Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
New CARB-X funding announced for Staphylococcus vaccine candidate
CARB-X yesterday announced additional funding to expand development of a vaccine against Staphylococcus aureus.
The award of $1.6 million will allow Integrated Biotherapeutics (IBT) of Rockville, Maryland, to expand research and development efforts for IBT-V02, a multivalent vaccine for the prevention of S aureus infections, including those caused by methicillin-resistant S aureus (MRSA). With the additional funding, IBT will evaluate the efficacy of the vaccine against strains of S aureus circulating in developing nations, and explore development of a freeze-dried version for use in regions where cold storage systems aren't available.
"Effective vaccines can prevent life-threatening bacterial infections and help reduce overuse and misuse of antibiotics, which is a particular problem in many developing nations and a threat to global health security as it fuels the spread of antibiotic resistance," M. Javad Aman, PhD, IBT president and chief science officer, said in a CARB-X press release.
CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) awarded IBT up to $8.5 million in 2017 to complete pre-clinical studies and a phase 1 clinical trial for IBT-V02. The additional support comes from two CARB-X partners—the UK government's Global Antimicrobial Resistance Innovation Fund and the Bill & Melinda Gates Foundation—that have earmarked funds specifically for development of antibacterial approaches that can be used in low- and middle-income countries.
Aug 15 CARB-X press release
Brooklyn study describes emerging delafloxin resistance in MRSA
More than 20% of MRSA isolates collected from seven hospitals in Brooklyn were resistant to delafloxacin, researchers reported yesterday in Clinical Infectious Diseases.
During a surveillance study conducted by researchers from the State University of New York (SUNY)-Downstate Medical Center in 2017, 757 unique patient isolates of S aureus were collected. Among the MRSA isolates, 60 (22%) were non-susceptible to delafloxicin.
Sequence typing of 16 delafloxacin-resistant representatives from each of the seven hospitals showed that 15 were MRSA, and 14 of these belonged to sequence type (ST)105, a healthcare-associated MRSA strain, along with one methicillin-susceptible isolate. The other MRSA isolate belonged to ST8, a community-associated strain. Whole-genome sequencing of six of the isolates found multiple mutations involving gyrase and topoisomerase IV genes, which are targeted by delafloxacin.
Clinical data on seven patients with delafloxacin-resistant isolates showed that all had extensive contact with the healthcare system and multiple medical problems, and five had previously been on fluoroquinolones.
The researchers note that the isolates were collected in early 2017, prior to the Food and Drug Administration (FDA) approval and availability of delafloxacin. The FDA approved the drug for treatment of acute bacterial skin and skin-structure infections.
Aug 15 Clin Infect Dis abstract
Study links rates of intrinsically resistant bacteria with acquired resistance
Originally published by CIDRAP News Aug 15
An analysis of data from routine antibiotic susceptibility testing in 30 European countries shows a strong correlation between the rates of intrinsically antibiotic-resistant bacterial species and the rates of acquired resistance in gram-negative bacterial species, a team of European researchers reported today in Eurosurveillance.
Using data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net), the researchers set out to compare the country-specific distribution of four gram-negative species (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp.) and the proportions of selected acquired resistance traits within these species. Data included isolates from blood and cerebrospinal fluid, both considered markers of bloodstream infections. The study was limited to only include antibiotics commonly used for first-line treatment of bacteremia caused by gram-negative species and routinely included in susceptibility testing.
The country-specific species distribution varied considerably. While E coli accounted for 31.9% (Greece) to 81% (Iceland) of all reported isolates, the two most common intrinsically resistant species, P aeruginosa and Acinetobacter spp., combined accounted for 5.5% (Norway) to 39.2% (Greece) of all isolates. Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems, and fluoroquinolones.
The analysis found a strong positive rank correlation between the country-specific percentages of P aeruginosa and Acinetobacter spp. combined and the percentages of non-susceptibility to the above antibiotics in all four species, with Spearman's rank correlation co-efficient (a measurement of the strength and direction of association between two variables) being greater than 0.75 for 10 of the 11 pairs of variables tested.
