Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
CDC surveillance estimates nearly 23,000 US candidemia cases
A population-based surveillance study estimates that there were nearly 23,000 cases of candidemia in the United States in 2017, researchers from the US Centers for Disease Control and Prevention (CDC) and several state health departments reported today in Clinical Infectious Diseases.
The surveillance, conducted in 45 counties in 9 states through the CDC's Emerging Infections Program, identified 1,226 cases of candidemia—a bloodstream infection caused by species of the fungus Candida—in 1,140 patients in 2017. The all-cause mortality rate within 7 days of candidemia diagnosis was 15%, and 25% for the entire hospitalization. Based on this, the researchers estimated that 22,600 US candidemia cases occurred in 2017, with an estimated 3,380 deaths within 7 days and 5,628 deaths during the entire hospital stay.
The overall estimated incidence of candidemia was 7.0 cases per 100,000 people, with the highest rates in adults 65 and older (20.1/100,000), men (7.9/100,000), and African Americans (12.3/100,000).
This is the first estimate of the burden of candidemia in the United States. The authors of the study say that since candidemia is only one form of invasive candidiasis, the true burden of invasive infections caused by Candida species is likely higher. They also noted that changes in the burden and epidemiology of candidemia may occur in the near future as Candida auris, which was first identified in the United States in 2016, continues to emerge as a major healthcare-associated pathogen.
Feb 28 Clin Infect Dis abstract
New global AMR surveillance partnership announced
Originally published by CIDRAP News Feb 26
The International Society for Infectious Diseases' (ISID's) Program for Monitoring Emerging Diseases (ProMED) today announced that it is teaming up with Public Health England to boost global antimicrobial resistance (AMR) surveillance efforts.
The organizations will collaborate on a surveillance platform, called ProMED-AMR, that will use digital detection methods and non-traditional sources to collect information on resistance trends, clusters of AMR, and newly identified cases in all World Health Organization regions. The platform will collect data on resistant pathogens in humans, animals, and the environment, and disseminate vetted and analyzed reports to an international audience of subscribers in real time.
"Antimicrobial resistant organisms have become major emerging pathogens of our era and ProMED-AMR will apply the same approaches to this problem as it has used so successfully in detecting and monitoring other emerging disease threats," ISID president Marc Mendelson, MBBS, PhD, said in a news release.
All information from the platform will be available free of charge.
Feb 26 ISID news release
Study: Antibiotics fail in 22% of pneumonia outpatients
Originally published by CIDRAP News Feb 26
An analysis of US health insurance claims data has found that antibiotic treatment failure occurs in 22% of adult patients receiving outpatient care for community-acquired pneumonia (CAP), a team of US researchers reported today in Open Forum Infectious Diseases.
For the retrospective cohort analysis, the researchers combed through data from the Marketscan commercial and Medicare supplemental databases to identify adults who were diagnosed and treated for CAP in the outpatient setting from 2011 through 2015 and received an antibiotic within 3 days of diagnosis. The primary outcome was antibiotic treatment failure, and secondary outcomes included 30-day all-cause mortality and CAP-related healthcare costs within the 30-day follow-up period.
A total of 251,947 unique patients met the criteria for the study. Their mean age was 52.2 years old, and 47.7% were men. The majority of patients were prescribed azithromycin (39.5%) or levofloxacin (36.9%). Overall, antibiotic treatment failure occurred in 22.1% of patients, but was higher in patients over 65 (25.7%, compared with 21.2% for adults aged 18 to 64). In both groups, treatment failure most frequently occurred with beta-lactam antibiotics. The most common type of treatment failure was a change to a new prescription.
Overall, all-cause mortality within 30 days of index treatment occurred in 7.6% of patients, but it was significantly higher in the antibiotic failure patients compared with the antibiotic success cohort (18.1% vs 4.6%), and the differences in 30-day mortality between antibiotic failure groups increased as a function of age. Mean 30-day CAP-related healthcare costs were also much higher in the patients who experienced treatment failure relative to those that did not ($2,140 vs. $54, respectively).
The authors of the study call the poor patient outcomes observed in patients who experienced antibiotic treatment failure "both clinically relevant and highly concerning."
"Collectively, our findings indicate significant shortcomings in the current treatment approach to managing patients with CAP in the outpatient setting, especially among those who are not responsive to initial therapy," they write. "The results of this study also identify great opportunities to improve the clinical management plans, including appropriate allocation of healthcare resources to avoid adverse outcomes for patients with CAP."
Feb 26 Open Forum Infect Dis abstract
CARB-X to fund development of broad-spectrum peptide antibiotics
Originally published by CIDRAP News Feb 25
CARB-X announced today that it will award Peptilogics of Pittsburgh up to $2.56 million in funding to develop a new class of peptide antibiotics with broad activity against drug-resistant bacteria.
