ASP Scan (Weekly) for Oct 27, 2017

Hospital antibiotic consumption
Antibiotic use, resistance indicators
Prolonged antibiotics for sepsis
Resistant bacteria in seafood
MRSA vaccine candidate
Provider role in CRE spread
Airborne resistant pathogens
Patient movement and C diff
Resistant salmonella in pigs
Antimicrobial resistance research awards

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study looks at relationship between hospitals' antibiotic use, resistance

Canadian researchers have found that hospital-specific antibiotic usage was associated with increased, rather than decreased, antibiotic susceptibility in a study yesterday in Infection Control and Hospital Epidemiology.

In the multicenter observational ecological study, researchers evaluated the relationship between antibiotic use and antibiotic resistance in common nosocomial bacteria by looking at the antibiograms and antibiotic consumption data from 30 acute care hospitals in Ontario. From the antibiograms, antibiotic susceptibilities of Escherichia coli, Klebsiella spp, Pseudomonas aeruginosaEnterobacter spp, Enterococcus spp, and Staphylococcus aureus were extracted. Multivariate regression was performed, with the antibiotic susceptibility of the individual pathogens as the primary outcome, and antibiotic consumption as the main predictor.

Multivariate regression analyses showed that increased antibiotic consumption, expressed in defined daily doses per 1,000 patient days (DDDs/1,000 PD), was associated with decreased antibiotic susceptibility for P aeruginosa (-0.162% per DDD/1,000 PD). But that trend was not considered statistically significant. In contrast, increased antibiotic consumption predicted increased antibiotic susceptibility for E coli (0.173% per DDD/1,000 PD), Klebsiella (0.124% per DDD/1,000 PD), Enterobacter (0.194% per DDD/1,000 PD), Enterococcus (0.309% per DDD/1,000 PD), and non-significantly for S aureus (0.012% per DDD/1,000 PD).

The authors say the results may be explained by the community origins of infections caused by many of the evaluated pathogens. If these infections are derived from strains acquired before hospitalization, they suggest, hospital-specific antibiotic usage wouldn't necessarily predict resistance rates.

The only pathogen that showed decreased susceptibility was P aeruginosa, which is most likely to be acquired in the hospital. And because antibiograms use patients' initial microbial cultures and are therefore weighted toward community-acquired pathogens, clinicians may be basing their prescribing decisions on community-weighted resistance prevalence, which would lead them to choose antibiotics with less resistance.
Oct 26 Infect Control Hosp Epidemiol abstract


European officials establish indicators for progress on AMR

Originally published by CIDRAP News Oct 26

European health and food safety agencies have established a set of indicators to assess progress in combating antimicrobial resistance (AMR) and reducing antimicrobial use in humans and food-producing animals.

According to a news release today from the European Food Safety Authority (EFSA), health officials will be monitoring the proportion of S aureus bacteria that are resistant to methicillin and the proportion of E coli bacteria that are resistant to third-generation cephalosporins to assess AMR in human medicine. For veterinary medicine, the indicator will be the proportion of E coli in food-producing animals that are susceptible or resistant to a number of antibiotics.

In terms of consumption, the indicators are the human consumption of all antimicrobials and the overall sales of veterinary antibiotics.

"Without these indicators, we would not be able to assess our progress in tackling the serious health threat posed by AMR," European Commissioner for Health and Food Safety Vytenis Andriukaitis said.

The indicators were agreed to by members of EFSA, the European Medicines Agency, and the European Centre for Disease Prevention and Control, based on data gathered through existing European Union monitoring networks.
Oct 26 EFSA news release


Review supports long-term over short-term beta-lactams for sepsis

Originally published by CIDRAP News Oct 26

A meta-analysis by Greek experts that included 22 studies has found that prolonged infusion of antipseudomonal beta-lactam antibiotics for treating sepsis is associated with significantly lower mortality than short-term infusion, according to their review yesterday in The Lancet Infectious Diseases.

Because the findings of randomized controlled trials (RCTs), observational studies, and previous meta-analyses have varied, the team aimed to pinpoint the effectiveness of the therapy by pooling data from 22 of the highest-quality RCT studies they found via a literature search.

The researchers found that, based on the Grading of Recommendations Assessment, Development, and Evaluation tool, the quality of evidence for mortality was high among the studies. They also determined that prolonged infusion of beta-lactams was associated with a 30% lower risk of all-cause mortality compared with short-term infusion. And they found no evidence of publication bias.

An accompanying commentary by scientists not involved in the study said, "With current evidence it seems that we should standardise prolonged dosing of beta-lactams in ICUs."
Oct 25 Lancet Infect Dis study
Oct 25 Lancet Infect Dis commentary


Resistant bacteria identified in German seafood

Originally published by CIDRAP News Oct 26

Berlin researchers have identified carbapenemase-producing bacteria in Enterobacteriaceae isolated from German retail clams and shrimp, they note in a report today in Eurosurveillance.