"In short, the higher the proportion of the two most intrinsically resistant species P aeruginosa and Acinetobacter spp., the higher the percentages of acquired non-susceptibility in E coli, K pneumoniae, P aeruginosa, and Acinetobacter spp., a point that directly indicates the burden of intrinsic resistance," the authors of the study write.
The authors suggest the differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.
Aug 15 Eurosurveill study
Analysis points to gaps in the antibiotics pipeline
Originally published by CIDRAP News Aug 15
A new analysis of the small-molecule antibiotics pipeline highlights some of the key gaps in antibiotic development.
The analysis from the Pew Charitable Trusts, published yesterday in Nature Reviews Drug Discovery, found that of the 67 antibiotic candidates that have been in some stage of clinical development since 2014, only 10 have been approved by the FDA, while 17 have been either suspended or discontinued and an additional 10 candidates have stalled. Only two of the 10 approved drugs are novel treatments, and none target the type of multidrug-resistant gram-negative organisms that the World Health Organization has identified as high-priority pathogens.
Of the 67 antibiotic candidates analyzed, 41 target gram-positive pathogens, which are typically less challenging to treat than gram-negatives.
"A continued area of unmet need is new treatments for bacterial infections caused by multidrug- or extensively drug-resistant gram-negative pathogens," the authors write.
The authors conclude that while there are several promising initiatives focused on boosting research and discovery efforts, innovative economic models are needed to ensure the availability of new antibiotics.
Aug 14 Nat Rev Drug Discov article
Ohio senator reintroduces antibiotic resistance legislation
Originally published by CIDRAP News Aug 14
US Sen. Sherrod Brown, D-Ohio, yesterday reintroduced legislation to strengthen the federal government's response to antibiotic resistance.
Brown's bill, the Strategies to Address Antibiotic Resistance (STAAR) Act, emphasizes enhanced data collection and increased federal investment in efforts to monitor, prevent, and control drug-resistant pathogens. It would reauthorize the Interagency Antimicrobial Resistance Task Force, codify sections of the National Action Plan for Combating Antibiotic-Resistant Bacteria, enact key Centers for Disease Control and Prevention (CDC) recommendations for bolstering federal surveillance, prevention, control, and research efforts, and allow the CDC to partner with state health departments to implement prevention collaboratives.
The legislation also calls for the federal government to authorize the use of grants to healthcare facilities to study the development and implementation of antimicrobial stewardship programs.
"Antibiotics do a world of good for Ohioans fighting infections and illness, but now antibiotics are becoming less effective, putting people at risk from dangerous infections that can't be cured," Brown said in a press release. "We should address this growing crisis head on, both to stop the spread of deadly superbugs and to preserve antibiotics as a tool to fight disease."
Aug 12 Sen. Brown press release
British study finds opportunities to improve prescribing for UTIs
Originally published by CIDRAP News Aug 14
A study of patients diagnosed with lower urinary tract infections (UTIs) in England has found that more than 85% receive antibiotics on the day they were diagnosed, and 83% had no record of a urine sample collection, researchers from the University of Leeds reported in EClinicalMedicine.
Using a large healthcare research database containing records from English primary care practices, the researchers examined data on patients diagnosed with a lower UTI from 2011 through 2015 at 390 practices. They looked specifically at UTI investigation, antibiotic treatment, and antibiotic re-prescription within 28 days according to guideline-defined patient groups, and assessed risk factors for re-prescription.
During the study period, a total of 494,675 lower UTI episodes were diagnosed in 300,354 patients, 83.3% of whom were women. Antibiotics were prescribed on the same day of diagnosis for 85.7% of UTIs, and only 17% of those who received antibiotics had a recorded urine test within 10 days of diagnosis. The most common antibiotics initially prescribed were trimethoprim (56.8%) and nitrofurantoin (23.9%).
The antibiotic re-prescription rate was low (4.1%), increasing slightly over time in men (from 5.2% in 2011 to 6.2% in 2015), and 21.1% of re-prescriptions were for the same antibiotic. The risk of antibiotic re-prescription increased with age, calendar year, recent antibiotic prescribing, and treatment with antibiotic other than trimethoprim or nitrofurantoin.
