ASP Scan (Weekly) for Jan 18, 2019

New CARB-X funding
VRE in Swiss hospitals
Antibiotic overprescribing in tots
Fast track for new C diff drug
Stewardship in pediatric surgery
MRSA decline in Germany
Antibiotic resistance on pig farms
Resistance genes in Bolivian river
Stewardship in English hospitals
Whiff of C diff in pets
Fecal microbiota transplant trial

CARB-X provides additional funds for phage lysin to treat Pseudomonas

Contrafect Corporation announced yesterday that it has received an additional $2.3 million in funding over the next 2 years from CARB-X for the development of a phage lysin therapy to treat drug-resistant Pseudomonas aeruginosa infections.

Contrafect, of Yonkers, N.Y., was among the first wave of companies to receive funding from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) in March 2017, when it was awarded $2.1 million for development of a lysin that would selectively kill P aeruginosa. Lysins are enzymes produced by bacteriophages, the viruses that infect and destroy bacteria, to cut through the bacterial cell wall. The therapy is one of more than 30 projects targeting drug-resistant bacteria that CARB-X is funding.

"We view this additional funding from CARB-X as continued validation of our novel lysin platform, which underscores the opportunity to combat highly resistant Gram-negative pathogens, considered to be the greatest threats to global health by both the CDC and WHO, with our proprietary lysin candidates," Steven C. Gilman, PhD, chairman and CEO of ContraFect, said in a press release.

Earlier this month, Contrafect announced that another lysin candidate, execebase (CF-301), had shown positive results in a phase 2 clinical trial in patients with Staphylococcus aureus bacteremia, including endocarditis. Execebase, when used in combination with standard-of-care antibiotics, improved clinical outcomes compared with antibiotics alone and demonstrated safety and tolerability. The company said the data support progression to a phase 3 trial.
Jan 17 Contrafect press release
Jan 7 Contrafect press release


Increase in vancomycin-resistant enterococci reported in Swiss hospitals

In a study yesterday in Antimicrobial Resistance and Infection Control, Swiss researchers reported an increasing number of vancomycin-resistant enterococci (VRE) colonizations and infections in Swiss hospitals.

The findings come from a survey on infection control sent to 205 inpatient institutions in Switzerland in 2018. Overall, 142 institutions responded to the survey, with 46 (32%) reporting 625 VRE patients, of which 67 (11%) represented invasive infections. Analysis of epidemiologic data on VRE cases showed that the total number of cases per year rose from 96 in 2015 to 146 through the first 3 months of 2018, while the incidence rate increased from 0.26 cases per day in 2015 to 1.58 cases per day in 2018.

The researchers also reported that 23 outbreaks occurred during the study period. Among the 20 major outbreaks analyzed, 250 VRE cases were observed, including 10 cases (4%) of VRE bacteremia. Seventy percent (102 of 146) of new VRE cases in 2018 were outbreak-related. One of the outbreaks included the emergent clone VRE ST976, which had previously been reported only in Australia and New Zealand, where it exhibited high transmissibility.

The authors of the study said that the increase paralletls an increasing number of VRE outbreaks reported in the German-speaking parts of Switzerland in the first 3 months of 2018, and is in line with rising VRE prevalence and outbreaks reported in Germany and Italy. "A harmonized nationwide strategy for VRE containment that includes active screening surveillance, uniform standards of detection and outbreak management, reporting at a national level with a central surveillance as well as guidance for patient transfers should therefore be implemented," they concluded.
Jan 17 Antimicrob Resist Infect Control study


Analysis finds antibiotic use still routine in infants with viral lung infections

Originally published by CIDRAP News Jan 17

About one fourth of children younger than age 2 who are seen in US emergency departments (EDs) for bronchiolitis, a common viral lung infection in that age-group, received an antibiotic prescription, despite 2006 recommendations against the treatment in the absence of documented bacterial infection.

Researchers from Canada's McGill University based their findings on data from an annual survey on ED visits by the US Centers for Disease Control and Prevention (CDC), publishing their findings today in the Journal of the Pediatric Infectious Diseases Society.

They found that, from 2007 to 2015, about 25% of children younger than 2 years who were seen in the ED for bronchiolitis received antibiotics, reflecting only a minimal improvement compared with earlier years and no significant changes in antibiotic prescription rates during the 9 years that followed the 2006 American Academy of Pediatrics guidance. Of kids who received antibiotics, 70% didn't have a documented bacterial infection.

Also, the team found an association between increased antibiotic prescribing for the condition and hospitals that weren't teaching hospitals nor pediatric hospitals, suggesting that those facilities might benefit most from efforts to encourage providers to follow the guidelines.

