Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Report highlights ideas to improve UK government's AMR response
A report today from a British think tank says critical gaps remain in the United Kingdom's efforts to address antimicrobial resistance (AMR), and it calls for more focus on vaccines, diagnostic, and public awareness.
While the acknowledging that the UK government has been at the forefront of efforts to battle AMR, highlighted by its recent adoption of a novel reimbursement model to accelerate investment in antibiotic development, the report from Reform argues that a multifaceted approach is needed to build on that momentum and ensure that commitments translate into concrete action. The group suggests that the government should harness the lessons learned from the COVID-19 pandemic as it responds to the growing threat of drug-resistant pathogens.
"As attention turns to building back our health systems and economies from COVID-19, we must also build our resilience to tackle AMR," Dame Sally Davies, UK special envoy on AMR, writes in the foreword. "Without sufficient and timely action worldwide, drug resistance will have deeper and even farther-reaching consequences for all countries' health systems and the world economy than COVID-19 is having."
The report lays out seven key ideas to bolster the government's AMR response. These include greater focus on the role of vaccines and point-of-care diagnostics in combating AMR, closing gaps in clinical care, enhanced surveillance of AMR and antibiotic prescribing, and the creation of an awareness and education campaign that highlights the experiences of people living with drug-resistant infections.
It also calls for the creation of a national fund to pilot, evaluate, and develop community engagement approaches to tackle AMR.
Sep 18 Reform news release and full report
Phase 3 trial shows some promise for bacteriophages for UTI treatment
Originally published by CIDRAP News Sep 17
The results of a randomized, controlled clinical trial show that intravesical bacteriophage treatment was non-inferior to standard-of-care antibiotic treatment and safe for treating urinary tract infection (UTI) patients, but it was not superior to placebo in terms of efficacy or safety, researchers reported yesterday in the Lancet Infectious Diseases.
In the trial, which was conducted by Swiss and Georgian researchers at a urology clinic in Tblisi, Georgia, 113 men who had complicated UTI or recurrent uncomplicated UTI and were scheduled for transurethral reaction of the prostate (TURP) were randomized 1:1:1 to receive three different treatments for 7 days: the bacteriophage cocktail Pyophage (37 men), bladder irrigation with an intravesical placebo solution (38), or systematically applied antibiotics (38). The primary outcome was microbiologic treatment response after 7 days, measured by urine culture. Secondary outcomes included clinical and safety parameters.
Rates of treatment success did not differ significantly between the three groups. After 7 days of treatment, normalization of urine culture was achieved in 27 of 97 patients (28%): 5 of 28 (18%) in the Pyophage group, compared with 9 of 32 (28%) in the placebo group (odds ratio [OR], 1.60; 95% confidence interval [CI], 0.45 to 5.71; P = 0.47) and 13 of 37 (35%) in the antibiotic group (OR, 2.66; 95% CI, 0.79 to 8.22; P = 0.11). Adverse events occurred in 6 of 28 patients (21%) in the Pyophage group compared with 13 of 32 patients (41%) in the placebo group and 11 of 37 patients (30%) in the antibiotic group.
The authors of the study say that while the results revealed little about the efficacy of bacteriophage therapy for treating UTI patients undergoing TURP, they confirm the safety profile of bacteriophage application.
"In conclusion, our findings are encouraging and provide important stimuli for physicians and authorities to support further large-scale clinical studies using bacteriophages for otherwise virtually untreatable infections, in order to further establish their efficacy," they wrote.
Sep 16 Lancet Infect Dis abstract
Study: Long antibiotic duration for many common conditions
Originally published by CIDRAP News Sep 17
An analysis of the duration of antibiotic therapy for common outpatient conditions found that in many cases prescribers are exceeding guideline-recommended durations, researchers from the Centers for Disease Control and Prevention (CDC) and the University of Utah reported yesterday in Clinical Infectious Diseases.
Using the National Disease and Therapeutic Index dataset for 2017, the researchers identified antibiotic prescriptions (excluding azithromycin) associated with sinusitis, pharyngitis, acute otitis media (AOM), community-acquired pneumonia (CAP), skin and other soft-tissue infection (SSTI), and acute cystitis, including adult and pediatric prescriptions. They then estimated the proportions of prescriptions by course duration and median duration and interquartile range (IQR) and calculated potentially excessive days above minimum recommended duration.