The award will support the development of Peptilogics' lead compound, PLG0206, a novel peptide that has demonstrated potent antibacterial activity against multidrug-resistant gram-positive and gram-negative pathogens, with a good safety profile in animals. Because of its ability to disrupt biofilm formation, PLG0206 will be initially aimed at treating serious infections associated with implants such as prosthetic knees and hips.
"Joint replacements are an increasingly common surgical procedure, and infections are the most serious and costly complication of joint replacements," Erin Duffy, PhD, chief of research and development at CARB-X (The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), said in a press release. "The project is still in the early phases of development, but if successful and approved for use in patients, it could represent tremendous improvement in the treatment of periprosthetic joint infections."
Peptilogics could receive up to $9.61 million in additional funding if the project achieves certain development milestones.
Since launching in 2016, CARB-X has awarded more than $195.6 million to support the development of new antibiotics, diagnostics, vaccines, and other products to combat drug-resistant infections.
Feb 25 CARB-X press release
New drug for complicated urinary tract infections available in US
Originally published by CIDRAP News Feb 25
Drug maker Shionogi & Co. of Osaka, Japan, announced yesterday that cefiderocol, a newly approved antibiotic for treatment of complicated urinary tract infections (cUTIs) caused by gram-negative bacteria is now available for US adults who have limited or no treatment options.
Cefiderocol, sold under the brand name Fetroja, is a cephalosporin antibiotic with a novel mechanism of penetrating the tough outer membrane of gram-negative bacteria and the ability to overcome resistance mechanism used by gram-negative pathogens to evade antibiotics. It was approved by the US Food and Drug Administration (FDA) on Nov 14, 2019, based on results from a phase 2 clinical trial.
"The infectious disease community faces a serious challenge in combating cUTIs caused by Gram-negative pathogens, leading to high mortality rates," Shionogi president and CEO Akira Kato, PhD, said in a company news release. "This illustrates a dire need for a treatment option able to overcome many mechanisms of resistance in Gram-negative bacteria."
The labeling for cefiderocol comes with a warning about higher all-cause mortality found in patients with highly drug-resistant infections who were treated with the drug in another clinical trial, compared with patients treated with the best available therapy. The cause of the increase in mortality has not been established.
Feb 24 Shionogi press release
OIE: 77% of nations don't use antibiotics to promote animal growth
Originally published by CIDRAP News Feb 25
The World Organization for Animal Health (OIE) yesterday said more than three fourths of countries do not use any antibiotics for animal growth promotion, according to findings in its fourth annual report on global use of antibiotics in food-producing animals.
The report includes information on veterinary antibiotic use submitted by 153 OIE members in 2018, an increase of 18% since data collections began in 2015. Of these 153 countries, 118 (77%) provided data on quantities of antimicrobial agents sold for use in food-producing animals, an increase of 33% since 2015. Most countries (111 of 118, 94%) submitted data for only 1 year from 2016 to 2018. Progress was observed from 31 countries that had reported barriers in reporting quantitative antibiotic data during previous rounds of data collection.
A total of 118 countries (77%) reported that they did not use any antibiotics for growth promotion in animals as of 2018, either with or without legislation or regulations.
The report also includes an estimate of antibiotic use adjusted by animal biomass in 92 countries, which helps provide context for antibiotic sales data and can help explain trends and fluctuations in antibiotic use over time and between regions. The global estimate of antibiotics used in animals in 2016 adjusted by animal biomass was 144.39 milligrams per kilogram (mg/kg).
Regional comparison showed that Asia, the Far East, and Oceania reported the most antibiotics intended for use in animals (273.72 mg/kg) among the four global regions. Comparisons of the 2016 data with data from 2014 and 2015 showed that Europe's reported antibiotic use adjusted by animal biomass fell from 2014 to 2016, while Africa's remained at a similar level despite the contributions from more countries, and animal antibiotic use rose in the Americas. But the OIE cautions that changes in reporting countries and in regional biomass coverage across years of analysis, as well as differences in species composition, leave room for uncertainty.
The OIE says that, as more data on animal populations become globally available, the methodology for calculation of animal biomass will be refined.
Feb 24 OIE report
Analysis links outpatient penicillin prescribing with sepsis mortality rates
Originally published by CIDRAP News Feb 24
A new study by researchers from Harvard TH Chan School of Public Health suggests that outpatient prescribing of penicillins is associated with rates of mortality with sepsis in older US adults.
The study, published in BMC Infectious Diseases, used a multivariable mixed-effects model to relate state-specific rates of outpatient prescribing for oral fluoroquinolones, penicillins, macrolides, and cephalosporins in 2014 and 2015 to state-specific rates of mortality with sepsis in different age-groups of US adults in the same years, adjusting for additional covariates and random effects associated with 10 US Department of Health and Human Services regions. The aim was to see whether use of different antibiotics in the community might be linked to rising rates of hospitalization with sepsis and associated mortality.
The results of the analysis suggest a positive association between rates of outpatient prescribing of oral penicillins and rates of mortality with sepsis in individuals aged 75 to 84 years and those 85 and older.