Brett Burstein, MD, PhD, MPH, senior author of the study, said in a Pediatric Infectious Disease Society (PIDS) press release today that targeted interventions to reduce inappropriate prescribing are essential. "But at the same time, informing the lay public about the potential downstream consequences and why it is important not to over-treat viral conditions are equally important," he added.
Jan 17 J Pediatric Infect Dis Soc abstract
Jan 17 PIDS press release


FDA grants Fast Track status to new C difficile antibiotic

Originally published by CIDRAP News Jan 17

The US Food and Drug Administration (FDA) has granted Fast Track designation to a new investigational antibiotic for Clostridioides difficile infection (CDI), according to a press release yesterday from Acurx Pharmaceuticals.

ACX-362E is a novel, narrow-spectrum oral antibiotic based on inhibition of the enzyme DNA polymerase IIIC, which is required for bacterial replication and pathogenesis in C difficile. The drug is currently being tested in a phase 1 clinical trial. The company expects to launch a phase 2 trial at the end of year.

Under the Fast Track designation, ACX-362E will receive expedited review from the FDA. The agency grants the designation to drugs that treat serious or life-threatening conditions and fulfill an unmet medical need. The CDC has identified C difficile, which sickens nearly 500,000 Americans each year, as an urgent threat.

"If approved, we believe our new antibacterial, ACX-362E, will be an important therapeutic alternative for patients with CDI," Acurx managing partner Robert DeLuccia said in the press release. "The Fast Track designation will allow Acurx to work more closely with the FDA to bring ACX-362E to physicians and patients as soon as possible."
Jan 16 Acurx Pharmaceuticals press release


Clinical pathway linked to improved antibiotic prophylaxis in peds surgery

Originally published by CIDRAP News Jan 16

Italian researchers report that an antimicrobial stewardship program based on a clinical pathway (CP) was associated with both an improved choice of antibiotic and duration of perioperative antibiotic prophylaxis (PAP) in pediatric surgical patients. The findings appeared yesterday in Antimicrobial Resistance and Infection Control.

The pre-post quasi-experimental study, conducted in the pediatric surgical unit of Padua University Hospital, assessed the changes in PAP appropriateness and the effect on surgical-site infections (SSIs) in the 6 months preceding CP implementation and the 6 months after implementation. The CP, which details all the steps needed to administer correct PAP to pediatric surgical patients, was developed by a multidisciplinary group of pediatric infectious disease, microbiology, and pediatric surgery specialists and based on the main guidelines for PAP in adult surgical patients.

The study included 766 children from 1 month to 15 years of age, with 394 in the pre-intervention group and 372 in the post-intervention group. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (from 81% to 91.9%, P = 0.02) and combination therapy (from 65.9% to 100%, P = 0.004).

The duration of prophylaxis also decreased after CP implementation, with an increase in correct PAP discontinuation from 45.1% in the pre-intervention period to 66.7% post-intervention (P < 0.001). Despite the greater use of narrow-spectrum antibiotic for fewer days, there was no increase in SSIs (10/394 (2.5%) pre-intervention vs. 7/372 (1.9%) post-intervention, P = 0.54).

The authors of the study conclude, "CPs with a proper educational intervention can be a useful tool to improve the choice of first-line antibiotic and the duration of PAP in pediatric patients."
Jan 15 Antimicrob Resist Infect Control study


Study: Healthcare-related MRSA rates drop almost in half in Germany

Originally published by CIDRAP News Jan 16

From 2007 to 2016, nonsocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) dropped significantly in German intensive care units (ICUs) and surgical departments, according to a study published in Journal of Infection

The study was based on data collected from the voluntary German National Nosocomial Infection Surveillance System and included information from 1,218 intensive care units (ICUs) and 1,556 surgical departments. A total of 14,408 nosocomial MRSA infections were documented during the study period.

The overall decrease in the proportion of MRSA among all healthcare-associated S aureus infections dropped from 37.1% to 20.0% during the 10-year period, a 46.1% decline. In both ICUs and surgical wards, MRSA rates decreased from 37.1% to 21.8% (a 42.4% reduction) in bloodstream infections and 38.7% to 19.2% (50.4% drop) in lower respiratory tract infections. Surgical-site infections caused by MRSA decreased from 21.1% to 7.4%, a 64.9% reduction.

An especially impressive decrease was seen in surgical departments, where overall MRSA proportions fell from 20.4% to 9.4%, a 53.9% drop.