The authors of the study say the results—the high proportion of same-day antibiotic treatment, lack of microbiological investigation, lack of diversity in antibiotic treatment, and the proportion of re-prescriptions for the same antibiotic as was initially prescribed—present several opportunities to optimize antibiotic prescribing for UTIs that could potentially reduce the risk of antibiotic resistance.
Aug 12 EClinicalMedicine study
Adding beta-lactam to daptomycin improves MRSA outcomes, study finds
Originally published by CIDRAP News Aug 13
The addition of a beta-lactam antibiotic to daptomycin is associated with improved clinical outcomes in patients with MRSA bloodstream infections (MRSA BSIs), researchers reported yesterday in Clinical Infectious Diseases.
In the retrospective observational study, conducted at two academic medical centers in Detroit from 2008 through 2018, researchers from Wayne State University compared two groups of adults who had MRSA BSIs; one group was treated with daptomycin plus a beta-lactam (DAP+BL), and the other group received daptomycin monotherapy. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence).
A total of 229 patients were included in the study, with 72 receiving DAP+BL and 157 receiving daptomycin monotherapy. Overall, 52 patients (22.7%) experienced clinical failure, including 43 (27.4%) in the daptomycin group and 9 (12.5%) in the DAP+BL group. In unadjusted and inverse probability of treatment weighted (IPTW)-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], 0.164 to 0.801; adjusted OR, 0.386; 95% CI, 0.175 to 0.853). Lower clinical failure was also consistently demonstrated in all pre-specified subgroups across the spectrum of host and infection characteristics.
The authors of the study say the findings add to a growing body of evidence that beta-lactams, which are ineffective on their own against MRSA, can enhance the bactericidal activity of daptomycin against invasive MRSA infections.
Aug 12 Clin Infect Dis abstract
Study: Electronic medical records aid ICU stewardship program
Originally published by CIDRAP News Aug 13
The integration of electronic medical record (EMR) data with an intensive care unit antimicrobial stewardship (ICU-AMS) program was associated with high clinician compliance with recommendations and improved antibiotic appropriateness, Australian researchers reported today in Infection Control and Hospital Epidemiology.
The primary objective of the study was to examine the impact of an EMR-driven ICU-AMS program at Austin Health, a tertiary care referral hospital in Australia, on clinician compliance with a range of AMS recommendations. The service utilized EMR data coupled with face-to-face consultations with an infectious disease (ID) physician, an ID fellow, and an AMS pharmacist. The recommendations were defined by an internally developed "5 Moments of Antimicrobial Prescribing" metric: (1) escalation, (2) de-escalation, (3) discontinuation, (4) switch, and (5) optimization. The secondary objectives included measuring the impact of this service on antibiotic appropriateness and use of high-priority target antimicrobials. The impact of the ICU-AMS round on antimicrobial appropriateness was evaluated using point-prevalence survey data.
For the 202 patients reviewed over 5 months (from implementation in August 2017 through December 2017), 412 recommendations were made in accordance with the "5 Moments" metric. The most common recommendation made by the ICU-AMS team was moment 3 (discontinuation), which comprised 173 of 412 recommendations (42.0%), with an acceptance rate of 83.8% (145 of 173). Data collected for point-prevalence surveys showed an increase in prescribing appropriateness from 21 of 45 (46.7%) recommendations pre-intervention (October 2016) to 30 of 39 (76.9%) during the study period (September 2017).
The ICU-AMS service was also associated with an immediate reduction in the use of several key target antibiotics, including meropenem (−40.5%; 95% CI, −52.9% to −24.8%), piperacillin-tazobactam (−39.8%; 95% CI, −50.8% to −26.6%), and vancomycin (−36.6%; 95% CI, −48.3% to −22.4%), and with a significant reduction in the monthly trend in use of vancomycin (−13.2%; 95% CI, −17.9%, −8.4%]).
"In conclusion, the use of an EMR-driven ICU-AMS model demonstrated a decrease in target antibiotic utilization as well as an increase in the appropriateness of antimicrobials," the authors of the study write. "ICU-AMS models that integrate the EMR should be encouraged in centers with appropriate digital resources to achieve subsequent positive impacts on antibiotic prescribing."
Aug 13 Infect Control Hosp Epidemiol abstract