An increase in the rate of prescribing of oral penicillins by 1 annual dose per 1,000 state residents was associated with increases in annual rates of mortality with sepsis of 0.95 (95% confidence interval [CI], 0.02 to 1.88) per 1,000 persons aged 75 to 84 years, and 2.97 (95% CI, 0.72 to 5.22) per 1,000 persons over 85. Additionally, the percent of individuals among those aged 50 to 64 who lacked health insurance and the percent of individuals aged 65 to 84 who were African-American were both associated with higher rates of mortality with sepsis in the corresponding age-groups.
The authors of the study note that the findings support the results of a previous analysis that showed an association between the use of penicillins and rates of septicemia hospitalization in older US adults, and are also in agreement with the fact that prevalence of resistance to penicillins, particularly in older adults, is high for a variety of gram-negative and gram-positive infections.
They conclude, "While these findings support the potential utility of replacement of penicillins by other antibiotics with the goal of reducing the rates of sepsis and associated mortality, further studies, including individual-level analyses are needed to better understand the effect of replacement of certain antibiotics, particularly penicillins by other antibiotics in the treatment of different syndromes, well as the effect of reduction in antibiotic prescribing in the treatment of certain conditions on the rates of severe outcomes associated with bacterial infections."
Feb 22 BMC Infect Dis study
Rapid test for tigecycline resistance genes performs well in lab study
Originally published by CIDRAP News Feb 24
A simple, rapid, and cost-effective assay for detecting genes that confer high-level resistance to tigecycline showed high sensitivity and specificity in lab tests, Chinese researchers reported today in the Journal of Antimicrobial Chemotherapy.
The assay, called the tetracycline inactivation method (TIM), was developed to detect the tet(X3/X4) genes, which are present on mobile plasmids and can directly inactivate tetracycline antibiotics, including the newly approved eravacycline and omadacycline. The test uses Bacillus stearothermophilus as the indicator strain, coupled with a pH-sensitive dye (bromecresol purple), to determine the production of tet(X3/X4) in bacterial strains. If the test strain carries the plasmid-encoded tet(X3/X4) genes, eravacycline will be degraded, allowing the growth of the susceptible indicator strain, and a yellow colorimetric zone will develop; otherwise, the color will be purple.
To evaluate the TIM assay, researchers from South China Agricultural University tested it on 118 isolates obtained from feces, soil, dust, sewage, and vegetable samples, including 30 tet(X4)-positive Escherichia coli, 30 tet(X3)-positive Acinetobacter spp., and 58 tet-negative E coli and Acinetobacter spp. The results showed the sensitivity and specificity for E coli carrying tet(X4) was 96.7% and 100%, respectively, while sensitivity and susceptibility for Acinetobacter spp. carrying tet(X3) were both 100%. The assay can be completed in 6.5 hours.
"Overall, the high sensitivity and specificity of TIM combined with its rapid readout make it a useful tool in clinical microbiology laboratories for the detection of plasmid-mediated high-level tigecycline resistance in E. coli and Acinetobacter spp.," the authors of the study write. They add that evaluation off the assay in clinical samples is worth further study.
Feb 24 J Antimicrob Chemother study
FDA grants breakthrough status to lysin therapy for MRSA bloodstream infections
Originally published by CIDRAP News Feb 24
Biotechnology company ContraFect Corporation, of Yonkers, New York, announced today that the FDA has granted Breakthrough Therapy designation to execabase, a recombinantly produced lysin, for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections.
According to a company press release, the designation was based on results of a phase 2 superiority trial that evaluated whether the addition of execabase to standard-of-care (SOC) antibiotic therapy in patients with S aureus bloodstream infections improved clinical response rates compared with SOC antibiotic therapy alone. In a pre-specified analysis of the subgroup with MRSA infections, the clinical responder rate at day 14 among exebacase-treated patients was 42.8 percentage points higher than the responder rate among patients treated with SOC antibiotics alone (74.1% vs 31.3%, respectively, P = 0.010).
Treatment with exebacase was also associated with a 21-percentage-point reduction in the 30-day all-cause mortality (P = 0.056), a 4-day reduction in length of hospital stay, and meaningful reductions in 30-day hospital readmission rates in MRSA-infected patients.
"The decision by the FDA to grant Breakthrough Therapy designation to exebacase recognizes the urgent need for new therapies that can impact the lives of patients with these MRSA infections," ContraFect President and CEO Roger Pomerantz, MD, said. "Based on the Phase 2 data, we believe exebacase could be the first anti-infective agent to demonstrate superior outcomes for these patients."
Execebase is the first lysin to enter human clinical trials in the United States. It works by targeting the peptidoglycan cell wall, which is vital to S aureus bacteria.
Breakthrough Therapy designation expedites development and review of drugs for serious or life-threatening diseases that have provided preliminary clinical evidence that they may demonstrate substantial improvement over available therapies on at least one clinically significant end point.
Feb 24 ContraFect press release