The investigators analyzed 160 seafood samples (80 shrimp, 49 blue mussels, 15 Venus clams, 11 razor shells and five cockles) taken from 12 retail outlets in Berlin from December 2015 to August 2016. They found 45 Enterobacteriaceae from the samples, with Klebsiella pneumoniae (13), E coli (12), Enterobacter cloacae (6), and Citrobacter freundii (5) the most common.

The team found several resistance genes among the isolates, most notably the carbapenemase gene blaVIM-1 in E coli from a Venus clam harvested in the Mediterranean Sea near Italy. The bacterium contained other resistance genes, as well. The researchers note, "It has to be taken into account that Venus clams are also served as a raw appetiser and that seafood is preferred raw in some regions, providing ideal conditions for the transmission and spread of the carbapenemase-producing bacteria or a transfer of the respective plasmids."

The authors conclude, "These results confirm previous observations that carbapenemase-producing bacteria have reached the food chain and are of increasing concern for public health."
Oct 26 Eurosurveill report


Good phase 1 results noted for vaccine against MRSA, other pathogens

Originally published by CIDRAP News Oct 25

Alopexx Vaccine LLC today reported positive phase 1 results for its broad-spectrum antimicrobial vaccine, which targets drug-resistant bacteria, including methicillin-resistant S aureus (MRSA) and serious infections like pneumonia, meningitis, bloodstream infections, and gonorrhea.

Alopexx, based in Concord, Mass., says it will begin larger phase 2 trials in the first quarter of 2018, according to a company news release.

The phase 1 trial included 16 healthy volunteers who received one of four vaccine doses, ranging from 15 milligrams (mg) to 150 mg. The vaccine, AV0328, targets the broadly expressed microbial antigen, poly-N-acetyl glucosamine (PNAG). AV0328 was safe and well-tolerated in the study, with only minor and transient injection-site reactions in each dosing group.

In addition, researchers noted "clear increases" in antibody titers against PNAG at the two highest doses—75 mg and 150 mg—as well as complement activation and binding to the PNAG antigen. In cell culture, "robust bactericidal killing of N. gonorrhea, including antibiotic-resistant strains, and N. meningitidis (serogroups A, B, C, W, Y), as well as opsonic killing of S. pneumoniae, multi-drug resistant Klebsiella pneumonia, colistin and multi-drug resistant strains of E. coli and S. aureus, including MRSA clinical isolates, was observed," according to the release.

"We are very encouraged by these early clinical data demonstrating the safety, tolerability, and initial indications of clinical activity of AV0328 in humans," said Hal Landy, MD, Alopexx chief medical officer. "We look forward to further evaluating AV0328 against a breadth of infections caused by PNAG-expressing pathogens, including serious soft-tissue infections caused by methicillin-resistant S. aureus (MRSA), pneumonia, meningitis, tuberculosis, and sexually transmitted diseases, including those caused by antibiotic-resistant organisms."
Oct 25 Alopexx news release


Study looks at role of shared providers in transmission of CRE infections

Originally published by CIDRAP News Oct 25

A new study by researchers at the University of Virginia suggests that hospital patients who shared healthcare providers with carbapenem-resistant Enterbacteriaceae (CRE) patients may have an increased risk of acquiring a CRE infection.

In a paper published yesterday in Infection Control and Hospital Epidemiology, the researchers describe a 1:4 case-control study conducted at a tertiary care hospital in central Virginia from May 2011 through March 2015. The objective of the study was to investigate the role healthcare providers play in patient-to-patient CRE transmission in a facility with a robust CRE surveillance program. With a mortality rate of nearly 50%, CRE are among the most urgent drug-resistant healthcare threats.

The study included case-patients with one or more negative CRE tests followed by a positive culture and a length of stay of more than 9 days. The controls were patients with two negative test results who were staying at the hospital at approximately the same time as the case-patients. Nonphysician providers were compared between study patients and sources during their evaluation windows. Dichotomous and continuous exposures were developed from the number of source-shared providers and were used in univariate and multivariate regression.

A total of 121 cases and 484 controls were included in the study. Multivariate analysis showed that the odds of a case being exposed to one or more shared-source providers was 2.27 times the odds of a control being exposed to one or more shared-source providers. Multivariate continuous exposure showed odds of 1.02 for case patients compared with controls.

"In summary, results from this study indicate an important relationship between sharing providers with CRE patients and increasing the risk of CRE acquisition," the authors write. "This finding indicates the importance of hand hygiene in infection prevention as well as the potential for limiting shared providers through additional regulation and improved cohorting of CRE patients, particularly in high-risk units."
Oct 24 Infect Control Hosp Epidemiol abstract 


Ethiopian scientists detect resistant pathogens in hospital air

Originally published by CIDRAP News Oct 25

Ethiopian researchers detected extended-spectrum-beta-lactamase (ESBL)–producing and Metallo-beta-lactamase (MBL)–producing P aeruginosa and Acinetobacter baumannii in air samples in their referral hospital, according to a study this week in Antimicrobial Resistance and Infection Control.

The team conducted a cross-sectional study at Wolaita Sodo University Teaching and Referral Hospital from Dec 1, 2015, to Apr 30, 2016. They collected 216 total indoor air samples during the first week of each month on Mondays and Fridays. They obtained 67 isolates (43 A baumannii and 24 P aeruginosa), for an overall isolation rate of 31%.