Among more than 28 million prescriptions, median antibiotic course duration was 10 days for every condition except acute cystitis, for which the median duration was 7 days (IQR 5 to 7 days). Overall, 55% (95% CI, 53% to 58%) of non-azithromycin courses exceeded the guideline-recommended minimum effective durations, translating to up to 54,496,316 excessive days of therapy.
The authors of the study note that recent guidelines recommend shorter antibiotic courses of 5 to 7 days for many of these conditions, and that the longer-than-necessary courses are likely driven by clinician habit.
"For some conditions and age groups, such as pharyngitis, pediatric sinusitis, and pediatric AOM, 10 days of antibiotic therapy aligns with guidelines. However, for many conditions, specifically sinusitis and CAP in adults and cellulitis, 10 days of antibiotic therapy is likely excessive for most patients based on guideline recommendations," the authors wrote.
"Increased focus on appropriate duration of antibiotic therapy for these common conditions could reduce unnecessary outpatient antibiotic use," they concluded.
Sep 16 Clin Infect Dis abstract
Vaccine candidate fails to reduce C difficile infection in phase 3 trial
Originally published by CIDRAP News Sep 16
A phase 3 trial for a bivalent Clostridioides difficile toxoid vaccine was terminated because of futility, an international team of investigators led by scientists from Sanofi Pasteur reported yesterday in The Lancet Infectious Diseases.
In the observer-blind, randomized controlled trial, which was conducted in 326 hospitals in the United States, Canada, Latin America, Europe, and the Asia-Pacific region, adults 50 years or older with increased risk of C difficile infection were randomized 2:1 to receive one dose of Sanofi Pasteur's C difficile vaccine candidate (containing toxoids A and B) or one dose of placebo. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection.
From Jul 30, 2013, through Nov 17, 2017, 9,302 participants were enrolled, with 6,201 in the C difficile vaccine group and 3,101 in the placebo group. The first planned interim analysis reported 34 C difficile infections over 11,697.2 person-years at risk (0.29 infections per 100 person years) in the vaccine group compared with 16 C difficile infections over 5,789.4 person-years at risk (0.28 infections per 100 person-years) in the placebo group, indicating a vaccine effectiveness of –5.2% (95% CI, –104.1% to 43.5%). Because of those results, futility was concluded and the trial was terminated
The safety analysis found that 2,847 of 6,113 participants (46.6%) in the vaccine group reported an adverse event within 30 days of injection, compared with 1,282 of 3,057 (41.9%) in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4.8% in both groups.
The investigators suggest several factors may have played a role in the vaccine not being effective, despite showing good immunogenicity. Among the explanations are that vaccination did not generate appropriate antibody function to effectively neutralize toxin in the intestinal environment. An aging or frail immune system and previous exposure to C difficile could also be factors, they said.
"In conclusion, although the candidate vaccine was immunogenic, it failed to reduce the incidence of symptomatic C difficile infection in participants at risk," they wrote. "The findings from this trial highlight the important challenges associated with the development of vaccines against bacterial nosocomial infections, and they will inform future vaccine development."
The trial was funded and designed by Sanofi Pasteur.
Sep 15 Lancet Infect Dis abstract
Study finds use of prior patient cultures linked to better empiric antibiotics
Originally published by CIDRAP News Sep 16
An intervention that alerted prescribers when antibiotic prescriptions were discordant with a patient's previous culture results was associated with improved empiric antibiotic prescribing at a tertiary care academic hospital, Canadian researchers reported yesterday in Clinical Infectious Diseases.
The intervention at Sunnybrook Health Sciences Centre in Toronto was a prospective audit-and-feedback intervention in which pharmacists provided early suggestions to prescribers when a patient's initial empiric antibiotic therapy was discordant with their most recent methicillin-resistant Staphylococcus aureus (MRSA) swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and most recent culture for a gram-negative (GN) organism. The researchers analyzed the impact of the intervention using a quasi-experimental design comparing the 9-month period before and after implementation.