"MRSA still remain[s] a relevant part of healthcare associated infections due to Staphylococcus aureus in Germany. Nonetheless, a significant decrease of its proportion occurred over the course of the past 10 years," the authors concluded. 
Jan 15 J Infect study


Pig farm study notes ties between resistome, antimicrobials, biosecurity

Originally published by CIDRAP News Jan 15

A study of pig farms in nine European countries suggests antimicrobial use during the fattening phase is associated with antimicrobial resistance, researchers from the European Union Ecology from Farm to Fork Of microbial drug Resistance and Transmission (EFFORT) project reported yesterday in the Journal of Antimicrobial Chemotherapy.

The analysis, conducted from June 2014 to Dec 2015, looked at fecal samples from 176 conventional pig farms in Belgium, Bulgaria, Denmark, France, Germany, Italy, the Netherlands, Poland, and Spain. The investigators also surveyed farms about practices such as antimicrobial use. Resistomes—the profile of resistance genes in microorganisms and microbial populations—were determined using shotgun metagenomics and the Resfinder reference database.

For the positive association the researchers found between fattening and antibiotic use, the pattern was especially evident for widely used macrolides and tetracyclines, with antimicrobial resistance genes corresponding to their respective antimicrobial classes. However, they didn't see the same link for beta lactams, and they saw only a few colisitin resistance genes, despite the drug class's high use in younger pigs.

Increased biosecurity was related to higher abundance of resistance genes, mainly those that encode macrolide resistance. Adjusted models suggested that biosecurity effects were independent of antimicrobial use.

The authors said the study was the first of its kind and adds accuracy to earlier observations of the associations between antimicrobial use and antimicrobial resistance.
Jan 14 J Antimicrob Chemother abstract


Study finds diarrheal pathogens, resistance genes in Bolivian river

Originally published by CIDRAP News Jan 15

A team of Bolivian and Swedish researchers has found evidence of diarrheal pathogens and antibiotic-resistant bacteria in samples from an urban waterway in Bolivia, according to a study yesterday in PLOS One.

In the study, the researchers aimed to analyze the occurrence and bacterial load of diarrheal pathogens in water, soil, and vegetable samples from the Choqueyapu River—which receives wastewater from urban, medical, and industrial sources—and other affluent rivers in the La Paz River basin. They collected samples from four different points from April 2013 to March 2014 and conducted quantitative real-time polymerase chain reaction (qPCR) to detect the presence of genes indicating enterobacterial contamination. They also tested for the presence of diarrheagenic Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Shigella spp, and for antibiotic resistance genes.

The most abundant genes found in the water, soil, and vegetable samples were gapA, which indicates the presence of enterobacteria, and eltB, an indicator of enterotoxigenic E coli carrying the heat labile toxin. Pathogen levels in the samples were significantly positively associated with high water conductivity—which can signify high levels of metals, pollutants, and bacteria in the water—and low water temperature.

In addition, 101 bacterial isolates obtained from the samples were found to be resistant to multiple antibiotics, and qPCR identified the extended-spectrum beta-lactamase (ESBL) gene blaCTX-M, along with several other resistance genes and a high number of plasmids. Whole-genome sequencing identified three of the isolates as E coli and one as Enterobacter cloacae. The E coli isolates belonged to three emerging, globally disseminated, multidrug-resistant lineages.

"In conclusion, this study evidences the risk of transmission of diarrheal diseases directly or indirectly from the Choqueyapu River and its basin due to the presence of diarrheal pathogens in river water, vegetables and agricultural soils," the authors of the study wrote. "Bacterial isolates carrying ESBL genes and conjugative resistant plasmids obtained from the basin indicate that the risk is not only associated with the transmission of infectious bacteria, but also with the possibility of transmission of antibiotic resistant bacteria and the resistance genes they carry from the environment to the community."
Jan 14 PLOS One study


Study evaluates stewardship uptake, antimicrobial usage in England

Originally published by CIDRAP News Jan 14

Researchers with Public Health England (PHE) report that a survey of England's National Health Service (NHS) hospitals found that the vast majority have made progress in establishing antimicrobial stewardship programs (ASPs), but many lack senior leadership and dedicated funding, and there was no significant correlation between stewardship scores and antimicrobial usage.

In an article published in the Journal of Antimicrobial Chemotherapy, the researchers evaluated ASP structures and processes through an online survey of 152 NHS hospitals. Scores were assigned to quality indicators based on resource- and labor-intensiveness, and the investigators analyzed the association between stewardship scores and prescribing, with a particular focus on World Health Organization–categorized Access, Watch, and Reserve (AWaRe) antibiotics.