ESBL production was observed in 24 (55.8%) of the isolates and MBL production in 13 (30.2%). Five isolates (11.6%) contained both.

The authors conclude, "Though the current isolates were not identified from patients in this study, the role of contaminated indoor air for the production of ESBL and MBL isolates could play a major role if contact is established."
Oct 23 Antimicrob Resist Infect Control study


Researchers use electronic health records to track C difficile exposure

Originally published by CIDRAP News Oct 24

Using electronic health record (EHR) data to track patient movement enabled researchers to identify a previously unrecognized source of Clostridium difficile infection (CDI) at a large university hospital, according to a research letter published yesterday in JAMA Internal Medicine.

In the study, researchers with the University of California, San Francisco Medical Center analyzed EHR data from all adult hospitalizations from January 2013 to December 2015 and followed patients for the development of CDI for 60 days from the time they passed through a given space. Their aim was to track patient movement to see whether using a hospital space—particularly a procedural or diagnostic common area—within 24 hours of a CDI patient's use was associated with an increased risk of CDI.

Patients with CDI were considered positive for infection from the time the positive test was ordered until discharge, and hospital spaces were considered potentially contaminated for 24 hours after a patient with CDI visited them. All patients who had not yet tested positive for CDI and passed through a space while it was potentially contaminated were considered exposed to C difficile, while patients who occupied the same space at any other time were part of the unexposed control group.

Overall, there were 86,648 adult hospitalizations and 434,475 patient location changes during the study period, and 1,152 CDI-positive patients moved through a mean 4.2 hospital locations.

While exposure and risk varied across those locations, the researchers observed that the computer tomography scanner in the emergency department was the only area where exposure to CDI was significantly associated with CDI developmentI (incidence, 4%; odds ratio [OR], 2.5). The association remained significant (OR, 2.7) after the researchers extended the incubation period to 72 hours and adjusted for covariates. A follow-up investigation revealed that cleaning practices for the scanner table had not been updated to match methods applied in other radiology suites.

The authors of the letter say using EHR data for spatial and temporal analytics could be a strategy for infection control at other hospitals. 
Oct 23 JAMA Intern Med research letter


Salmonella strain in US pigs linked to resistant group from Europe

Originally published by CIDRAP News Oct 23

A new study published in Clinical infectious Diseases suggests that a Salmonella strain circulating in pigs in the US Midwest is part of an emerging clade from Europe that is resistant to multiple antibiotics and may pose a public health risk.

The strain, Salmonella 4,[5],12:i:-, causes many foodborne disease outbreaks mostly tied to pigs and pork products and is expanding in the United States, according to the report by researchers from Minnesota and the United Kingdom.

The team used whole-genome sequencing to assess the relatedness of 659 S 4,[5],12:i:- isolates and 325 S Typhimurium isolates from various sources and locations in the United States and Europe. They also searched for resistance genes and other virulence factors and, for 50 livestock isolates and 22 human isolates, determined the antimicrobial resistance phenotypes.

The researchers found that the S 4,[5],12:i:- isolates fell into two main clades, regardless of their host or place of origin. Eighty-four percent of the US isolates recovered from 2014 through 2016, including nearly all those from pigs in the Midwest, were part of an emerging clade. This clade carried multiple genetic markers for antimicrobial resistance, including resistance to ampicillin, streptomycin, sulphonamides, and tetracyclines.

In addition, phenotypic (actual) resistance to enrofloxacin and ceftiofur was found in 11 of the 50 tested livestock isolates and 9 of the 22 human isolates. This was accompanied by plasmid-mediated resistance genes.

The authors conclude that S 4,[5],12:i:- strains circulating in Midwestern swine herds "are likely part of an emerging multidrug resistant clade first reported in Europe, and can carry plasmid-mediated resistance genes that may be transmitted horizontally to other bacteria and thus could represent a public-health concern."
Oct 23 Clin Infect Dis abstract


CDC awards $9 million more for research to slow antibiotic resistance

Originally published by CIDRAP News Oct 23

The US Centers for Disease Control and Prevention (CDC) today announced $9 million in awards to support research into new ways to combat antibiotic resistance and to identify knowledge gaps related to the problem. The support will go to 25 centers, including several major universities and other institutions, such as the Children's Hospital of Philadelphia and the J. Craig Venter Institute.

In its announcement, the CDC said the awards are part of its Antibiotic Resistance Solutions Initiative, intended to grow innovative approaches to fighting antibiotic resistance. In fiscal years 2016 and 2017 the initiative awarded more than $24 million.

The CDC said in a press release e-mailed to journalists that the latest round of awards is targeted to discovering and testing new strategies to protect patients from resistance threats in healthcare settings, investigate the threat from the human microbiome, and probe the impact of antibiotic resistance elements—genetic material that can move between and combine with bacteria—from environmental sources such as surface water and soil.

Newly funded projects are detailed in a list on the CDC's website.
Oct 23 CDC announcement

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