Clinically significant discordance was identified 99 times in the pre-intervention period and 86 times in the intervention period. The proportion of patients who received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = 0.01). The proportion increased in the MRSA subgroup from 86% to 93% (P = 0.39), in the prior GN subgroup from 50% to 83% (P = 0.069), and in the ESBL subgroup from 43% to 77% (P = 0.16) for the control and intervention groups, respectively.
The median time to concordant therapy was shorter in the intervention group (25 hours vs 55 hours; P < 0.001).
The authors of the study suggest the intervention should be further evaluated in large randomized clinical trials to determine if the changes in empiric prescribing affect clinical outcomes.
Sep 15 Clin Infect Dis abstract
New guidelines issued for S aureus prevention, control in NICUs
Originally published by CIDRAP News Sep 15
The CDC has issued new recommendations for the prevention and control of S aureus in neonatal intensive care unit (NICU) patients.
The guidelines are based on current understanding of the transmission dynamics of S aureus in the NICU and were developed through a systematic review of the best available literature available through August 2019. The review was guided by questions about the most effective strategies for preventing S aureus transmission from colonized or infected NICU patients, which sampling sites and laboratory assays most effectively identify colonization in NICU patients, and what risk factors exist for S aureus infection in NICU patients.
The guidelines recommend performing active surveillance testing at regular intervals for S aureuscolonization in NICU patients when there is increased evidence of infection or in an outbreak setting, and for methicillin-resistant S aureus colonization when there is evidence of ongoing healthcare-associated transmission. Active surveillance can be conducted using either culture-based or polymerase chain reaction detection methods, and samples should be collected from the nostrils. The authors conditionally recommend testing of infants from other newborn care units, and targeted decolonization for colonized NICU patients.
S aureus is the most common healthcare-associated pathogen in US NICUs, with an estimated incidence of up to 45 infections per 100,000 hospitalized infants, and rates of invasive S aureusinfection are especially high in preterm and low birthweight infants. While infants may acquire the bacteria as part of their normal developing microbiota, those who are colonized with S aureus are at increased risk of infection.
A companion document from the Society for Healthcare Epidemiology of America (SHEA), published yesterday in Infection Control and Hospital Epidemiology, answers some of the questions that clinicians may have about S aureus detection and prevention in the NICU.
September CDC recommendations
Sep 14 SHEA white paper
Rapid diagnostics, stewardship linked to quicker time to optimal antibiotics
Originally published by CIDRAP News Sep 14
The introduction of a rapid diagnostic test (RDT) in conjunction with antimicrobial stewardship (AMS) activities and infectious disease (ID) consultation at an academic tertiary medical center was associated with shortened time to optimal antibiotic therapy in patients with bloodstream infections, University of Maryland researchers reported in Open Forum Infectious Diseases.
In the retrospective quasi-experimental study, researchers with the University of Maryland's School of Medicine and School of Pharmacy compared time to optimal antibiotic therapy and clinical outcomes in patients with gram-negative bloodstream infection (GN BSI) during three different periods: pre-RDT/AMS, post-RDT/pre-AMS, and post-RDT/AMS.
Rapid testing was conducted with Verigene Blood-Culture Gram-Negative, a microarray RDT that detect eight key organisms and six genetic resistance determinants within 2.5 hours. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infections.
Altogether, 832 patients were included in the study; 237 pre-RDT/AMS, 308 post-RDT/pre-AMS, and 237 post-RDT/AMS. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%, P < 0.0001), and the time to optimal therapy decreased with the introduction of RDT (47 hours vs 24.9 hours vs 26.5 hours, P = 0.09).
Using multivariable modeling, the researchers determined that ID consult was an effect modifier, and therefore the results were stratified by presence of ID consult. Within the ID consult stratum, controlling for source infection and for intensive care unit stay, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04 to 1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01 to 1.64) improved time to optimal therapy compared with the pre-RDT/AMS period. The effect was not observed in the stratum without ID consult.
"In conclusion, introduction of RDT in GN BSI resulted in significant decrease in time to optimal antibiotic therapy, by a median of approximately 22 hours from blood culture draw," the study authors wrote. "Additionally, the overall proportion of patients placed on optimal antibiotic therapy increased."