Overall, 148 of 152 hospitals responded to the survey, and over 80% had high scores on antimicrobial policies, stewardship team structure, designated stewardship leads and antimicrobial pharmacists, and policies and access to outpatient parenteral antimicrobial therapy. But less than 50% had senior clinical leadership support and dedicated program funding. High-process performance (above 80%) was observed for antimicrobial pre-authorization, prescribing review and feedback, restricted susceptibility reporting, antimicrobial consumption monitoring, adherence to guidelines, and junior doctor training, while less than 50% of hospitals distributed resistance surveillance data and educated senior clinicians on appropriate prescribing.

From 2016 through 2017, there was no significant change in mean total antimicrobial prescribing (incidence rate ratio [IRR], 1.02; 95% confidence interval [CI], 1.00 to 1.05, P = 0.116) for all participating hospitals, and there were no major changes in the prescribing of antimicrobials from the AWaRe categories. But there were some noteworthy associations. While carbapenem prescribing fell by 7% (IRR, 0.93; 95% CI, 0.88 to 0.98) in non-teaching hospitals, prescribing of Watch antibiotics increased for specialist hospitals (odds ratio [OR], 1.10; 95% CI, 1.01 to 1.20), as did Reserve category prescribing for teaching (OR, 1.58; 95% CI 1.23 to 3.02) and specialist hospitals (OR 3.09; 95% CI, 2.02 to 4.74). A higher process score was associated with lower baseline prescribing of Reserve antimicrobials (OR, 0.82; 95% CI, 0.67 to 1.01).

The authors of the study say further studies are needed with better defined primary outcomes such as burden of disease or attributable mortality due to antimicrobial resistance to assess the true impact of ASP interventions over time.
Jan 11 J Antimicrob Chemother study


Chinese study identifies cats, dogs as potential C diff sources

Originally published by CIDRAP News Jan 14

A new study by Chinese scientists suggests that companion animals could be a source of pathogenic C difficile. The findings appear in BMC Infectious Diseases.

To assess the burden of C difficile carriage and shedding by household pets, researchers from Xuzhou Medical University collected fecal samples of adult pets in pet shops in Xuzhou City in China's Jiangsu province, then identified and isolated C difficile strains. They used multilocus sequence typing (MLST) to identify sequence types and assess the possibility of transmission between pets and humans, employed multiplex polymerase chain reaction to detect toxin genes, and performed antimicrobial susceptibility testing.

A total of 175 fecal samples were collected from 146 healthy dogs and 29 cats, and C difficile was isolated from only 3 samples (1.7%)—2/29 cat samples (7.0%) and 1/146 (0.7%) dog samples.

The isolates were categorized into three MLST sequence types that have been identified in patients in eastern China and belong to the clade that contains most human C difficile sequence types. They were susceptible to chloramphenicol, tetracycline, metronidazole, and moxifloxacin and resistant to ampicillin, clindamycin, and cefoxitin. Notably, one strain recovered in the feces of a healthy dog, D141–1, carried toxin genes, implying a potential association between pets and pathogenic C difficileinfections in humans.

"Since there is intimate contact between humans and their pets, the isolation of C. difficile from pets in this study suggests a possibility that humans may be colonized by C. difficile carried by pets, although faecal shedding of pathogenic C. difficile was not common among healthy dogs and cats," the authors write.
Jan 11 BMC Infect Dis study


Trial will evaluate safety, efficacy of fecal transplant for recurrent C diff

Originally published by CIDRAP News Jan 14

The National Institute of Allergy and Infectious Diseases announced today that a research consortium has begun enrolling patients in a clinical trial to determine whether fecal microbiota transplantation (FMT) delivered by enema is a safe and effective treatment for recurrent C difficileinfection (CDI).

FMT for recurrent CDI has produced strong results in several small clinical trials in recent years, with cure rates as high as 90%, but the long-term safety has not been established. Although the FDA still considers FMT an investigational treatment, physicians are allowed to perform the procedure using screened stool if recurrent CDI patients aren't responding to antibiotic treatments. According to the Centers for Disease Control and Prevention, roughly 20% of CDI patients treated with antibiotics experience a recurrence of symptoms.

The multicenter randomized controlled trial will enroll 162 adult volunteers who've had at least two episodes of CDI within the previous 6 months. One group of patients will take anti-diarrheal medication and receive FMT via enema, while the other group will take anti-diarrheal medication and receive a placebo solution via enema. The trial is part of a larger effort to gather data on how to standardize FMT, which can be delivered by several methods, including enema, upper gastrointestinal endoscopy, colonoscopy, or pill.

Trial sites include Emory University, Duke University Medical Center, and Vanderbilt University Medical Center. 
Jan 14 NIAID news release

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