the study period.
The analysis showed a substantial drop in AMR in both pathogens following decreased sales of amoxicillin and trimethoprim/sulfamethoxazole. The researchers also noticed, however, that increased sales of ciprofloxacin were associated with increased ciprofloxacin resistance and increased prevalence of extended-spectrum beta-lactamase–positive isolates in E coli, while increased sales of azithromycin after 2013 were associated with erythromycin resistance in S pneumoniae.
"Restricting OTC antimicrobial sales was associated with a drop in resistance to amoxicillin and trimethoprim/sulfamethoxazole but not to quinolones, macrolides, or cephalexin," the study authors wrote. "Our findings suggest that strategies to reduce overdependence on antimicrobial drugs might have an effect on resistance in those drugs. However, any such strategy will likely need to be multifaceted, because AMR is a complex problem."
Dec 13 Emerg Infect Dis study
Stewardship intervention tied to better antibiotic use in hospitalized kids
Originally published by CIDRAP News Dec 14
A multifaceted intervention to enhance timely conversion of intravenous (IV) to oral antibiotic therapy in children helped safely optimize pediatric antibiotic use in Australian hospitals, researchers reported yesterday in the Journal of Global Antimicrobial Resistance.
The study, conducted in seven healthcare facilities in Queensland, evaluated a package of interventions to guide the timing and process of switching from IV to oral antibiotics in children hospitalized with community-acquired pneumonia and skin and other soft-tissue infections. The package included clinician guidelines, medication review stickers, patient information leaflets, and educational resources.
Over a period of 7 months, which included the baseline and intervention periods, the researchers collected data on time taken to switch patients from IV to oral antibiotics, length of hospital stay, duration of IV and oral antibiotic therapies, and adverse events. A total of 357 pediatric patients were enrolled in the study, with 178 in the baseline and 179 in the intervention phase.
The percentage of patients who were eligible to switch to oral therapy within 24 hours of eligibility increased from 87.6% (156/178) in the baseline phase to 97.2% (174/179) in the intervention phase (P = 0.003). The average number of extra IV days decreased from 0.45 days in the baseline period to 0.18 days in the intervention period (P < 0.001). The median patient length of stay was 2 days for both phases. The only adverse events recorded were line-associated infiltrates, with a decrease from 34.3% (61/178) in the baseline period to 17.9% (32/179) in the intervention period (P < 0.001).
"In conclusion, a multifaceted package of tailored interventions to enhance timely IV to oral conversion of antibiotic therapy for children in remote and regional facilities is an effective antimicrobial stewardship initiative," the study authors wrote.
Dec 13 J Glob Antimicrob Resist study
UK study shows drop in antibiotics for respiratory infections during COVID
Originally published by CIDRAP News Dec 13
Antibiotic prescribing for respiratory tract infections (RTIs) fell in England during the first year of the pandemic, researchers reported today in the Journal of Antimicrobial Chemotherapy.
To assess changes in antibiotic prescribing for RTIs for 2020-2021, researchers with England's National Institute for Health Research extracted data from two large UK databases for primary and secondary care. They measured RTI antibiotic prescribing in prescription items per 1,000 population from January 2014 through February 2021 for primary care, and in defined daily doses per 1,000 population per day from January 2016 through February 2021 for secondary care. Previous research has shown that antibiotic prescribing in primary care in England fell by 14% from 2015 through 2019.
The analysis found that during 2020-2021, antibiotic prescriptions for RTIs in primary care fell an additional 12.4% per season compared with the pre-COVID period, with a sharp drop during the winter—a season that typically sees the highest level of antibiotic prescribing for RTIs. In winter 2020-2021, during the pandemic, RTI antibiotic prescriptions were cut nearly in half compared with the 2019-2020 winter. When the researchers combined antibiotic prescribing for RTIs in primary care with that of hospital emergency departments to account for possible shifts in health-seeking behaviors, the trend was similar to that primary care prescribing alone.
The study authors say COVID-19 restrictions, drastic reductions in person-to-person contact, and avoidance of healthcare settings likely all played a role in reduced RTI prescribing. They also note that the findings highlight the need for better rapid diagnostics to further reduce unnecessary antibiotics for RTIs.
"Rapid diagnostics in the community, such as lateral flow tests, have been effective in detecting SARS-CoV-2 and are quicker and cheaper than PCR tests," they write. "Diagnostics to differentiate viral and bacterial aetiologies could spare unnecessary antibacterial use and reduce GP [general practitioner] attendance in future winters."
Dec 13 J Antimicrob Chemother study
Resistance genes, multidrug resistance rising in E coli from food animals
Originally published by CIDRAP News Dec 13
In another study published today in the same journal, a team of Swiss researchers found that the prevalence of antimicrobial resistance genes (ARGs) and multidrug resistance (MDR) in E coli obtained from food-producing animals has been rising since 1980.
For the study, researchers with Switzerland's Institute of Integrative Biology and Institute for Environmental Decisions retrieved 7,632 E coli genomes from poultry, cattle, and swine from public databases and screened them for ARGs. They then compared resistance trends inferred from the genomic data with trends reported by phenotypic surveillance systems in the United States and Europe. The genomes originated predominantly from the United States (63.4%), followed by Europe (17.3%), Asia (13.2%), Africa (1.7%), Central and South America (1.7%), and Oceania (1.2%).
The analysis showed an increase in multidrug resistance (MDR) over time. In 1980, the E coli genomes carried, on average, genes conferring resistance to 1.69 antimicrobial classes in swine, 1.41 in swine, and 1 in cattle. By 2018, MDR rates increased 1.6 times, with E coli genomes carrying an average of genes conferring resistance to 2.65 antimicrobial classes in swine, 2.22 in poultry, and 1.58 in cattle.
The highest resistance levels were observed for tetracyclines (42.2% to 69.1%), penicillins (19.4% to 47.5%), and streptomycin (28.6% to 56.6%). The trends were consistent with resistance trends reported from phenotypic international surveillance programs.
Among the specific ARGs in which an increase was observed was the extended-spectrum cephalosporin gene blacmy-2, which is noteworthy because extended-spectrum beta-lactam antibiotics are not approved for use as growth promoters in Europe or the United States. The study authors say the presence of this ARG could be linked to use of these antimicrobials in food-producing animals prior to their ban, or to co-selection with other resistance genes.
"Furthermore, the increase in blacmy-2 is concerning as this gene has been commonly identified in plasmids that might facilitate its dissemination in food animals," they write.
Dec 13 J Antimicrob Chemother abstract