Sep 12 Open Forum Infect Dis abstract
UK study supports oral antibiotics for patients with bone, joint infections
Originally published by CIDRAP News Sep 14
A study by UK researchers published today in Clinical Infectious Diseases indicates that findings of the Oral Versus Intravenous Antibiotics (OVIVA) trial can be implemented into clinical practice.
The OVIVA trial, conducted in the United Kingdom, found that oral antibiotic therapy was non-inferior to intravenous therapy when used during the first 6 weeks in patients with bone and joint infections (BJIs). The results of the trial were initially presented in 2017 and published in 2019, but to date there have been no reports describing their reproducibility in real-world settings.
To determine whether the OVIVA findings can be replicated, researchers with the Royal National Orthopaedic Hospital, which implemented changes in practice in 2017 based on the results, looked at all patients diagnosed as having BSI at the hospital in the 12 months pre- and post-implementation. Outcomes included treatment failure, adverse drug reactions (ADRs), ADR-related hospital readmission, hospital length of stay (LOS), and treatment costs. Patient follow-up was conducted by an outpatient parenteral antibiotic therapy (OPAT) service.
In their analysis of 328 patients (145 pre- and 183 post-implementation), the researchers found that 66.1% of patients were switched to a suitable oral antibiotic regimen post-implementation. The rate of treatment failure was more common post-implementation (18.6%) compared with pre-implementation (13.6%), but Kaplan-Meier analysis of infection-free survival at 12 months did not demonstrated any statistical difference between the two groups (P = .154). Subgroup analysis showed that in the post-implementation period, treatment failure was more common in patients who required IV antibiotics due to lack of suitable options (IV, 26.7% vs oral, 14.3%).
ADRs requiring close monitoring or change of treatment were more common post-implementation (37.1% vs 21% pre-implementation), but ADR-related hospital readmissions were similar in both groups (2.2% vs 2.1%). The post-implementation group showed a reduction in 4 days in the median LOS and a median cost reduction of £ 2,764.28 (US $3,558) per patient.
The authors of the study conclude, "These findings provide a useful guide for hospitals implementing the results of the OVIVA trial. Larger multicenter studies are required to better understand the differences in antibiotic regimens in varying patient groups and against specific pathogens."
Sep 14 Clin Infect Dis study
Antibiotic overuse noted after discharge in pneumonia, UTI patients
Originally published by CIDRAP News Sep 14
A study of patients diagnosed as having pneumonia and UTIs at 46 hospitals in Michigan found that about half had antibiotic overuse after discharge, researchers reported late last week in Clinical Infectious Diseases.
The retrospective cohort study, led by researchers with Michigan Medicine, looked at patients treated for pneumonia or UTI at hospitals in the Michigan Hospital Medicine Safety Consortium from July 2017 through 2019 to quantify the proportion of patients discharged with antibiotic overuse, which was defined as unnecessary antibiotic use, excess antibiotic duration, or suboptimal fluoroquinolone use. The researchers used linear regression analysis to assess hospital-level association between antibiotic overuse after discharge in patients treated for pneumonia versus patients treated for UTI.
Of the 21,825 patients treated for infection (12,445 pneumonia, 9,380 UTI), 49.1% had antibiotic overuse after discharge, including 56.9% of patients treated for pneumonia and 38.7% of patients treated for UTI. The median duration of antibiotic overuse after discharge was 4 days. In patients treated for pneumonia, 63.1% of overuse days after discharge were due to excess antibiotic duration, while in patients treated for UTI, 43.9% of overuse days were due to unnecessary antibiotic treatment of asymptomatic bacteriuria.
The percentage of patients discharged with antibiotic overuse varied fivefold among hospitals, from 15.9% to 80.6%, and was strongly correlated between conditions. For every 10% increase in patients treated at a hospital for UTI who had overuse after discharge there was an 8.5% increase in patients treated for pneumonia who had overuse after discharge.
The authors of the study said the findings suggest prescribing culture, physician behavior, and organizational processes all play a role in overprescribing after discharge.
"Given the ubiquity of overuse after discharge, it is imperative that stewardship programs enact interventions to improve prescribing—which often means stopping antibiotics—at care transitions," they wrote, adding that easier methods of tracking antibiotics at discharge could enable more complete national measures of antibiotic use.
Sep 11 Clin Infect Dis abstract